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Colorectal cancer (CRC), found in the intestinal tract, is initiated and progresses through various mechanisms, including the dysregulation of signaling pathways. Several signaling pathways, such as EGFR and MAPK, involved in cell proliferation, migration, and apoptosis, are often dysregulated in CRC. Although cannabidiol (CBD) has previously induced apoptosis and cell cycle arrest in vitro in CRC cell lines, its effects on signaling pathways have not yet been determined. An in silico analysis was used here to assess partner proteins that can bind to CBD, and docking simulations were used to predict precisely where CBD would bind to these selected proteins. A survey of the current literature was used to hypothesize the effect of CBD binding on such proteins. The results predict that CBD could interact with EGFR, RAS/RAF isoforms, MEK1/2, and ERK1/2. The predicted CBD-induced inhibition might be due to CBD binding to the ATP binding site of the target proteins. This prevents the required phosphoryl transfer to activate substrate proteins and/or CBD binding to the DFG motif from taking place, thus reducing catalytic activity.

HBeAg is a non-structural, secreted protein of hepatitis B virus (HBV). Its p25 precursor is post-translationally modified in the endoplasmic reticulum. The G1862T precore mutation leads to the accumulation of P25 in the endoplasmic reticulum and activation of unfolded protein response. Using mass spectrometry, comparative proteome profiling of Huh-7 cells transfected with wildtype (WT) or G1862T revealed significantly differentially expressed proteins resulting in 12 dysregulated pathways unique to WT-transfected cells and 7 shared between cells transfected with either WT or G1862T. Except for the p38 MAPK signalling pathway, WT showed a higher number of DEPs than G1862T-transfected cells in all remaining six shared pathways. Two signalling pathways: oxidative stress and cell cycle signalling were differentially expressed only in cells transfected with G1862T. Fifteen pathways were dysregulated in G1862T-transfected cells compared to WT. The 15 dysregulated pathways were involved in the following processes: MAPK signalling, DNA synthesis and methylation, and extracellular matrix organization. Moreover, proteins involved in DNA synthesis signalling (replication protein A (RPA) and DNA primase (PRIM2)) were significantly upregulated in G1862T compared to WT. This upregulation was confirmed by mRNA quantification of both genes and immunofluorescent confocal microscopy for RPA only. The dysregulation of the pathways involved in these processes may lead to immune evasion, persistence, and uncontrolled proliferation, which are hallmarks of cancer.

The central Arctic cryosphere is influenced by the Arctic amplification (AA) and is warming faster than the lower latitudes. AA affects the formation, loss, and transport of aerosols. Efforts to assess the underlying processes determining aerosol variability are currently limited due to the lack of ground-based and space-borne aerosol observations with high spatial coverage in this region. This study addresses the observational gap by making use of total aerosol optical depth (AOD) datasets retrieved by the AEROSNOW algorithm over the vast cryospheric region of the central Arctic during Arctic spring and summer. GEOS-Chem (GC) simulations combined with AEROSNOW-retrieved data are used to investigate the processes controlling aerosol loading and distribution at different temporal and spatial scales. For the first time, an integrated study of AOD over the Arctic cryosphere during sunlight conditions was possible with the AEROSNOW retrieval and GC simulations. The results show that the spatial patterns observed by AEROSNOW differ from those simulated by GC. During spring, which is characterized by long-range transport of anthropogenic aerosols in the Arctic, GC underestimates the AOD in the vicinity of Alaska in comparison with AEROSNOW retrieval. At the same time, it overestimates the AOD along the Bering Strait, northern Europe, and the Siberian central Arctic sea-ice regions, with differences of −12.3 % and 21.7 %, respectively. By contrast, GC consistently underestimates AOD compared with AEROSNOW in summer, when transport from lower latitudes is insignificant and local natural processes are the dominant source of aerosol, especially north of 70° N. This underestimation is particularly pronounced over the central Arctic sea-ice region, where it is −10.6 %. Conversely, GC tends to overestimate AOD along the Siberian and Greenland marginal sea-ice zones by 19.5 % but underestimates AOD along the Canadian Archipelago by −9.3 %. The differences in summer AOD between AEROSNOW data products and GC-simulated AOD highlight the need to integrate improved knowledge of the summer aerosol process into existing models in order to constrain its effects on cloud condensation nuclei, on ice nucleating particles, and on the radiation budget over the central Arctic sea ice during the developing AA period.

The climate in the Arctic has warmed much more quickly in the last 2 to 3 decades than at the mid-latitudes, i.e., during the Arctic amplification (AA) period. Radiative forcing in the Arctic is influenced both directly and indirectly by aerosols. However, their observation from ground or airborne instruments is challenging, and thus measurements are sparse. In this study, total aerosol optical depth (AOD) is determined from top-of-atmosphere reflectance measurements by the Advanced Along-Track Scanning Radiometer (AATSR) on board ENVISAT over snow and ice in the Arctic using a retrieval called AEROSNOW for the period 2003 to 2011. AEROSNOW incorporates an existing aerosol retrieval algorithm with a cloud-masking algorithm, alongside a novel quality-flagging methodology specifically designed for implementation in the high Arctic region (≥ 72∘ N). We use the dual-viewing capability of the AATSR instrument to accurately determine the contribution of aerosol to the reflection at the top of the atmosphere for observations over the bright surfaces of the cryosphere in the Arctic. The AOD is retrieved assuming that the surface reflectance observed by the satellite can be well parameterized by a bidirectional snow reflectance distribution function (BRDF). The spatial distribution of AOD shows that high values in spring (March, April, May) and lower values in summer (June, July, August) are observed. The AEROSNOW AOD values are consistent with those from collocated Aerosol Robotic Network (AERONET) measurements, with no systematic bias found as a function of time. The AEROSNOW AOD in the high Arctic was validated by comparison with ground-based measurements at the PEARL, OPAL, Hornsund, and Thule stations. The AEROSNOW AOD value is less than 0.15 on average, and the linear regression of AEROSNOW and AERONET total AOD yields a slope of 0.98, a Pearson correlation coefficient of R=0.86, and a root mean square error (RMSE) of =0.01 for the monthly scale in both spring and summer. The AEROSNOW observation of increased AOD values over the high Arctic cryosphere during spring confirms clearly that Arctic haze events were well captured by this dataset. In addition, the AEROSNOW AOD results provide a novel and unique total AOD data product for the springtime and summertime from 2003 to 2011. These AOD values, retrieved from spaceborne observation, provide a unique insight into the high Arctic cryospheric region at high spatial resolution and temporal coverage.

