A faint companion around CrA-9: protoplanet or obscured binary?

Understanding how giant planets form requires observational input from directly imaged protoplanets. We used VLT/NACO and VLT/SPHERE to search for companions in the transition disc of 2MASS J19005804-3645048 (hereafter CrA-9), an accreting M0.75 dwarf with an estimated age of 1-2 Myr. We found a faint point source at $\sim$0.7'' separation from CrA-9 ($\sim$108 au projected separation). Our 3-epoch astrometry rejects a fixed background star with a $5\sigma$ significance. The near-IR absolute magnitudes of the object point towards a planetary-mass companion. However, our analysis of the 1.0-3.8$\mu$m spectrum extracted for the companion suggests it is a young M5.5 dwarf, based on both the 1.13-$\mu$m Na index and comparison with templates of the Montreal Spectral Library. The observed spectrum is best reproduced with high effective temperature ($3057^{+119}_{-36}$K) BT-DUSTY and BT-SETTL models, but the corresponding photometric radius required to match the measured flux is only $0.60^{+0.01}_{-0.04}$ Jovian radius. We discuss possible explanations to reconcile our measurements, including an M-dwarf companion obscured by an edge-on circum-secondary disc or the shock-heated part of the photosphere of an accreting protoplanet. Follow-up observations covering a larger wavelength range and/or at finer spectral resolution are required to discriminate these two scenarios.Comment: 24 pages, 14 figures, 4 tables, to be published in MNRA

Crystallization and Preliminary Analysis of Crystals of the 24-Meric Hemocyanin of the Emperor Scorpion (Pandinus imperator)

Hemocyanins are giant oxygen transport proteins found in the hemolymph of several invertebrate phyla. They constitute giant multimeric molecules whose size range up to that of cell organelles such as ribosomes or even small viruses. Oxygen is reversibly bound by hemocyanins at binuclear copper centers. Subunit interactions within the multisubunit hemocyanin complex lead to diverse allosteric effects such as the highest cooperativity for oxygen binding found in nature. Crystal structures of a native hemocyanin oligomer larger than a hexameric substructure have not been published until now. We report for the first time growth and preliminary analysis of crystals of the 24-meric hemocyanin (MW = 1.8 MDa) of emperor scorpion (Pandinus imperator), which diffract to a resolution of 6.5 Å. The crystals are monoclinc with space group C 1 2 1 and cell dimensions a = 311.61 Å, b = 246.58 Å and c = 251.10 Å (α = 90.00°, β = 90.02°, γ = 90.00°). The asymmetric unit contains one molecule of the 24-meric hemocyanin and the solvent content of the crystals is 56%. A preliminary analysis of the hemocyanin structure reveals that emperor scorpion hemocyanin crystallizes in the same oxygenated conformation, which is also present in solution as previously shown by cryo-EM reconstruction and small angle x-ray scattering experiments

Separating extended disc features from the protoplanet in PDS 70 using VLT/SINFONI

Transition discs are prime targets to look for protoplanets and study planet–disc interactions. We present VLT/SINFONI observations of PDS 70, a transition disc with a recently claimed embedded protoplanet. We take advantage of the angular and spectral diversity present in our data for an optimal PSF modelling and subtraction using principal component analysis (PCA). We report the redetection of PDS 70 b, both the front and far side of the outer disc edge, and the detection of several extended features in the annular gap. We compare spectral differential imaging applied before (PCA-SADI), and after (PCA-ASDI) angular differential imaging. Our tests suggest that PCA-SADI better recovers extended features, while PCA-ASDI is more sensitive to point sources. We adapted the negative fake companion (NEGFC) technique to infer the astrometry of the companion, and derived r = 193.5 ± 4.9 mas and PA =158.7° ± 3.0°. We used both NEGFC and ANDROMEDA to infer the K-band spectro-photometry of the protoplanet, and found results consistent with recent VLT/SPHERE observations, except for their 2018/02 epoch measurement in the K2 filter. Finally, we derived an upper limit of Ṁb < 1.26 × 10^(−7) [5M_(Jup)/M_b][R_b/R_(Jup)]M_(Jup) yr^(−1) for the accretion rate of the companion based on an adaptation of PCA-SADI/PCA-ASDI around the Brγ line (assuming no extinction)

Separating extended disc features from the protoplanet in PDS 70 using VLT/SINFONI

