Amores y estocadas: vida turbulenta de Don Francisco de Quevedo

Novela histórica recuperada de los archivos del olvido por Ignacio Arellano, aficionado lector, incitado por el reclamo de la vieja colección Capa y Espada ("Amor, aventuras e intriga en el escenario caballeresco y romático de nuestra historia"

Catalytic Intermolecular Hetero-Dehydro-Diels–Alder Cycloadditions: Regio- and Diasteroselective Synthesis of 5,6-Dihydropyridin-2-ones

A novel catalyzed intermolecular heterodehydro-Diels–Alder reaction between push–pull 1,3-dien-5-ynes and aldimines or silylaldimines is reported. The sequence is promoted both by gold(I) or silver(I) catalysts and leads to the diastereo- and regioselective formation of 5,6-dihydropyridin-2-onesMICINN (Spain) (grants CTQ2009-09949, CTQ2010-16790, PTA2008-1524-P contract to J.M.F.-G. and Ramon y Cajal postdoctoral contract to M.A.F.-R.) and FICYT (project IB08-088)This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/page/policy/articlesonrequest/index.htm

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074

El conflicto entre cristianos y musulmanes en las relaciones de sucesos : la liberación de Buda

Este trabajo propone el análisis de una selección de textos escritos en romance sobre la derrota turca y la toma de la ciudad de Buda en 1686, que denuncian la exultante acogida popular de la noticia de las gestas cristianas en Centroeuropa, la percepción del eterno conflicto entre Oriente y Occidente y la proyección del imaginario colectivo del siglo xvii acerca de la lucha contra los infieles.This paper offers the analysis of a selection of texts, written in Romance languages, about the Turkish defeat and the conquest of the city of Buda in 1686, which provide evidence of the popular exultation at the news of the Christian achievements in Central Europe, the perception of the eternal conflict between East and West, and the projection of the seventeenth-century collective imagination regarding the struggle against the infidel

The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

The CARMENES search for exoplanets around M dwarfs Guaranteed time observations Data Release 1 (2016-2020)