In West Africa, the zonal band of precipitation is generally located around the southern coast in June before migrating northward towards the Sahel in late June/early July. This gives way to a relative dry season for coastal regions from Côte d'Ivoire to Benin called “little dry season”, which lasts until September–October. Previous studies have noted that the coastal rainfall cessation in early July seems to coincide with the emergence of an upwelling along the Guinea coast. The aim of this study is to investigate the mechanisms by which this upwelling impacts precipitation, using a set of numerical simulations performed with the Weather Research and Forecasting regional atmospheric model (WRF v 3.7.1). Sensitivity experiments highlight the response of the atmospheric circulation to an intensification or reduction of the strength of the coastal upwelling. They clearly show that the coastal upwelling emergence is responsible for the cessation of coastal precipitation by weakening the northward humidity transport, thus decreasing the coastal convergence of the humidity transport and inhibiting the deep atmospheric convection. In addition, the diurnal cycle of the low-level circulation plays a critical role: the land breeze controls the seaward convergence of diurnal anomaly of humidity transport, explaining the late night–early morning peak observed in coastal precipitation. The emergence of the coastal upwelling strongly attenuates this peak because of a reduced land–sea temperature gradient in the night and a weaker land breeze. The impact on the inland transport of anthropogenic pollution is also shown with numerical simulations of aerosols using the CHIMERE chemistry-transport model: warmer (colder) sea surface temperature (SST) increases (decreases) the inland transport of pollutants, especially during the night, suggesting an influence of the upwelling intensity on the coastal low-level jet. The mechanisms described have important consequences for inland humidity transport and the predictability of the West African monsoon precipitation in summer.

Low-level stratiform clouds (LLSCs) covering a large area appear frequently during the wet monsoon season in southern West Africa. This region is also a place where different types of aerosols coexist, including biomass burning aerosols coming from central and southern Africa and aerosols emitted by local anthropogenic activities. We investigate the indirect and semi-direct effects of these aerosols on the life cycle of LLSCs by conducting a case study based on airborne and ground-based observations from the field campaign of Dynamic-Aerosol-Chemistry-Cloud-Interaction in West Africa (DACCIWA). This case is modeled using a large-eddy-simulation (LES) model with fine resolution and in situ aerosol measurements, including size distribution and chemical composition. The model has successfully reproduced the observed life cycle of the LLSC, from stratus formation to stabilization during the night and to upward development after sunrise until break-up of the cloud deck in the late afternoon. Additional sensitivity simulations using different measured aerosol profiles also suggest that aerosols can affect the cloud life cycle through both the indirect and semi-direct effects. As expected, modeled cloud microphysical features, including cloud droplet number concentration, mean radius, and thus cloud reflectivity, are all controlled by aerosol concentration. However, it is found that the variation in cloud reflectivity induced by different aerosol profiles is not always the only factor in determining the incoming solar radiation at the ground and thus for the cloud life cycle after sunrise. Instead, the difference in cloud fraction brought by dry-air entrainment from above and thus the speed of consequent evaporation – also influenced by aerosol concentration – is another important factor to consider. Clouds influenced by higher aerosol concentrations and thus with a higher number concentration and smaller sizes of cloud droplets are found to evaporate more easily and thus impose a lower cloud fraction. In addition, our sensitivity runs including versus excluding aerosol direct radiative effects have also demonstrated the impacts specifically of solar absorption by black carbon on the cloud life cycle. The semi-direct effect resulting from an excessive atmospheric heating of up to 12 K d−1 by black carbon in our modeled cases is found to lower the cloud top as well as the liquid water path, reducing surface incoming solar radiation and dry entrainment and increasing the cloud fraction.

In sub-Saharan Africa (SSA), the (sub)genotypes A1, D3, and E of the hepatitis B virus (HBV) prevail. Individuals infected with subgenotype A1 have a 4.5-fold increased risk of HCC compared to those infected with other (sub)genotypes. The effect of (sub)genotypes on protein expression and host signalling has not been studied. Mass spectrometry was used to analyse the proteome of Huh7 cells transfected with replication-competent clones. Proteomic analysis revealed significantly differentially expressed proteins between SSA (sub)genotypes. Different (sub)genotypes have the propensity to dysregulate specific host signalling pathways. Subgenotype A1 resulted in dysregulation within the Ras pathway. Ras-associated protein, RhoC, was significantly upregulated in cells transfected with subgenotype A1 compared to those transfected with other (sub)genotypes, on both a proteomic (>1.5-fold) and mRNA level (p < 0.05). Two of the main cellular signalling pathways involving RHOC, MAPK and PI3K/Akt/mTOR, regulate cell growth, motility, and survival. Downstream signalling products of these pathways have been shown to increase MMP2 and MMP9 expression. An extracellular MMP2 and MMP9 ELISA revealed a non-significant increase in MMP2 and MMP9 in the cells transfected with A1 compared to the other (sub)genotypes (p < 0.05). The upregulated Ras-associated proteins have been implicated as oncoproteins in various cancers and could contribute to the increased hepatocarcinogenic potential of A1.

During the West African summer monsoon, pollutants emitted in urbanized coastal areas modify cloud cover and precipitation patterns. The Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa (DACCIWA) field campaign provided numerous aircraft-based and ground-based observations, which are used here to evaluate two experiments made with the coupled WRF–CHIMERE model, integrating both the direct and indirect aerosol effect on meteorology. During one well-documented week (1–7 July 2016), the impacts of anthropogenic aerosols on the diurnal cycle of low-level clouds and precipitation are analyzed in detail using high and moderate intensity of anthropogenic emissions in the experiments. Over the continent and close to major anthropogenic emission sources, the breakup time of low-level clouds is delayed by 1 hour, and the daily precipitation rate decreased by 7.5 % with the enhanced anthropogenic emission experiment (with high aerosol load). Despite the small modifications on daily average of low-level cloud cover (+2.6 %) with high aerosol load compared to moderate, there is an increase by more than 20 % from 14:00 to 22:00 UTC on hourly average. Moreover, modifications of the modeled low-level cloud and precipitation rate occur far from the major anthropogenic emission sources, to the south over the ocean and to the north up to 11∘ N. The present study adds evidence to recent findings that enhanced pollution levels in West Africa may reduce precipitation.

