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Median of the shRNAs and RSA values. File containing median counts and log fold changes of each gene from Supplementary Data File S1. According significance values of each gene as activator or sensitizer compared to DMSO control (see Methods) are included.

Activation of p53 by inhibitors of the p53–MDM2 interaction is being pursued as a therapeutic strategy in p53 wild-type cancers. Here, we report distinct mechanisms by which the novel, potent, and selective inhibitor of the p53–MDM2 interaction HDM201 elicits therapeutic efficacy when applied at various doses and schedules. Continuous exposure of HDM201 led to induction of p21 and delayed accumulation of apoptotic cells. By comparison, high-dose pulses of HDM201 were associated with marked induction of PUMA and a rapid onset of apoptosis. shRNA screens identified PUMA as a mediator of the p53 response specifically in the pulsed regimen. Consistent with this, the single high-dose HDM201 regimen resulted in rapid and marked induction of PUMA expression and apoptosis together with downregulation of Bcl-xL in vivo. Knockdown of Bcl-xL was identified as the top sensitizer to HDM201 in vitro, and Bcl-xL was enriched in relapsing tumors from mice treated with intermittent high doses of HDM201. These findings define a regimen-dependent mechanism by which disruption of MDM2–p53 elicits therapeutic efficacy when given with infrequent dosing. In an ongoing HDM201 trial, the observed exposure–response relationship indicates that the molecular mechanism elicited by pulse dosing is likely reproducible in patients. These data support the clinical comparison of daily and intermittent regimens of p53–MDM2 inhibitors.Significance: Pulsed high doses versus sustained low doses of the p53-MDM2 inhibitor HDM201 elicit a proapoptotic response from wild-type p53 cancer cells, offering guidance to current clinical trials with this and other drugs that exploit the activity of p53. Cancer Res; 78(21); 6257–67. ©2018 AACR.

Supplementary material and methods include the description for the bioanalytical method for HDM201 detection in plasma and tumor, the human and mouse gene expression analysis in vitro and in vivo, the live-cell quantification of cleaved-caspase activation, the western blot analysis, the immunohistochemistry, the splinkerette PCR for the amplification of transposon integration sites and the tumor sequencing, mapping of insertion sequences to the mouse genome and identification of common integration site, additional information on the shRNA screen and the tumor models and supplementary references. Supplementary figures include: • Fig S1: the SJSA-1 inhibition growth curves when treated with HDM201 at different doses and for different times and the data for MOLM-3. • Fig S2: the cumulative percentage of cleaved-caspase-3/7 positive cells over the time, the GI50 of HDM201, CGM097 or nutlin-3a on SJSA-1 cells and the cellular apoptosis, as judged by AUC of cleaved-caspase-3/7 positive cells, induced by these compounds. • Fig S3: the PK profile in plasma and tumor of HDM201 in SJSA-1 tumors-bearing rat after p.o. and i.v. treatment, the Bcl-xl mRNA levels in tumors after HDM201 treatment, representative images of SJSA-1 tumors stained with p53 and cleaved-caspase 3 antibodies after HDM201 treatment and the individual data for the efficacy experiment in SJSA-1 tumor-bearing rats. • Fig S4: the PD of HDM201 in PB tumor bearing nude mice after single dose administration. Supplementary tables include: • Table S1: Biochemical profile of HDM201. • Table S2: List of cell lines tested for their sensitivity to HDM201 (n=291) • Table S3: Contingency table indicating association between sensitivity to HDM201 and TP53 wild-type status. • Table S4: List of cell lines tested for their sensitivity to both MDM2 knock-down by shRNA and HDM201 (n=261) • Table S5: Contingency table indicating association between sensitivity to HDM201 and sensitivity to MDM2 shRNA. • Table S6: List of significant rescuer and sensitizer genes following both HDM201 treatment types • Table S7: Pharmacokinetic parameters for HDM201 after p.o. and i.v. dosing in rat. • Table S8: Summary of primary PK parameters for HDM201 daily regimen after single dose (Day 1) in patients. • Table S9: Summary of primary PK parameters for HDM201 daily regimen on Day 14 in patients. • Table S10: Summary of primary PK parameters for HDM201 q3w regimen after single dose in patients.

