ExTrA: Exoplanets in Transit and their Atmospheres

The ExTrA facility, located at La Silla observatory, will consist of a near-infrared multi-object spectrograph fed by three 60-cm telescopes. ExTrA will add the spectroscopic resolution to the traditional differential photometry method. This shall enable the fine correction of color-dependent systematics that would otherwise hinder ground-based observations. With both this novel method and an infrared-enabled efficiency, ExTrA aims to find transiting telluric planets orbiting in the habitable zone of bright nearby M dwarfs. It shall have the versatility to do so by running its own independent survey and also by concurrently following-up on the space candidates unveiled by K2 and TESS. The exoplanets detected by ExTrA will be amenable to atmospheric characterisation with VLTs, JWST, and ELTs and could give our first peek into an exo-life laboratory.Comment: 15 pages, 11 figures, SPIE 201

First experimental results of very high accuracy centroiding measurements for the neat astrometric mission

NEAT is an astrometric mission proposed to ESA with the objectives of detecting Earth-like exoplanets in the habitable zone of nearby solar-type stars. NEAT requires the capability to measure stellar centroids at the precision of 5e-6 pixel. Current state-of-the-art methods for centroid estimation have reached a precision of about 2e-5 pixel at two times Nyquist sampling, this was shown at the JPL by the VESTA experiment. A metrology system was used to calibrate intra and inter pixel quantum efficiency variations in order to correct pixelation errors. The European part of the NEAT consortium is building a testbed in vacuum in order to achieve 5e-6 pixel precision for the centroid estimation. The goal is to provide a proof of concept for the precision requirement of the NEAT spacecraft. In this paper we present the metrology and the pseudo stellar sources sub-systems, we present a performance model and an error budget of the experiment and we report the present status of the demonstration. Finally we also present our first results: the experiment had its first light in July 2013 and a first set of data was taken in air. The analysis of this first set of data showed that we can already measure the pixel positions with an accuracy of about 1e-4 pixel.Comment: SPIE conference proceeding

A detector interferometric calibration experiment for high precision astrometry

Context: Exoplanet science has made staggering progress in the last two decades, due to the relentless exploration of new detection methods and refinement of existing ones. Yet astrometry offers a unique and untapped potential of discovery of habitable-zone low-mass planets around all the solar-like stars of the solar neighborhood. To fulfill this goal, astrometry must be paired with high precision calibration of the detector. Aims: We present a way to calibrate a detector for high accuracy astrometry. An experimental testbed combining an astrometric simulator and an interferometric calibration system is used to validate both the hardware needed for the calibration and the signal processing methods. The objective is an accuracy of 5e-6 pixel on the location of a Nyquist sampled polychromatic point spread function. Methods: The interferometric calibration system produced modulated Young fringes on the detector. The Young fringes were parametrized as products of time and space dependent functions, based on various pixel parameters. The minimization of func- tion parameters was done iteratively, until convergence was obtained, revealing the pixel information needed for the calibration of astrometric measurements. Results: The calibration system yielded the pixel positions to an accuracy estimated at 4e-4 pixel. After including the pixel position information, an astrometric accuracy of 6e-5 pixel was obtained, for a PSF motion over more than five pixels. In the static mode (small jitter motion of less than 1e-3 pixel), a photon noise limited precision of 3e-5 pixel was reached

High Resolution Spectroscopy and Spectropolarimetry of some late F-/early G-type sun-like stars as targets for Zeeman Doppler imaging

High resolution spectroscopy and spectropolarimetry have been undertaken at the Anglo-Australian Telescope in order to identify suitable targets for magnetic studies of young sun-like stars, for the proxy study of early solar evolution. This study involved the investigation of some variable late F-/early G-type sun-like stars originally identified by the Hipparcos mission. Of the 38 stars observed for this study, HIP 31021, HIP 64732, HIP 73780 were found to be spectroscopic binary stars while HIP 19072, HIP 67651 and HIP 75636 are also likely to be binaries while HIP 33111 could even be a triple system. Magnetic fields were detected on a number of the survey stars: HIP 21632, HIP 43720, HIP 48770, HIP 62517, HIP 71933, HIP 77144, HIP 89829, HIP 90899 and HIP 105388, making these stars good candidates for follow-up Zeeman Doppler imaging studies.Comment: 16 pages, 16 figures, 4 tables Accepted for publication in PAS

Preparation of anti-vicinal amino alcohols: asymmetric synthesis of D-erythro-Sphinganine, (+)-spisulosine and D-ribo-phytosphingosine

Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM-ether directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, while the Overman rearrangement of chiral allylic trichloroacetimidates generated by asymmetric reduction of an alpha,beta-unsaturated methyl ketone allowed rapid access to both D-ribo-phytosphingosine and L-arabino-phytosphingosine

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

International audienceBACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients

S1P lyase regulates DNA damage responses through a novel sphingolipid feedback mechanism

