First direct detection of an exoplanet by optical interferometry; Astrometry and K-band spectroscopy of HR8799 e

To date, infrared interferometry at best achieved contrast ratios of a few times $10^{-4}$ on bright targets. GRAVITY, with its dual-field mode, is now capable of high contrast observations, enabling the direct observation of exoplanets. We demonstrate the technique on HR8799, a young planetary system composed of four known giant exoplanets. We used the GRAVITY fringe tracker to lock the fringes on the central star, and integrated off-axis on the HR8799e planet situated at 390 mas from the star. Data reduction included post-processing to remove the flux leaking from the central star and to extract the coherent flux of the planet. The inferred K band spectrum of the planet has a spectral resolution of 500. We also derive the astrometric position of the planet relative to the star with a precision on the order of 100$\,\mu$as. The GRAVITY astrometric measurement disfavors perfectly coplanar stable orbital solutions. A small adjustment of a few degrees to the orbital inclination of HR 8799 e can resolve the tension, implying that the orbits are close to, but not strictly coplanar. The spectrum, with a signal-to-noise ratio of $\approx 5$ per spectral channel, is compatible with a late-type L brown dwarf. Using Exo-REM synthetic spectra, we derive a temperature of $1150\pm50$\,K and a surface gravity of $10^{4.3\pm0.3}\,$cm/s$^{2}$. This corresponds to a radius of $1.17^{+0.13}_{-0.11}\,R_{\rm Jup}$ and a mass of $10^{+7}_{-4}\,M_{\rm Jup}$, which is an independent confirmation of mass estimates from evolutionary models. Our results demonstrate the power of interferometry for the direct detection and spectroscopic study of exoplanets at close angular separations from their stars.Comment: published in A&

T-type channel blockade impairs long-term potentiation at the parallel fiber-Purkinje cell synapse and cerebellar learning

CaV3.1 T-type channels are abundant at the cerebellar synapse between parallel fibers and Purkinje cells where they contribute to synaptic depolarization. So far, no specific physiological function has been attributed to these channels neither as charge carriers nor more specifically as Ca 2+ carriers. Here we analyze their incidence on synaptic plasticity, motor behavior, and cerebellar motor learning, comparing WT animals and mice where T-type channel function has been abolished either by gene deletion or by acute pharmacological blockade. At the cellular level, we show that Ca V3.1 channels are required for long-term potentiation at parallel fiber-Purkinje cell synapses. Moreover, basal simple spike discharge of the Purkinje cell in KO mice is modified. Acute or chronic T-type current blockade results in impaired motor performance in particular when a good body balance is required. Because motor behavior integrates reflexes and past memories of learned behavior, this suggests impaired learning. Indeed, subjecting the KO mice to a vestibulo-ocular reflex phase reversal test reveals impaired cerebellum-dependent motor learning. These data identify a role of low-voltage activated calcium channels in synaptic plasticity and establish a role for CaV3.1 channels in cerebellar learning

PREMIUM, a benchmark on the quantification of the uncertainty of the physical models in the system thermal-hydraulic codes: methodologies and data review

The objective of the Post-BEMUSE Reflood Model Input Uncertainty Methods (PREMIUM) benchmark is to progress on the issue of the quantification of the uncertainty of the physical models in system thermalhydraulic codes by considering a concrete case: the physical models involved in the prediction of core reflooding. The present document was initially conceived as a final report for the Phase I “Introduction and Methodology Review” of the PREMIUM benchmark. The objective of Phase I is to refine the definition of the benchmark and publish the available methodologies of model input uncertainty quantification relevant to the objectives of the benchmark. In this initial version the document was approved by WGAMA and has shown its usefulness during the subsequent phases of the project. Once Phase IV was completed, and following the suggestion of WGAMA members, the document was updated adding a few new sections, particularly the description of four new methodologies that were developed during this activity. Such developments were performed by some participants while contributing to PREMIUM progress (which is why this report arrives after those of other phases). After this revision the document title was changed to “PREMIUM methodologies and data review”. The introduction includes first a chapter devoted to contextualization of the benchmark in nuclear safety research and licensing, followed by a description of the PREMIUM objectives. Next, a description of the Phases in which the benchmark is divided and its organization is explained. Chapter two consists of a review of the involvement of the different participants, making a brief explanation of the input uncertainty quantification methodologies used in the activity. The document ends with some conclusions on the development of Phase I, some more general remarks and some statements on the benefits of the benchmark, which can be briefly summarized as it follows: - Contribution to development of tools and experience related to uncertainty calculation and promotion of the use of BEPU approaches for licensing and safety assessment purposes; - Contribution to prioritization of improvements to thermal-hydraulic system codes; - Contribution to a fluent and close interaction between the scientific community and regulatory organizations. Appendices include the complete description of the experimental data FEBA/SEFLEX used in the benchmark and the methodologies CIRCÉ and FFTBM and the general requirements and description specification used for Phase I. Due to the revision of the document, four extra appendixes have been added related to the methods developed during the activity, MCDA DIPE, Tractebel IUQ and PSI methods

