Antigen quality determines the efficiency of antitumor immune responses generated in the absence of regulatory T cells

The observation that depletion or inhibition of regulatory T cells (Tregs) unleashes efficient antitumor effector immune responses that can lead to tumor eradication in mice has opened new perspectives for the development of cancer immunotherapy. The quality and overall efficiency of the effector immune responses induced in the absence of Tregs seem to depend on multiple factors that determine the result of a battle involving effector T cells (Teffs), Tregs and tumor cells. In this study, we investigated the quality of tumor-associated antigens (TAAs) as one such factor. We show that the presence of a strong dominant antigen is required for the induction of effector responses capable of tumor eradication in the absence of Tregs. The sole addition of a dominant antigen on tumor cells does not change tumor growth in unmanipulated mice, but improves tumor eradication rate from a few to almost 100% in the absence of Tregs. This eradication can be shown to result from the recruitment and activation of specific Teffs recognizing this antigen. We also show that the presence of such dominant antigens has the side effect of restricting the breadth of the immune response to other TAAs, which could favor the generation of escape mutant by tumor editing. Taken together, our results highlight the potential, and some requirements for cancer immunotherapy based on Treg depletion. They also show that, ultimately, tumor fate depends on multiple factors that should all be taken into consideration for the design of more efficient immunotherapy

Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius

We report the discovery of very shallow (DF/F = 3.4 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as due to the presence of a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We use CoRoT color information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy and preliminary results from Radial Velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star are derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. We examine carefully all conceivable cases of false positives, and all tests performed support the planetary hypothesis. Blends with separation larger than 0.40 arcsec or triple systems are almost excluded with a 8 10-4 risk left. We conclude that, as far as we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 +/- 3 10-5 day and a radius of Rp = 1.68 +/- 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. CoRoT-7b is very likely the first Super-Earth with a measured radius.Comment: Accepted in Astronomy and Astrophysics; typos and language corrections; version sent to the printer w few upgrade

THERMAP: a mid-infrared spectro-imager for space missions to small bodies in the inner solar system

We present THERMAP, a mid-infrared (8-16 μm) spectro-imager for space missions to small bodies in the inner solar system, developed in the framework of the MarcoPolo-R asteroid sample return mission. THERMAP is very well suited to characterize the surface thermal environment of a NEO and to map its surface composition. The instrument has two channels, one for imaging and one for spectroscopy: it is both a thermal camera with full 2D imaging capabilities and a slit spectrometer. THERMAP takes advantage of the recent technological developments of uncooled microbolometers detectors, sensitive in the mid-infrared spectral range. THERMAP can acquire thermal images (8-18 μm) of the surface and perform absolute temperature measurements with a precision better than 3.5 K above 200 K. THERMAP can acquire mid-infrared spectra (8-16 μm) of the surface with a spectral resolution Δλ of 0.3 μm. For surface temperatures above 350 K, spectra have a signal-to-noise ratio >60 in the spectral range 9-13 μm where most emission features occur

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

Transiting exoplanets from the CoRoT space mission. VIII. CoRoT-7b: the first super-Earth with measured radius

Copyright © The European Southern Observatory (ESO)Aims. We report the discovery of very shallow (ΔF/F ≈ 3.4×10−4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results. We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40'' or triple systems are almost excluded with a 8 × 10−4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10−5 day and a radius of Rp = 1.68 ± 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. Conclusions. CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800–2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived

Etude expérimentale du chargement latéral de couples de pieux battus

National audienceMost of the investigations on laterally loaded piles groups effect concern the load distribution on different piles of the group, the spacing effect and the direction of the load on the piles' behaviour. The concept of reduction factors applied to P-Y curves for a single pile taking into account the group effect has been proposed by few authors. However any complete study of group effect on P-Y curves for the different piles has not yet been performed. The main reasons of this fact are the difficulties to get experimentally these subgrade reaction curves. In this paper, results tests of laterally loaded couples of piles in centrifuge are explained and discussed. All the tests have been run at the Laboratoire des Ponts et Chaussées of Nantes.La plupart des recherches menées sur l'effet de groupe ont essentiellement porté sur la répartition des efforts entre les différents pieux du groupe, et sur l'influence de l'espacement entre les pieux et la direction de la charge sur le comportement de ces pieux. Le concept de coefficient de réduction pouvant être appliqué aux courbes P-Y du pieu isolé pour prendre en compte l'effet de groupe a été évoqué par quelques auteurs. Aucune étude systématique de l'effet de groupe sur les courbes P-Y des différents pieux n'a cependant été entreprise. La raison en est sans doute la difficulté d'obtenir expérimentalement ces courbes de réaction. L'étude réalisée au LCPC de Nantes sur des modèles réduits centrifugés de couples de pieux chargés latéralement, dans un massif sableux, est présentée. L'analyse concerne à la fois les courbes de chargement, la distribution des moments de flexion et les courbes de réaction P-Y

Laterally loaded piles in sand: slope effect on P-Y reaction curves

International audienceAn extensive program of centrifuge tests was undertaken to study the effect of slopes on P-Y curves in dry sand. The paper concerns the method developed in a previous series of centrifuge tests to experimentally determine P-Y curves. Bending-moment curves are fitted by local quintic spline functions through a crossed validation method and then differentiated twice. These experimental P-Y curves are validated by back analysis. The program of tests on piles near slopes is given. It includes studies of the effect of distance to the slope, slope angle, and soil properties. Sample preparation method, model piles, and the lateral-loading device are described. Deflection versus load curves, bending-moment curves, and derived P-Y curves for piles close to slopes are compared to horizontal-ground response. The coefficients that can apply to the P-Y reaction curves of the reference piles (a single pile in horizontal ground) are proposed for use in practice.Key words: pile, slope effets, models, centrifuge, bending moment, P-Y reaction curves

Non-Linear Behavior of Lateral-Loaded Pile Taking into Account the Shear Stress at the Sand

International audienceDue to recent research advances in understanding mechanisms that govern deep behavior foundations, vertical piles can now be used to correctly support lateral loads. This paper concerns the development of a computer program for studying non-linear behavior of lateral-loaded piles taking into account the shear stress at the sand. Some examples issued from the numerical code are compared with experimental results from centrifuge modeling loaded piles tests and with other numerical results from a well-known code used in France. The influence of shear stress at the soil on the behavior laterally loaded piles was also studied

Étude expérimentale du comportement de groupe de pieux chargés latéralement et de l’effet de leur mise en place dans un massif sableux

National audienc