: peel it

International audienceThree-dimensional structures of proteins are the support of their biological functions. Their folds are maintained by inter-residue interactions which are one of the main focuses to understand the mechanisms of protein folding and stability. Furthermore, protein structures can be composed of single or multiple functional domains that can fold and function independently. Hence, dividing a protein into domains is useful for obtaining an accurate structure and function determination. In previous studies, we enlightened protein contact properties according to different definitions and developed a novel methodology named Protein Peeling. Within protein structures, Protein Peeling characterizes small successive compact units along the sequence called protein units (PUs). The cutting done by Protein Peeling maximizes the number of contacts within the PUs and minimizes the number of contacts between them. This method is so a relevant tool in the context of the protein folding research and particularly regarding the hierarchical model proposed by George Rose. Here, we accurately analyze the PUs at different levels of cutting, using a non-redundant protein databank. Distribution of PU sizes, number of PUs or their accessibility are screened to determine their common and different features. Moreover, we highlight the preferential amino acid interactions inside and between PUs. Our results show that PUs are clearly an intermediate level between secondary structures and protein structural domains

Moment tensors for rapid characterization of megathrust earthquakes: the example of the 2011 M9 Tohoku-oki, Japan earthquake

The rapid detection and characterization of megathrust earthquakes is a difficult task given their large rupture zone and duration. These events produce very strong ground vibrations in the near field that can cause weak motion instruments to clip, and they are also capable of generating large-scale tsunamis. The 2011 M9 Tohoku-oki earthquake that occurred offshore Japan is one member of a series of great earthquakes for which extended geophysical observations are available. Here, we test an automated scanning algorithm for great earthquakes using continuous very long-period (100-200 s) seismic records from K-NET strong-motion seismograms of the earthquake. By continuously performing the cross-correlation of data and Green's functions (GFs) in a moment tensor analysis, we show that the algorithm automatically detects, locates and determines source parameters including the moment magnitude and mechanism of the great Tohoku-oki earthquake within 8 min of its origin time. The method does not saturate. We also show that quasi-finite-source GFs, which take into account the effects of a finite-source, in a single-point source moment tensor algorithm better fit the data, especially in the near-field. We show that this technique allows the correct characterization of the earthquake using a limited number of stations. This can yield information usable for tsunami early warnin

Muscle volume quantification: guiding transformers with anatomical priors

Muscle volume is a useful quantitative biomarker in sports, but also for the follow-up of degenerative musculo-skelletal diseases. In addition to volume, other shape biomarkers can be extracted by segmenting the muscles of interest from medical images. Manual segmentation is still today the gold standard for such measurements despite being very time-consuming. We propose a method for automatic segmentation of 18 muscles of the lower limb on 3D Magnetic Resonance Images to assist such morphometric analysis. By their nature, the tissue of different muscles is undistinguishable when observed in MR Images. Thus, muscle segmentation algorithms cannot rely on appearance but only on contour cues. However, such contours are hard to detect and their thickness varies across subjects. To cope with the above challenges, we propose a segmentation approach based on a hybrid architecture, combining convolutional and visual transformer blocks. We investigate for the first time the behaviour of such hybrid architectures in the context of muscle segmentation for shape analysis. Considering the consistent anatomical muscle configuration, we rely on transformer blocks to capture the longrange relations between the muscles. To further exploit the anatomical priors, a second contribution of this work consists in adding a regularisation loss based on an adjacency matrix of plausible muscle neighbourhoods estimated from the training data. Our experimental results on a unique database of elite athletes show it is possible to train complex hybrid models from a relatively small database of large volumes, while the anatomical prior regularisation favours better predictions

Vienne 38 - Cathédrale Saint-Maurice - Façade nord - Travées 5 à 13 -: Rhône-Alpes / Département de l'Isère (38)