Phenotype Frequencies of Autosomal Minor Histocompatibility Antigens Display Significant Differences among Populations

Minor histocompatibility (H) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen–matched solid organ and stem cell transplantation (SCT). Minor H antigens are instrumental in the processes of transplant rejection, graft-versus-host disease, and in the curative graft-versus-tumor effect of SCT. The latter characteristic enabled the current application of selected minor H antigens in clinical immunotherapeutic SCT protocols. No information exists on the global phenotypic distribution of the currently identified minor H antigens. Therefore, an estimation of their overall impact in human leukocyte antigen–matched solid organ and SCT in the major ethnic populations is still lacking. For the first time, a worldwide phenotype frequency analysis of ten autosomal minor H antigens was executed by 31 laboratories and comprised 2,685 randomly selected individuals from six major ethnic populations. Significant differences in minor H antigen frequencies were observed between the ethnic populations, some of which appeared to be geographically correlated

Efficacy and safety of long-acting pasireotide or everolimus alone or in combination in patients with advanced carcinoids of the lung and thymus (LUNA): an open-label, multicentre, randomised, phase 2 trial

BACKGROUND: There are no data from prospective studies focused exclusively on patients with advanced lung and thymic carcinoids. We aimed to assess the efficacy and safety of long-acting pasireotide and everolimus, administered alone or in combination, in patients with advanced carcinoids of the lung or thymus. METHODS: LUNA was a prospective, multicentre, randomised, open-label, phase 2 trial of adult patients (aged >18 years) with advanced (unresectable or metastatic), well differentiated carcinoid tumours of the lung or thymus, with radiological progression within 12 months before randomisation, and a WHO performance status of 0-2. At each centre, the investigator or their designee registered each patient using an interactive voice recognition system into one of the three treatment groups. The randomisation allocation sequence was generated by an external company; patients were randomly assigned (1:1:1) to receive treatment with long-acting pasireotide (60 mg intramuscularly every 28 days), everolimus (10 mg orally once daily), or both in combination, for the core 12-month treatment period. Patients were stratified by carcinoid type (typical vs atypical) and line of study treatment (first line vs others). The primary endpoint was the proportion of patients progression-free at month 9, defined as the proportion of patients with overall lesion assessment at month 9 showing a complete response, partial response, or stable disease according to local Response Evaluation Criteria in Solid Tumors, version 1.1, assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. The trial is registered with ClinicalTrials.gov, number NCT01563354. The extension phase of the study is ongoing. FINDINGS: Between Aug 16, 2013, and Sept 30, 2014, 124 patients were enrolled from 36 centres in nine countries: 41 were allocated to the long-acting pasireotide group, 42 to the everolimus group, and 41 to the combination group. At month 9, the proportion of patients with an overall lesion assessment of complete response, partial response, or stable disease was 16 of 41 patients (39·0%, 95% CI 24·2-55·5) in the long-acting pasireotide group, 14 of 42 patients (33·3%, 19·6-49·5) in the everolimus group, and 24 of 41 patients (58·5%, 42·1-73·7) in the combination group. The most common grade 1-2 adverse events with a suspected association with long-acting pasireotide monotherapy were diarrhoea (15 [37%] of 41), hyperglycaemia (17 [41%]), and weight loss (8 [20%]); those with a suspected association with everolimus monotherapy were stomatitis (26 [62%] of 42) and diarrhoea (16 [38%]); and those suspected to be associated with combination treatment were hyperglycaemia (27 [66%] of 41]), diarrhoea (19 [46%]), and asthenia (8 [20%]). The most common grade 3-4 adverse events with a suspected association with long-acting pasireotide monotherapy were γ-glutamyltransferase increased (four [10%] of 41 patients), diarrhoea (three [7%]), and hyperglycaemia (three [7%]); those for everolimus were hyperglycaemia (seven [17%] of 42 patients), stomatitis (four [10%]), and diarrhoea (three [7%]); those for combination treatment were hyperglycaemia (nine [22%] of 41 patients) and diarrhoea (four [10%]). 11 patients died during the core 12-month treatment phase or up to 56 days after the last study treatment exposure date: two (5%) of 41 in the long-acting pasireotide group, six (14%) of 42 in the everolimus group, and three (7%) of 41 in the combination group. No deaths were suspected to be related to long-acting pasireotide treatment. One death in the everolimus group (acute kidney injury associated with diarrhoea), and two deaths in the combination group (diarrhoea and urinary sepsis in one patient, and acute renal failure and respiratory failure in one patient) were suspected to be related to everolimus treatment. In the latter patient, acute renal failure was not suspected to be related to everolimus treatment, but respiratory failure was suspected to be related. INTERPRETATION: The study met the primary endpoint in all three treatment groups. Safety profiles were consistent with the known safety profiles of these agents. Further studies are needed to confirm the antitumour efficacy of the combination of a somatostatin analogue with everolimus in lung and thymic carcinoids. FUNDING: Novartis Pharma AG

