Calculations of fire smokes behaviour in long rail tunnels

In order to simulate fire consequences in complex underground networks, we want to implement a coupling between a ID ventilation code and a CFD model or a zone model. The project consists in 3 main steps: the development of a ID ventilation code whose programming structure will support a coupling with another code, the definition of exchange of boundary conditions between the 2 codes and the validation of this exchange. In this paper we present our new ID code developed in this framework. A case study shows the global reaction of the flow to a fire and proves the interest of keeping into account the whole network instead limiting the calculation domain to a zone closed to the accident

SARS CoV subunit vaccine: Antibodymediated neutralisation and enhancement

1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcγR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation)

Characterization of the ligand binding site of the bovine IgA Fc receptor (bFcαR)

Recently, we identified a bovine IgA Fc receptor (bFcαR), which shows high homology to the human myeloid FcαR, CD89. IgA binding has previously been shown to depend on several specific residues located in the B-C and F-G loops of the membrane-distal extracellular domain 1 of CD89. To compare the ligand binding properties of these two FcαRs, we have mapped the IgA binding site of bFcαR. We show that, in common with CD89, Tyr-35 in the B-C loop is essential for IgA binding. However, in contrast to earlier observations on CD89, mutation of residues in the F-G loop did not significantly inhibit IgA binding.</p

G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2

Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR γ-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cγ (PLCγ). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5′-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR γ-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation

Magnetic fingerprint of southern Portuguese speleothems and implications for paleo- and environmental magnetism

Environmental magnetism of speleothems is still in its early stage of development. Here we report on our investigation of the environmental and paleomagnetic information that has been recorded in speleothems, and what are the factors that control its preservation and reliability. To address these issues, we used a multidisciplinary approach, including rock magnetism, petrography, scanning electron microscopy, stable carbon and oxygen isotope compositions, and major and trace element concentrations. We applied this to a set of samples from different stages of speleothem evolution: present-day dripwater (glass plates), a weathered stalactite, a fresh stalagmite, cave sediments, and terra rossa soils. These samples come from the Penico and Excentricas caves, located in two distinct aquifers of the Algarve region, South Portugal. Our results show that the main magnetic carriers of the speleothems under study are primary (detrital) and consist of maghemite (and magnetite?). Similarities in coercivity and temperature dependence of the studied set of samples suggest that iron oxides are inherited from the terra rossa soils that cap the cave and were transported to the speleothems by dripwater. Hence, they represent a regional environmental signature. Interestingly, a stable and probably detrital remanent magnetization could be isolated in the fresh stalagmite, whereas the weathered stalactite yielded chaotic magnetic directions and very low remanent intensities. We propose that these low intensities can be the result from(i) different remanence acquisition mechanisms between stalagmite and stalactite and/or (ii) iron dissolution by fungal activity. We also suggest that magnetic properties and color and the content in detrital elements in the fresh speleothem inform about environmental processes acting on the interface of rock (soil)-atmosphere, while oxygen isotope composition and alkaline-earth element concentrations inform about calcite-water interaction processes. These results provide a better understanding of how environmental information is recorded in speleothems and what the factors are that control the reliability of the paleomagnetic and paleo-environmental signal.info:eu-repo/semantics/acceptedVersio

Paleoseismic History of the Dead Sea Fault Zone

International audienceThe aim of this entry is to describe the DSF as a transform plate boundary pointing out the rate of activedeformation, fault segmentation, and geometrical complexities as a control of earthquake ruptures. Thedistribution of large historical earthquakes from a revisited seismicity catalogue using detailedmacroseismic maps allows the correlation between the location of past earthquakes and fault segments.The recent results of paleoearthquake investigations (paleoseismic and archeoseismic) with a recurrenceinterval of large events and long-term slip rate are presented and discussed along with the identification ofseismic gaps along the fault. Finally, the implications for the seismic hazard assessment are also discussed

Fcγ Receptors in Solid Organ Transplantation.

