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The equilibrium climate sensitivity, that is, the global‐mean surface‐air temperature change in response to a doubling of the carbon dioxide concentration is a widely used metric in climate change studies. Its exact value is rarely known because its estimation requires a long integration time of several thousand years. We propose a method to estimate an accurate value of the equilibrium response from fully coupled climate models at a reasonable computational cost. Using this method, our state‐of‐the‐art climate model CNRM‐CM6‐1 reaches a stationary state after only few hundred of years of integration. This "Fast‐Forward" method consists of an optimal two‐step forcing pathway designed using the framework of a two‐layer energy balance model. It can be applied easily to any coupled climate model. Key Points: A simple method for estimating the equilibrium climate sensitivity is proposedThe method allows to simulate the stationary climate corresponding to any given radiative perturbation with a limited computational costThe method can be applied to any atmosphere‐ocean coupled climate model [ABSTRACT FROM AUTHOR]

Diabatic heating plays a crucial role in the formation and maintenance of the West African Monsoon. A dynamical core configuration of a General Circulation Model (GCM) is used to test the influence of diabatic heating from different sources and regions on the strength and northward penetration of the monsoon circulation. The dynamical core is able to capture the main features of the monsoon flow, and when forced with heating tendencies from various different GCMs it recreates many of the differences seen between the full GCM monsoon circulations. Differences in atmospheric short-wave absorption over the Sahara and Sahel regions are a key driver of variation in the models' monsoon circulations, and this is likely to be linked to how aerosols, clouds and surface albedo are represented across the models. The magnitude of short-wave absorption also appears to affect the strength and position of the African easterly jet (AEJ), but not that of the tropical easterly jet (TEJ). The dynamical core is also used here to understand circulation changes that occur during the ongoing model development process that occurs at each modeling centre, providing the potential to trace these changes to specific alterations in model physics. [ABSTRACT FROM AUTHOR]

Vertical and horizontal distributions of diabatic heating in the West African monsoon (WAM) region as simulated by four model families are analyzed in order to assess the physical processes that affect the WAM circulation. For each model family, atmosphere-only runs of their CMIP5 configurations are compared with more recent configurations which are on the development path toward CMIP6. The various configurations of these models exhibit significant differences in their heating/moistening profiles, related to the different representation of physical processes such as boundary layer mixing, convection, large-scale condensation and radiative heating/cooling. There are also significant differences in the models' simulation of WAM rainfall patterns and circulations. The weaker the radiative cooling in the Saharan region, the larger the ascent in the rainband and the more intense the monsoon flow, while the latitude of the rainband is related to heating in the Gulf of Guinea region and on the northern side of the Saharan heat low. Overall, this work illustrates the difficulty experienced by current climate models in representing the characteristics of monsoon systems, but also that we can still use them to understand the interactions between local subgrid physical processes and the WAM circulation. Moreover, our conclusions regarding the relationship between errors in the large-scale circulation of the WAM and the structure of the heating by small-scale processes will motivate future studies and model development. [ABSTRACT FROM AUTHOR]

As part of an international intercomparison project, the weak temperature gradient (WTG) and damped gravity wave (DGW) methods are used to parameterize large-scale dynamics in a set of cloud-resolving models (CRMs) and single column models (SCMs). The WTG or DGW method is implemented using a configuration that couples a model to a reference state defined with profiles obtained from the same model in radiative-convective equilibrium. We investigated the sensitivity of each model to changes in SST, given a fixed reference state. We performed a systematic comparison of the WTG and DGW methods in different models, and a systematic comparison of the behavior of those models using the WTG method and the DGW method. The sensitivity to the SST depends on both the large-scale parameterization method and the choice of the cloud model. In general, SCMs display a wider range of behaviors than CRMs. All CRMs using either the WTG or DGW method show an increase of precipitation with SST, while SCMs show sensitivities which are not always monotonic. CRMs using either the WTG or DGW method show a similar relationship between mean precipitation rate and column-relative humidity, while SCMs exhibit a much wider range of behaviors. DGW simulations produce large-scale velocity profiles which are smoother and less top-heavy compared to those produced by the WTG simulations. These large-scale parameterization methods provide a useful tool to identify the impact of parameterization differences on model behavior in the presence of two-way feedback between convection and the large-scale circulation. [ABSTRACT FROM AUTHOR]

