Iris-Wasm: robust and modular verification of WebAssembly programs

WebAssembly makes it possible to run C/C++ applications on the web with near-native performance. A WebAssembly program is expressed as a collection of higher-order ML-like modules, which are composed together through a system of explicit imports and exports using a host language, enabling a form of higher- order modular programming. We present Iris-Wasm, a mechanized higher-order separation logic building on a specification of Wasm 1.0 mechanized in Coq and the Iris framework. Using Iris-Wasm, we are able to specify and verify individual modules separately, and then compose them modularly in a simple host language featuring the core operations of the WebAssembly JavaScript Interface. Building on Iris-Wasm, we develop a logical relation that enforces robust safety: unknown, adversarial code can only affect other modules through the functions that they explicitly export. Together, the program logic and the logical relation allow us to formally verify functional correctness of WebAssembly programs, even when they invoke and are invoked by unknown code, thereby demonstrating that WebAssembly enforces strong isolation between modules

Gas emissions and active tectonics within the submerged section of the North Anatolian Fault zone in the Sea of Marmara

The submerged section of the North Anatolian fault within the Marmara Sea was investigated using acoustic techniques and submersible dives. Most gas emissions in the water column were found near the surface expression of known active faults. Gas emissions are unevenly distributed. The linear fault segment crossing the Central High and forming a seismic gap – as it has not ruptured since 1766, based on historical seismicity, exhibits relatively less gas emissions than the adjacent segments. In the eastern Sea of Marmara, active gas emissions are also found above a buried transtensional fault zone, which displayed micro-seismic activity after the 1999 events. Remarkably, this zone of gas emission extends westward all along the southern edge of Cinarcik basin, well beyond the zone where 1999 aftershocks were observed. The long term monitoring of gas seeps could hence be highly valuable for the understanding of the evolution of the fluid-fault coupling processes during the earthquake cycle within the Marmara Sea

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Tidally-induced thermonuclear Supernovae

We discuss the results of 3D simulations of tidal disruptions of white dwarfs by moderate-mass black holes as they may exist in the cores of globular clusters or dwarf galaxies. Our simulations follow self-consistently the hydrodynamic and nuclear evolution from the initial parabolic orbit over the disruption to the build-up of an accretion disk around the black hole. For strong enough encounters (pericentre distances smaller than about 1/3 of the tidal radius) the tidal compression is reversed by a shock and finally results in a thermonuclear explosion. These explosions are not restricted to progenitor masses close to the Chandrasekhar limit, we find exploding examples throughout the whole white dwarf mass range. There is, however, a restriction on the masses of the involved black holes: black holes more massive than $2\times 10^5$ M$_\odot$ swallow a typical 0.6 M$_\odot$ dwarf before their tidal forces can overwhelm the star's self-gravity. Therefore, this mechanism is characteristic for black holes of moderate masses. The material that remains bound to the black hole settles into an accretion disk and produces an X-ray flare close to the Eddington limit of $L_{\rm Edd} \simeq 10^{41} {\rm erg/s} M_{\rm bh}/1000 M$_\odot$), typically lasting for a few months. The combination of a peculiar thermonuclear supernova together with an X-ray flare thus whistle-blows the existence of such moderate-mass black holes. The next generation of wide field space-based instruments should be able to detect such events.Comment: 8 pages, 2 figures, EuroWD0

Gas and seismicity within the Istanbul seismic gap

Understanding micro-seismicity is a critical question for earthquake hazard assessment. Since the devastating earthquakes of Izmit and Duzce in 1999, the seismicity along the submerged section of North Anatolian Fault within the Sea of Marmara (comprising the “Istanbul seismic gap”) has been extensively studied in order to infer its mechanical behaviour (creeping vs locked). So far, the seismicity has been interpreted only in terms of being tectonic-driven, although the Main Marmara Fault (MMF) is known to strike across multiple hydrocarbon gas sources. Here, we show that a large number of the aftershocks that followed the M 5.1 earthquake of July, 25th 2011 in the western Sea of Marmara, occurred within a zone of gas overpressuring in the 1.5–5 km depth range, from where pressurized gas is expected to migrate along the MMF, up to the surface sediment layers. Hence, gas-related processes should also be considered for a complete interpretation of the micro-seismicity (~M < 3) within the Istanbul offshore domain

Subduction controls the distribution and fragmentation of Earth’s tectonic plates

International audienceThe theory of plate tectonics describes how the surface of the Earth is split into an organized jigsaw of seven large plates 1 of similar sizes and a population of smaller plates, whose areas follow a fractal distribution 2,3. The reconstruction of global tectonics during the past 200 My 4 suggests that this layout is probably a long-term feature of our planet, but the forces governing it are unknown. Previous studies 3,5,6 , primarily based on statistical properties of plate distributions, were unable to resolve how the size of plates is determined by lithosphere properties and/or underlying mantle convection. Here, we demonstrate that the plate layout of the Earth is produced by a dynamic feedback between mantle convection and the strength of the lithosphere. Using 3D spherical models of mantle convection with plate-like behaviour that match the plate size-frequency distribution observed for Earth, we show that subduction geometry drives the tectonic fragmentation that generates plates. The spacing between slabs controls the layout of large plates, and the stresses caused by the bending of trenches, break plates into smaller fragments. Our results explain why the fast evolution in small back-arc plates 7,8 reflects the dramatic changes in plate motions during times of major reorganizations. Our study opens the way to use convection simulations with plate-like behaviour to unravel how global tectonics and mantle convection are dynamically connected

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.

