Transient micro-elastography:A novel non-invasive approach to measure liver stiffness in mice

AIM:To develop and validate a transient micro-elastography device to measure liver stiffness(LS) in mice.METHODS:A novel transient micro-elastography(TME) device,dedicated to LS measurements in mice with a range of measurement from 1-170 kPa,was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston.The novel probe was validated in a classical fibrosis model(CCl4) and in a transgenic murine model of systemic amyloidosis.RESULTS:TME could be successfully performed in control mice below the xiphoid cartilage,with a mean LS of 4.4 ± 1.3 kPa,a mean success rate of 88%,and an excellent intra-observer agreement(0.98).Treatment with CCl4 over seven weeks drastically increased LS as compared to controls(18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa).Moreover,fibrosis stage was highly correlated with LS(Spearman coefficient = 0.88,P < 0.01).In the amyloidosis model,much higher LS values were obtained,reaching maximum values of > 150 kPa.LS significantly correlated with the amyloidosis index(0.93,P < 0.0001) and the plasma concentration of mutant hapoA-□(0.62,P < 0.005).CONCLUSION:Here,we have established the first non-invasive approach to measure LS in mice,and have successfully validated it in two murine models of high LS.

Contrasted continental rifting via plume-craton interaction： Applications to Central East African Rift

The East African Rift system （EARS） provides a unique system with the juxtaposition of two contrasting yet simultaneously formed rift branches, the eastern, magma-rich, and the western, magma-poor, on either sides of the old thick Tanzanian craton embedded in a younger lithosphere. Data on the pre-rifr, syn-rift and post-rift far-field volcanic and tectonic activity show that the EARS formed in the context of the interaction between a deep mantle plume and a horizontally and vertically heterogeneous lithosphere under far-field tectonic extension. We bring quantitative insights into this evolution by implementing high-resolution 3D thermo-mechanical numerical deformation models of a lithosphere of realistic rheology. The models focus on the central part of the EARS. We explore scenarios of plumelithosphere interaction with plumes of various size and initial position rising beneath a tectonically pre-stretched lithosphere. We test the impact of the inherited rheological discontinuities （suture zones） along the craton borders, of the rheological structure, of lithosphere plate thickness variations, and of physical and mechanical contrasts between the craton and the embedding lithosphere. Our experiments indicate that the ascending plume material is deflected by the cratonic keel and preferentially channeled along one of its sides, leading to the formation of a large rift zone along the eastern side of the craton, with significant magmatic activity and substantial melt amount derived from the mantle plume material. We show that the observed asymmetry of the central EARS, with coeval amagmatic （western） and magmatic （eastern） branches, can be explained by the splitting of warm material rising from a broad plume head whose initial position is slightly shifted to the eastern side of the craton. In that case, neither a mechanical weakness of the contact between the craton and the embedding lithosphere nor the presence of second plume are required to produce simulations that match observations. This result reconciles the passive and active rift models and demonstrates the possibility of development of both magmatic and amagmatic rifts in identical geotectonic environments.

High-temperature granulites and supercontinents

The formation of continents involves a combination of magmatic and metamorphic processes. These processes become indistinguishable at the crust-mantle interface, where the pressure-temperature（P-T）conditions of（ultra） high-temperature granulites and magmatic rocks are similar. Continents grow laterally, by magmatic activity above oceanic subduction zones（high-pressure metamorphic setting）, and vertically by accumulation of mantle-derived magmas at the base of the crust（high-temperature metamorphic setting）. Both events are separated from each other in time; the vertical accretion postdating lateral growth by several tens of millions of years. Fluid inclusion data indicate that during the high-temperature metamorphic episode the granulite lower crust is invaded by large amounts of low H2O-activity fluids including high-density CO2 and concentrated saline solutions（brines）. These fluids are expelled from the lower crust to higher crustal levels at the end of the high-grade metamorphic event. The final amalgamation of supercontinents corresponds to episodes of ultra-high temperature metamorphism involving large-scale accumulation of these low-water activity fluids in the lower crust.This accumulation causes tectonic instability, which together with the heat input from the subcontinental lithospheric mantle, leads to the disruption of supercontinents. Thus, the fragmentation of a supercontinent is already programmed at the time of its amalgamation.