Considered as a “strategic” resource for both local communities and extra-local public authorities, Lake Guiers is subject to a variety of practices and uses (agricultural, industrial, fish farming and domestic) that currently impact its ecological quality. This article analyses the “low-noise mobilisations”, developed on the fringes of the institutional mechanism, with the aim of preserving the water resource and its uses. We explain their organization, evolution, and functioning, trying to demonstrate how these actors (as policy brokers) co-construct an ideal of ecological action, use social, cultural, political and economical resources, form alliances, and fit into a larger institutional framework. We also analyze the socio-economic, ecological and political motivations of the actors involved with the communities in the mobilisations for the preservation of Lake Guiers.

In order to fight the spread of the global COVID-19 pandemic, most of the world's countries have taken control measures such as lockdowns during a few weeks to a few months. These lockdowns had significant impacts on economic and personal activities in many countries. Several studies using satellite and surface observations have reported important changes in the spatial and temporal distributions of atmospheric pollutants and greenhouse gases. Global and regional chemistry-transport model studies are being performed in order to analyze the impact of these lockdowns on the distribution of atmospheric compounds. These modeling studies aim at evaluating the impact of the regional lockdowns at the global scale. In order to provide input for the global and regional model simulations, a dataset providing adjustment factors (AFs) that can easily be applied to current global and regional emission inventories has been developed. This dataset provides, for the January–August 2020 period, gridded AFs at a 0.1×0.1 latitude–longitude degree resolution on a daily or monthly basis for the transportation (road, air and ship traffic), power generation, industry and residential sectors. The quantification of AFs is based on activity data collected from different databases and previously published studies. A range of AFs are provided at each grid point for model sensitivity studies. The emission AFs developed in this study are applied to the CAMS global inventory (CAMS-GLOB-ANT_v4.2_R1.1), and the changes in emissions of the main pollutants are discussed for different regions of the world and the first 6 months of 2020. Maximum decreases in the total emissions are found in February in eastern China, with an average reduction of 20 %–30 % in NOx, NMVOCs (non-methane volatile organic compounds) and SO2 relative to the reference emissions. In the other regions, the maximum changes occur in April, with average reductions of 20 %–30 % for NOx, NMVOCs and CO in Europe and North America and larger decreases (30 %–50 %) in South America. In India and African regions, NOx and NMVOC emissions are reduced on average by 15 %–30 %. For the other species, the maximum reductions are generally less than 15 %, except in South America, where large decreases in CO and BC (black carbon) are estimated. As discussed in the paper, reductions vary highly across regions and sectors due to the differences in the duration of the lockdowns before partial or complete recovery. The dataset providing a range of AFs (average and average ± standard deviation) is called CONFORM (COvid-19 adjustmeNt Factors fOR eMissions) (https://doi.org/10.25326/88; Doumbia et al., 2020). It is distributed by the Emissions of atmospheric Compounds and Compilation of Ancillary Data (ECCAD) database (https://eccad.aeris-data.fr/, last access: 23 August 2021).

The energy demand for heating and cooling buildings is changing with global warming. Here the authors show that trends in cooling energy demands are increasing, although the magnitude is extremely uncertain, which highlights challenges for future energy demand quantification.

The world has seen the emergence of a new virus in 2019, SARS-CoV-2, causing the COVID-19 pandemic and millions of deaths worldwide. Microscopy can be much more informative than conventional detection methods such as RT-PCR. This review aims to present the up-to-date microscopy observations in patients, the in vitro studies of the virus and viral proteins and their interaction with their host, discuss the microscopy techniques for detection and study of SARS-CoV-2, and summarize the reagents used for SARS-CoV-2 detection. From basic fluorescence microscopy to high resolution techniques and combined technologies, this article shows the power and the potential of microscopy techniques, especially in the field of virology.

Abstract HBeAg, a non-particulate protein of hepatitis B virus (HBV), is translated from the precore/core region as a precursor, which is post-translationally modified. Subgenotype A1 of HBV, which is a risk factor for hepatocellular carcinoma (HCC), has unique molecular characteristics in the basic core promoter/precore regions. Carriers of A1 exhibit early HBeAg loss. We sought to further characterize the precore proteins of A1 in vitro. HuH-7 cells were transfected with subgenomic constructs expressing individual precore proteins. Western blot analysis using DAKO anti-core antibody showed the expected sizes and a 1 kDa larger band for P22, P20 and P17. Using confocal microscopy, a cytoplasmic accumulation of HBeAg and precursors was observed with P25-expressing plasmid, whereas P22 localized both in the cytoplasm and nucleus. P20 and P17, which lack the carboxy end of P22 showed strong nuclear accumulation, implicating a nuclear localization signal in the N-terminal 10 amino acids. G1862T, unique to subgenotype A1, is frequently found in HBV from HCC patients. P25 with G1862T showed delayed and reduced HBeAg expression/secretion. Knock-out of core in the replication competent clones led to precore protein accumulation in the cytoplasm/perinuclear region, and decreased HBeAg secretion. Knock-out of precore proteins increased HBsAg secretion but intracellular HBsAg expression was unaffected. Over-expression of precore proteins in trans led to decreased HBsAg expression and secretion. Intracellular trafficking of HBV A1 precore proteins was followed. This was unaffected by the CMV promoter and different cell types. In the viral context, precore protein expression was affected by absence of core, and affected HBsAg expression, suggesting an interrelationship between precore proteins, HBcAg and HBsAg. This modulatory role of HBeAg and its precursors may be important in viral persistence and ultimate development of HCC.

Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous manipulation of immunity and cell fate decisions. The persistence of HBV infection is associated with the pathogenesis of hepatocellular carcinoma, and various HBV proteins have been implicated in promoting this persistence. The precursor of hepatitis e antigen (HBeAg), is translated from the precore/core region and is post-translationally modified to yield HBeAg, which is secreted in the serum. HBeAg is a non-particulate protein of HBV and can act as both a tolerogen and an immunogen. HBeAg can protect hepatocytes from apoptosis by interfering with host signalling pathways and acting as a decoy to the immune response. By evading the immune response and interfering with apoptosis, HBeAg has the potential to contribute to the hepatocarcinogenic potential of HBV. In particular, this review summarises the various signalling pathways through which HBeAg and its precursors can promote hepatocarcinogenesis via the various hallmarks of cancer.