Miller-Dieker syndrome is caused by a multiple gene deletion, including PAFAH1B1 and YWHAE. Although deletion of PAFAH1B1 causes lissencephaly unambiguously, deletion of YWHAE alone has not clearly been linked to a human disorder. Cases with YWHAE variants were collected through international data sharing networks. To address the specific impact of YWHAE loss of function, we phenotyped a mouse knockout of Ywhae. We report a series of 10 individuals with heterozygous loss-of-function YWHAE variants (3 single-nucleotide variants and 7 deletions &lt;1 Mb encompassing YWHAE but not PAFAH1B1), including 8 new cases and 2 follow-ups, added with 5 cases (copy number variants) from literature review. Although, until now, only 1 intragenic deletion has been described in YWHAE, we report 4 new variants specifically in YWHAE (3 splice variants and 1 intragenic deletion). The most frequent manifestations are developmental delay, delayed speech, seizures, and brain malformations, including corpus callosum hypoplasia, delayed myelination, and ventricular dilatation. Individuals with variants affecting YWHAE alone have milder features than those with larger deletions. Neuroanatomical studies in Ywhae &lt;sup&gt;-/-&lt;/sup&gt; mice revealed brain structural defects, including thin cerebral cortex, corpus callosum dysgenesis, and hydrocephalus paralleling those seen in humans. This study further demonstrates that YWHAE loss-of-function variants cause a neurodevelopmental disease with brain abnormalities

The diameter of the CoRoT target HD 49933. Combining the 3D limb darkening, asteroseismology, and interferometry

Context. The interpretation of stellar pulsations in terms of internal structure depends on the knowledge of the fundamental stellar parameters. Long-base interferometers permit us to determine very accurate stellar radii, which are independent constraints for stellar models that help us to locate the star in the HR diagram. Aims: Using a direct interferometric determination of the angular diameter and advanced three-dimensional (3D) modeling, we derive the radius of the CoRoT target HD 49933 and reduce the global stellar parameter space compatible with seismic data. Methods: The VEGA/CHARA spectro-interferometer is used to measure the angular diameter of the star. A 3D radiative hydrodynamical simulation of the surface is performed to compute the limb darkening and derive a reliable diameter from visibility curves. The other fundamental stellar parameters (mass, age, and Teff) are found by fitting the large and small p-mode frequency separations using a stellar evolution model that includes microscopic diffusion. Results: We obtain a limb-darkened angular diameter of {\theta}LD = 0.445 \pm 0.012 mas. With the Hipparcos parallax, we obtain a radius of R = 1.42 \pm 0.04 Rsun. The corresponding stellar evolution model that fits both large and small frequency separations has a mass of 1.20 \pm 0.08 Msun and an age of 2.7 Gy. The atmospheric parameters are Teff = 6640 \pm 100 K, log g = 4.21 \pm 0.14, and [Fe/H] = -0.38.Comment: 4 pages, 4 figure

Previously described sequence variant in CDK5RAP2 gene in a Pakistani family with autosomal recessive primary microcephaly

<p>Abstract</p> <p>Background</p> <p>Autosomal Recessive Primary Microcephaly (MCPH) is a disorder of neurogenic mitosis. MCPH leads to reduced cerebral cortical volume and hence, reduced head circumference associated with mental retardation of variable degree. Genetic heterogeneity is well documented in patients with MCPH with six loci known, while pathogenic sequence variants in four respective genes have been identified so far. Mutations in <it>CDK5RAP2 </it>gene at MCPH3 locus have been least involved in causing MCPH phenotype.</p> <p>Methods</p> <p>All coding exons and exon/intron splice junctions of <it>CDK5RAP2 </it>gene were sequenced in affected and normal individuals of Pakistani MCPH family of Kashmiri origin, which showed linkage to MCPH3 locus on chromosome 9q33.2.</p> <p>Results</p> <p>A previously described nonsense mutation [243 T>A (S81X)] in exon 4 of <it>CDK5RAP2 </it>gene has been identified in the Pakistani family, presented here, with MCPH Phenotype. Genomic and cDNA sequence comparison revealed that the exact nomenclature for this mutation is 246 T>A (Y82X).</p> <p>Conclusion</p> <p>Recurrent observation of Y82X mutation in <it>CDK5RAP2 </it>gene in this Pakistani family may be a sign of confinement of a rare ancestral haplotype carrying this pathogenic variant within Northern Pakistani population, as this has not been reported in any other population.</p