Cell lines and patient-derived xenografts are essential to cancer research, however, the results derived from such models often lack clinical translatability, as these models do not fully recapitulate the complex cancer biology. It is critically important to better understand the systematic differences between cell lines, xenografts and clinical tumors, and to be able to identify pre-clinical models that sufficiently resemble the biological characteristics of clinical tumors across different cancers. On another side, direct comparison of transcriptional profiles from pre-clinical models and clinical tumors is infeasible due to the mixture of technical artifacts and inherent biological signals.To address these challenges, we developed MOBER, Multi-Origin Batch Effect Remover method, to simultaneously extract biologically meaningful embeddings and remove batch effects from transcriptomic datasets of different origin. MOBER consists of two neural networks: conditional variational autoencoder and source discriminator neural network that is trained in adversarial fashion. We applied MOBER on transcriptional profiles from 932 cancer cell lines, 434 patient-derived tumor xenografts and 11’159 clinical tumors and identified pre-clinical models with greatest transcriptional fidelity to clinical tumors, and models that are transcriptionally unrepresentative of their respective clinical tumors. MOBER can conserve the biological signals from the original datasets, while generating embeddings that do not encode confounder information. In addition, it allows for transformation of transcriptional profiles of pre-clinical models to resemble the ones of clinical tumors, and therefore can be used to improve the clinical translation of insights gained from pre-clinical models. As a batch effect removal method, MOBER can be applied widely to transcriptomics datasets of different origin, allowing for integration of multiple datasets simultaneously.

Alternative splicing is critical for human gene expression regulation and plays an important role in multiple human diseases. In this context, RNA sequencing has emerged as powerful approach to detect alternative splicing events.In parallel, fast alignment-free methods have emerged as a viable alternative to quantify gene and transcript level abundance from RNAseq data. However, the ability to detect differential splicing events is dependent on the annotation of the transcript reference provided by the user.Here, we introduce a new reference transcriptome aware of splicing events, TRAWLING, which simplifies the detection of aberrant splicing events in a fast and simple way. In addition, we evaluate the performances and the benefits of aligning transcriptome data to TRAWLING using three different RNA sequencing datasets: whole transcriptome sequencing, single cell RNA sequencing and Digital RNA with pertUrbation of Genes.Collectively, our comprehensive evaluation underlines the value of using TRAWLING in transcriptomic data analysis.Availability and implementationOur code is available athttps://github.com/Novartis/TRAWLING

2020 has been a key year in the MeteoSat Third Generation (MTG), with the integration and tests of the Flexible Combined Imager (FCI) proto-flight model(PFM). The FCI is the imaging instrument of the MeteoSat Third Generation mission, whose first satellite MTG-I1 will be launched in the second half of 2022. Its large spectral coverage, its fast and flexible scanning, associated with demanding radiometric and optical performances will allow a step forward in Europe weather nowcasting. In 2018, three complementary development models were successfully integrated and tested. The Engineering Model validated the optical and radiometric performances of the detection chain. The Structural and Thermal Model qualified the robustness of the design against launch and in-orbit environments and validated the consistency with the thermal and microvibration mathematical model predictions. The Avionic Test Bench with the software which reached a very good level of maturity, validated the control, command and data handling of the instrument. The completion of these developments enabled to successfully hold the instrument Critical Design Review (CDR) end 2018. In 2019, the two main components of the instrument, namely the telescope assembly and the detection control electronics assembly (DCEA) successfully passed the acceptance tests and have been delivered. The article will present first an overview of the instrument design and the main outcomes of the development models. Then, it will discuss the up-to-date status of the FCI PFM development. Finally, it will introduce the overall planning for the four FCI models to be delivered to the MTG-I satellite series. This work has been performed under an ESA contract to Thales Alenia Space-France.

The Atmospheric LAser Doppler INstrument (ALADIN) is the payload of the ESA’s ADMAEOLUS mission, which aims at measuring wind profiles as required by the climatology and meteorology users. ALADIN belongs to a new class of Earth Observation payloads and will be the first European Lidar in space. The instrument comprises a diode-pumped high energy Nd:YAG laser and a direct detection receiver operating on aerosol and molecular backscatter signals in parallel. In addition to the Proto- Flight Model (PFM)., two instrument models are developed: a Pre-development Model (PDM) and an Opto-Structure-Thermal Model (OSTM). The flight instrument design and the industrial team has been finalised and the major equipment are now under development. This paper describes the instrument design and performance as well as the development and verification approach. The main results obtained during the PDM programme are also reported. The ALADIN instrument is developed under prime contractorship from EADS Astrium SAS with a consortium of thirty European companies.