As part of an international intercomparison project, a set of single-column models (SCMs) and cloud-resolving models (CRMs) are run under the weak-temperature gradient (WTG) method and the damped gravity wave (DGW) method. For each model, the implementation of the WTG or DGW method involves a simulated column which is coupled to a reference state defined with profiles obtained from the same model in radiative-convective equilibrium. The simulated column has the same surface conditions as the reference state and is initialized with profiles from the reference state. We performed systematic comparison of the behavior of different models under a consistent implementation of the WTG method and the DGW method and systematic comparison of the WTG and DGW methods in models with different physics and numerics. CRMs and SCMs produce a variety of behaviors under both WTG and DGW methods. Some of the models reproduce the reference state while others sustain a large-scale circulation which results in either substantially lower or higher precipitation compared to the value of the reference state. CRMs show a fairly linear relationship between precipitation and circulation strength. SCMs display a wider range of behaviors than CRMs. Some SCMs under the WTG method produce zero precipitation. Within an individual SCM, a DGW simulation and a corresponding WTG simulation can produce different signed circulation. When initialized with a dry troposphere, DGW simulations always result in a precipitating equilibrium state. The greatest sensitivities to the initial moisture conditions occur for multiple stable equilibria in some WTG simulations, corresponding to either a dry equilibrium state when initialized as dry or a precipitating equilibrium state when initialized as moist. Multiple equilibria are seen in more WTG simulations for higher SST. In some models, the existence of multiple equilibria is sensitive to some parameters in the WTG calculations. [ABSTRACT FROM AUTHOR]

RATIONALE: New treatment strategies are needed to improve airway clearance and reduce the morbidity and the time burden associated with cystic fibrosis (CF). OBJECTIVES: To determine whether long-term treatment with inhaled mannitol, an osmotic agent, improves lung function and morbidity. METHODS: Double-blind, randomized, controlled trial of inhaled mannitol, 400 mg twice a day (n = 192, 'treated' group) or 50 mg twice a day (n = 126, 'control' group) for 26 weeks, followed by 26 weeks of open-label treatment. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was absolute change in FEV(1) from baseline in treated versus control groups, averaged over the study period. Secondary endpoints included other spirometric measurements, pulmonary exacerbations, and hospitalization. Clinical, microbiologic, and laboratory safety were assessed. The treated group had a mean improvement in FEV(1) of 105 ml (8.2% above baseline). The treated group had a relative improvement in FEV(1) of 3.75% (P = 0.029) versus the control group. Adverse events and sputum microbiology were similar in both treatment groups. Exacerbation rates were low, but there were fewer in the treated group (hazard ratio, 0.74; 95% confidence interval, 0.42-1.32; P = 0.31), although this was not statistically significant. In the 26-week open-label extension study, FEV(1) was maintained in the original treated group, and improved in the original control group to the same degree. CONCLUSIONS: Inhaled mannitol, 400 mg twice a day, resulted in improved lung function over 26 weeks, which was sustained after an additional 26 weeks of treatment. The safety profile was also acceptable, demonstrating the potential role for this chronic therapy for CF. Clinical trial registered with www.clinicaltrials.gov (NCT 00630812). [ABSTRACT FROM AUTHOR]

Abstract: Gelatinase A, a member of the matrix metalloproteinase family, contains three fibronectin type II (FnII)-like modules that are inserted within its catalytic domain. These FnII modules, defined as exosites, play an essential role in targeting the enzyme to matrix macromolecules, a process which can down-regulate membrane-type metalloproteinase-driven progelatinase A activation. The exosite/substrate-directed gelatinase inhibitors has been proposed as an alternative approach to disappointing active site-directed inhibitors, to control gelatinase A activity. In preliminary experiments, we evidenced that long-chain unsaturated fatty acids could bind preferentially to the first FnII module of gelatinase A. This interaction inhibits the activity of this enzyme towards proteins (type I gelatin and collagen) and an octapeptide substrate, with K i in the micromolar range. Since gelatinase A-catalyzed matrix proteolysis might display a positive or negative influence (depending on the substrate cleaved), the design of exosite-specific compounds for noncatalytic targeting of gelatinase A would necessitate an extensive degradomic analysis. [Copyright &y& Elsevier]

Abstract: The term “matrikines” was coined for designating peptides liberated by partial proteolysis of extracellular matrix macromolecules, which are able to regulate cell activities. Among these peptides, some of them may modulate proliferation, migration, protease production, or apoptosis. In this review, we summarize the activity of matrikines derived from elastin and interstitial or basement membrane collagens on the regulation of matrix metalloproteinases expression and/or activation, and on the plasminogen/plasmin system. Due to their activity, matrikines may play a significant role in physiological or pathological processes such as wound healing or tumor invasion. [Copyright &y& Elsevier]