The aerosol direct and indirect effects are studied over west Africa in the summer of 2016 using the coupled WRF-CHIMERE regional model including aerosol–cloud interaction parameterization. First, a reference simulation is performed and compared with observations acquired during the Dynamics-aerosol-chemistry-cloud interactions in West Africa (DACCIWA) field campaign which took place in June and July 2016. Sensitivity experiments are also designed to gain insights into the impact of the aerosols dominating the atmospheric composition in southern west Africa (one simulation with halved anthropogenic emissions and one with halved mineral dust emissions). The most important effect of aerosol–cloud interactions is found for the mineral dust scenario, and it is shown that halving the emissions of mineral dust decreases the 2 m temperature by 0.5 K and the boundary layer height by 25 m on a monthly average (July 2016) and over the Saharan region. The presence of dust aerosols also increases (decreases) the shortwave (longwave) radiation at the surface by 25 W m−2. It is also shown that the decrease of anthropogenic emissions along the coast has an impact on the mineral dust load over west Africa by increasing their emissions in the Saharan region. It is due to a mechanism where particulate matter concentrations are decreased along the coast, imposing a latitudinal shift of the monsoonal precipitation and, in turn, an increase of the surface wind speed over arid areas, inducing more mineral dust emissions.

Abstract Using the CAM‐chem Model, we simulate the response of chemical species in the free troposphere to scenarios of primary pollutant emission reductions during the COVID‐19 pandemic. Zonally averaged ozone in the free troposphere during Northern Hemisphere spring and summer is found to be 5%–15% lower than 19‐yr climatological values, in good agreement with observations. About one third of this anomaly is attributed to the reduction scenario of air traffic during the pandemic, another third to the reduction scenario of surface emissions, the remainder to 2020 meteorological conditions, including the exceptional springtime Arctic stratospheric ozone depletion. For the combined emission reductions, the overall COVID‐19 reduction in northern hemisphere tropospheric ozone in June is less than 5 ppb below 400 hPa, but reaches 8 ppb at 250 hPa. In the Southern Hemisphere, COVID‐19 related ozone reductions by 4%–6% were masked by comparable ozone increases due to other changes in 2020.

In the framework of the European DACCIWA (Dynamics–Aerosol–Chemistry–Cloud Interactions in West Africa) project, the airborne study APSOWA (Atmospheric Pollution from Shipping and Oil platforms of West Africa) was conducted in July 2016 to study oil rig emissions off the Gulf of Guinea. Two flights in the marine boundary layer were focused on the floating production storage and offloading (FPSO) vessel operating off the coast of Ghana. Those flights present simultaneous sudden increases in NO2 and aerosol concentrations. Unlike what can be found in flaring emission inventories, no increase in SO2 was detected, and an increase in CO is observed only during one of the two flights. Using FLEXPART (FLEXible PARTicle dispersion model) simulations with a regional NO2 satellite flaring inventory in forward-trajectory mode, our study reproduces the timing of the aircraft NO2 enhancements. Several sensitivity tests on the flux and the injection height are also performed, leading to the conclusion that a lower NO2 flux helps in better reproducing the measurements and that the modification of the injection height does not impact the results of the simulations significantly.

During the monsoon season, pollutants emitted by large coastal cities and biomass burning plumes originating from central Africa have complex transport pathways over southern West Africa (SWA). The Dynamics–Aerosol–Chemistry–Cloud Interactions in West Africa (DACCIWA) field campaign has provided numerous dynamical and chemical measurements in and around the super-site of Savè in Benin ( ≈ 185 km away from the coast), which allows quantification of the relative contribution of advected pollutants. Through the combination of in situ ground measurements with aircraft, radio-sounding, satellite, and high-resolution chemistry-transport modeling with the CHIMERE model, the source attribution and transport pathways of pollutants inland (here, NOx and CO) are carefully analyzed for the 1–7 July 2016 period. The relative contributions of different sources (i.e., emissions from several large coastal cities) to the air quality in Savè are characterized. It is shown that a systematic diurnal cycle exists with high surface concentrations of pollutants from 18:00 to 22:00 UTC. This evening peak is attributed to pollution transport from the coastal city of Cotonou (Benin). Numerical model experiments indicate that the anthropogenic pollutants are accumulated during the day close to the coast and transported northward as soon as the daytime convection in the atmospheric boundary layer ceases after 16:00 UTC, reaching 8° N at 21:00 UTC. When significant biomass burning pollutants are transported into continental SWA, they are mixed with anthropogenic pollutants along the coast during the day, and this mixture is then transported northward. At night, most of the coastal anthropogenic plumes are transported within the planetary boundary layer (below about 500 m above ground level), whereas the biomass burning pollutants are mostly transported above it, thus generally not impacting ground level air quality.

Abstract The lockdown period (March–May 2020) during the COVID‐19 pandemic in Europe led to a reduction in the anthropogenic emissions of primary pollutants. For three‐quarters of over 1,100 available monitoring stations, the average nitrogen dioxide (NO2) concentrations decreased by at least 2.7 μg·m−3 (or 25%) compared with the average concentrations recorded during the same period of the previous seven years. This reduction was not specific to urban or rural areas because the relative reduction was of similar magnitude in both areas. The ozone (O3) response differed spatially, with positive anomalies in Northern Europe and negative anomalies in Southwestern Europe. Reduced cloudiness and related enhanced radiation in Northern Europe played a significant role in the increase of surface O3 concentrations by shifting the photochemical partitioning between NO2 and O3 toward more O3. The level of total oxidant (Ox = O3 + NO2) remained unchanged, except in Southwestern Europe where it decreased. Several episodes lasting a few days of a high level of total oxidants were observed in Northern Europe. The results illustrate the complexity of the atmospheric response to the unprecedented reduction in the emission of primary pollutants.