In the current era, one of the major factors limiting graft survival is chronic antibody-mediated rejection (ABMR), whilst patient survival is impacted by the effects of immunosuppression on susceptibility to infection, malignancy and atherosclerosis. IgG antibodies play a role in all of these processes, and many of their cellular effects are mediated by Fc gamma receptors (FcγRs). These surface receptors are expressed by most immune cells, including B cells, natural killer cells, dendritic cells and macrophages. Genetic variation in FCGR genes is likely to affect susceptibility to ABMR and to modulate the physiological functions of IgG. In this review, we discuss the potential role played by FcγRs in determining outcomes in solid organ transplantation, and how genetic polymorphisms in these receptors may contribute to variations in transplant outcome.MRC is supported by the NIHR Cambridge BRC, the NIHR Blood and Transplant Research Unit (Cambridge) and by a Medical Research Council New Investigator Grant (MR/N024907/1).This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s40472-016-0116-

Targeting platelet inhibition receptors for novel therapies: PECAM-1 and G6b-B

While current oral antiplatelet therapies benefit many patients, they deregulate the haemostatic balance leaving patients at risk of systemic side-effects such as haemorrhage. Dual antiplatelet treatment is the standard approach, combining aspirin with P2Y12 blockers. These therapies mainly target autocrine activation mechanisms (TxA2, ADP) and, more recently, the use of thrombin or thrombin receptor antagonists have been added to the available approaches. Recent efforts to develop new classes of anti-platelet drugs have begun to focus on primary platelet activation pathways such as through the immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor GPVI/FcR-chain complex. There are already encouraging results from targeting GPVI, with reduced aggregation and smaller arterial thrombi, without major bleeding complications, likely due to overlapping activation signalling pathways with other receptors such as the GPIb–V–IX complex. An alternative approach to reduce platelet activation could be to inhibit this signalling pathway by targeting the inhibitory pathways intrinsic to platelets. Stimulation of endogenous negative modulators could provide more specific inhibition of platelet function, but is this feasible? In this review, we explore the potential of the two major platelet immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing inhibitory receptors, G6b-B and PECAM-1, as antithrombotic targets

Reconstruction of the Temperature Conditions of Burial-Related Pressure Solution by Clumped Isotopes Validates the Analysis of Sedimentary Stylolites Roughness as a Reliable Depth Gauge

Rough surfaces known as stylolites are common geological features that are developed by pressure solution, especially in carbonate rocks, where they are used as strain markers and as stress gauges. As applications are developing in various geological settings, questions arise regarding the uncertainties associated with quantitative estimates of paleostress using stylolite roughness. This contribution reports for the first time a measurement of the temperature at which pressure solution was active by applying clumped isotopes thermometry to calcite cement found in jogs linking the tips of the stylolites. This authigenic calcite formed as a redistribution of the surrounding dissolved material by the same dissolution processes that formed the extensive stylolite network. We compare the depth derived from these temperatures to the depth calculated from the vertical stress inversion of a bedding parallel stylolite population documented on a slab of the Calcare Massiccio formation (early Jurassic) formerly collected in the Umbria-Marches Arcuate Ridge (Northern Apennines, Italy). We further validate the coevality between the jog development and the pressure solution by simulating the stress field around the stylolite tip. Calcite clumped isotopes constrain crystallization to temperatures between 35 and 40 °C from a common fluid with a δ 18 O signature around −1.3‰ SMOW. Additional δ 18 O isotopes on numerous jogs allows the range of precipitation temperature to be extended to from 25 to 53 °C, corresponding to a depth range of 650 to 1900 m. This may be directly compared to the results of stylolite roughness inversion for stress, which predict a range of vertical stress from 14 to 46 MPa, corresponding to depths from 400 to 2000 m. The overall correlation between these two independent depth estimates suggests that sedimentary stylolites can reliably be used as a depth gauge, independently of the thermal gradient. Beyond the method validation, our study also reveals some mechanisms of pressure solution and the associated p,T conditions favouring their development in carbonates.This work has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement 316889 (FlowTrans ITN). Part of the analyses were funded through the ISITE programme E2S, supported by ANR PIA and Région Nouvelle-Aquitaine.European Union’s Seventh Framework Programme for research, technological development and demonstrationANR PIA and Région Nouvelle-Aquitain