Ethane-beta-Sultam Modifies the Activation of the Innate Immune System Induced by Intermittent Ethanol Administration in Female Adolescent Rats

Intermittent ethanol abuse or ‘binge drinking’ during adolescence induces neuronal damage, which may be associated with cognitive dysfunction. To investigate the neurochemical processes involved, rats were administered either 1 g/kg or 2 g/kg ethanol in a ‘binge drinking’ regime. After only 3 weeks, significant activation of phagocytic cells in the peripheral (alveolar macrophages) and the hippocampal brain region (microglia cells) was present,as exemplified by increases in the release of pro-inflammatory cytokines in the macrophages and of iNOS in the microglia. This was associated with neuronal loss in the hippocampus CA1 region. Daily supplementation with a taurine prodrug, ethane-β-sultam, 0.028 g/kg, during the intermittent ethanol loading regime, supressed the release of the pro-inflammatory cytokines and of reactive nitrogen species, as well as neuronal loss, particularly in the rats administered the lower dose of ethanol, 1 g/kg. Plasma, macrophage and hippocampal taurine levels increased marginally after ethane-β-sultam supplementation. The ‘binge drinking’ ethanol rats administered 1 g/kg ethanol showed increased latencies to those of the control rats in their acquisition of spacial navigation in the Morris Water Maze, which was normalised to that of the controls values after ethane-β-sultam administration. Such results confirm that the administration of ethane-β-sultam to binge drinking rats reduces neuroinflammation in both the periphery and the brain, suppresses neuronal loss, and improved working memory of rats in a water maze study

Machine Learning Can Predict the Timing and Size of Analog Earthquakes

Despite the growing spatiotemporal density of geophysical observations at subduction zones, predicting the timing and size of future earthquakes remains a challenge. Here we simulate multiple seismic cycles in a laboratory‐scale subduction zone. The model creates both partial and full margin ruptures, simulating magnitude M_w 6.2–8.3 earthquakes with a coefficient of variation in recurrence intervals of 0.5, similar to real subduction zones. We show that the common procedure of estimating the next earthquake size from slip‐deficit is unreliable. On the contrary, machine learning predicts well the timing and size of laboratory earthquakes by reconstructing and properly interpreting the spatiotemporally complex loading history of the system. These results promise substantial progress in real earthquake forecasting, as they suggest that the complex motion recorded by geodesists at subduction zones might be diagnostic of earthquake imminence

A lattice Boltzmann study of non-hydrodynamic effects in shell models of turbulence

A lattice Boltzmann scheme simulating the dynamics of shell models of turbulence is developed. The influence of high order kinetic modes (ghosts) on the dissipative properties of turbulence dynamics is studied. It is analytically found that when ghost fields relax on the same time scale as the hydrodynamic ones, their major effect is a net enhancement of the fluid viscosity. The bare fluid viscosity is recovered by letting ghost fields evolve on a much longer time scale. Analytical results are borne out by high-resolution numerical simulations. These simulations indicate that the hydrodynamic manifold is very robust towards large fluctuations of non hydrodynamic fields.Comment: 17 pages, 3 figures, submitted to Physica

On the Three-dimensional Central Moment Lattice Boltzmann Method

A three-dimensional (3D) lattice Boltzmann method based on central moments is derived. Two main elements are the local attractors in the collision term and the source terms representing the effect of external and/or self-consistent internal forces. For suitable choices of the orthogonal moment basis for the three-dimensional, twenty seven velocity (D3Q27), and, its subset, fifteen velocity (D3Q15) lattice models, attractors are expressed in terms of factorization of lower order moments as suggested in an earlier work; the corresponding source terms are specified to correctly influence lower order hydrodynamic fields, while avoiding aliasing effects for higher order moments. These are achieved by successively matching the corresponding continuous and discrete central moments at various orders, with the final expressions written in terms of raw moments via a transformation based on the binomial theorem. Furthermore, to alleviate the discrete effects with the source terms, they are treated to be temporally semi-implicit and second-order, with the implicitness subsequently removed by means of a transformation. As a result, the approach is frame-invariant by construction and its emergent dynamics describing fully 3D fluid motion in the presence of force fields is Galilean invariant. Numerical experiments for a set of benchmark problems demonstrate its accuracy.Comment: 55 pages, 8 figure