From granulite fluids to quartz-carbonate megashear zones:The gold rush

At peak granulite-facies metamorphic conditions, lower continental crust is arguably fluxed by large amounts of two key low water activity fluids： （i） high-density CO2 and/or （ii） concentrated saline so- lutions. These fluids are either internally-derived, generated by mineral reactions or dehydration melting or, notably for CO2, externally-derived, issued from the underlying mantle. Postmetamorphic evolution results in complete disappearance of these fluids, except for minute remnants preserved in minerals as fluid inclusions. Two major processes are involved： （i） at peak conditions, granitoid magmas form, migrate upward, and crystallize as shallow intrusions in the upper crust （mineralized porphyry types or reduced intrusions）; （ii） during the rapid decompression which almost systematically follows a period of post-peak isobaric cooling, especially for ultrahigh-temperature granulites （anticlockwise P-T paths）, quartz-carbonate megashear zones are formed by repeated periods of seismic activity. Seismic activity may continue until all free fluids have disappeared, resulting in the ultramylonites and pseudotachylites that are found in many granulite domes. A great majority of vein-type Au deposits worldwide occur in the above-mentioned settings or nearby. We suggest that the Au has been scavenged by the granulite fluids, then redistributed and concentrated during the formation of veins and related phenomena.

Chemical Bonding and Interpretation of Time-Dependent Electronic Processes with Maximum Probability Domains

Tools have been designed obtain information about chemical bonds from quantum mechanical calculations.They work well for solutions of the stationary Schr?dinger equation, but it is not clear whether Lewis electron pairs they aim to reproduce survive in time-dependent processes, in spite of the underlying Pauli principle being obeyed in this regime. A simple model of two same-spin non-interacting fermions in a one-dimensional box with an opaque wall, is used to study this problem, because it allows presenting the detailed structure of the wave function. It is shown that i)oscillations persisting after the Hamiltonian stopped changing produce for certain time intervals states where Lewis electron pairs are spatially separated, and ii) methods(like density analysis, or the electron localization function) that are widely used for describing bonding in the stationary case, have limitations in such situations. An exception is provided by the maximum probability domain(the spatial domain that maximizes the probability to find a given number of particles in it). It is conceptually simple, and satisfactorily describes the phenomenon.

胚胎巨噬细胞和小胶质细胞消融调控小鼠胚胎背根神经节感觉神经元的发育

众所周知,小胶质细胞可以调节中枢神经系统发育的一些方面。在第11.5天的小鼠胚胎中的小胶质细胞定殖脊髓时,它们与背根神经节感觉神经元(SN)的生长中心轴突相互作用,这表明它们可能在SN发育中发挥一定功能。为了解决这个问题,我们使用缺乏胚胎巨噬细胞(PU.1敲除小鼠)和免疫细胞消融的小鼠胚胎分析胚胎巨噬细胞消融对SNs早期发育的影响。我们发现,除小胶质细胞外,胚胎巨噬细胞还与来自第11.5天的小鼠胚胎的原肌球蛋白受体激酶(Trk)C+感觉神经元,TrkB+感觉神经元和TrkA+感觉神经元外周神经突产生交联。免疫细胞剥夺会导致第11.5天的小鼠胚胎的TrkC+感觉神经元和TrkB+感觉神经元初始数量的减少,这与其发育细胞死亡(DCD)的改变有关联的可能性较小,因为其后在第12.5天的胚胎中的数量有短暂增加。在分析的发育期(第11.5~15.5天),它也导致TrkA+感觉神经元数量减少,尽管我们没有观察到他们的DCD有任何变化。与神经元祖细胞可能存在一致性的脑脂肪酸结合蛋白(BFABP-)阴性细胞的增殖在第11.5天的胚胎中增加,而它们的增殖在第12.5天的胚胎减少,这可部分解释从11.5 d观察到的SN亚型产生的改变。此外,我们观察到在缺乏胚胎巨噬细胞的情况下神经胶质细胞祖细胞(BFABP+细胞)增殖的改变。我们的数据表明,胚胎巨噬细胞和小胶质细胞消融调控SN的发育。

Sickle-cell and alpha-thalassemia traits resulting in nonatherosclerotic myocardial infarction:Beyond coincidence?