REMORIN proteins belong to a plant-specific multigene family that localise in plasma membrane nanodomains and in plasmodesmata. We previously showed that in Nicotiana benthamiana, group 1 StREM1.3 limits the cell-to-cell spread of a potexvirus without affecting viral replication. This prompted us to check whether an effect on viral propagation could apply to potyvirus species Turnip mosaic virus (TuMV) and Potato virus A (PVA). Our results show that StREM1.3 transient or stable overexpression in transgenic lines increases potyvirus propagation, while it is slowed down in transgenic lines underexpressing endogenous NbREMs, without affecting viral replication. TuMV and PVA infection do not alter the membranous localisation of StREM1.3. Furthermore, StREM1.3-membrane anchoring is necessary for its agonist effect on potyvirus propagation. StREM1.3 phosphocode seems to lead to distinct plant responses against potexvirus and potyvirus. We also showed that StREM1.3 interacts in yeast and in planta with the key potyviral movement protein CI (cylindrical inclusion) at the level of the plasma membrane but only partially at plasmodesmata pit fields. TuMV infection also counteracts StREM1.3-induced plasmodesmata callose accumulation at plasmodesmata. Altogether, these results showed that StREM1.3 plays an agonistic role in potyvirus cell-to-cell movement in N. benthamiana.

Human single-stranded DNA-binding protein 1 (hSSB1), encoded by OBFC2B, was recently characterized as an essential factor for the initiation of DNA damage checkpoints and the maintenance of genomic stability. Here, we report that loss of Obfc2b in mice results in perinatal lethality characterized by growth delay and skeletal abnormalities. These abnormalities are associated with accumulation of γH2ax, apoptosis and defective pre-cartilage condensation, which is essential for normal bone formation. However, deficiency of Obfc2b does not affect the initiation of DNA damage checkpoints, Atm activation, or the maintenance of genomic stability in B lymphocytes and primary fibroblasts. Loss of Obfc2b results in increased expression of its homologue Obfc2a (hSSB2). In contrast to Obfc2b deficiency, depletion of Obfc2a in fibroblasts results in impaired proliferation, accumulation of γH2ax and increased genomic instability. Thus, the hSSB1 orthologue Obfc2b has a unique function during embryogenesis limited to cell types that contribute to bone formation. While being dispensable in most other cell lineages, its absence leads to a compensatory increase in Obfc2a protein, a homologue required for the maintenance of genomic integrity.

Monitoring of cyanobacteria in freshwater ecosystems is a complex task, which is time consuming and expensive due to the chaotic population dynamics and highly heterogeneous distribution of cyanobacteria populations in water bodies. The financial cost constitutes a strong limitation for the implementation of long-term monitoring programs in developing countries, particularly in Africa. The work presented here was performed in the framework of an international project addressing the sustainable monitoring and management of surface water resources used for the production of drinking water in three African countries. We tested the potential of a citizen approach for monitoring cyanobacterial blooms, which are a growing threat to the drinking water supply. This pilot study was designed, implemented and evaluated in close interaction with the Pasteur Institute of the Ivory Coast and with the populations of three villages located on the shoreline of a freshwater lagoon located near Abidjan city. Based on the use of a smartphone application, the citizens of the three villages were invited to report water color changes, as these changes could reflect cyanobacteria proliferations. A two-year experimentation period has shown that it is possible to mobilize the local populations to monitor cyanobacterial blooms. The data collected by citizens were consistent with the data obtained by a classical monitoring of cyanobacteria performed over seven months, but it appeared that new approaches were needed to validate the citizen data. This participatory approach also provided great improvements to the understanding and awareness of local populations regarding water quality and cyanobacterial bloom issues. Finally, we discuss some of the difficulties and limitations of our participatory monitoring approach that should be considered by further implementations. Despite these difficulties, our work suggests that citizen monitoring is a promising approach that may complement the classical approach to sustainable monitoring of cyanobacteria in developing countries.

The complex vertical distribution of aerosols over coastal southern West Africa (SWA) is investigated using airborne observations and numerical simulations. Observations were gathered on 2 July 2016 offshore of Ghana and Togo, during the field phase of the Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa project. This was the only flight conducted over the ocean during which a downward-looking lidar was operational. The aerosol loading in the lower troposphere includes emissions from coastal cities (Accra, Lomé, Cotonou, and Lagos) as well as biomass burning aerosol and dust associated with long-range transport from central Africa and the Sahara, respectively. Our results indicate that the aerosol distribution on this day is impacted by subsidence associated with zonal and meridional regional-scale overturning circulations associated with the land–sea surface temperature contrast and orography over Ghana and Togo, as typically observed on hot, cloud-free summer days such as 2 July 2016. Furthermore, we show that the zonal circulation evidenced on 2 July is a persistent feature over the Gulf of Guinea during July 2016. Numerical tracer release experiments highlight the dominance of aged emissions from Accra on the observed pollution plume loadings over the ocean, in the area of aircraft operation. The contribution of aged emission from Lomé and Cotonou is also evident above the marine boundary layer. Given the general direction of the monsoon flow, the tracer experiments indicate no contribution from Lagos emissions to the atmospheric composition of the area west of Cotonou, where our airborne observations were gathered. The tracer plume does not extend very far south over the ocean (i.e. less than 100 km from Accra), mostly because emissions are transported northeastward near the surface over land and westward above the marine atmospheric boundary layer. The latter is possible due to interactions between the monsoon flow, complex terrain, and land–sea breeze systems, which support the vertical mixing of the urban pollution. This work sheds light on the complex – and to date undocumented – mechanisms by which coastal shallow circulations can distribute atmospheric pollutants over the densely populated SWA region.

In the framework of the Dynamics–Aerosol–Chemistry–Cloud Interactions in West Africa (DACCIWA) project, the tropospheric chemical composition in large cities along the Gulf of Guinea is studied using the Weather and Research Forecast and CHIMERE regional models. Simulations are performed for the May–July 2014 period, without and with biomass burning emissions. Model results are compared to satellite data and surface measurements. Using numerical tracer release experiments, it is shown that the biomass burning emissions in Central Africa are impacting the surface aerosol and gaseous species concentrations in Gulf of Guinea cities such as Lagos (Nigeria) and Abidjan (Ivory Coast). Depending on the altitude of the injection of these emissions, the pollutants follow different pathways: directly along the coast or over land towards the Sahel before being vertically mixed in the convective boundary layer and transported to the south-west and over the cities. In July 2014, the maximum increase in surface concentrations due to fires in Central Africa is ≈ 150 µg m−3 for CO, ≈ 10 to 20 µg m−3 for O3 and ≈ 5 µg m−3 for PM10. The analysis of the PM10 chemical composition shows that this increase is mainly related to an increase in particulate primary and organic matter.