Depuis avril 2008, plusieurs campagnes archéologiques ont été menées, à la demande de la Ville de Vienne, sur les façades nord de l’ancienne cathédrale Saint-Maurice. La cathédrale, qui domine les quartiers établis sur la rive gauche du Rhône, fut érigée en étapes successives comprises entre le XIIe et le XVIe siècle. Plusieurs auteurs se sont attachés à décrire cette évolution mais sans que celle-ci ne se fonde sur une étude archéologique fine des parements. Les données les mieux connues proviennent de la lecture des textes d’archive et de l’analyse stylistique de l’architecture et des chapiteaux. La restauration des façades septentrionales a été l’occasion pour la société Archeodunum de conduire une opération archéologique du bâti suivant les objectifs fixés dans le cahier des charges du SRA Rhône-Alpes.Cette intervention, répartie en quatre tranches, s’est déroulée suivant les travaux de restauration qui ont progressé de deux travées en deux travées depuis l’ouest. Les campagnes archéologiques ont débuté à partir de la travée 5. Pour chaque tranche l’examen a porté sur les murs gouttereaux de la nef et des chapelles mais aussi sur les arcs-boutants. Les données recueillies ont permis de circonscrire les restaurations réalisées par les architectes Charles-Auguste Questel et Eugène Senès, respectivement aux XIXe et XXe siècles. Mais surtout, les nombreux indices archéologiques, enregistrés entre les travées 5 et 13 nord, révèlent quatre états de construction réalisés en plusieurs phases de chantiers.On a pu ainsi cerner, les travaux du XIIIe siècle réalisés sous l’épiscopat de Jean de Bernin (1218-1266) a qui l’on doit la reconstruction de la cathédrale gothique en installant un chevet précédé de deux travées de chœur contre la nef du XIIe siècle. L’étude des travées du clair-étage a montré que leur construction au cours du XIVe siècle se poursuivait par à coup, sur la nef du XIIe siècle, indépendamment du chantier des chapelles qui progresse en ceinturant et en éventrant le mur du bas-côté nord de la nef romane entre ses contreforts.Au niveau du clair-étage, l’avancement des chantiers du XIVe siècle détruit au fur et à mesure la nef romane pour mettre en place le triforium au-dessus de ses grandes arcades et au revers de ses contreforts. Grâce à la mise en évidence des contreforts romans sur toute l’élévation du comble, nous avons acquis la certitude que l’ancienne nef s’élevait au moins 5 mètres au-dessus de l’appui du triforium du projet gothique. Nous serions même tentés d’envisager, au regard de ces indices, mais aussi du raffinement et de la quantité des ornements architecturaux sculptés, que la cathédrale des archevêques Pierre (1121-1125) ou Étienne 1er (1129-1145) était finie au moins jusqu’à la naissance des voûtes. Nous ne pouvons préciser si la voûte a été construite ou si une charpente l’a remplacée ; en tout cas les piles fasciculées ont été pensées à dessein et les organes d’épaulement bâtis jusqu’au toit.Nous avons acquis aussi la certitude que le triforium gothique était ouvert sur le comble par des arcades jumelées. Certes, ces ouvertures étaient indispensables puisque la circulation horizontale depuis le triforium était condamnée par une tour d’escalier et un contrefort. Mais au lieu de ménager de simples portes à l’arrière du triforium, le projet a été bien plus ambitieux, il a consisté à ouvrir entièrement le triforium sur le comble à la manière d’une grande tribune capable d’accueillir du monde. Ce comble ouvert était aussi un moyen de relier la tour d’escalier adossée au bas-côté aux tours du clair-étage. Toutes ces questions de circulation mériteraient d’être étudiées avec plus de précision

Clinical outcomes and characteristics of critically ill patients with influenza- and COVID-19-induced ARDS: A retrospective, matched cohort study

IntroductionSeasonal epidemic influenza and SARS-CoV-2 are the most frequent viruses causing acute respiratory distress syndrome (ARDS). To what extent these two etiologies differ in ICU patients remains uncertain. We, therefore, aimed at comparing the severity and outcomes of influenza and SARS-CoV-2-induced ARDS in mechanically ventilated patients.MethodsThis retrospective, analytic, single-center study was conducted in the medical ICU of Nancy University Hospital in France. Adult patients hospitalized with confirmed influenza (from 2009 to 2019) or SARS-CoV-2-induced ARDS (between March 2020 and May 2021) and those under mechanical ventilation were included. Each patient with influenza was matched with two patients with COVID-19, with the same severity of ARDS. The primary endpoint was death in ICU on day 28. The secondary endpoints were the duration of vasopressors, the use of renal replacement therapy, the duration of mechanical ventilation, and the ICU length of stay.ResultsA total of 42 patients with influenza were matched with 84 patients with COVID-19. They had similar sex distribution, age, Charlson comorbidity index, and ARDS severity. On day 28, 11 (26.2%) patients in the influenza group and nine (10.7%) patients in the COVID-19 group had died (p = 0.0084, HR = 3.31, CI 95% [1.36–8.06]). In the univariate Cox model, being infected with SARS-CoV-2, SOFA and SAPS II scores, initial arterial pH, PaCO2, PaO2/FiO2, serum lactate level, platelet count, and use of renal replacement therapy were significantly associated with mortality. In the multivariate Cox model, the SOFA score at admission (p < 0.01, HR = 1.284, CI 95% [1.081; 1.525]) and the initial pH (p < 0.01, HR = 0.618, CI 95% [0.461; 0.828]) were the only predictors of mortality. The type of virus had no influence on mortality, though patients with COVID-19 underwent longer mechanical ventilation and received more neuromuscular blockers and prone positioning.ConclusionIn mechanically ventilated patients with ARDS, 28-day mortality was higher among patients with influenza as compared to patients with COVID-19 because of a higher initial extra-pulmonary severity. However, the type of virus was not, by itself, correlated with mortality

Regional-scale paleofluid system across the Tuscan Nappe–Umbria–Marche Apennine Ridge (northern Apennines) as revealed by mesostructural and isotopic analyses of stylolite–vein networks