The wind and the magnetospheric accretion onto the T Tauri star S Coronae Australis at sub-Au resolution

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Aims. To investigate the inner regions of protoplanetary discs, we performed near-infrared interferometric observations of the classical T Tauri binary system S CrA. Methods. We present the first VLTI-GRAVITY high spectral resolution (R - 4000) observations of a classical T Tauri binary, S CrA (composed of S CrAN and S CrAS and separated by -10:04), combining the four 8m telescopes in dual-field mode. Results. Our observations in the near-infrared K-band continuum reveal a disc around each binary component, with similar halfflux radii of about 0.1 au at d - 130 pc, inclinations (i = 28 - 3-and i = 22 - 6-), and position angles (PA = 0- 6- and PA = -2-12-), suggesting that they formed from the fragmentation of a common disc. The S CrAN spectrum shows bright He i and Br line emission exhibiting inverse P Cygni profiles, typically associated with infalling gas. The continuum-compensated Br line visibilities of S CrAN show the presence of a compact Br emitting region whose radius is about -0.06 au, which is twice as big as the truncation radius. This component is mostly tracing a wind. Moreover, a slight radius change between the blue-And red-shifted Br line components is marginally detected. Conclusions. The presence of an inverse P Cygni profile in the He i and Br lines, along with the tentative detection of a slightly larger size of the blue-shifted Br line component, hint at the simultaneous presence of a wind and magnetospheric accretion in S CrA N.Science Foundation IrelandAlexander von Humboldt Foundation Fellowship ProgrammeFrench PNPSLabEx OSUG@202

Submilliarcsecond Optical Interferometry of the High-mass X-Ray Binary BP Cru with VLTI/GRAVITY

This is the final version. Available from American Astronomical Society via the DOI in this recordWe observe the high-mass X-ray binary (HMXB) BP Cru using interferometry in the near-infrared K band with VLTI/GRAVITY. Continuum visibilities are at most partially resolved, consistent with the predicted size of the hypergiant. Differential visibility amplitude () and phase () signatures are observed across the He i and Brγ lines, the latter seen strongly in emission, unusual for the donor star's spectral type. For a baseline m, the differential phase rms corresponds to an astrometric precision of . We generalize expressions for image centroid displacements and variances in the marginally resolved limit of interferometry to spectrally resolved data, and use them to derive model-independent properties of the emission such as its asymmetry, extension, and strong wavelength dependence. We propose geometric models based on an extended and distorted wind and/or a high-density gas stream, which has long been predicted to be present in this system. The observations show that optical interferometry is now able to resolve HMXBs at the spatial scale where accretion takes place, and therefore to probe the effects of the gravitational and radiation fields of the compact object on its environment