As part of the Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa (DACCIWA) project, an airborne campaign was designed to measure a large range of atmospheric constituents, focusing on the effect of anthropogenic emissions on regional climate. The presented study details results of the French ATR42 research aircraft, which aimed to characterize gas-phase, aerosol and cloud properties in the region during the field campaign carried out in June/July 2016 in combination with the German Falcon 20 and the British Twin Otter aircraft. The aircraft flight paths covered large areas of Benin, Togo, Ghana and Côte d'Ivoire, focusing on emissions from large urban conurbations such as Abidjan, Accra and Lomé, as well as remote continental areas and the Gulf of Guinea. This paper focuses on aerosol particle measurements within the boundary layer ( Background concentrations (i.e. outside urban plumes) observed from the ATR42 indicate a fairly polluted region during the time of the campaign, with average concentrations of carbon monoxide of 131 ppb, ozone of 32 ppb, and aerosol particle number concentration ( > 15 nm) of 735 cm−3 stp. Regarding submicron aerosol composition (considering non-refractory species and black carbon, BC), organic aerosol (OA) is the most abundant species contributing 53 %, followed by SO4 (27 %), NH4 (11 %), BC (6 %), NO3 (2 %) and minor contribution of Cl (1 in the region was 5.9 µg m−3 stp. During measurements of urban pollution plumes, mainly focusing on the outflow of Abidjan, Accra and Lomé, pollutants are significantly enhanced (e.g. average concentration of CO of 176 ppb, and aerosol particle number concentration of 6500 cm−3 stp), as well as PM1 concentration (11.9 µg m−3 stp). Two classes of organic aerosols were estimated based on C-ToF-AMS: particulate organic nitrates (pONs) and isoprene epoxydiols secondary organic aerosols (IEPOX–SOA). Both classes are usually associated with the formation of particulate matter through complex interactions of anthropogenic and biogenic sources. During DACCIWA, pONs have a fairly small contribution to OA (around 5 %) and are more associated with long-range transport from central Africa than local formation. Conversely, IEPOX–SOA provides a significant contribution to OA (around 24 and 28 % under background and in-plume conditions). Furthermore, the fractional contribution of IEPOX–SOA is largely unaffected by changes in the aerosol composition (particularly the SO4 concentration), which suggests that IEPOX–SOA concentration is mainly driven by pre-existing aerosol surface, instead of aerosol chemical properties. At times of large in-plume SO4 enhancements (above 5 µg m−3), the fractional contribution of IEPOX–SOA to OA increases above 50 %, suggesting only then a change in the IEPOX–SOA-controlling mechanism. It is important to note that IEPOX–SOA constitutes a lower limit to the contribution of biogenic OA, given that other processes (e.g. non-IEPOX isoprene, monoterpene SOA) are likely in the region. Given the significant contribution to aerosol concentration, it is crucial that such complex biogenic–anthropogenic interactions are taken into account in both present-day and future scenario models of this fast-changing, highly sensitive region.

Carbon monoxide, CO, and fine atmospheric particulate matter, PM2.5, are analyzed over the Guinean Gulf coastal region using the WRF-CHIMERE modeling system and observations during the beginning of the monsoon 2006 (from May to July), corresponding to the Africa Multidisciplinary Monsoon Analysis (AMMA) campaign period. Along the Guinean Gulf coast, the contribution of long-range pollution transport to CO or PM2.5 concentrations is important. The contribution of desert dust PM2.5 concentration decreases from ∼ 38 % in May to ∼ 5 % in July. The contribution of biomass burning PM2.5 concentration from Central Africa increases from ∼ 10 % in May to ∼ 52 % in July. The anthropogenic contribution is ∼ 30 % for CO and ∼ 10 % for PM2.5 during the whole period. When focusing only on anthropogenic pollution, frequent northward transport events from the coast to the Sahel are associated with periods of low wind and no precipitation. In June, anthropogenic PM2.5 and CO concentrations are higher than in May or July over the Guinean coastal region. Air mass dynamics concentrate pollutants emitted in the Sahel due to a meridional atmospheric cell. Moreover, a part of the pollution emitted remotely at the coast is transported and accumulated over the Sahel. Focusing the analysis on the period 8–15 June, anthropogenic pollutants emitted along the coastline are exported toward the north especially at the beginning of the night (18:00 to 00:00 UTC) with the establishment of the nocturnal low level jet. Plumes originating from different cities are mixed for some hours at the coast, leading to high pollution concentration, because of specific disturbed meteorological conditions.

In June and July 2016 the Dynamics–Aerosol–Chemistry–Cloud Interactions in West Africa (DACCIWA) project organised a major international field campaign in southern West Africa (SWA) including measurements from three inland ground supersites, urban sites in Cotonou and Abidjan, radiosondes, and three research aircraft. A significant range of different weather situations were encountered during this period, including the monsoon onset. The purpose of this paper is to characterise the large-scale setting for the campaign as well as synoptic and mesoscale weather systems affecting the study region in the light of existing conceptual ideas, mainly using objective and subjective identification algorithms based on (re-)analysis and satellite products. In addition, it is shown how the described synoptic variations influence the atmospheric composition over SWA through advection of mineral dust, biomass burning and urban pollution plumes.The boreal summer of 2016 was characterised by Pacific La Niña, Atlantic El Niño and warm eastern Mediterranean conditions, whose competing influences on precipitation led to an overall average rainy season. During the relatively dusty pre-onset Phase 1 (1–21 June 2016), three westward-propagating coherent cyclonic vortices between 4 and 13° N modulated winds and rainfall in the Guinea coastal area. The monsoon onset occurred in connection with a marked extratropical trough and cold surge over northern Africa, leading to a breakdown of the Saharan heat low and African easterly jet and a suppression of rainfall. During this period, quasi-stationary low-level vortices associated with the trough transformed into more tropical, propagating disturbances resembling an African easterly wave (AEW). To the east of this system, moist southerlies penetrated deep into the continent. The post-onset Phase 2 (22 June–20 July 2016) was characterised by a significant increase in low-level cloudiness, unusually dry conditions and strong northeastward dispersion of urban pollution plumes in SWA as well as rainfall modulation by westward-propagating AEWs in the Sahel. Around 12–14 July 2016 an interesting and so-far undocumented cyclonic–anticyclonic vortex couplet crossed SWA. The anticyclonic centre had its origin in the Southern Hemisphere and transported unusually dry air filled with aged aerosol into the region. During Phase 3 (21–26 July 2016), a similar vortex couplet slightly farther north created enhanced westerly moisture transports into SWA and extraordinarily wet conditions, accompanied by a deep penetration of the biomass burning plume from central Africa. Finally, a return to more undisturbed monsoon conditions took place during Phase 4 (27–31 July 2016). The in-depth synoptic analysis reveals that several significant weather systems during the DACCIWA campaign cannot be attributed unequivocally to any of the tropical waves and disturbances described in the literature and thus deserve further study.