The Meteosat Third Generation (MTG) Programme is being realised through the well-established and successful Cooperation between EUMETSAT and ESA. It will ensure the future continuity of MSG with the capabilities to enhance nowcasting, global and regional numerical weather prediction, climate and atmospheric chemistry monitoring data from Geostationary Orbit. This will be achieved through a series of 6 satellites named MTG-I and MTG-S to bring to the meteorological community continuous high spatial, spectral and temporal resolution observations and geophysical parameters of the Earth based on sensors from the geo-stationary orbit. In particular, the imagery mission MTG-I will bring an improved continuation of the MSG satellites series with the Flexible Combined Imager (FCI) a broad spectral range (from UV to LWIR) with better spatial and spectral resolutions. The FCI will be able to take high spatial resolution pictures of the Earth within 8 VNIR and 8 IR channels. As one of the mission of this instrument is to provide a quantitative analysis of atmosphere compounds, the absolute observed radiance needs to be known with a specified accuracy for VNIR as low as to 5% at k=3 over its full dynamic. While the FCI is regularly recalibrated every 6 month at equinoxes, it is however requiring initial ground calibration for the beginning of its mission. The Multi Optical Test Assembly (MOTA) is one of the Optical Ground Support Equipment (OGSE) dedicated to various missions necessary for the integration of the FCI . This equipment, provided by Bertin Technologies, will be delivered to TAS-F by the end of 2016. One of its mission, is the on-ground absolute calibration of VNIR channels. In order to handle this, the MOTA will be placed in front of the FCI under representative vacuum conditions and will be able to project a perfectly known, calibrated radiance level within the full dynamic of FCI instrument. The main difficulty is the very demanding calibration level with respect to primary standards down to 3% (k=3) coupled with constraining environment (vacuum), large dynamic (up to factor 100), high spectral resolution of 3 nm. Another main difficulty is to adapt the specific MOTA etendue (300 mm pupil, 9 mrad field) to available primary standards. Each of these constraints were addressed by specific tool design and production, a fine optimization of the calibration procedure with a large involvement of metrology laboratories. This paper introduces the missions of MTG satellites and particularly of the FCI instrument. The requirements regarding the absolute calibration over the different spectrometric channels and the global strategy to fulfill them are described. The MOTA architecture and calibration strategy are then discussed and final expected results are presented, showing state of the art performances.

International audience; Beef industry operators often use a "grain of meat" assessment to aid in selecting carcasses according to their tenderness potential. The first aim of this study was to formalise this empirical notion by building a scoring scale for grain of meat. Two experts, regular users of this notion, were called upon to build the assessment grade. A group of 16 criteria was identified on the carcass as being effective in predicting an overall "grain of meat" score. The second aim of this study was to establish the relationship between the meat grain score estimated on the carcass and the tenderness of the longissimus thoracis muscle estimated by sensory evaluations. Some individual criteria such as "nerve presence", "marbling", and "touch of muscles" appeared to be linked to muscular characteristics such as collagen content, lipid content and shear force. No significant relationship was identified between grain of meat and either tenderness (initial: p = 0.58; overall: p = 0.50), shear force (p = 0.33), or collagen content and collagen solubility (p = 0.23; p = 0.33). (c) 2012 Elsevier Ltd. All rights reserved.

The new French guidelines on Peritoneal Dialysis (PD) were published in october 2008 by the "Haute Autorite de Sante (HAS)". The field of these guidelines concerned the choice between PD and Hemodialysis (HD), on a strict medical point of view. This paper summarizes the main French PD guidelines, highlighting the new insights compared to previous guidelines. For the first time, guidelines described 5 clinical situations requiring the choice between PD or HD : 1) criteria for choosing PD in a new dialysis patient ; 2) criteria for switching a patient from PD to HD ; 3) criteria for switching a patient from HD to PD ; 4) PD or HD before kidney transplantation ; 5) PD or HD after graft failure. For a new dialysis patient, PD is recommended, more than HD, for cirrhotic patients with ascites, kidney failure due to cholesterol embolism, difficulties for HD-vascular access. PD is not recommended in only a few cases : morbid obesity (BMI>45 kg /m(2)), irreparable abdominal hernias. It is recommended to switch from PD to HD, patients with more than 3 peritonitis/year, due to digestive bacteria ; weight gain > 15 % per year ; triglycerid serum level > 10 g/l ; loss of peritoneal efficiency. It is recommended to switch from HD to PD patients with vascular access failure ; hemodynamic instability during HD sessions ; severe congestive heart failure. PD or HD can be indistinctly used before kidney or combined pancreas-kidney graft. These new French guidelines are more complete and more accurate than the previous French or international guidelines.

