Time-of-flight methodologies with large-area diamond detectors for the effectively characterization of tens MeV protons

A novel detector based on a polycrystalline diamond sensor is here employed in an advanced time-of-flight scheme for the characterization of energetic ions accelerated during laser-matter interactions. The optimization of the detector and of the advanced TOF methodology allow to obtain signals characterized by high signal-to-noise ratio and high dynamic range even in the most challenging experimental environments, where the interaction of high-intensity laser pulses with matter leads to effective ion acceleration, but also to the generation of strong Electromagnetic Pulses (EMPs) with intensities up to the MV/m order. These are known to be a serious threat for the fielded diagnostic systems. In this paper we report on the measurement performed with the PW-class laser system Vega 3 at CLPU (30 J energy, 1021 W/cm2 intensity, 30 fs pulses) irradiating solid targets, where both tens of MeV ions and intense EMP fields were generated. The data were analyzed to retrieve a calibrated proton spectrum and in particular we focus on the analysis of the most energetic portion (E > 5.8 MeV) of the spectrum showing a procedure to deal with the intrinsic lower sensitivity of the detector in the mentioned spectral-range

Proton stopping measurements at low velocity in warm dense carbon

: Ion stopping in warm dense matter is a process of fundamental importance for the understanding of the properties of dense plasmas, the realization and the interpretation of experiments involving ion-beam-heated warm dense matter samples, and for inertial confinement fusion research. The theoretical description of the ion stopping power in warm dense matter is difficult notably due to electron coupling and degeneracy, and measurements are still largely missing. In particular, the low-velocity stopping range, that features the largest modelling uncertainties, remains virtually unexplored. Here, we report proton energy-loss measurements in warm dense plasma at unprecedented low projectile velocities. Our energy-loss data, combined with a precise target characterization based on plasma-emission measurements using two independent spectroscopy diagnostics, demonstrate a significant deviation of the stopping power from classical models in this regime. In particular, we show that our results are in closest agreement with recent first-principles simulations based on time-dependent density functional theory

Innovative education and training in high power laser plasmas (PowerLaPs) for plasma physics, high power laser matter interactions and high energy density physics: experimental diagnostics and simulations

The second and final year of the Erasmus Plus programme "Innovative Education and Training in high power laser plasmas", otherwise known as PowerLaPs, is described. The PowerLaPs programme employs an innovative paradigm in that it is a multi-centre programme where teaching takes place in five separate institutes with a range of different aims and styles of delivery. The "in class" time is limited to four weeks a year, and the programme spans two years. PowerLaPs aims to train students from across Europe in theoretical, applied, and laboratory skills relevant to the pursuit of research in laser plasma interaction physics and inertial confinement fusion (ICF). Lectures are intermingled with laboratory sessions, and continuous assessment activities. The programme, which is led by workers from the Hellenic Mediterranean University, and supported by co-workers from Queens University Belfast, the University of Bordeaux, the Czech Technical University in Prague, Ecole Polytechnique, the University of Ioannina, the University of Salamanca, and the University of York, has just finished its second and final year. Six Learning Teaching Training (LTT) activities have been held, at the Queens University Belfast, the University of Bordeaux, the Czech Technical University, the University of Salamanca, and the Institute of Plasma Physics and Lasers (CPPL) of the Hellenic Mediterranean University. The last of these institute hosted two two-week long Intensive Programmes (IPs), whilst the activities at the other four universities were each five days in length. In addition to this a "Multiplier Event" was held at the University of Ioannina, which will be briefly described. In this second year the work has concentrated upon training in both experimental diagnostics and simulation techniques appropriate to the study of Plasma Physics, High Power Laser-Matter Interactions and High Energy Density Physics. The nature of the programme will be described in detail and some metrics relating to the activities carried out will be presented. In particular this paper will focus upon the overall assessment of the programme