The presence of airborne aerosols affects the meteorology as it induces a perturbation in the radiation budget, the number of cloud condensation nuclei and the cloud micro-physics. Those effects are difficult to model at regional scale as regional chemistry-transport models are usually driven by a distinct meteorological model or data. In this paper, the coupling of the CHIMERE chemistry-transport model with the WRF meteorological model using the OASIS3-MCT coupler is presented. WRF meteorological fields along with CHIMERE aerosol optical properties are exchanged through the coupler at a high frequency in order to model the aerosol–radiation interactions. The WRF-CHIMERE online model has a higher computational burden than both models run separately in offline mode (up to 42 % higher). This is mainly due to some additional computations made within the models such as more frequent calls to meteorology treatment routines or calls to optical properties computation routines. On the other hand, the overall time required to perform the OASIS3-MCT exchanges is not significant compared to the total duration of the simulations. The impact of the coupling is evaluated on a case study over Europe, northern Africa, the Middle East and western Asia during the summer of 2012, through comparisons of the offline and two online simulations (with and without the aerosol optical properties feedback) to observations of temperature, aerosol optical depth (AOD) and surface PM10 (particulate matter with diameters lower than 10 µm) concentrations. The result shows that using the optical properties feedback induces a radiative forcing (average forcing of −4.8 W m−2) which creates a perturbation in the average surface temperatures over desert areas (up to 2.6° locally) along with an increase in both AOD and PM10 concentrations.

Produire des indicateurs de qualité des écosystèmes aquatiques anthropisés tenant compte des différents usages qui leur sont associés est un défi important qui ne peut être relevé qu’à l’interface de la recherche et de l’action. Dans cette optique, les auteurs portent un regard rétrospectif sur le travail mené pendant quatre ans au sein du programme de recherche PULSE afin d’évaluer la qualité des plans d’eau en Île-de-France. Après avoir montré l’intérêt d’étudier les plans d’eau périurbains, nous présentons comment le projet PULSE aborde ces objets hybrides, à mi-chemin entre « infrastructure urbaine » et « milieu naturel », à travers une approche transdisciplinaire centrée sur les usages de ces espaces. Nous discutons de la diversité des savoirs, des critères de valorisation de l’état de ces écosystèmes et des actions de gestion à travers lesquels les acteurs définissent la « qualité d’un plan d’eau ». Nous montrons ensuite jusqu’à quel point la transdisciplinarité permet d’imaginer des systèmes de caractérisation innovants et adaptés à la spécificité régionale de ces milieux et à leurs différents usages, tout en sachant que l’évaluation de ces systèmes n’échappe cependant pas à la nécessité, tant pour les scientifiques que pour les gestionnaires, de se référer à des critères de qualité universels et normatifs.

Plants respond to pathogens through dynamic regulation of plasma membrane-bound signaling pathways. To date, how the plant plasma membrane is involved in responses to viruses is mostly unknown. Here, we show that plant cells sense the Potato virus X (PVX) COAT PROTEIN and TRIPLE GENE BLOCK 1 proteins and subsequently trigger the activation of a membrane-bound calcium-dependent kinase. We show that the Arabidopsis thaliana CALCIUM-DEPENDENT PROTEIN KINASE 3-interacts with group 1 REMORINs in vivo, phosphorylates the intrinsically disordered N-terminal domain of the Group 1 REMORIN REM1.3, and restricts PVX cell-to-cell movement. REM1.3's phospho-status defines its plasma membrane nanodomain organization and is crucial for REM1.3-dependent restriction of PVX cell-to-cell movement by regulation of callose deposition at plasmodesmata. This study unveils plasma membrane nanodomain-associated molecular events underlying the plant immune response to viruses.

Stormwater source control is becoming a common strategy for urban stormwater management in many countries. It relies on regulations or other policy instruments compelling or inciting implementation, for each new urban development, of small-scale facilities to locally store and manage stormwater. Local authorities that pioneered source control since the 1980s have already observed that small-scale facilities systematically implemented over a catchment are able to influence its hydrological behaviour. This capability is the main strength of source control, as it allows compensation for the negative effects of urbanization. Yet, it also represents its main risk: if initial decision-making is not sufficiently accurate, source control can produce long-term negative effects. Because of its current spreading, source control will acquire an increasing role as a driver of hydrological changes in urban catchments, and the directions of these changes depend on current policy-making practices. This paper presents an analysis and a critical discussion of the main objectives that policy-makers attribute to stormwater source control. The investigation is based on a sample of French case studies, completed by a literature review for international comparison. It identifies four main objectives, some typical of urban stormwater management and some more innovative: flood reduction, receiving waters protection, sustainable development, costs reduction. The discussion focuses on how current policy-making practices are able to translate these objectives in concrete policy instruments, and on which knowledge and tools could improve this process. It is shown that for some objectives, basic knowledge is available, but the creation of policy instruments which are effective at the catchment scale and adapted to local conditions is still problematic. For other objectives, substantial lacks of knowledge exist, casting doubts on long-term effectiveness of current policy instruments. Research directions are identified to improve source control policies and thus the future hydrologic behaviour of many urban catchments.

The (re)construction of the ecological continuity is stated as one of the main objectives of the European Water Framework Directive for watershed management in Europe. Analysing the social, political, technical and scientific processes characterising the implementation of different projects of ecological continuity in two adjacent peri-urban territories in Ile-de-France, we observed science-driven approaches disregarding the social contexts. We show that, in urbanized areas, ecological continuity requires not only important technical and ecological expertise, but also social and political participation to the definition of a common vision and action plan. Being a challenge for both, technical water management institutions and “classical” ecological policies, we propose some social science contributions to deal with ecological unpredictability and reconsider stakeholder resistance to this kind of project.