Alpha-thalassemia trait and sickle trait are not commonly considered risk factors of ischemic heart disease.We report the case of a non-atherosclerotic silent myocardial infarction in a 46-year-old woman,carrier of the alphathalassemia trait(homozygous deletion of locus-3.7) combined with sickle cell trait.While the patient was included as healthy volunteer for a metabolic study,we performed cardiac magnetic resonance imagery showing a left ventricle apicolateral myocardial infarction.Coronary computed tomography angiography showed normal coronary arteries with a coronary calcium score of 0.The patient was treated with low-dose aspirin in secondary prevention afterwards.This case allows us to discuss cardiovascular risk among patients presenting with both alpha-thalassemia trait and sickle cell trait and the indication of cardiac imagery in such patients even when considered as low-cardiovascular risk.

New insights into sodium transport regulation in the distal nephron:Role of G-protein coupled receptors

The renal handling of Na^+ balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part(i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na^+ excretion and are the target of many different regulatory processes that modulate Na^+ retention more or less efficiently. G-protein coupled receptors(GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na^+ absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na^+ excretion, this review also highlights the complexity of these different pathways, and the connections between them.

Optimising repetitive transcranial magnetic stimulation for neural circuit repair following traumatic brain injury

While it is well-known that neuronal activity promotes plasticity and connectivity, the success of activity-based neural rehabilitation programs remains extremely limited in human clinical experience because they cannot adequately control neuronal excitability and activity within the injured brain in order to induce repair. However, it is possible to non-invasively modulate brain plasticity using brain stimu- lation techniques such as repetitive transcranial （rTMS） and transcranial direct current stimulation （tDCS） techniques, which show promise for repairing injured neural circuits （Henrich-Noack et al., 2013; Lefaucher et al., 2014）. Yet we are far from having full control of these techniques to repair the brain following neurotrauma and need more fundamen- tal research （Ellaway et al., 2014; Lefaucher et al., 2014）. In this perspective we discuss the mechanisms by which rTMS may facilitate neurorehabilitation and propose experimental techniques with which magnetic stimulation may be investi- gated in order to optimise its treatment potential.

Geofluids:Developments in Microthermometry,Spectroscopy,Thermodynamics and Stable Isotopes

Fluid （and melt） inclusion studies have shown a marked devel- opment in the last decades, as indicated by the increasing number of papers and as covered under major themes in specialized meetings （e.g. ECROFI in Europe, PACROFI in America, ACROFI in Asia）. However, a basic text book is lacking in current literature, available information being either somewhat outdated （e,g. Roedder, 1984） or scattered in multi-author ＂short course＂, mainly organized by the Mineralogical Societies of Canada, America or Europe. A result is that basic features of fluid inclusion studies, notably its key technique, microthermometry, and recently supplemented by micro Raman of infrared spectroscopy, is rarely taught in most universities, leaving the student alone to discover a field of study which has grown to the dimensions of a major science.

X-ray spectroscopy evidence for plasma shell formation in experiments modeling accretion columns in young stars

Recent achievements in laboratory astrophysics experiments with high-power lasers have allowed progress in our understanding of the early stages of star formation.In particular,we have recently demonstrated the possibility of simulating in the laboratory the process of the accretion of matter on young stars[G.Revet et al.,Sci.Adv.3,e1700982(2017)].The present paper focuses on x-ray spectroscopy methods that allow us to investigate the complex plasma hydrodynamics involved in such experiments.We demonstrate that we can infer the formation of a plasma shell,surrounding the accretion column at the location of impact with the stellar surface,and thus resolve the present discrepancies between mass accretion rates derived from x-ray and optical-radiation astronomical observations originating from the same object.In our experiments,the accretion column ismodeled by having a collimated narrow(1 mm diameter)plasma stream first propagate along the lines of a large-scale external magnetic field and then impact onto an obstacle,mimicking the high-density region of the stellar chromosphere.A combined approach using steady-state and quasi-stationarymodels was successfully applied tomeasure the parameters of the plasma all along its propagation,at the impact site,and in the structure surrounding the impact region.The formation of a hot plasma shell,surrounding the denser and colder core,formed by the incoming stream of matter is observed near the obstacle using x-ray spatially resolved spectroscopy.