I. Ribas et al.[Context] The CARMENES instrument, installed at the 3.5 m telescope of the Calar Alto Observatory in Almería, Spain, was conceived to deliver high-accuracy radial velocity (RV) measurements with long-term stability to search for temperate rocky planets around a sample of nearby cool stars. Moreover, the broad wavelength coverage was designed to provide a range of stellar activity indicators to assess the nature of potential RV signals and to provide valuable spectral information to help characterise the stellar targets.[Aims] We describe the CARMENES guaranteed time observations (GTO), spanning from 2016 to 2020, during which 19 633 spectra for a sample of 362 targets were collected. We present the CARMENES Data Release 1 (DR1), which makes public all observations obtained during the GTO of the CARMENES survey.[Methods] The CARMENES survey target selection was aimed at minimising biases, and about 70% of all known M dwarfs within 10 pc and accessible from Calar Alto were included. The data were pipeline-processed, and high-level data products, including 18 642 precise RVs for 345 targets, were derived. Time series data of spectroscopic activity indicators were also obtained.[Results] We discuss the characteristics of the CARMENES data, the statistical properties of the stellar sample, and the spectroscopic measurements. We show examples of the use of CARMENES data and provide a contextual view of the exoplanet population revealed by the survey, including 33 new planets, 17 re-analysed planets, and 26 confirmed planets from transiting candidate follow-up. A subsample of 238 targets was used to derive updated planet occurrence rates, yielding an overall average of 1.44 ± 0.20 planets with 1 M⊕ < Mpl sin i < 1000 M⊕ and 1 day < Porb < 1000 days per star, and indicating that nearly every M dwarf hosts at least one planet. All the DR1 raw data, pipeline-processed data, and high-level data products are publicly available online.[Conclusions] CARMENES data have proven very useful for identifying and measuring planetary companions. They are also suitable for a variety of additional applications, such as the determination of stellar fundamental and atmospheric properties, the characterisation of stellar activity, and the study of exoplanet atmospheres.CARMENES is an instrument at the Centro Astronómico Hispano en Andalucía (CAHA) at Calar Alto (Almería, Spain), operated jointly by the Junta de Andalucía and the Instituto de Astrofísica de Andalucía (CSIC). CARMENES was funded by the Max-Planck-Gesellschaft (MPG), the Consejo Superior de Investigaciones Científicas (CSIC), the Ministerio de Economía y Competitividad (MINECO) and the European Regional Development Fund (ERDF) through projects FICTS-2011-02, ICTS-2017-07-CAHA-4, and CAHA16-CE-3978, and the members of the CARMENES Consortium (Max-Planck-Institut für Astronomie, Instituto de Astrofísica de Andalucía, Landessternwarte Königstuhl, Institut de Ciències de l’Espai, Institut für Astrophysik Göttingen, Universidad Complutense de Madrid, Thüringer Landessternwarte Tautenburg, Instituto de Astrofísica de Canarias, Hamburger Sternwarte, Centro de Astrobiología and Centro Astronómico Hispano-Alemán), with additional contributions by the MINECO, the Deutsche Forschungsgemeinschaft (DFG) through the Major Research Instrumentation Programme and Research Unit FOR2544 “Blue Planets around Red Stars”, the Klaus Tschira Stiftung, the states of Baden-Württemberg and Niedersachsen, and by the Junta de Andalucía. We acknowledge financial support from the Spanish Agencia Estatal de Investigación of the Ministerio de Ciencia e Innovación (AEI-MCIN) and the ERDF “A way of making Europe” through projects PID2020-117493GB-I00, PID2019-109522GB-C5[1:4], PID2019-110689RB-I00, PID2019-107061GB-C61, PID2019-107061GB-C64, PGC2018-098153-B-C33, PID2021-125627OB-C31/AEI/10.13039/501100011033, and the Centre of Excellence “Severo Ochoa” and “María de Maeztu” awards to the Institut de Ciències de l’Espai (CEX2020-001058-M), Instituto de Astrofísica de Canarias (CEX2019-000920-S), Instituto de Astrofísica de Andalucía (SEV-2017-0709), and Centro de Astrobiología (MDM-2017-0737). We also benefited from additional funding from: the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and the Agència de Gestió d’Ajuts Universitaris i de Recerca of the Generalitat de Catalunya, with additional funding from the European FEDER/ERDF funds, and from the Generalitat de Catalunya/CERCA programme; the DFG through the Major Research Instrumentation Programme and Research Unit FOR2544 “Blue Planets around Red Stars” (RE 2694/8-1); the University of La Laguna through the Margarita Salas Fellowship from the Spanish Ministerio de Universidades ref. UNI/551/2021-May-26, and under the EU Next Generation funds; the Gobierno de Canarias through projects ProID2021010128 and ProID2020010129; the Spanish MICINN under Ramón y Cajal programme RYC-2013-14875; the “Fondi di Ricerca Scientifica d’Ateneo 2021” of the University of Rome “Tor Vergata”; and the programme “Alien Earths” supported by the National Aeronautics and Space Administration (NASA) under agreement No. 80NSSC21K0593. TPeer reviewe

International lower limb collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures

Trauma remains a major cause of mortality and disability across the world1, with a higher burden in developing nations2. Open lower extremity injuries are devastating events from a physical3, mental health4, and socioeconomic5 standpoint. The potential sequelae, including risk of chronic infection and amputation, can lead to delayed recovery and major disability6. This international study aimed to describe global disparities, timely intervention, guideline-directed care, and economic aspects of open lower limb injuries

