Research Activities for the DORIS Contribution to the Next International Terrestrial Reference Frame

For the preparation of ITRF2008, the IDS processed data from 1993 to 2008, including data from TOPEX/Poseidon, the SPOT satellites and Envisat in the weekly solutions. Since the development of ITRF2008, the IDS has been engaged in a number of efforts to try and improve the reference frame solutions. These efforts include (i) assessing the contribution of the new DORIS satellites, Jason-2 and Cryosat2 (2008-2011), (ii) individually analyzing the DORIS satellite contributions to geocenter and scale, and (iii) improving orbit dynamics (atmospheric loading effects, satellite surface force modeling. . . ). We report on the preliminary results from these research activities, review the status of the IDS combination which is now routinely generated from the contributions of the IDS analysis centers, and discuss the prospects for continued improvement in the DORIS contribution to the next international reference frame

Semi-kinematic mount of the FIREBALL large optics

In the context of the NASA CNES FIREBALL balloon borne experiment, we present the design of a semi-kinematic mount to hold the 1 meter class mirrors of this mission. To maintain these large optics in a reasonable mass and price budgets we choose thin ULE mirrors with a thickness over diameter ratio of 1/16. Such thin mirrors require a multi support mount to reduce self weight deflection. Classical multi support mount used for ground based telescope would not survive the level of shock observed in a balloon experiment either at parachute opening or landing. To firmly maintain these mirrors in several points without noticeably deforming them we investigated the design of a two stages semi-kinematic mount composed of 24 monopods. We present the detailed design of this innovative mirror mount, the finite element modeling with the deduced optical wavefront deformation. During the FIREBALL integration and flight campaign in July 2007 at CSBF, we confirmed the validity of the mechanical concept by obtaining an image quality well within the required specifications. Variants of this approach are potentially applicable to large thin mirrors on ground-based observatories

E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Higher-precision radial velocity measurements with the SOPHIE spectrograph using octagonal-section fibers

High-precision spectrographs play a key role in exoplanet searches using the radial velocity technique. But at the accuracy level of 1 m.s-1, required for super-Earth characterization, stability of fiber-fed spectrograph performance is crucial considering variable observing conditions such as seeing, guiding and centering errors and, telescope vignetting. In fiber-fed spectrographs such as HARPS or SOPHIE, the fiber link scrambling properties are one of the main issues. Both the stability of the fiber near-field uniformity at the spectrograph entrance and of the far-field illumination on the echelle grating (pupil) are critical for high-precision radial velocity measurements due to the spectrograph geometrical field and aperture aberrations. We conducted tests on the SOPHIE spectrograph at the 1.93-m OHP telescope to measure the instrument sensitivity to the fiber link light feeding conditions: star decentering, telescope vignetting by the dome,and defocussing. To significantly improve on current precision, we designed a fiber link modification considering the spectrograph operational constraints. We have developed a new link which includes a piece of octagonal-section fiber, having good scrambling properties, lying inside the former circular-section fiber, and we tested the concept on a bench to characterize near-field and far-field scrambling properties. This modification has been implemented in spring 2011 on the SOPHIE spectrograph fibers and tested for the first time directly on the sky to demonstrate the gain compared to the previous fiber link. Scientific validation for exoplanet search and characterization has been conducted by observing standard stars.Comment: 12 pages, 9 figures, Proceedings of SPIE 201

APRIL is overexpressed in cancer: link with tumor progression

<p>Abstract</p> <p>Background</p> <p>BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.</p> <p>Methods</p> <p>We compared the expression of <it>BAFF, APRIL, TACI and BAFF-R </it>gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.</p> <p>Results</p> <p>We found significant overexpression of <it>TACI </it>in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, <it>BAFF and APRIL </it>are overexpressed in many cancers and we show that <it>APRIL </it>expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.</p> <p>Conclusion</p> <p>Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.</p

Melanoma Cell Expression of CD200 Inhibits Tumor Formation and Lung Metastasis via Inhibition of Myeloid Cell Functions

CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16 melanoma cells inhibited tumor formation and growth in C57BL/6 mice but not in Rag1−/−C57BL/6 mice. However, i.v. injection of CD200-positive B16 melanoma cells dramatically inhibited tumor foci formation in the lungs of both C57BL/6 and Rag1−/−C57BL6 mice. Flow cytometry analysis revealed higher expression of CD200R in Gr1+ myeloid cells in the lung than in peripheral myeloid cells. Depletion of Gr1+ cells or stimulation of CD200R with an agonistic antibody in vivo dramatically inhibited tumor foci formation in the lungs. In addition, treatment with tumor antigen specific CD4 or CD8 T cells or their combination yielded a survival advantage for CD200 positive tumor bearing mice over mice bearing CD200-negative tumors. Taken together, we have revealed a novel role for CD200-CD200R interaction in inhibiting tumor formation and metastasis. Targeting CD200R may represent a novel approach for cancer immunotherapy