Role of NRG1 in Mouse Heart Development

During embryonic development, cellular interactions are crucial to orchestrate the processes that give rise to the final body plan. The heart is the first organ to form and function during development. The formation of trabeculae, myocardial protrusions covered by endocardium that grow towards the lumen of the ventricles, is the first sign of chamber development, and occurs in response to signals from the endocardium that activate the overlying myocardium. Trabeculae are crucial for increasing the internal ventricular surface, favouring oxygen exchange and nourishment of the cardiomyocytes. Previous studies in mice have shown that NEUREGULIN1 (NRG1), a ligand belonging to the Epidermal Growth Factor family expressed in the endocardium, and its more widespread receptors -ERBB2,4- are crucial for ventricular trabeculation, but the cellular processes affected by Nrg1 loss in the heart are not well understood. To gain an insight into the role of NRG1 in heart development, we have used conditional loss- and gain-of-function mouse models. We have found that endothelial-specific, Tie2Cre-mediated, Nrg1 inactivation disrupts trabecular morphology and patterning, and reduces ventricular cardiomyocyte proliferation, while paradoxically, the compact myocardium appeared thickened. Global gene expression analysis in embryonic hearts by RNA-seq revealed a dysregulation of apico-basal polarity marker genes. We thus examined whether cellular polarity and oriented cell division were affected in chamber cardiomyocytes. We observed a loss of polarity (LAMININS-ITGα6, PKC, N-CADHERIN) in cardiomyocytes, and an increase in parallel divisions in chamber cardiomyocytes of Nrg1flox;Tie2Cre mutants. This finding would explain the thickened compact myocardium and the impaired trabeculation of these mice. In addition to trabeculation defects, Nrg1flox;Tie2Cre mutant hearts show hypoplastic valves, due to impaired epithelial-mesenchyme transition (EMT) of presumptive valve endocardial cells, presumably because binding and activation of the receptor ERBB2,3 by NRG1 in this region is impaired. To study the function of NRG1 signalling at later stages of ventricular chamber development, we have induced Nrg1 deletion during compaction, using the Cdh5CreERT2 driver. Late Nrg1 inactivation in cardiac endothelium leads to a thinner compact myocardium, and defective myocardial patterning and coronary vessel morphogenesis. We have also generated a conditional gain-of-function transgenic line for NRG1. Tie2Cre-mediated Nrg1 overexpression lead to thickened valves, and Nkx2.5Cre-mediated Nrg1 lead also to thickened valves, ventricular septal defect and ventricular chamber dilation. Our results indicate that NRG1 is essential from early to late stages of ventricular wall development. NRG1 is required for cardiomyocyte polarization and oriented cell division during trabeculation, for endocardial cushion formation during valve development, and for chamber maturation and coronary vessel formation during compaction.This work was performed in Dr. José Luis de la Pompa laboratory at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) in Madrid. This study was funded by grants SAF2013-45543-R, SAF2016-78370-R, CB16/11/00399 (CIBER CV) and RD16/0011/0021 (TERCEL) from the Ministerio de Ciencia, Innovación y Universidades, and grants from the Fundación BBVA (Ref.: BIO14_298) and Fundación La Marató (Ref.: 20153431) to JLDLP… Paula Gómez Apiñániz held a PhD fellowship from MEIC FPI Program with the reference BES- 2014-068818

Impact of a resistive superconductive fault current limiter in a multi-terminal HVDC grid

The relevance of multi-terminal HVDC grids is expected to increase in next years. However, there are still several technical, economical and legal limitations that interfere with the construction of those multi-terminal links. One of the main technical obstacles is the handling of DC fault currents, because the interruption of DC currents in HVDC systems is nowadays a challenge. Among other proposals, the application of Superconducting Fault Current Limiters (SFCLs) combined with a mechanical Circuit Breaker (CB) solves technically that issue, according to the analysis and simulation results presented in this paper.The authors thank the support from the Spanish Ministry of Economy, Industry and Competitiveness (project ENE2016-79145-R AEI/FEDER, UE), the Basque Government (project ELKARTEK KK-2017/00083 and GISEL research group IT1083-16), as well as from the University of the Basque Country UPV/EHU (project EHUA15/25 and research group funding PPG17/23)

Nrg1 Regulates Cardiomyocyte Migration and Cell Cycle in Ventricular Development.