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.We thank all members of the Brain Metastasis Group and A. Chalmers, E. Wagner, O. Fernández-Capetillo, R. Ciérvide and A. Hidalgo for critical discussion of the manuscript; the CNIO Core Facilities for their excellent assistance; and Fox Chase Cancer Center Transgenic Facility for generation of S100A9 mice. We thank EuCOMM repository for providing S100A9 targeted embryonic stem cells. We also thank J. Massagué (MSKCC) for some of the BrM cell lines and M. Bosenberg (Yale) for the YUMM1.1 cell line. Samples from patients included in this study that provided by the Girona Biomedical Research Institute (IDIBGI) (Biobanc IDIBGI, B.0000872) are integrated into the Spanish National Biobanks Network and in the Xarxa de Bancs de Tumors de Catalunya (XBTC) financed by the Pla Director d’Oncologia de Catalunya. All patients consented to the storage of these samples in the biobank and for their use in research projects. This study was funded by MINECO (SAF2017-89643-R) (M.V.), Fundació La Marató de TV3 (201906-30-31-32) (J.B.-B., M.V. and A.C.), Fundación Ramón Areces (CIVP19S8163) (M.V.) and CIVP20S10662 (E.O.P.), Worldwide Cancer Research (19-0177) (M.V. and E.C.-J.M.), Cancer Research Institute (Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC (Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Portuguese Foundation for Science and Technology (SFRH/bd/100089/2014) (C.M.), Boehringer-Ingelheim Fonds MD Fellowship (L.M.), La Caixa International PhD Program Fellowship-Marie Skłodowska-Curie (LCF/BQ/DI17/11620028) (P.G.-G.), La Caixa INPhINIT Fellowship (LCF/BQ/DI19/11730044) (A.P.-A.), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A.-E.) and an AECC postdoctoral fellowship (POSTD19016PRIE) (N.P.). M.V. is an EMBO YIP member (4053). Additional support was provided by Gertrud and Erich Roggenbuck Stiftung (M.M.), Science Foundation Ireland Frontiers for the Future Award (19/FFP/6443) (L.Y.), Science Foundation Ireland Strategic Partnership Programme, Precision Oncology Ireland (18/SPP/3522) (L.Y.), Breast Cancer Now Fellowship Award with the generous support of Walk the Walk (2019AugSF1310) (D.V.), Science Foundation Ireland (20/FFP-P/8597) (D.V.), Paradifference Foundation (C.F.-T.), “la Caixa” Foundation (ID 100010434) (A.I.), European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement 847648 (CF/BQ/PI20/11760029) (A.I.), Champalimaud Centre for the Unknown (N.S.), Lisboa Regional Operational Programme (Lisboa 2020) (LISBOA01-0145-FEDER-022170) (N.S.), NCI (R01 CA227629; R01 CA218133) (S.I.G.), Fundació Roses Contra el Càncer (J.B.-B.), Ministerio de Universidades FPU Fellowship (FPU 18/00069) (P.T.), MICIN-Agencia Estatal de Investigación Fellowships (PRE2020-093032 and BES-2017-080415) (P.M. and E. Cintado, respectively), Ministerio de Ciencia, Innovación y Universidades-E050251 (PID2019-110292RB-I00) (J.L.T.), FCT (PTDC/MED-ONC/32222/2017) (C.C.F.), Fundação Millennium bcp (C.C.F.), private donations (C.C.F.) and the Foundation for Applied Cancer Research in Zurich (E.L.R. and M.W.)