Semi-kinematic mount of the FIREBALL large optics

In the context of the NASA CNES FIREBALL balloon borne experiment, we present the design of a semi-kinematic mount to hold the 1 meter class mirrors of this mission. To maintain these large optics in a reasonable mass and price budgets we choose thin ULE mirrors with a thickness over diameter ratio of 1/16. Such thin mirrors require a multi support mount to reduce self weight deflection. Classical multi support mount used for ground based telescope would not survive the level of shock observed in a balloon experiment either at parachute opening or landing. To firmly maintain these mirrors in several points without noticeably deforming them we investigated the design of a two stages semi-kinematic mount composed of 24 monopods. We present the detailed design of this innovative mirror mount, the finite element modeling with the deduced optical wavefront deformation. During the FIREBALL integration and flight campaign in July 2007 at CSBF, we confirmed the validity of the mechanical concept by obtaining an image quality well within the required specifications. Variants of this approach are potentially applicable to large thin mirrors on ground-based observatories

Differential effects of lenalidomide during plasma cell differentiation.

Thalidomide, lenalidomide and pomalidomide have greatly improved the outcome of patients with multiple myeloma. However, their effects on plasma cells, the healthy counterpart of myeloma cells, are unknown. Here, we investigated lenalidomide effects on normal human plasma cell generation using an in vitro model. Lenalidomide inhibited the generation of pre-plasmablasts and early plasma cells, while it moderately affected plasmablast production. It also reduced the expression level of Ikaros, Aiolos, and IRF4 transcription factors, in plasmablasts and early plasma cells. This suggests that their differential sensitivity to lenalidomide is not due to a difference in Ikaros or Aiolos degradation. Lenalidomide also inhibited long-lived plasma cell generation, but did not impair their long-term survival once generated. This last observation is in agreement with the finding that lenalidomide treatment for 3-18 months did not affect the bone marrow healthy plasma cell count in allografted patients with multiple myeloma. Our findings should prompt to investigate whether lenalidomide resistance in patients with multiple myeloma could be associated with the emergence of malignant plasmablasts or long-lived plasma cells that are less sensitive to lenalidomide

Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays

<p>Abstract</p> <p>Background</p> <p>Multiple myeloma (MM) is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC). In the past few years, many myeloma growth factors (MGF) have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them.</p> <p>Methods</p> <p>We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR) using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM) microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts).</p> <p>Results</p> <p>4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC) and BM plasma cell (BMPC) compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A) and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC.</p> <p>Conclusions</p> <p>Two major messages arise from this analysis 1) The majority of MGF genes is expressed by the bone marrow environment. 2) Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM.</p

Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 2: Untangling climatic, edaphic, management and nitrogen deposition effects on carbon sequestration potentials

The effects of atmospheric nitrogen deposition (N$_{dep}$) on carbon (C) sequestration in forests have often been assessed by relating differences in productivity to spatial variations of N$_{dep}$ across a large geographic domain. These correlations generally suffer from covariation of other confounding variables related to climate and other growth-limiting factors, as well as large uncertainties in total (dry+wet) reactive nitrogen (N$_{r}$) deposition.We propose a methodology for untangling the effects of N$_{dep}$ from those of meteorological variables, soil water retention capacity and stand age, using a mechanistic forest growth model in combination with eddy covariance CO$_{2}$ exchange fluxes from a Europe-wide network of 22 forest flux towers. Total N$_{r}$ deposition rates were estimated from local measurements as far as possible. The forest data were compared with data from natural or semi-natural, non-woody vegetation sites. The response of forest net ecosystem productivity to nitrogen deposition (dNEP= dN$_{dep}$) was estimated after accounting for the effects on gross primary productivity (GPP) of the co-correlates by means of a meta-modelling standardization procedure, which resulted in a reduction by a factor of about 2 of the uncorrected, apparent dGPP/dN$_{dep}$ value. This model-enhanced analysis of the C and N$_{dep}$ flux observations at the scale of the European network suggests a mean overall dNEP/dN$_{dep}$ response of forest lifetime C sequestration to N$_{dep}$ of the order of 40–50 g C per g N, which is slightly larger but not significantly different from the range of estimates published in the most recent reviews. Importantly, patterns of gross primary and net ecosystem productivity versus N$_{dep}$ were non-linear, with no further growth responses at high N$_{dep}$ levels (N$_{dep}$ >2.5–3 gNm$^{-2}$ yr$^{-1}$) but accompanied by increasingly large ecosystem N losses by leaching and gaseous emissions. The reduced increase in productivity per unit N deposited at high N$_{dep}$ levels implies that the forecast increased N$_{r}$ emissions and increased Ndep levels in large areas of Asia may not positively impact the continent’s forest CO$_{2}$ sink. The large level of unexplained variability in observed carbon sequestration efficiency (CSE) across sites further adds to the uncertainty in the dC/dN response