We report the results of a multiproxy study that combines structural analysis of a fracture–stylolite network and isotopic characterization of calcite vein cements and/or fault coating. Together with new paleopiezometric and radiometric constraints on burial evolution and deformation timing, these results provide a first-order picture of the regional fluid systems and pathways that were present during the main stages of contraction in the Tuscan Nappe and Umbria–Marche Apennine Ridge (northern Apennines). We reconstruct four steps of deformation at the scale of the belt: burial-related stylolitization, Apenninic-related layer-parallel shortening with a contraction trending NE–SW, local extension related to folding, and late-stage fold tightening under a contraction still striking NE–SW. We combine the paleopiezometric inversion of the roughness of sedimentary stylolites – that constrains the range of burial depth of strata prior to layer-parallel shortening – with burial models and U–Pb absolute dating of fault coatings in order to determine the timing of development of mesostructures. In the western part of the ridge, layer-parallel shortening started in Langhian time (∼15 Ma), and then folding started at Tortonian time (∼8 Ma); late-stage fold tightening started by the early Pliocene (∼5 Ma) and likely lasted until recent/modern extension occurred (∼3 Ma onward). The textural and geochemical (δ18O, δ13C, Δ47CO2 and 87Sr∕86Sr) study of calcite vein cements and fault coatings reveals that most of the fluids involved in the belt during deformation either are local or flowed laterally from the same reservoir. However, the western edge of the ridge recorded pulses of eastward migration of hydrothermal fluids (>140 ∘C), driven by the tectonic contraction and by the difference in structural style of the subsurface between the eastern Tuscan Nappe and the Umbria–Marche Apennine Ridge

Observatoire Scientifique en Appui à la GEstion de la Santé sur un territoire (OSAGE-S)

Dans le contexte « environnement-santé », l’équipe interdisciplinaire (biologistes, médecins, épidémiologistes, modélisateurs, écologues, géographes, informaticiens) qui travaille sur la dynamique de maladies infectieuses dans le Sud-Est asiatique, propose de mettre en commun la connaissance qu’elle a des agents biologiques pathogènes et des processus qui interviennent dans les milieux et les sociétés et de partager expériences de terrain, de laboratoire, clinique pour aborder les questions de recherche, de suivi des maladies et de gestion de la santé. Pour ce faire, l’idée d’une plateforme intégrative a été avancée et nous a permis de décliner la proposition de mise en œuvre d’un Observatoire Scientifique en Appui à la GEstion de la Santé sur un territoire (OSAGE-S). Les prémices de ce travail sont d’une part d’ordre générique et épistémologique : ils explicitent formellement la formule « environnement-santé » pour y positionner le pathosystème, l’environnement et l’observatoire ; d’autre part d’ordre opérationnel par explicitation du concept d’observatoire en appui à la gestion de la Santé. Par la suite nous illustrerons nos propos autour d’OSAGE-S, à partir d’une étude de cas, la maladie du Chikungunya en Indonésie.Within the “Health and Environment” framework, a group of scientists in disciplinary fields as diverse as biology, medical sciences, modelling, ecology, geography, computer sciences, are collaborating to study the dynamics of infectious diseases in Southeast Asia. In this paper they propose to pool their knowledge on biological pathogens, environment and societies and to share their field, laboratory and clinical expertise to address questions on research, disease monitoring and health management. An integrative platform has been suggested and organised in order to implement a Scientific Observatory (OSAGE-S), dedicated to supporting Health Management in a Territory. The first part of this work addresses generic and epistemological questions, formally explicits the formula “Health and Environment” in order to relate it to concepts such as « pathological system », « environment » and « observatory » ; the second part relates to further operational issues for the observatory concept dedicated to the support of Health management. Thereafter we illustrate our proposition with a case study, the Chikungunya disease in Indonesia

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Full, constrained and stochastic source inversions support evidence for volumetric changes during the Basel earthquake sequence

Co-seismic volumetric changes are often interpreted as tensile fracturing in response to fluid injection during geothermal reservoir stimulation. Such volumetric changes manifest themselves as isotropic moment tensor components, which may thus constitute a measure for hydraulic stimulation efficiency. Recent analyses found significant isotropic moments of M2+ earthquakes during the 2006 hydraulic stimulation of a geothermal reservoir in Basel, Switzerland. The results contradicted first-motion focal mechanisms, which are in close agreement with shear sources without volumetric changes. Here we revisit the magnitude 1.7+ Basel events with full and stochastic moment tensor inversions in order to provide additional and/or supporting evidences for the occurrence of volumetric sources, if any. We furthermore apply purely deviatoric, and superimposed tensile and shear fault mechanisms, which we believe are meaningful constraints for fluid-induced earthquakes. As a result, we only find a single earthquake with statistically significant volumetric faulting. Spatial and temporal patterns of fluid-induced sources therefore have to be taken as indicative only, even though they suggest a clear relationship between fluid injections and fault mechanisms. On the other hand, we confirm that most inverted moment tensors (including the statistically significant one) show some inconsistencies with first motion focal mechanisms. We suggest that this is a manifestation of a more complicated fault geometry, which none of our moment tensor constraints can describe