Fluid-rock interaction in retrograde granulites of the Southern Marginal Zone,Limpopo high grade terrain,South Africa

Fluid infiltration into retrograde granulites of the Southern Marginal Zone （Limpopo high grade terrain） is exemplified by hydration reactions, shear zone hosted metasomatism, and lode gold mineralisation. Hydration reactions include the breakdown of cordierite and orthopyroxene to gedrite ＋ kyanite, and anthophyllite, respectively. Metamorphic petrology, fluid inclusions, and field data indicate that a low H2O-activity carbon-saturated CO2-rich and a saline aqueous fluid infiltrated the Southern Marginal Zone during exhumation. The formation of anthophyllite after orthopyroxene established a regional retrograde anthophyllite-in isograd and occurred at P-Tconditions of -6 kbar and 610 ℃, which fixes the minimum mole fraction of H20 in the CO2-rich fluid phase at ~ 0.1. The maximum H20 mole fraction is fixed by the lower temperature limit （~800 ℃） for partial melting at -0.3. C-O-H fluid calculations show that the CO2-rich fluid had an oxygen fugacity that was 0.6 log10 units higher than that of the fayalite-magnetite- quartz buffer and that the CO2/（CO2＋CH4） mole ratio of this fluid was 1. The presence of dominantly relatively low density CO2-rich fluid inclusions in the hydrated granulites indicates that the fluid pressure was less than the lithostatic pressure. This can be explained by strike slip faulting and/or an increase of the rock permeability caused by hydration reactions.

Alignment of solid targets under extreme tight focus conditions generated by an ellipsoidal plasma mirror

The design of ellipsoidal plasma mirrors(EPMs)for the PEARL laser facility is presented.The EPMs achieve a magnification of 0.32 in focal spot size,and the corresponding increase in focused intensity is expected to be about 8.Designing and implementing such focusing optics for short-pulse(<100 fs)systems paves the way for their use in future high-power facilities,where they can be used to achieve intensities beyond 1023W/cm^(2).A retro-imaging-based target alignment system is also described,which is used to align solid targets at the output of the ellispoidal mirrors(with a numerical aperture of 0.75 in this case).

Evaluation of the Impact of Truck Overloading on Flexible Compacted Gravel Lateritic Soil’s Pavements by FEM with Cast3M^&copy;

Within the framework of a FEM of the nonlinear behavior of lateritic pavement of Senegal, the effect of truck overloading is studied to estimate its impact on the deformability of road pavement on compacted gravel lateritic soils. For that purpose, various loading conditions were tested to measure the impact on the critical response parameters of road pavement design. The implementation of the models was realized with Cast3M&copy;. This study allowed us to point out that the observed variations are linear and would help to plan in advance the impact of axle overloads for a better evaluation within the framework of the mechanistic (M. E.) design of pavements.

Detailed characterization of a laboratory magnetized supercritical collisionless shock and of the associated proton energization

Collisionless shocks are ubiquitous in the Universe and are held responsible for the production of nonthermal particles and high-energy radiation.In the absence of particle collisions in the system,theory shows that the interaction of an expanding plasma with a pre-existing electromagnetic structure(as in our case)is able to induce energy dissipation and allow shock formation.Shock formation can alternatively take place when two plasmas interact,through microscopic instabilities inducing electromagnetic fields that are able in turn to mediate energy dissipation and shock formation.Using our platform in which we couple a rapidly expanding plasma induced by high-power lasers(JLF/Titan at LLNL and LULI2000)with high-strength magnetic fields,we have investigated the generation of a magnetized collisionless shock and the associated particle energization.We have characterized the shock as being collisionless and supercritical.We report here on measurements of the plasma density and temperature,the electromagnetic field structures,and the particle energization in the experiments,under various conditions of ambient plasma and magnetic field.We have also modeled the formation of the shocks using macroscopic hydrodynamic simulations and the associated particle acceleration using kinetic particle-in-cell simulations.As a companion paper to Yao et al.[Nat.Phys.17,1177–1182(2021)],here we show additional results of the experiments and simulations,providing more information to allow their reproduction and to demonstrate the robustness of our interpretation of the proton energization mechanism as being shock surfing acceleration.