Les conditions de développement d’une production de bœufs Charolais de 26 mois à l’herbe en Bourgogne sont analysées à différents niveaux : l’étude des pratiques des éleveurs, le choix des itinéraires techniques avec mise en évidence de l’intérêt d’une castration précoce, une analyse de filière pour évaluer les attentes des entreprises régionales et enfin une simulation de l’intérêt économique pour l’exploitation. Produire un bœuf jeune en valorisant au mieux les fourrages de l’exploitation est techniquement réalisable dans des conditions extrêmement variées comme les itinéraires techniques testés, de même que les observations réalisées en élevage, l’ont montré. Certains de ces itinéraires permettent de maximiser l’apport en herbe dans l’alimentation. La castration précoce peut aider à la réalisation de l’objectif, sans préjudice sur le produit et sans perturber l’animal. Au final, ces jeunes bœufs produisent des carcasses de 400 à 440 kg proches de celles des vaches de réforme (à l’exception d’une couleur parfois plus claire), suffisamment engraissées à la fois dans les conditions de plaine ou de montagne. La filière régionale se montre peu intéressée par ce type de produit sauf peut-être en complément des vaches, au printemps en « soudure » ou pour renforcer l’offre de bœufs croisés ou encore dans le cadre d’une marque régionale. Selon les simulations économiques, cette production apporte la même marge au niveau de l’exploitation que le jeune bovin ou le maigre repoussé. Toutefois, il est probable que, sans évolution notable de la conjoncture, les éleveurs ne souhaiteront pas modifier leurs choix actuels de production., The requirements for the extension, featuring and enhancement of the marketing value of meat from 26 month old Charolais steers were studied in Burgundy. The livestock husbandry practices are described by farm management surveys. Several experiments were conducted to assess the effects of early castration and to suggest a steer management pattern over time. Moreover, the economic points of view of the meat marketing chain and those of the farmers were examined. The young steer meat production from grass was quite practical. Castration at 2 months of age vs 9 months did not affect neither the carcass characteristics nor the meat quality. The steers' carcasses weighed 400-440 kg on average and were equivalent to culled cow carcasses with a lighter meat colour. In the context of the French beef crisis, the regional meat marketing chain showed little interest in the young Charolais steers. However, these steers could complete in the spring the cow supply and that of the crossbreed steers. Some regional meat brands could also use this production. For farm economics, the young steers were equivalent to the young bulls or the store animals.

We present a comparative study, down to the single-molecule level, of the linewidth and multiplet structure of the optical transitions of 2.3,8.9-dibenzanthanthrene (DBATT) in shock-frozen solutions of n-decane, n-undecane, and n-tetradecane. The n-alkane matrices show weak structural ordering and distinct incorporations of the DBATT molecules have been recognized. The order does not increase, nor does the ensemble optical linewidth decrease going from bulk to sub-volumes of less than 1 μm3. The relation between lateral position, orientation of the transition moment, and transition frequency has been investigated using single-molecule fluorescence-excitation and polarization spectroscopy. The distribution of the orientation is found not to depend on frequency and vice versa. Structural ordering on a microscopic scale is found not to be decisive as regards the linewidth and multiplet structure.

Optical far-field imaging of single molecules in a frozen solution at 1.2 K with a lateral resolution of 3.4 nm is reported. The mechanical stability of the fluorescence microscope, especially of the low-temperature insert, allows for the localization of fluorescing molecules with a reproducibility of better than 5 nm within observation times up to 10 min. For observation times of 9 h the reproducibility of the lateral position is limited to about 20 nm due to mechanical drift. Lateral position and orientation of 314 single molecules, present within the confocal detection volume of approximately 10 microm(3), are obtained. The possibility to correct for mechanical drift by monitoring the position of a spatial reference in the sample is demonstrated.

