Sensing the turbulent large-scale motions with their wall signature

This study assesses the capability of extended proper orthogonal decomposition (EPOD) and convolutional neural networks (CNNs) to reconstruct large-scale and very-large-scale motions (LSMs and VLSMs respectively) employing wall-shear-stress measurements in wall-bounded turbulent flows. Both techniques are used to reconstruct the instantaneous LSM evolution in the flow field as a combination of proper orthogonal decomposition (POD) modes, employing a limited set of instantaneous wall-shear-stress measurements. Due to the dominance of nonlinear effects, only CNNs provide satisfying results. Being able to account for nonlinearities in the flow, CNNs are shown to perform significantly better than EPOD in terms of both instantaneous flow-field estimation and turbulent-statistics reconstruction. CNNs are able to provide a more effective reconstruction performance employing more POD modes at larger distances from the wall and employing lower wall-measurement resolutions. Furthermore, the capability of tackling nonlinear features of CNNs results in estimation capabilities that are weakly dependent on the distance from the wall.This work has been partially supported by Grant No. DPI2016-79401-R funded by the Spanish State Research Agency (SRA) and the European Regional Development Fund (ERDF). A.G. acknowledges Dr. A. Sánchez for insightful discussions about CNN architecture. The authors acknowledge Dr. R. Vinuesa for insightful comments and discussions

Aberration-free ultra-thin flat lenses and axicons at telecom wavelengths based on plasmonic metasurfaces

The concept of optical phase discontinuities is applied to the design and demonstration of aberration-free planar lenses and axicons, comprising a phased array of ultrathin subwavelength spaced optical antennas. The lenses and axicons consist of radial distributions of V-shaped nanoantennas that generate respectively spherical wavefronts and non-diffracting Bessel beams at telecom wavelengths. Simulations are also presented to show that our aberration-free designs are applicable to high numerical aperture lenses such as flat microscope objectives

Cynara cardunculus L. gasification in a bubbling fluidized bed: the effect of magnesite and olivine on product gas, tar and gasification performance

peer-reviewedGasification of Cynara cardunculus L. was performed in a bubbling fluidized bed (BFB) using air as gasifying agent and, magnesite and olivine as different bed materials. Temperature was varied during the experiments (700-800 degrees C) with fixed biomass feeding and air flow rate. The effect of using the magnesite and olivine on gas and tar composition, carbon and biomass conversion, and cold gas efficiency was investigated. The product gas showed high hydrogen content (13-16% v/v) for both magnesite and olivine in the studied temperature range. Higher heating value and gas yield were improved with increasing the temperature from 700 to 800 degrees C. Biomass and carbon conversion were greater than 75%, obtaining values higher than 90% for both 700 and 800 degrees C in magnesite and for 800 degrees C in olivine. Small differences in total tar were observed between materials, although tar composition was very different. BTEX were higher for olivine and similar PAHs was obtained for both magnesite and olivine. A higher catalytic activity at 800 degrees C was observed for magnesite. Gasification performance was better with magnesite at 700 degrees C while olivine showed better properties at 800 degrees C. (C) 2016 Elsevier Ltd. All rights reserved.ACCEPTEDpeer-reviewe

Specific targeting of the NRF2/β-TrCP axis promotes beneficial effects in NASH

Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease that compromises liver function, for which there is not a specifically approved medicine. Recent research has identified transcription factor NRF2 as a potential therapeutic target. However, current NRF2 activators, designed to inhibit its repressor KEAP1, exhibit unwanted side effects. Alternatively, we previously introduced PHAR, a protein-protein interaction inhibitor of NRF2/β-TrCP, which induces a mild NRF2 activation and selectively activates NRF2 in the liver, close to normal physiological levels. Herein, we assessed the effect of PHAR in protection against NASH and its progression to fibrosis. We conducted experiments to demonstrate that PHAR effectively activated NRF2 in hepatocytes, Kupffer cells, and stellate cells. Then, we used the STAM mouse model of NASH, based on partial damage of endocrine pancreas and insulin secretion impairment, followed by a high fat diet. Non-invasive analysis using MRI revealed that PHAR protects against liver fat accumulation. Moreover, PHAR attenuated key markers of NASH progression, including liver steatosis, hepatocellular ballooning, inflammation, and fibrosis. Notably, transcriptomic data indicate that PHAR led to upregulation of 3 anti-fibrotic genes (Plg, Serpina1a, and Bmp7) and downregulation of 6 pro-fibrotic (including Acta2 and Col3a1), 11 extracellular matrix remodeling, and 8 inflammatory genes. Overall, our study suggests that the mild activation of NRF2 via the protein-protein interaction inhibitor PHAR holds promise as a strategy for addressing NASH and its progression to liver fibrosisThis research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) (grants PID2019-110061RB-I00, PID-2021-122766OB-100 and PDC2021-121421-I00, PDC2022-133765-I00, MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe” by the European Union.), CIBERdem and CIBERned (ISCIII), and The Autonomous Community of Madrid (grant P2022/BMD-7230). RFG enjoyed a FPI contract of MINECO (FPI-2017). DCS is a holder of a FPI contract of MICINN (Ministry of Science and Innovation, FPI-2020, PRE2020-091886). JJV is holder of a FPU contract of MIU (Ministry of Universities, FPU2020, FPU20/03326

ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology

© 2021 The Authors.Sorafenib is a multikinase inhibitor widely used in cancer therapy with an antitumour effect related to biological processes as proliferation, migration or invasion, among others. Initially designed as a Raf inhibitor, Sorafenib was later shown to also block key molecules in tumour progression such as VEGFR and PDGFR. In addition, sorafenib has been connected with key signalling pathways in cancer such as EGFR/EGF. However, no definitive clue about the molecular mechanism linking sorafenib and EGF signalling pathway has been established so far. Our data in HeLa, U2OS, A549 and HEK293T cells, based on in silico, chemical and genetic approaches demonstrate that the MEK5/ERK5 signalling pathway is a novel target of sorafenib. In addition, our data show how sorafenib is able to block MEK5-dependent phosphorylation of ERK5 in the Ser218/Tyr220, affecting the transcriptional activation associated with ERK5. Moreover, we demonstrate that some of the effects of this kinase inhibitor onto EGF biological responses, such as progression through cell cycle or migration, are mediated through the effect exerted onto ERK5 signalling pathway. Therefore, our observations describe a novel target of sorafenib, the ERK5 signalling pathway, and establish new mechanistic insights for the antitumour effect of this multikinase inhibitor.This work was supported by grants from Fundación Leticia Castillejo Castillo, Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-094093-B-I00) to RSP and MJRH. OR holds a contract for accessing the Spanish System of Science, Technology, and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013). RSP and MJRH's Research Institute, and the work carried out in their laboratory, received partial support from the European Community through the FEDER. RPS and EAL hold a research predoctoral contract cofounded by the European Social Fund and UCLM. The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21) and the Generalitat Valenciana (PROMETEO/2016/006) support work in the Encinar´s laboratory. Authors are grateful to Dr.G- Ferrer Mayorga for her assistance in the transwell assays, and to the ‘Centro de Computación Científica’ (CCC-UAM) for letting us to take advantage of the computer cluster Cibeles (https://www.ccc.uam.es/) and for providing computing facilities