The miniJPAS survey: A search for extreme emission-line galaxies

This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Context. Galaxies with extreme emission lines (EELGs) may play a key role in the evolution of the Universe, as well as in our understanding of the star formation process itself. For this reason an accurate determination of their spatial density and fundamental properties in different epochs of the Universe will constitute a unique perspective towards a comprehensive picture of the interplay between star formation and mass assembly in galaxies. In addition to this, EELGs are also interesting in order to explain the reionization of the Universe, since their interstellar medium (ISM) could be leaking ionizing photons, and thus they could be low z, analogous of extreme galaxies at high z. Aims. This paper presents a method to obtain a census of EELGs over a large area of the sky by detecting galaxies with rest-frame equivalent widths ≥300 Å in the emission lines [O II]λλ3727,3729Å, [O III]λ5007Å, and Hα. For this, we aim to use the J-PAS survey, which will image an area of ≈8000 deg2 with 56 narrow band filters in the optical. As a pilot study, we present a methodology designed to select EELGs on the miniJPAS images, which use the same filter dataset as J-PAS, and thus will be exportable to this larger survey. Methods. We make use of the miniJPAS survey data, conceived as a proof of concept of J-PAS, and covering an area of ≈1 deg2. Objects were detected in the rSDSS images and selected by imposing a condition on the flux in a given narrow-band J-PAS filter with respect to the contiguous ones, which is analogous to requiring an observed equivalent width larger than 300 Å in a certain emission line within the filter bandwidth. The selected sources were then classified as galaxies or quasi-stellar objects (QSOs) after a comparison of their miniJPAS fluxes with those of a spectral database of objects known to present strong emission lines. This comparison also provided a redshift for each source, which turned out to be consistent with the spectroscopic redshifts when available (|Δz/(1 + zspec)| ≤ 0.01). Results. The selected candidates were found to show a compact appearance in the optical images, some of them even being classified as point-like sources according to their stellarity index. After discarding sources classified as QSOs, a total of 17 sources turned out to exhibit EW0 ≥ 300 Å in at least one emission line, thus constituting our final list of EELGs. Our counts are fairly consistent with those of other samples of EELGs in the literature, although there are some differences, which were expected due to biases resulting from different selection criteria. © J. Iglesias-Páramo et al. 2022.This work has been partially funded by projects PID2019-107408GB-C44 from the Spanish PNAYA, co-funded with FEDER, and grand P18-FR-2664, funded by Junta de Andalucía. We acknowledge financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). RGD and LADG acknowledge financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709), and PID2019-109067-GB100. IM acknowledges financial support from the State Agency for Research of the Spanish MCIU through the PID2019-106027GB-C41. JCM acknowledges partial support from the Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE) through the grant PGC2018-097585-B-C22. SDP is grateful to the Fonds de Recherche du Québec – Nature et Technologies. LSJ acknowledges the support of CNPq (304819/2017-4) and FAPESP (2019/10923-5). JAFO acknowledges the financial support from the Spanish Ministry of Science and Innovation and the European Union – NextGenerationEU through the Recovery and Resilience Facility project ICTS-MRR-2021-03- CEFCA. Funding for the J-PAS Project has been provided by the Governments of España and Aragón though the Fondo de Inversión de Teruel, European FEDER funding and the MINECO and by the Brazilian agencies FINEP, FAPESP, FAPERJ and by the National Observatory of Brazil. Based on observations made with the JST/T250 telescope and PathFinder camera for the miniJPAS project at the Observatorio Astrofísico de Javalambre (OAJ), in Teruel, owned, managed, and operated by the Centro de Estudios de Física del Cosmos de Aragón (CEFCA). We acknowledge the OAJ Data Processing and Archiving Unit (UPAD) for reducing and calibrating the OAJ data used in this work. Funding for OAJ, UPAD, and CEFCA has been provided by the Governments of Spain and Aragón through the Fondo de Inversiones de Teruel; the Aragón Government through the Research Groups E96, E103, and E16_17R; the Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE) with grant PGC2018-097585-B-C21; the Spanish Ministry of Economy and Competitiveness (MINECO/FEDER, UE) under AYA2015-66211-C2-1-P, AYA2015-66211-C2-2, AYA2012-30789, and ICTS-2009-14; and European FEDER funding (FCDD10-4E-867, FCDD13-4E-2685). This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Funding for SDSS-IV has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science. The SDSS-IV web site is https://www.sdss.org/. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 898633.Peer reviewe