L'évaluation du « grain de viande » est une appréciation subjective, utilisée par certains chevillards et bouchers pour sélectionner et orienter les carcasses, un grain extrêmement fin étant synonyme de qualité. Pour évaluer la pertinence de cette notion quatre études ont permis i) d’objectiver la notion de grain de viande par une approche ethnologique, ii) de formaliser ce savoir-faire dans une grille de notation en vif et en carcasse, iii) d’évaluer les propriétés physicochimiques des quatre muscles utilisés par les experts pour juger une carcasse, et iv) d’évaluer l’existence d’un lien entre l’évaluation du grain de viande et la qualité sensorielle des viandes. Les seize indicateurs consignés dans la grille établie sur la carcasse sont répétables et facilement utilisables en abattoir. Sur le muscle longissimus thoracis, les grains fins ont été caractérisés par des teneurs en lipides intramusculaires significativement plus faibles que les grains grossiers, conduisant à des notes d’intensité de flaveur également significativement plus faibles, mais sans répercussions sur les notes de jutosité. Il n’est pas apparu de différence significative de tendreté entre les muscles à grains fins et grossiers. Au niveau physicochimique, le grain fin a été associé à des muscles nécessitant une moindre force de cisaillement sur la viande cuite et présentant une moindre teneur en collagène, sans différence sur sa solubilité, laissant supposer un effet favorable sur les propriétés sensorielles. Les écarts sont cependant très dépendants du muscle étudié et méritent d’être confirmés à plus grande échelle., The assessment of the meat “grain” size is an empirical method used by some butchers in France to predict the tenderness of meat: the finer the grain the higher the quality. Four studies are presented here. After a characterization of this notion using an ethnological approach, two grids were built to objectivate the way of evaluating grain of meat on live animals and carcasses. The second aim was to characterize the main muscles used by the experts to rate the grain of meat. The last aim was to establish the relation between the score of meat grain estimated on the carcass and the tenderness of the longissimus thoracis muscles estimated by sensory evaluations. A group of 16 criteria were identified on the carcass as effective to anticipate overall “grain of meat” score. “Fine grain” carcasses were associated with lower lipid content than “coarse grain” in longissimus thoracis muscles, leading to significantly lower scores of flavor intensity without any impact on juiciness scores. No significant relation appeared between grain of meat and tenderness. The shear force needed to cut a broiled sample was found significantly higher for “coarse grain” carcasses than for “fine grain” ones. The total collagen in the “coarse grain” group was significantly higher than those from the “fine grain” group without any impact on collagen solubility. Taken together, these results allow hypothesizing that “fine grain” could have a positive impact on meat quality traits. The differences underlined are nevertheless very muscle-dependant and remain to be confirmed in larger trials.

I Two experiments were perfonned irliApril and December 1992 in the French Alps using simultaneous relnote sensing and grolJnd truth data. Snow grain site and soot content of samples collected in the field were measured. ~he Landsat thematic mapper (TM) sensor was used because it has a good spatial resolution, a middle infrared channel which is ~ensitive to grain size and a the'nnal infrared channel. Firstj the reflectance data were compared with the theoretical results obtained from a bidirectional reflectance model. Then, some remote sehstng-derived snow parameters wbre compared iWith the outpllt ofa snow metamorphism model (CROCUS),viz., lower elevation of the snowcover, lhe surface grl1in size and the surface temperature. A digital elevation model was used to obtain the local incidenc:f angles and the elevation of each snow pixel. The pixels were then grouped according to CROCUS classification (range, elevation, slope, and orientation) and th~ mean snow chart;1cteristics for each class were .compared with the tROCUS results. The lower limit of snow and the surface grain size derived from TM data were compAred favourably with the model results. Larger differences were found for the temperature, because it varies rapidly and is very sensitive to shadowing by the snrroun4ing mountains and also because its remote measurement is dependent on atmospheric conditions. I

The numerical snow metamorphism model CROCUS derives a complete description of the snow cover according to its geographical location (range), elevation, slope, and orientation. From the remote sensing data, snow parameters that were comparable to the model results were derived: the lower elevation of the snow cover, the surface grain size, and the surface temperature. The Landsat Thematic Mapper sensor was used because it has a good spatial resolution, a short wave infrared channel which is sensitive to grain size, and a thermal infrared channel. A first Landsat TM (Thematic Mapper) scene was acquired on 24 April 1992 and a second one on 11 December 1992. A DEM (digital elevation model) was used to obtain the local incidence angles and the elevation of each snow pixel. The pixels were then grouped according to the CROCUS classification (range, elevation, slope, orientation), and the mean snow characteristics for each class were compared with the CROCUS results. The lower limit of snow and the surface grain size derived from TM data compared favorably with the model results even if those parameters were not always easy to define. Larger differences were found for the temperature because it varies rapidly and is very sensitive to shadowing by surrounding mountains and also because its remote measurement is dependent on atmospheric conditions.