BACKGROUND Cardiac ventricles provide the contractile force of the beating heart throughout life. How the primitive endocardium-layered myocardial projections called trabeculae form and mature into the adult ventricles is of great interest for biology and regenerative medicine. Trabeculation is dependent on the signaling protein Nrg1 (neuregulin-1). However, the mechanism of action of Nrg1 and its role in ventricular wall maturation are poorly understood. METHODS We investigated the functions and downstream mechanisms of Nrg1 signaling during ventricular chamber development using confocal imaging, transcriptomics, and biochemical approaches in mice with cardiac-specific inactivation or overexpression of Nrg1. RESULTS Analysis of cardiac-specific Nrg1 mutant mice showed that the transcriptional program underlying cardiomyocyte-oriented cell division and trabeculae formation depends on endocardial Nrg1 to myocardial ErbB2 (erb-b2 receptor tyrosine kinase 2) signaling and phospho-Erk (phosphorylated extracellular signal-regulated kinase; pErk) activation. Early endothelial loss of Nrg1 and reduced pErk activation diminished cardiomyocyte Pard3 and Crumbs2 (Crumbs Cell Polarity Complex Component 2) protein and altered cytoskeletal gene expression and organization. These alterations are associated with abnormal gene expression related to mitotic spindle organization and a shift in cardiomyocyte division orientation. Nrg1 is crucial for trabecular growth and ventricular wall thickening by regulating an epithelial-to-mesenchymal transition-like process in cardiomyocytes involving migration, adhesion, cytoskeletal actin turnover, and timely progression through the cell cycle G2/M phase. Ectopic cardiac Nrg1 overexpression and high pErk signaling caused S-phase arrest, sustained high epithelial-to-mesenchymal transition-like gene expression, and prolonged trabeculation, blocking compact myocardium maturation. Myocardial trabecular patterning alterations resulting from above- or below-normal Nrg1-dependent pErk activation were concomitant with sarcomere actin cytoskeleton disorganization. The Nrg1 loss- and gain-of-function transcriptomes were enriched for Yap1 (yes-associated protein-1) gene signatures, identifying Yap1 as a potential downstream effector. Furthermore, biochemical and imaging data reveal that Nrg1 influences pErk activation and Yap1 nuclear-cytoplasmic distribution during trabeculation. CONCLUSIONS These data establish the Nrg1-ErbB2/ErbB4-Erk axis as a crucial regulator of cardiomyocyte cell cycle progression and migration during ventricular development.This study was supported by grants PID2019-104776RB-I00 and PID2020- 120326RB-I00, CB16/11/00399 (Centro de investigación Biomédica en Red Cardiovascular [CIBER CV]) from Ministerio de Ciencia e Innovación (MCIN)/ Agencia Española de Investigación (AEI)/10.13039/501100011033, Fundación Banco Bilbao Vizcaya Argentaria (BBVA; reference number: BIO14_298), Fundació La Marató de TV3 (reference number: 20153431), and the Spanish Society for Cardiology (SECSCFG-INV-CFG 21/004) to J.L. de la Pompa. J. Grego-Bessa was funded by Programa Atracción de Talento from Comunidad de Madrid (reference number 2016T1/BMD1540). Support for this publication also came from the European Regional Development Fund. The Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), MCIN, and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S) financed by MCIN/ AEI/10.13039/501100011033.S

Thermal wave scattering by two overlapping and parallel cylinders

In this paper an analytical solution of the temperature of an opaque material containing two overlapping and parallel subsurface cylinders, illuminated by a modulated light beam, is presented. The method is based on the expansion of plane and cylindrical thermal waves in series of Bessel and Hankel functions. This model is addressed to the study of heat propagation in composite materials with interconnection between inclusions, as is the case of inverse opals and fiber reinforced composites. Measurements on calibrated samples using lock-in infrared thermography confirm the validity of the model

Myocardial Bmp2 gain causes ectopic EMT and promotes cardiomyocyte proliferation and immaturity

International audienceDuring mammalian heart development, restricted myocardial Bmp2 expression is a key patterning signal for atrioventricular canal specification and the epithelial-mesenchyme transition that gives rise to the valves. Using a mouse transgenic line conditionally expressing Bmp2, we show that widespread Bmp2 expression in the myocardium leads to valve and chamber dysmorphogenesis and embryonic death by E15.5. Transgenic embryos show thickened valves, ventricular septal defect, enlarged trabeculae and dilated ventricles, with an endocardium able to undergo EMT both in vivo and in vitro. Gene profiling and marker analysis indicate that cellular proliferation is increased in transgenic embryos, whereas chamber maturation and patterning are impaired. Similarly, forced Bmp2 expression stimulates proliferation and blocks cardiomyocyte differentiation of embryoid bodies. These data show that widespread myocardial Bmp2 expression directs ectopic valve primordium formation and maintains ventricular myocardium and cardiac progenitors in a primitive, proliferative state, identifying the potential of Bmp2 in the expansion of immature cardiomyocytes