The indirect effects of aerosol are particularly important over regions where meteorological conditions and aerosol content are favourable to cloud formation. This was observed during the Intensive Cloud Aerosol Measurement Campaign (IMPACT) (European Integrated project on Aerosol Cloud Climate and Air quality Interaction (EUCAARI) project) in the Benelux Union during May 2008. To better understand this cloud formation variability, the indirect effects of aerosol have been included within the WRF-CHIMERE online model. By comparing model results to the aircraft measurements of IMPACT, to surface measurements from EMEP and AIRBASE and to MODIS satellite measurements, we showed that the model is able to simulate the variability and order of magnitude of the observed number of condensation nuclei (CN), even if some differences are identified for specific aerosol size and location. To quantify the impact of the local anthropogenic emissions on cloud formation, a sensitivity study is performed by halving the surface emissions fluxes. It is shown that the indirect radiative effect (IRE) at the surface is positive for both shortwave and longwave with a net warming of +0.99 W/m2. In addition, important instantaneous changes are modelled at local scale with up to ±6 °C for temperatures and ±50 mm/day for precipitation.

Effort to narrow the gap between the production and use of scientific knowledge for environmental decision-making is gaining traction, yet in practice, supply and demand remains largely unbalanced. A qualitative study based on empirical analysis offers a novel approach to exploring key factors, focussing on seven water models in the context of two organisations at the science-policy interface: the PIREN-Seine in France and the CRC for Water Sensitive Cities in Australia. Tentative linkages drawn from these examples identify: (1) objective and expertise; (2) knowledge and tools; and (3) support structures as main drivers influencing the production of scientific knowledge which, in turn, affect the use and utility of modelling tools. Further insight is gained by highlighting the wide spectrum of uses and utilities existing in practice, suggesting that such ‘boundary organisations’ facilitate interactions and exchanges that give added value to scientific knowledge. Coordinated strategies that integrate inter-, extra-, and intra-boundary activities, framed through collaborative scenario building and the use of interactive modelling platforms, may offer ways to enhance the use and utility of scientific knowledge (and its tools) to better support water resources management, policy and planning decisions, thus promoting a more cohesive relationship between science and policy.

In the rural areas of the developing countries, the access to water supply and sanitation services is still largely inadequate. Poor governance of the water sector is frequently singled out as a cause and reforms are required. Studies analyzing the great diversity of restructuring efforts currently being undertaken in the water sector have not succeeded in determining the most appropriate institutional and economic framework for such reforms. Moreover they underline the lack of documentation on actual projects and call for concrete models and tools for improving water and sanitation services (WSS) and for adapting water utility practice to real conditions. In this context, the Vida no Vale (Life in the Valley) project is aimed at bringing universal access to WSS for all inhabitants of both urban and rural areas, in the north-eastern area of the Brazilian State of Minas Gerais. The project takes sustainable development as its guiding principle, and relies on the joint implementation of an innovative technical design, a governance model involving public participation and subsidiarity, and an economic structure combining financial viability and social equity. Designed at a consistent geographical and hydrological scale, it includes the creation of a regional subsidiary of the existing state water company as a keystone element. The institutional organisation also relies on the creation of a public board consisting of the 92 municipalities of the project region and of the State of Minas Gerais. This board will be in charge of the system's governance. This paper presents the first step of the project (2006), consisting of a feasibility study and the implementation of 9 pilot sub-projects. During the feasibility study, the supply, demand and capacity to pay for water services were defined, existing infrastructure appraised, the necessary amount of investment assessed and an innovative operational model and a sustainable management system, including civil society participation, defined. The main features of the Vida no Vale project have been tested in 9 pilot sub-projects, and implemented in municipalities chosen for their low Human Development Index and for the lack of WSS, in both urban and rural areas. A second phase corresponding to the project's final implementation will run from 2007 to 2011. The Vida no Vale project design resulted in a logical and extensive framework which could be used for developing similar WSS projects in other poor, rural regions, its adaptiveness being a key feature for taking into account the specific, local conditions.

This paper aims at understanding the social and political uses of the principle of integrated management and its possible impacts on the elaboration and implementation processes of public policies in the French water management sector. The academic and political innovations developed by scientists and agents of the administration these last 25 years are analysed, using some of the theoretical tools developed by the science studies and public policy analysis. We first focus on the construction of intellectual public policy communities such as the GIP Hydro systems, at the origin of large interdisciplinary research programs in the 1990s. A common cognitive framework is clearly built during this period on the good governance of the aquatic ecosystems and on the corresponding needs and practices of research. The second part of the paper focuses on the possibilities to build political communities and more or less integrated expertises in the decision making processes concerning various issues related to water management. Eutrophication and its inscription on the French political agenda is a very significant case for analysing the difficulty to build such a political community. On the contrary, when there is an opportunity for policy evaluation, which was the case concerning the management of wetlands in France or the implementation of compulsory flows on the French rivers, these communities can emerge. However, the type of integrated expertise and management proposed in these cases of policy evaluations much depends on their methodological choices.

This paper focuses on the process of inscription on the national and local political agendas of the issue of rainwater reuse. This process led to the implementation of different types of financial incentives. The 2006 Water Act provisions dedicated to rainwater reuse and 32 different types of local incentives are here presented. The analysis is completed through a deep analysis of eight cases, typical of the various types of financial incentives and success or failure recorded. This analysis enlighten the existing relations in between this types of policy instruments and the political territories involved in their implementation and, on the contrary, the lack of consideration for the hydrological and social characteristics of the concerned areas.Even though these incentives are very heterogeneous, they present a common characteristic: they all seem to be designed without concern for their efficiency. The purpose is more to encourage the awareness of an ecological value of the water rather than to maximise the number of subsidised people or the volume of reused water. In the paper we test the hypothesis of this policy of financial incentives being driven by a will to build a symbolic value of rainwater. The statement of this symbolic value is a good way to free from controversies regarding the economic and social benefits of the water reuse. Rain water is per se good and therefore should be used. Use drinkable water, at least for outdoor purposes, is to waste and to spoil it. Therefore the inclination of local technicians and elected representatives for this type of policy instruments is meaningful. Financial incentives are good tools for encouraging inhabitants willing to conform to the moral value of rainwater. As a significant contribution is required from the ones benefiting the subsidy, the incentive operates as a reward for the people willing not to spoil anymore the “providential” rainwater. Even though these local policies are territorialised, responding to a will of local stakeholders to mobilise the inhabitants, they do not take into account the territorial and environmental context of their implementation.