The mechanisms of the aqueous photoreactions of 4-fluorophenol, 4-bromophenol and 4-iodophenol have been studied by steady state photolysis and by nanosecond laser flash photolysis. The same photoproducts are obtained as were found in the photolysis of aqueous 4-chlorophenol although the photoreaction quantum yields vary considerably across the series of compounds. As for 4-chlorophenol the carbene 4-oxocyclohexa-2,5-dienylidene is formed from the halogenophenol by loss of HX and this species reacts efficiently with oxygen to form 1,4-benzoquinone O-oxide which subsequently yields 1,4-benzoquinone. Consideration of the reaction quantum yields together with the photophysical properties of the four halogenophenols suggests that the carbene is derived from the first excited singlet state rather than a triplet excited state.

We introduce a variational data assimilation scheme to assimilate X-band Synthetic Aperture Radar (SAR) data into a snowpack evolution model. The structure properties of a snowpack, such as snow density and grain optical diameter of each layer, are simulated over a period of time by the snow metamorphism model Crocus, fed by the local reanalysis SAFRAN at a French alpine location. These parameters are used as inputs of an Electromagnetic Backscattering Model (EBM) based on Dense Media Radiative Transfer (DMRT) theory, which calculates the simulated total backscattering coefficient. Next, 3D-VAR data assimilation is implemented in order to minimize the discrepancies between model simulations and observations obtained from SAR acquisitions, by modifying the parameters of a multilayer snowpack calculated by Crocus. The algorithm then reinitializes Crocus with the optimized snowpack structure properties, and therefore allows it to continue the simulation of snowpack evolution where adjustments based on remote sensing data has been taken into account. Results obtained using TerraSAR-X acquisitions on Argentière Glacier (Mont-Blanc massif, French Alps) show the high potential of this method for improving snow cover simulation.

The mechanism of the aqueous photoreaction of 4-chlorophenol was studied by nanosecond laser flash photolysis. The carbene 4-oxocyclohexa-2,5-dienylidene is formed from the chlorophenol by loss of HCl. This species reacts efficiently with oxygen to form 1,4-benzoquinone-O-oxide which subsequently yields 1,4-benzoquinone. The carbene also undergoes reaction with water and coupling reactions to produce 1,4-hydroquinone and polyhydroxybiphenyls respectively.

The flash-induced photolysis of 4-chlorophenol in water has been re-studied by HPLC and by LC-MS. Contrary to our previous finding, para-benzoquinone is absent from the photoproducts when molecular oxygen is totally removed from the solution. Some of the products under these conditions have been identified by the use of the LC-MS technique.

This study describes a method to retrieve snow specific surface area (SSA) from satellite radiance reasurements in mountainous terrain. It aims at comparing different retrieval methods and at addressing topographic corrections of reflectance, namely slope and aspect of terrain and multiple reflections on neighbouring slopes. We use an iterative algorithm to compute reflectance from radiance of the MODerate resolution Imaging Spectrometer (MODIS) with a comprehensive correction of local illumination with regards to topography. The retrieved SSA is compared to the results of the snowpack model Crocus, fed by driving data from the SAFRAN meteorological analysis, over a large domain in the French Alps. We compared SSA retrievals with and without topographic or anisotropy correction, and with a spherical or non-spherical snow reflectance model. The topographic correction enables SSA to be retrieved in better agreement with those from SAFRAN-Crocus. The root mean square deviation is 10.0 m2 kg−1 and the bias is −0.6 m2 kg−1, over 3829 pixels representing seven different dates and snow conditions. The standard deviation of MODIS retrieved data, larger than the one of SAFRAN-Crocus estimates, is responsible for half this RMSD. It is due to the topographic classes used by SAFRAN-Crocus. In addition, MODIS retrieved data show SSA gradients with elevation and solar exposition, physically consistent and in good agreement with SAFRAN-Crocus.

In this study, snowpack scenarios are modelled across the French Alps using dynamically downscaled variables from the ALADIN Regional Climate Model (RCM) for the control period (1961–1990) and three emission scenarios (SRES B1, A1B and A2) by the mid- and late of the 21st century (2021–2050 and 2071–2100). These variables are statistically adapted to the different elevations, aspects and slopes of the alpine massifs. For this purpose, we use a simple analogue criterion with ERA40 series as well as an existing detailed climatology of the French Alps (Durand et al., 2009a) that provides complete meteorological fields from the SAFRAN analysis model. The resulting scenarios of precipitation, temperature, wind, cloudiness, longwave and shortwave radiation, and humidity are used to run the physical snow model CROCUS and simulate snowpack evolution over the massifs studied. The seasonal and regional characteristics of the simulated climate and snow cover changes are explored, as is the influence of the scenarios on these changes. Preliminary results suggest that the Snow Water Equivalent (SWE) of the snowpack will decrease dramatically in the next century, especially in the Southern and Extreme Southern part of the Alps. This decrease seems to result primarily from a general warming throughout the year, and possibly a deficit of precipitation in the autumn. The magnitude of the snow cover decline follows a marked altitudinal gradient, with the highest altitudes being less exposed to climate change. Scenario A2, with its high concentrations of greenhouse gases, results in a SWE reduction roughly twice as large as in the low-emission scenario B1 by the end of the century. This study needs to be completed using simulations from other RCMs, since a multi-model approach is essential for uncertainty analysis.

