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

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

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

Mining and the value of place in New Caledonia : negotiation, evaluation, recognition

Mining is a land-based activity and mining companies have to negotiate with local landowners their license to operate. Even when they succeed in negotiating impact and benefit agreements with local communities, and start their operations, companies can face various claims and contests arising at various moments of the project cycle and that they are often unable to anticipate or analyse. The program presented in this contribution - NERVAL: 'negotiate, evaluate, and recognise the value of place' funded by the agency CNRT 'Nickel and its environment' - was conceived on these premises by an interdisciplinary team of anthropologists, geographers, and economists. It developed, following a participatory and inter-sectoral logic, a research-based approach to provide stakeholders (mining companies, local governments, customary authorities) with an analytical grid helping them to decipher the land-related contexts and issues and to identify stakes and actors. Based on case studies carried out in mining localities of New Caledonia and a non-mining site, an analytical grid was developed around the four categories of territory, event, risk, and social actor. The paper presents and discusses this toolkit both in conceptual terms and as regards its operational potential

Measurements of undrained shear strength during natural drying

Considering protection of the environment and environmental regulations, the great volumes of dredged low and/or high sediments should be treated. Because of the types of dredgers and the presence of fine particles of the sediments, they have high moisture content. So it’s necessary to carry out the treatments of dehydration and drying for decreasing the wa-ter content. The objective of this study is to follow the natural drying evolution of the sediments by their mechanical characterization. Through the analysis of the physical and chemical properties (grading nature, moisture content, limits of Atterberg and organic matter content) of studied sediments, characterization of shear strength was carried out taking account the influence of water content. The relatively long process of natural drying is depending on the time and by the relation of Su-W which is established by two methods of testing in laboratory. This paper consists of the presentation of results performed with fall-cone test (FCT) and vane shear test (VST) on dam and marine sediments. Relationship between water content and undrained shear strength obtained from fall cone and from vane shear test is evaluated and given. Finally, the relationship is discussed regarding the two testing procedures and a pro-posed correction for FCT could be suggested for dam and marine sediments. But measurements of Su with FCT and VST pose problem due to their principle and their procedure of testing. FCT test is applied only on top of sediment layer and VST test gives discrete measures along the vertical depth layer. Considering these limitations, a continuous Su testing will be preferable. Applicability of T-Bar test to sediments is examined. T-Bar test may be a suitable method to calculate the undrained shear strength of sediments. However, the applicability of T-Bar test (TBT) is not evaluated yet