Variational Principles for Stellar Structure

The four equations of stellar structure are reformulated as two alternate pairs of variational principles. Different thermodynamic representations lead to the same hydromechanical equations, but the thermal equations require, not the entropy, but the temperature as the thermal field variable. Our treatment emphasizes the hydrostatic energy and the entropy production rate of luminosity produced and transported. The conceptual and calculational advantages of integral over differential formulations of stellar structure are discussed along with the difficulties in describing stellar chemical evolution by variational principles.Comment: 28 pages, LaTeX, requires AASTeX, 1 PostScript figure, revisions: erratum; accepted by Astrophysical Journa

Prehistory of Transit Searches

Nowadays the more powerful method to detect extrasolar planets is the transit method. We review the planet transits which were anticipated, searched, and the first ones which were observed all through history. Indeed transits of planets in front of their star were first investigated and studied in the solar system. The first observations of sunspots were sometimes mistaken for transits of unknown planets. The first scientific observation and study of a transit in the solar system was the observation of Mercury transit by Pierre Gassendi in 1631. Because observations of Venus transits could give a way to determine the distance Sun-Earth, transits of Venus were overwhelmingly observed. Some objects which actually do not exist were searched by their hypothetical transits on the Sun, as some examples a Venus satellite and an infra-mercurial planet. We evoke the possibly first use of the hypothesis of an exoplanet transit to explain some periodic variations of the luminosity of a star, namely the star Algol, during the eighteen century. Then we review the predictions of detection of exoplanets by their transits, those predictions being sometimes ancient, and made by astronomers as well as popular science writers. However, these very interesting predictions were never published in peer-reviewed journals specialized in astronomical discoveries and results. A possible transit of the planet beta Pic b was observed in 1981. Shall we see another transit expected for the same planet during 2018? Today, some studies of transits which are connected to hypothetical extraterrestrial civilisations are published in astronomical refereed journals. Some studies which would be classified not long ago as science fiction are now considered as scientific ones.Comment: Submiited to Handbook of Exoplanets (Springer

Signification géodynamique des calcaires de plate-forme en cours de subduction sous l'arc des Nouvelles-Hébrides (Sud-Ouest de l'océan Pacifique)

Note présentée par Jean DercourtInternational audienceThe analysis of carbonates from New Hébrides Trench shows that three main épisodes of shallow water carbonate déposition occurred during Late Eocene,Late Oligocene-Early Miocène,Mio-Pliocene-Quaternary, controlled by eustatism and tectonic.L'analyse de carbonates issus de la fosse des Nouvelles-Hébrides a permis de reconnaître trois périodes favorables au développement de plates-formes(Éocène supérieur,Oligocène supérieur-Miocène inférieur,Mio-Pliocène-Quaternaire)contrôlé par l'eustatisme et la tectonique

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

Three-dimensional lattice-Boltzmann simulations of critical spinodal decomposition in binary immiscible fluids

We use a modified Shan-Chen, noiseless lattice-BGK model for binary immiscible, incompressible, athermal fluids in three dimensions to simulate the coarsening of domains following a deep quench below the spinodal point from a symmetric and homogeneous mixture into a two-phase configuration. We find the average domain size growing with time as $t^\gamma$, where $\gamma$ increases in the range $0.545 < \gamma < 0.717$, consistent with a crossover between diffusive $t^{1/3}$ and hydrodynamic viscous, $t^{1.0}$, behaviour. We find good collapse onto a single scaling function, yet the domain growth exponents differ from others' works' for similar values of the unique characteristic length and time that can be constructed out of the fluid's parameters. This rebuts claims of universality for the dynamical scaling hypothesis. At early times, we also find a crossover from $q^2$ to $q^4$ in the scaled structure function, which disappears when the dynamical scaling reasonably improves at later times. This excludes noise as the cause for a $q^2$ behaviour, as proposed by others. We also observe exponential temporal growth of the structure function during the initial stages of the dynamics and for wavenumbers less than a threshold value.Comment: 45 pages, 18 figures. Accepted for publication in Physical Review