This contribution investigates the performance of discharge modelling when proceeding from rather simple methods of snowmelt modelling to more sophisticated, distributed approaches. In all cases, the conceptual HBV runoff model is used for the calculation of discharge from the Romanche River basin (French Alps, area = 224 km2,12.5 % glacierized), feeding the Lac de Chambon reservoir used for hydroelectric power production. The results show that when using temperature-index approaches, no gain in performance is achieved by the more detailed basin discretization. However, a clear gain is observed when the precipitation and air temperature distribution of the elaborate meteorological data analysis system “SAFRAN” is used as input to the conceptual snow model. When using the original version of the physically-based “CROCUS” snow model, a strong overestimation of discharge resulted during the main snow melt season. A revised SAFRAN model version employing a new radiation routine, and the use of a realistic distribution of snow cover in each sub-unit considered by CROCUS resulted in a discharge simulation performance which is as good as the one from the calibrated conceptual models. Sensitivity analyses of the various snow models investigating the hydrological consequences of climatic change show surprisingly similar results.

Habitat fragmentation can restrict geneflow, reduce neighbourhood effective population size, and increase genetic drift and inbreeding in small, isolated habitat remnants. The extent to which habitat fragmentation leads to population fragmentation, however, differs among landscapes and taxa. Commonly, researchers use information on the current status of a species to predict population effects of habitat fragmentation. Such methods, however, do not convey information on species-specific responses to fragmentation. Here, we compare levels of past population differentiation, estimated from microsatellite genotypes, with contemporary dispersal rates, estimated from multi-strata capture-recapture models, to infer changes in mobility over time in seven sympatric, forest-dependent bird species of a Kenyan cloud forest archipelago. Overall, populations of sedentary species were more strongly differentiated and clustered compared to those of vagile ones, while geographical patterning suggested an important role of landscape structure in shaping genetic variation. However, five of seven species with broadly similar levels of genetic differentiation nevertheless differed substantially in their current dispersal rates. We conclude that post-fragmentation levels of vagility, without reference to past population connectivity, may not be the best predictor of how forest fragmentation affects the life history of forest-dependent species. As effective conservation strategies often hinge on accurate prediction of shifts in ecological and genetic relationships among populations, conservation practices based solely upon current population abundances or movements may, in the long term, prove to be inadequate.

The flash-induced photolysis of 4-chlorophenol in water has been studied by high performance liquid chromatography. The primary photoproduct is confirmed as being p-benzoquinone. The role of molecular oxygen in the photochemistry has been investigated and we conclude that it is not involved in the formation of the p-benzoquinone although it does appear to protect the primary photoproduct from secondary photolysis. A photolysis mechanism based on the initial formation of a radical cation is proposed.

The Advanced Space Carbon and Climate Observation of Planet Earth (A-SCOPE) mission, a candidate for the next generation of European Space Agency Earth Explorer Core Missions, aims at measuring CO(2) concentration from space with an integrated path differential absorption (IPDA) lidar. We report the optimization of the lidar instrument operating wavelengths, building on two performance models developed to assess measurement random errors from the instrument, as well as knowledge errors on geophysical and spectral parameters required for the measurement processing. A promising approach to decrease sensitivity to water vapor errors by 1 order of magnitude is reported and illustrated. The presented methods are applicable for any airborne or spaceborne IPDA lidar.

A new call for Core Earth Explorer Ideas was released by the European Space Agency in March 2005. The Call focused on the global carbon and water cycles, atmospheric chemistry and climate, as well as the human element as a cross cutting issue. The proposals were peer reviewed by scientific panels, and also appraised technically and programmatically by ESA. This paper describes the Earth Explorer cycle and gives an overview of the six candidate missions selected for assessment studies.