The injurious consequences of ionizing radiation (IR) to normal human cells and the acquired radioresistance of cancer cells represent limitations to cancer radiotherapy. IR induces DNA damage response pathways that orchestrate cell cycle arrest, DNA repair or apoptosis such that irradiated cells are either repaired or eliminated. Concomitantly and independent of DNA damage, IR activates acid sphingomyelinase (ASMase), which generates ceramide, thereby promoting radiation-induced apoptosis. However, ceramide can also be metabolized to sphingosine-1-phosphate (S1P), which acts paradoxically as a radioprotectant. Thus, sphingolipid metabolism represents a radiosensitivity pivot point, a notion supported by genetic evidence in IR-resistant cancer cells. S1P lyase (SPL) catalyzes the irreversible degradation of S1P in the final step of sphingolipid metabolism. We show that SPL modulates the kinetics of DNA repair, speed of recovery from G2 cell cycle arrest and the extent of apoptosis after IR. SPL acts through a novel feedback mechanism that amplifies stress-induced ceramide accumulation, and downregulation/inhibition of either SPL or ASMase prevents premature cell cycle progression and mitotic death. Further, oral administration of an SPL inhibitor to mice prolonged their survival after exposure to a lethal dose of total body IR. Our findings reveal SPL to be a regulator of ASMase, the G2 checkpoint and DNA repair and a novel target for radioprotection

2012 Activity Report of the Regional Research Programme on Hadrontherapy for the ETOILE Center

2012 is the penultimate year of financial support by the CPER 2007-2013 for ETOILE's research program, sustained by the PRRH at the University Claude Bernard. As with each edition we make the annual review of the research in this group, so active for over 12 years now. Over the difficulties in the decision-making process for the implementation of the ETOILE Center, towards which all our efforts are focussed, some "themes" (work packages) were strengthened, others have progressed, or have been dropped. This is the case of the eighth theme (technological developments), centered around the technology for rotative beam distribution heads (gantries) and, after being synchronized with the developments of ULICE's WP6, remained so by ceasing its activities, coinciding also with the retirement of its historic leader at IPNL, Marcel Bajard. Topic number 5 ("In silico simulations") has suffered the departure of its leader, Benjamin Ribba, although the work has still been provided by Branka Bernard, a former postdoctoral fellow in Lyon Sud, and now back home in Croatia, still in contract with UCBL for the ULICE project. Aside from these two issues (and the fact that the theme "Medico-economical simulations" is now directly linked to the first one ("Medical Project"), the rest of the teams are growing, as evidenced by the publication statistics at the beginning of this report. This is obviously due to the financial support of our always faithful regional institutions, but also to the synergy that the previous years, the European projects, the arrival of the PRIMES LabEx, and the national France Hadron infrastructure have managed to impulse. The Rhone-Alpes hadron team, which naturally includes the researchers of LPC at Clermont, should also see its influence result in a strong presence in France Hadron's regional node, which is being organized. The future of this regional research is not yet fully guaranteed, especially in the still uncertain context of ETOILE, but the tracks are beginning to emerge to allow past and present efforts translate into a long future that we all want to see established. Each of the researchers in PRRH is aware that 2013 will be (and already is) the year of great challenge : for ETOILE, for the PRRH, for hadron therapy in France, for French hadrontherapy in Europe (after the opening and beginning of treatments in the German [HIT Heidelberg, Marburg], Italian [CNAO, Pavia] and Austrian [MedAustron, Wien Neuerstadt]) centers. Let us meet again in early 2014 for a comprehensive review of the past and a perspective for the future ..

Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression

BACKGROUND:Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder caused most commonly by a defect in the NPC1 protein and characterized by widespread intracellular accumulation of unesterified cholesterol and glycosphingolipids (GSLs). While current treatment therapies are limited, a few drugs tested in Npc1(-/-) mice have shown partial benefit. During a combination treatment trial using two such compounds, N-butyldeoxynojirimycin (NB-DNJ) and allopregnanolone, we noted increased lifespan for Npc1(-/-) mice receiving only 2-hydroxypropyl-beta-cyclodextrin (CD), the vehicle for allopregnanolone. This finding suggested that administration of CD alone, but with greater frequency, might provide additional benefit. METHODOLOGY/PRINCIPAL FINDINGS:Administration of CD to Npc1(-/-) mice beginning at either P7 or P21 and continuing every other day delayed clinical onset, reduced intraneuronal cholesterol and GSL storage as well as free sphingosine accumulation, reduced markers of neurodegeneration, and led to longer survival than any previous treatment regime. We reasoned that other lysosomal diseases characterized by cholesterol and GSL accumulation, including NPC disease due to NPC2 deficiency, GM1 gangliosidosis and mucopolysaccharidosis (MPS) type IIIA, might likewise benefit from CD treatment. Treated Npc2(-/-) mice showed benefits similar to NPC1 disease, however, mice with GM1 gangliosidosis or MPS IIIA failed to show reduction in storage. CONCLUSIONS/SIGNIFICANCE:Treatment with CD delayed clinical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan of both Npc1(-/-) and Npc2(-/-) mice. In contrast, CD failed to ameliorate cholesterol or glycosphingolipid storage in GM1 gangliosidosis and MPS IIIA disease. Understanding the mechanism(s) by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis