CONSTRUCTION AND CONVERGENCE STUDY OF SCHEMES PRESERVING THE ELLIPTIC LOCAL MAXIMUM PRINCIPLE

International audienceWe present a method to approximate (in any space dimension) diffusion equations with schemes having a specific structure; this structure ensures that the discrete local maximum and minimum principles are respected, and that no spurious oscillations appear in the solutions. When applied in a transient setting on models of concentration equations, it guaranties in particular that the approximate solutions stay between the physical bounds. We make a theoretical study of the constructed schemes, proving under a coercivity assumption that their solutions converge to the solution of the PDE. Several numerical results are also provided; they help us understand how the parameters of the method should be chosen. These results also show the practical efficiency of the method, even when applied to complex models

Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways.

During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional and epigenetic analyses with in vivo functional studies to demonstrate that Bcl6, a transcriptional repressor previously reported to promote cortical neurogenesis, acts as a driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 represses its targets through Sirt1 recruitment followed by histone deacetylation. Our data identify a molecular logic by which a single cell-intrinsic factor represses multiple extrinsic pathways that favor self-renewal, thereby ensuring robustness of neuronal fate transition

Directorium divini cultus ad Cathedralis Ecclesiae Minoriccensis : eiusque Dioecesis usum

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ECLAIRE: Effects of Climate Change on Air Pollution Impacts and Response Strategies for European Ecosystems. Project final report

The central goal of ECLAIRE is to assess how climate change will alter the extent to which air pollutants threaten terrestrial ecosystems. Particular attention has been given to nitrogen compounds, especially nitrogen oxides (NOx) and ammonia (NH3), as well as Biogenic Volatile Organic Compounds (BVOCs) in relation to tropospheric ozone (O3) formation, including their interactions with aerosol components. ECLAIRE has combined a broad program of field and laboratory experimentation and modelling of pollution fluxes and ecosystem impacts, advancing both mechanistic understanding and providing support to European policy makers. The central finding of ECLAIRE is that future climate change is expected to worsen the threat of air pollutants on Europe’s ecosystems. Firstly, climate warming is expected to increase the emissions of many trace gases, such as agricultural NH3, the soil component of NOx emissions and key BVOCs. Experimental data and numerical models show how these effects will tend to increase atmospheric N deposition in future. By contrast, the net effect on tropospheric O3 is less clear. This is because parallel increases in atmospheric CO2 concentrations will offset the temperature-driven increase for some BVOCs, such as isoprene. By contrast, there is currently insufficient evidence to be confident that CO2 will offset anticipated climate increases in monoterpene emissions. Secondly, climate warming is found to be likely to increase the vulnerability of ecosystems towards air pollutant exposure or atmospheric deposition. Such effects may occur as a consequence of combined perturbation, as well as through specific interactions, such as between drought, O3, N and aerosol exposure. These combined effects of climate change are expected to offset part of the benefit of current emissions control policies. Unless decisive mitigation actions are taken, it is anticipated that ongoing climate warming will increase agricultural and other biogenic emissions, posing a challenge for national emissions ceilings and air quality objectives related to nitrogen and ozone pollution. The O3 effects will be further worsened if progress is not made to curb increases in methane (CH4) emissions in the northern hemisphere. Other key findings of ECLAIRE are that: 1) N deposition and O3 have adverse synergistic effects. Exposure to ambient O3 concentrations was shown to reduce the Nitrogen Use Efficiency of plants, both decreasing agricultural production and posing an increased risk of other forms of nitrogen pollution, such as nitrate leaching (NO3-) and the greenhouse gas nitrous oxide (N2O); 2) within-canopy dynamics for volatile aerosol can increase dry deposition and shorten atmospheric lifetimes; 3) ambient aerosol levels reduce the ability of plants to conserve water under drought conditions; 4) low-resolution mapping studies tend to underestimate the extent of local critical loads exceedance; 5) new dose-response functions can be used to improve the assessment of costs, including estimation of the value of damage due to air pollution effects on ecosystems, 6) scenarios can be constructed that combine technical mitigation measures with dietary change options (reducing livestock products in food down to recommended levels for health criteria), with the balance between the two strategies being a matter for future societal discussion. ECLAIRE has supported the revision process for the National Emissions Ceilings Directive and will continue to deliver scientific underpinning into the future for the UNECE Convention on Long-range Transboundary Air Pollution

ECLAIRE third periodic report

The ÉCLAIRE project (Effects of Climate Change on Air Pollution Impacts and Response Strategies for European Ecosystems) is a four year (2011-2015) project funded by the EU's Seventh Framework Programme for Research and Technological Development (FP7)

Thermodynamic Control in the Catalytic Insertion Polymerization of Norbornenes as Rationale for the Lack of Reactivity of Endo-Substituted Norbornenes

The catalytic insertion polymerization of substituted norbornenes (NBEs) leads to the formation of a family of polymers which combine extreme thermomechanical properties as well as unique optical and electronic properties. However, this reaction is marred by the lack of reactivity of endo substituted monomers. It has long been assumed that these monomers chelate the metallic catalyst, leading to species which are inactive in polymerization. Here we examine the polymerization of <i>cis</i>-5-norbornene-2,3-dicarboxylic anhydride (so-called carbic anhydride, CA) with a naked cationic Pd catalyst. Although <i>exo</i>-CA can be polymerized, the polymerization of <i>endo</i>-CA stops after a single insertion. Surprisingly, no chelate is formed between the catalyst and <i>endo</i>-CA. Using DFT calculation, it is shown that while the insertion of <i>exo</i>-NBEs is exergonic, the insertion of two <i>endo</i>-CA in a row is endergonic. In this latter case, the enthalpy gain corresponding to the insertion of a double bond is not sufficient to overcome the entropic penalty associated with ligand binding. Thus, the different reactivity between endo and exo NBEs is thermodynamic in nature, and it is not controlled by kinetic factors. Interestingly, thermodynamics is also the main factor controlling the stereochemistry of the chain. For CA polymerization, and even for unsubstituted NBE polymerization, the formation of <i>r</i> and <i>m</i> dyads is, respectively, exergonic and endergonic, resulting in a polymer which is essentially disyndiotactic. Thus, this study demonstrates that thermodynamics can control the chemo- and stereoselectivity of a catalytic polymerization

Long-term disruption of growth, reproduction, and behavior after embryonic exposure of zebrafish to PAH-spiked sediment

A natural sediment spiked with three individual polycyclic aromatic hydrocarbons (PAHs; pyrene, phenanthrene and benzo[a]pyrene) was used to expose zebrafish embryos and larvae during 4 days. The total PAH concentration was 4.4 μg g−1 which is in the range found in sediment from contaminated areas. Quantification of metabolites in the larvae after exposure confirmed the actual contamination of the larvae and indicated an active metabolism especially for pyrene and benzo[a]pyrene. After a transfer in a clean medium, the larvae were reared to adulthood and evaluated for survival, growth, reproduction, and behavior. Measured endpoints revealed a late disruption of growth (appearing at 5 months) and a trend toward a lower reproductive ability. Adults of embryos exposed to sediment spiked with PAHs displayed lethargic and/or anxiety-like behaviors. This latter behavior was also identified in offspring at larval stage. All together, these effects could have detrimental consequences on fish performances and contribution to recruitment

Low performance of prognostic tools for predicting dialysis in elderly people with advanced CKD

International audienceIntroduction Clinical decision-making about care plans can be difficult for very elderly people with advanced chronic kidney disease (CKD). Current guidelines propose the use of prognostic tools predicting end stage renal disease (ESRD) to assist in a patient-centered shared decision-making approach. Our objective was to evaluate the existing risk model scores predicting ESRD, from data collected for a French prospective multicenter cohort of mainly octogenarians with advanced CKD. Methods We performed a rapid review to identify the risk model scores predicting ESRD developed from CKD patient cohorts and evaluated them with data from a prospective multicenter French cohort of elderly (&gt; 75 years) patients with advanced CKD (estimated glomerular filtration rate [eGFR] &lt; 20 mL/min/1.75m(2)), followed up for 5 years. We evaluated these scores (in absolute risk) for discrimination, calibration and the Brier score. For scores using the same time frame, we made a joint calibration curve and compared areas under the curve (AUCs). Results The PSPA cohort included 573 patients; their mean age was 83 years and their median eGFR was 13 mL/min/1.73 m(2). At the end of follow-up, 414 had died and 287 had started renal replacement therapy (RRT). Our rapid review found 12 scores that predicted renal replacement therapy. Five were evaluated: the TANGRI 4-variable, DRAWZ, MARKS, GRAMS, and LANDRAY scores. No score performed well in the PSPA cohort: AUCs ranged from 0.57 to 0.65, and Briers scores from 0.18 to 0.25. Conclusions The low predictiveness for ESRD of the scores tested in a cohort of octogenarian patients with advanced CKD underlines the need to develop new tools for this population. Graphic abstrac

The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic cell proliferation, induces angiogenesis in vitro and in vivo

The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP), purified from bone marrow and constitutively synthesized in vivo, belongs to the family of negative regulators of hematopoiesis. It protects the stem cell compartment from the toxicity of anticancer drugs and irradiation and consequently contributes to a reduction in marrow failure. This current work provides experimental evidence for another novel biologic function of AcSDKP. We report that AcSDKP is a mediator of angiogenesis, as measured by its ability to modulate endothelial cell function in vitro and angiogenesis in vivo.AcSDKP at nanomolar concentrations stimulates in vitro endothelial cell migration and differentiation into capillary-like structures on Matrigel as well as enhances the secretion of an active form of matrix metalloproteinase-1 (MMP-1). In vivo, AcSDKP promotes a significant angiogenic response in the chicken embryo chorioallantoic membrane (CAM) and in the abdominal muscle of the rat. Moreover, it induces the formation of blood vessels in Matrigel plugs implanted subcutaneously in the rat. This is the first report demonstrating the ability of AcSDKP to interact directlywith endothelial cells and to elicit an angiogenic response in vitro and in vivo