Within the context of ESA's Living Planet Programme, the European Space Agency has selected three missions embarking lidar instruments: ADM-Aeolus (Atmospheric Dynamics Mission) planed for launch in 2009 with a Doppler Wind Lidar, ALADIN, as unique payload; EarthCARE (Earth Clouds, Aerosols, and Radiation Explorer) planed for launch in 2013 including an ATmospheric backscatter LIDar (ATLID); at last, A-SCOPE (Advanced Space Carbon and Climate Observation of Planet Earth), candidate for the 7th Earth Explorer, relying on a CO2 Total Column Differential Absorption Lidar. To mitigate the technical risks for selected missions associated with the different sorts of lidar, ESA has undertaken critical technology developments, from the transmitter to the receiver and covering both components and sub-systems development and characterization. The purpose of this paper is to present the latest results obtained in the area of laser technology that are currently ongoing in support to EarthCARE, A-SCOPE and ADM-Aeolus.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Due for launch in 2013, EarthCARE (Earth Clouds, Aerosols and Radiation Explorer) has been selected as ESA's sixth Earth Explorer Missions within its Living Planet Programme. Its payload aims at providing measurements, in a radiatively consistent manner, of the global distribution of vertical profiles of clouds and aerosol field characteristics. The EarthCARE payload is composed of four instruments: an Atmospheric backscatter Lidar, a Cloud Profiling Radar, a Multi-Spectral Imager and a Broad Band Radiometer. The EarthCARE mission is a cooperative mission with Japan (JAXA and NiCT), which will provide the Cloud Profiling Radar. ESA will provide the ground segment and the rest of the space segment including the Lidar, the imager and the broadband radiometer. ESA and JAXA have initiated predevelopment activities to reduce technical and programmatic risks for the critical elements of the mission. Following a mission overview, this paper presents results of these pre-development activities mainly related to the ATLID instrument. The activities consist of designing, manufacturing and testing a functional representative model of the ATLID receiver critical units and laser source, of developing and assessing high-power pump laser diodes with extended lifetime and improved efficiency, and of demonstrating the performance of candidate detectors.

Hand allograft is a method in the stage of clinical experimentation, which is reserved in France for the treatment of bilateral traumatic amputees. This study reports the Lyon team experience, which is pioneer in this domain. Four patients (3 males and 1 female) underwent seven (one unilateral and three bilateral) hand transplantations from September 1998 to February 2007. The level of amputation was at the wrist or at the mid-forearm. Delay since hand loss ranged from 2.5 to 9 years. The surgical protocol was elaborated and planned case by case. All recipients received the same immunosuppressive treatment. Episodes of acute rejection were observed in the first 3 months after transplantation, which were easily managed after a few days increasing oral prednisone doses and applying topical immunosuppressants. Currently the patients receive the doses of immunosuppressants comparable to those in kidney-grafted patients. We have not registered any severe complication of immunosuppressive treatment up till now (7 years follow-up for the earliest graft). We performed analytical and functional clinical, as well as questionnaire evaluation of patients. The first case (unilateral graft) resulted in graft failure at 2 years due to non-compliance of the patient. The three bilateral graftees demonstrate a favorable evolution despite some immunological (hyperglycemia, serum sickness) and surgical (thrombosis, osteomyelitis, skin loss) complications, which could be managed. The middle and long-term follow-up evaluation revealed good to excellent sensorimotor recovery of 4 hands in both male recipients (4 and 7 years) with satisfactory social adaptation, higher or equal to those expected after post-traumatic replantations at the equivalent level and higher to those obtained with currently available myoelectric prosthesis. The last patient, a young female who has been grafted in February 2007, receives ongoing reeducation course and shows normal progress of functional restoration of both hands. The encouraging results of this clinical experimentation make us currently consider hand allografting as reasonable and useful both for the patients and for evolution of research in composite tissues allotransplantation (CTA). Further long-term careful research and worldwide monitoring of all patients with hand allografts is required to, on the one part, state on the authorization of this surgery, and, on the other part, to better elucidate the mechanisms of successful CTA.

A new call for Core Earth Explorer Ideas was released by the European Space Agency in March 2005. The Call focused on the global carbon and water cycles, atmospheric chemistry and climate, as well as the human element as a cross cutting issue. The proposals were peer reviewed by scientific panels, and also appraised technically and programmatically by ESA. This paper describes the Earth Explorer cycle and gives an overview of the six candidate missions selected for assessment studies.

The earth clouds, aerosols, and radiation explorer mission has been selected as the 6th earth explorer mission of ESA's living planet programme [1]. A suite of four instruments, active and passive, will be embarked on the same satellite to measure cloud and aerosol properties simultaneously with TOA radiances in order to derive TOA fluxes in relation to clouds and aerosols.