The CHARA Array is a six 1 m telescope optical/IR interferometric array located on Mount Wilson, California, designed and built by the Center for High Angular Resolution Astronomy of Georgia State ...University. In this paper we describe the main elements of the Array hardware and software control systems, as well as the data reduction methods currently being used. Our plans for upgrades in the near future are also described.
Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase ...inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date.
In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions).
Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1.
Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.
•The EGFR-TKI efficacy of in uncommon EGFR mutations generally considered TKI sensitive was validated.•Complex EGFR mutations containing exon19del or L858R were EGFR-TKI sensitive, independent of the combination partner.•Very rare single and complex mutations, comprising 40% of atypical mutations, show a high heterogeneity of TKI sensitivity.•TP53 co-mutations may confer a detrimental outcome in TKI-treated patients with very rare EGFR mutations and exon20ins.•We propose a novel nNGM classification for atypical EGFR mutations.
Context.Only a handful of debris disks have been imaged up to now. Due to the need for high dynamic range and high angular resolution, very little is known about the inner planetary region, where ...small amounts of warm dust are expected to be found. Aims.We investigate the close neighbourhood of Vega with the help of infrared stellar interferometry and estimate the integrated K-band flux originating from the central 8 AU of the debris disk. Methods.We performed precise visibility measurements at both short (~30 m) and long (~150 m) baselines with the FLUOR beam-combiner installed at the CHARA Array (Mt Wilson, California) in order to separately resolve the emissions from the extended debris disk (short baselines) and from the stellar photosphere (long baselines). Results.After revising Vega's K-band angular diameter ($\theta_{\rm UD} = 3.202$ ± 0.005 mas), we show that a significant deficit in squared visibility ($\Delta V^2 = 1.88$ ± 0.34%) is detected at short baselines with respect to the best-fit uniform disk stellar model. This deficit can be either attributed to the presence of a low-mass stellar companion around Vega, or as the signature of the thermal and scattered emissions from the debris disk. We show that the presence of a close companion is highly unlikely, as well as other possible perturbations (stellar morphology, calibration), and deduce that we have most probably detected the presence of dust in the close neighbourhood of Vega. The resulting flux ratio between the stellar photosphere and the debris disk amounts to 1.29 ± 0.19% within the FLUOR field-of-view (~7.8 AU). Finally, we complement our K-band study with archival photometric and interferometric data in order to evaluate the main physical properties of the inner dust disk. The inferred properties suggest that the Vega system could be currently undergoing major dynamical perturbations.
We have measured the angular diameters of six M dwarfs with the CHARA Array, a long-baseline optical interferometer located at Mount Wilson Observatory. Spectral types range from M1.0 V to M3.0 V and ...linear radii from 0.38 to 0.69 R sub( ). These results are consistent with the seven other M dwarf radii measurements from optical interferometry and with those for 14 stars in eclipsing binary systems. We compare all directly measured M dwarf radii to model predictions and find that current models underestimate the true stellar radii by up to 15%-20%. The differences are small among the metal-poor stars but become significantly larger with increasing metallicity. This suggests that theoretical models for low-mass stars may be missing some opacity source that alters the computed stellar radii.
A Reverse Shock in GRB 181201A Laskar, Tanmoy; Eerten, Hendrik van; Schady, Patricia ...
The Astrophysical journal,
10/2019, Letnik:
884, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We present comprehensive multiwavelength radio to X-ray observations of GRB 181201A spanning from 150 s to 163 days after the burst, comprising the first joint ALMA-VLA-GMRT observations of a ...gamma-ray burst (GRB) afterglow. The radio and millimeter-band data reveal a distinct signature at 3.9 days, which we interpret as reverse-shock (RS) emission. Our observations present the first time that a single radio-frequency spectral energy distribution can be decomposed directly into RS and forward shock (FS) components. We perform detailed modeling of the full multiwavelength data set, using Markov Chain Monte Carlo sampling to construct the joint posterior density function of the underlying physical parameters describing the RS and FS synchrotron emission. We uncover and account for all discovered degeneracies in the model parameters. The joint RS-FS modeling reveals a weakly magnetized ( 3 × 10−3), mildly relativistic RS, from which we derive an initial bulk Lorentz factor of Γ0 103 for the GRB jet. Our results support the hypothesis that low-density environments are conducive to the observability of RS emission. We compare our observations to other events with strong RS detections and find a likely observational bias selecting for longer lasting, nonrelativistic RSs. We present and begin to address new challenges in modeling posed by the present generation of comprehensive, multifrequency data sets.