Multichannel singular spectrum analysis of the axial atmospheric angular momentum

Earth＇s variable rotation is mainly produced by the variability of the AAM（atmospheric angular momentum）. In particular, the axial AAM component X_3, which undergoes especially strong variations,induces changes in the Earth＇s rotation rate. In this study we analysed maps of regional input into the effective axial AAM from 1948 through 2011 from NCEP/NCAR reanalysis. Global zonal circulation patterns related to the LOD（length of day） were described. We applied MSSA（Multichannel Singular Spectrum Analysis） jointly to the mass and motion components of AAM, which allowed us to extract annual, semiannual, 4-mo nth, quasi-biennial, 5-year, and low-frequency oscillations. PCs（Principal components） strongly related to ENSO（El Nino southern oscillation） were released. They can be used to study ENSO-induced changes in pressure and wind fields and their coupling to LOD. The PCs describing the trends have captured slow atmospheric circulation changes possibly related to climate variability.

Perspective:Chemical Information Encoded in Electron Density

In this perspective,we review the chemical information encoded in electron density and other ingredients used in semilocal functionals.This information is usually looked at from the functional point of view:the exchange density or the enhancement factor are discussed in terms of the reduced density gradient.However,what parts of a molecule do these 3D functions represent? We look atthese quantities in real space,aiming to understand the electronic structure information they encode and provide an insight from the quantum chemical topology(QCT).Generalized gradient approximations(GGAs) provide information about the presence of chemical interactions,whereas meta-GGAs can differentiate between the different bonding types.By merging these two techniques,we show new insight into the failures of semilocal functionals owing to three main errors:fractional charges,fractional spins,and non-covalent interactions.We build on simple models.We also analyze the delocalization error in hydrogen chains,showing the ability of QCT to reveal the delocalization error introduced by semilocal functionals.Then,we show how the analysis of localization can help understand the fractional spin error in alkali atoms,and how it can be used to correct it.Finally,we show that the poor description of GGAs of isodesmic reactions in alkanes is due to 1,3-interactions.

ON A SECOND ORDER DISSIPATIVE ODE IN HILBERT SPACE WITH AN INTEGRABLE SOURCE TERM

Asymptotic behaviour of solutions is studied for some second order equations including the model casex（t） ＋γx（t） ＋ ↓△φb（x（t）） = h（t） with γ 〉 0 and h ∈ L1（O, ＋∞; H）, φ being continuouly differentiable with locally Lipschitz continuous gradient and bounded from below. In particular when φ is convex, all solutions tend to minimize the potential φ as time tends to infinity and the existence of one bounded trajectory implies the weak convergence of all solutions to equilibrium points.

Assessing Ecotoxicity in Marine Environment Using Luminescent Microalgae: Where Are We At?

Nowadays, microalgae are particularly used to assess the environmental impact of contaminants in aquatic systems. Naturally present in some algal species, bioluminescence is highly used in application fields related to environmental monitoring. Bioluminescent dinoflagellates have played a pivotal role in this domain. When exposed to heavy metals or toxic organic compounds, bioluminescent dinoflagellates have the capacity to decrease light emission. In addition, new molecular tools allow the possibility to produce genetically modified microorganisms which are able to perform luminescence. Combined with the luciferase reporter gene, two main genetic constructions can be employed. Activation of a specific inducible promoter induces the luminescence gene transcription and this signal increases over time. Constitutive promoters result in a high basal expression level of the reporter gene. During exposure to a potential toxic pollutant, the basal expression level will decrease due to the toxic effect. Toxicity bioassays based on engineered luminescent Chlorophyta microalgae are among the most sensitive tests and are an invaluable complement to classical toxicity assays.