Transition discs are prime targets to look for protoplanets and study planet-disc interactions. We present VLT/SINFONI observations of PDS 70, a transition disc with a recently claimed embedded protoplanet. We take advantage of the angular and spectral diversity present in our data for an optimal PSF modelling and subtraction using principal component analysis (PCA). We report the redetection of PDS 70 b, both the front and far side of the outer disc edge, and the detection of several extended features in the annular gap. We compare spectral differential imaging applied before (PCA-SADI), and after (PCA-ASDI) angular differential imaging. Our tests suggest that PCA-SADI better recovers extended features, while PCA-ASDI is more sensitive to point sources. We adapted the negative fake companion (NEGFC) technique to infer the astrometry of the companion, and derived r = 193.5 ± 4.9 mas and PA =158.7° ± 3.0°. We used both NEGFC and ANDROMEDA to infer the K-band spectro-photometry of the protoplanet, and found results consistent with recent VLT/SPHERE observations, except for their 2018/02 epoch measurement in the K2 filter. Finally, we derived an upper limit of \dot{M_b} &lt; 1.26 10^{-7} \big [ 5 M_Jup/M_b \big ] \big [ R_b/R_Jup\big ] M_Jup yr-1 for the accretion rate of the companion based on an adaptation of PCA-SADI/PCA-ASDI around the Brγ line (assuming no extinction)

Separating extended disc features from the protoplanet in PDS 70 using VLT/SINFONI

International audienceTransition discs are prime targets to look for protoplanets and study planet-disc interactions. We present VLT/SINFONI observations of PDS 70, a transition disc with a recently claimed embedded protoplanet. We take advantage of the angular and spectral diversity present in our data for an optimal PSF modelling and subtraction using principal component analysis (PCA). We report the redetection of PDS 70 b, both the front and far side of the outer disc edge, and the detection of several extended features in the annular gap. We compare spectral differential imaging applied before (PCA-SADI), and after (PCA-ASDI) angular differential imaging. Our tests suggest that PCA-SADI better recovers extended features, while PCA-ASDI is more sensitive to point sources. We adapted the negative fake companion (NEGFC) technique to infer the astrometry of the companion, and derived r = 193.5 ± 4.9 mas and PA =158.7° ± 3.0°. We used both NEGFC and ANDROMEDA to infer the K-band spectro-photometry of the protoplanet, and found results consistent with recent VLT/SPHERE observations, except for their 2018/02 epoch measurement in the K2 filter. Finally, we derived an upper limit of \dot{M_b} -1 for the accretion rate of the companion based on an adaptation of PCA-SADI/PCA-ASDI around the Brγ line (assuming no extinction)

Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer

Antibodies against epidermal growth factor receptor (EGFR)--cetuximab and panitumumab--are widely used to treat colorectal cancer. Unfortunately, patients eventually develop resistance to these agents. We describe an acquired EGFR ectodomain mutation (S492R) that prevents cetuximab binding and confers resistance to cetuximab. Cells with this mutation, however, retain binding to and are growth inhibited by panitumumab. Two of ten subjects studied here with disease progression after cetuximab treatment acquired this mutation. A subject with cetuximab resistance harboring the S492R mutation responded to treatment with panitumumab

Ultra-selection of metastatic colorectal cancer patients using next-generation sequencing to improve clinical efficacy of anti-EGFR therapy

BACKGROUND: Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from antiepidermal growth factor receptor (EGFR) therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor. PATIENTS AND METHODS: Five hundred and eighty-one tumour samples from untreated mCRC patients from 7 clinical studies were collected. Mutational analysis was carried out by standard-of-care (therascreen pyro) with a sensitivity detection of 5% mutant allele fraction (MAF), and compared with NGS technology using 454GS Junior platform (Roche Applied Science, Germany) with a sensitivity of 1%. Molecular results were correlated with clinical outcomes. RESULTS: After quality assessment, 380 samples were evaluable for molecular analysis. Standard-of-care mutational analysis detected RAS, BRAFV600E or PIK3CA mutations in 56.05% of samples compared with 69.21% by NGS (P = 0.00018). NGS identified coexistence of multiple low-frequency mutant alleles in 96 of the 263 mutated cases (36.5%; range 2-7). Response rate (RR), progression-free survival (PFS) and overall survival (OS) were increasingly improved in patients with RAS wild-type, RAS/BRAF wild-type or quadruple (KRAS/NRAS/BRAF/PIK3CA) wild-type tumours treated with anti-EGFR, assessed by standard-of-care. No additional benefit in RR, PFS or OS was observed by increasing the detection threshold to 1% by NGS. An inverse correlation between the MAF of the most prevalent mutation detected by NGS and anti-EGFR response was observed (P = 0.039). EGFRS492Rmutation was not detected in untreated samples. CONCLUSIONS: No improvement in the selection of patients for anti-EGFR therapy was obtained by adjusting the mutation detection threshold in tissue samples from 5% to 1% MAF. Response to anti-EGFR was significantly better in patients with quadruple wild-type tumours