Pediatric Pulmonary Hypertension Ivy, D. Dunbar, MD; Abman, Steven H., MD; Barst, Robyn J., MD ...
Journal of the American College of Cardiology,
12/2013, Letnik:
62, Številka:
25
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Pulmonary hypertension (PH) is a rare disease in newborns, infants, and children that is associated with significant morbidity and mortality. In the majority of pediatric patients, PH is idiopathic ...or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Incidence data from the Netherlands has revealed an annual incidence and point prevalence of 0.7 and 4.4 for idiopathic pulmonary arterial hypertension and 2.2 and 15.6 for pulmonary arterial hypertension, respectively, associated with congenital heart disease (CHD) cases per million children. The updated Nice classification for PH has been enhanced to include a greater depth of CHD and emphasizes persistent PH of the newborn and developmental lung diseases, such as bronchopulmonary dysplasia and congenital diaphragmatic hernia. The management of pediatric PH remains challenging because treatment decisions continue to depend largely on results from evidence-based adult studies and the clinical experience of pediatric experts.
We report on K-band interferometric observations of the bright, rapidly rotating star Regulus (type B7 V) made with the CHARA Array on Mount Wilson, California. Through a combination of ...interferometric and spectroscopic measurements, we have determined for Regulus the equatorial and polar diameters and temperatures, the rotational velocity and period, the inclination and position angle of the spin axis, and the gravity darkening coefficient. These first results from the CHARA Array provide the first interferometric measurement of gravity darkening in a rapidly rotating star and represent the first detection of gravity darkening in a star that is not a member of an eclipsing binary system.
Polycrystalline (Cu1-xZnx)2OSeO3 (0≤x≤0.2) samples were synthesized using solid-state reaction and characterized by X-ray diffraction (XRD). The effect of Zn doping upon saturation magnetization (MS) ...indicates that the Zn favors to occupying Cu(II) square pyramidal crystallographic site. The AC susceptibility (χ'ac) was measured at various temperatures (χ'ac-T) and magnetic field strengths (χ'ac-H). The Zn doping concentration is found to affect greatly the M-T and χ'ac-T. The skyrmion phase has been inferred from the χ'ac-H data, and then indicated within the H-T phase diagrams for various Zn doping concentrations. The striking and unexpected observation is that the skyrmion phase region becomes split upon Zn doping concentration. Interestingly, second conical boundary accompanied by second skyrmion phase was also observed from dχ'ac/dH vs. H curves. Atomic site disorder created by the chemical doping modulates the delicate magnetic interactions via change in the Dzyaloshinskii-Moriya (DM) vector of distorted Cu(II) square pyramidal, thereby splitting of skyrmion phase might occur. These findings illustrate the potential of using chemical and atomic modification for tuning the temperature and field dependence of skyrmion phase of Cu2OSeO3.
Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia–reperfusion injury. Anaesthetic ...conditioning is a widely described strategy to attenuate ischaemia–reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation.
Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr.
Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO 952.8 (interquartile range 311.8–1893.0) pg mmol−1 compared with PROP 301.2 (202.0–504.7) pg mmol−1. This was the same for NAG: SEVO, 1.835 (1.162–2.457) IU mmol−1vs PROP, 1.078 (0.819–1.713) IU mmol−1. Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate (P=0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P=0.020). The difference between PROP and SEVO (11%) was not significant (P=0.110).
The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome.
NCT01248871.
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