144 research outputs found
Friedel–Crafts addition of indoles to nitrones promoted by trimethylsilyl trifluoromethanesulfonate
N-alkylindoles undergo Friedel–Crafts addition to aryl and secondary alkyl nitrones in the presence of trimethylsilyl trifluoromethanesulfonate and a trialkylamine to produce 3-(1- (silyloxyamino)alkyl)indoles. Spontaneous conversion to the bisindolyl(aryl)methanes, which is thermodynamically favored for nitrones derived from aromatic aldehydes, is suppressed under the reaction conditions. The silyloxyamino group can be deprotected with tetrabutylammonium fluoride to yield the hydroxylamine
Discovery of a Transiting Planet Near the Snow-Line
In most theories of planet formation, the snow-line represents a boundary
between the emergence of the interior rocky planets and the exterior ice
giants. The wide separation of the snow-line makes the discovery of transiting
worlds challenging, yet transits would allow for detailed subsequent
characterization. We present the discovery of Kepler-421b, a Uranus-sized
exoplanet transiting a G9/K0 dwarf once every 704.2 days in a near-circular
orbit. Using public Kepler photometry, we demonstrate that the two observed
transits can be uniquely attributed to the 704.2 day period. Detailed light
curve analysis with BLENDER validates the planetary nature of Kepler-421b to >4
sigmas confidence. Kepler-421b receives the same insolation as a body at ~2AU
in the Solar System and for a Uranian albedo would have an effective
temperature of ~180K. Using a time-dependent model for the protoplanetary disk,
we estimate that Kepler-421b's present semi-major axis was beyond the snow-line
after ~3Myr, indicating that Kepler-421b may have formed at its observed
location.Comment: 14 pages, 10 figures, 3 tables. Accepted in Ap
KELT-11b: A Highly Inflated Sub-Saturn Exoplanet Transiting the V=8 Subgiant HD 93396
We report the discovery of a transiting exoplanet, KELT-11b, orbiting the
bright () subgiant HD 93396. A global analysis of the system shows that
the host star is an evolved subgiant star with K,
, , log , and [Fe/H].
The planet is a low-mass gas giant in a day orbit,
with , , g cm, surface gravity log , and equilibrium temperature K. KELT-11 is the brightest known transiting exoplanet host
in the southern hemisphere by more than a magnitude, and is the 6th brightest
transit host to date. The planet is one of the most inflated planets known,
with an exceptionally large atmospheric scale height (2763 km), and an
associated size of the expected atmospheric transmission signal of 5.6%. These
attributes make the KELT-11 system a valuable target for follow-up and
atmospheric characterization, and it promises to become one of the benchmark
systems for the study of inflated exoplanets.Comment: 15 pages, Submitted to AAS Journal
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial
Background:
Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.
Methods:
In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.
Findings:
Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none).
Interpretation:
Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy.
Funding:
Clovis Oncology
Two warm, low-density sub-Jovian planets orbiting bright stars in K2 campaigns 13 and 14
We report the discovery of two planets transiting the bright stars HD 89345
(EPIC 248777106, , ) in K2 Campaign 14 and HD 286123 (EPIC
247098361, , ) in K2 Campaign 13. Both stars are G-type
stars, one of which is at or near the end of its main sequence lifetime, and
the other that is just over halfway through its main sequence lifetime. HD
89345 hosts a warm sub-Saturn (0.66 , 0.11 , K)
in an 11.81-day orbit. The planet is similar in size to WASP-107b, which falls
in the transition region between ice giants and gas giants. HD 286123 hosts a
Jupiter-sized, low-mass planet (1.06 , 0.39 , K)
in an 11.17-day, mildly eccentric orbit, with . Given that
they orbit relatively evolved main-sequence stars and have orbital periods
longer than 10 days, these planets are interesting candidates for studies of
gas planet evolution, migration, and (potentially) re-inflation. Both planets
have spent their entire lifetimes near the proposed stellar irradiation
threshold at which giant planets become inflated, and neither shows any sign of
radius inflation. They probe the regime where inflation begins to become
noticeable and are valuable in constraining planet inflation models. In
addition, the brightness of the host stars, combined with large atmospheric
scale heights of the planets, makes these two systems favorable targets for
transit spectroscopy to study their atmospheres and perhaps provide insight
into the physical mechanisms that lead to inflated hot Jupiters.Comment: 16 pages, 12 figures; accepted for publication in A
The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson\u27s disease: The GenePD study
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