Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization

Purpose: Scleritis is a severe inflammatory ocular disorder with unknown pathogenesis. We investigated healthy sclera as well as sclera affected by noninfectious scleritis for differentially expressed proteins using a mass spectrometry approach. Methods: We collected scleral samples of enucleated eyes due to severe noninfectious scleritis (n = 3), and control scleral tissues (n = 5), all exenterated eyes for eyelid carcinomas (n = 4), or choroidal melanoma (n = 1) without scleral invasion. Samples were prepared for the nano liquid-chromatography mass spectrometer (LC-MS), data were analyzed using proteomics software (Scaffold), and is available via ProteomeXchange (identifier PXD038727). Samples were also stained for immuno-histopathological evaluation. Results: Mass spectrometry identified 629 proteins within the healthy and diseased scleral tissues, whereof collagen type XII, VI, and I were the most abundantly expressed protein. Collagen type II-XII was also present. Filaggrin-2, a protein that plays a crucial role in epidermal barrier function, was found upregulated in all scleritis cases. In addition, other epithelial associated proteins were upregulated (such as keratin 33b, 34, and 85, epiplakin, transglutaminase-3, galectin 7, and caspase-14) in scleritis. Further, upregulated proteins involved in regulation of the cytoskeleton (vinculin and myosin 9), and housekeeping proteins were found (elongation factor-2 and cytoplasmic dynein 1) in our study. Upregulation of filaggrin-2 and myosin-9 was confirmed with immunohistochemistry, the latter protein showing co-localization with the endothelial cell marker ETC-related gene (ERG), indicating neovascularization in scleral tissue affected by scleritis. Conclusions: We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis. Further research, ideally including more scleritis cases, is needed to validate our findings.</p

Hazard-consistent response spectra in the Region of Murcia (Southeast Spain): comparison to earthquake-resistant provisions

Hazard-consistent ground-motion characterisations of three representative sites located in the Region of Murcia (southeast Spain) are presented. This is the area where the last three damaging events in Spain occurred and there is a significant amount of data for comparing them with seismic hazard estimates and earthquake-resistant provisions. Results of a probabilistic seismic hazard analysis are used to derive uniform hazard spectra (UHS) for the 475-year return period, on rock and soil conditions. Hazard deaggregation shows that the largest hazard contributions are due to small, local events for short-period target motions and to moderate, more distant events for long-period target motions. For each target motion and site considered, the associated specific response spectra (SRS) are obtained. It is shown that the combination of two SRS, for short- and long-period ground motions respectively, provides a good approximation to the UHS at each site. The UHS are compared to design response spectra contained in current Spanish and European seismic codes for the 475-year return period. For the three sites analysed, only the Eurocode 8 (EC8) type 2 spectrum captures the basic shape of the UHS (and not the EC8 type 1, as could be expected a priori). An alternative response spectrum, anchored at short- and long-period accelerations, is tested, providing a close match to the UHS spectra at the three sites. Results underline the important contribution of the frequent, low-to-moderate earthquakes that characterize the seismicity of this area to seismic hazard (at the 475-year return period)

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Le risque sismique dans la conception des installations nucléaires de base

Le bon comportement d'une installation au séisme dépend du niveau d'aléa sismique et de la robustesse de ses structures, équipements et systèmes. La réglementation liée à la détermination de l'aléa sismique pour les installations nucléaires a évolué récemment, afin de prendre en compte le retour d'expérience des grands tremblements de terre ainsi que les progrès scientifiques des deux dernières décennies. L'article présente les principales évolutions de la règle (RFS2001-01) et un rappel de la démarche globale de la détermination de l'aléa pour un site**

Dynamic transfer of rupture across differently oriented segments in a complex 3-D fault system

We simulate spontaneous dynamic propagation of rupture across two adjacent fault segments, subject to a triaxial compressive stress regime. These segments have different orientations and hence different focal mechanisms (vertical strike-slip and dipping thrust). Numerical simulations, using a BIEM (boundary integral equation method), have revealed that, under a typical triaxial homogeneous compressive stress regime where the magnitude of the intermediate principal stress lies halfway between those of the maximum and minimum ones, ruptures of different focal mechanisms are not likely to occur simultaneously in a single rupture event. Propagation of rupture from a vertical strike-slip fault segment to a pure dip-slip (normal/reverse) fault segment is possible only when the stress field is close to uniaxial compression, or when the intermediate stress magnitude is close either to the minimum or the maximum one. These findings are useful for evaluating possible earthquake scenarios along fault systems with complex 3D geometries. Copyright 2005 by the American Geophysical Union

Using Bayesian model averaging to improve ground motion predictions

International audienceIn low-seismicity areas such as Europe, seismic records do not cover the whole range of variable configurations required for seismic hazard analysis. Usually, a set of empirical models established in such context (the Mediterranean Basin, northeast U.S.A., Japan, etc.) is considered through a logic-tree-based selection process. This approach is mainly based on the scientist’s expertise and ignores the uncertainty in model selection. One important and potential consequence of neglecting model uncertainty is that we assign more precision to our inference than what is warranted by the data, and this leads to overly confident decisions and precision. In this paper, we investigate the Bayesian model averaging (BMA) approach, using nine ground-motion prediction equations (GMPEs) issued from several databases. The BMA method has become an important tool to deal with model uncertainty, especially in empirical settings with large number of potential models and relatively limited number of observations. Two numerical techniques, based on the Markov chain Monte Carlo method and the maximum likelihood estimation approach, for implementing BMA are presented and applied together with around 1000 records issued from the RESORCE-2013 database. In the example considered, it is shown that BMA provides both a hierarchy of GMPEs and an improved out-of-sample predictive performance