5,552 research outputs found
Drug susceptibility profile and pathogenicity of H7N9 influenza virus (Anhui1 lineage) with R292K substitution
Neuraminidase inhibitors (NAIs) are the only available licensed therapeutics against human H7N9 influenza virus infections. The emergence of NAI-resistant variants of H7N9viruses with an NA R292K mutation poses a therapeutic challenge. A comprehensive understanding of the susceptibility of these viruses to clinically available NAIs, non-NAIs and their combinations is crucial for effective treatment. In this study, by using limited serial passage and plaque purification, an R292K variant of the Anhui1 lineage was isolated from a patient with clinical evidence of resistance to oseltamivir. In vitro and cell-based assays confirmed a high level of resistance conferred by the R292K mutation to oseltamivir carboxylate and a moderate level of resistance to zanamivir and peramivir. Non-NAI antivirals, such as T-705, ribavirin and NT-300, efficiently inhibited both the variant and the wild-type in cell-based assays. A combination of NAIs and non-NAIs did not exhibit a marked synergistic effect against the R292K variant. However, the combination of two non-NAIs (T-705 and ribavirin) exhibited significant synergism against the mutant virus. In experimentally infected mice, the variant showed delayed onset of symptoms, a reduced viral load and attenuated lethality compared with the wild-type. Our study suggested non-NAIs should be tested clinically for H7N9 patients with a sustained high viral load. Possible drug combination regimens, such as T-705 plus ribavirin, should be further tested in animal models. The pathogenicity and transmissibility of the R292K H7N9 variant should be further assessed with genetically well-characterized pairs of viruses and, most-desirably, with competitive fitness experiments.published_or_final_versio
In-orbit demonstration of X-ray pulsar navigation with the Insight-HXMT satellite
In this work, we report the in-orbit demonstration of X-ray pulsar navigation
with Insight-Hard X-ray Modulation Telescope (Insight-HXMT), which was launched
on Jun. 15th, 2017. The new pulsar navigation method 'Significance Enhancement
of Pulse-profile with Orbit-dynamics' (SEPO) is adopted to determine the orbit
with observations of only one pulsar. In this test, the Crab pulsar is chosen
and observed by Insight-HXMT from Aug. 31th to Sept. 5th in 2017. Using the
5-day-long observation data, the orbit of Insight-HXMT is determined
successfully with the three telescopes onboard - High Energy X-ray Telescope
(HE), Medium Energy X-ray Telescope (ME) and Low Energy X-ray Telescope (LE) -
respectively. Combining all the data, the position and velocity of the
Insight-HXMT are pinpointed to within 10 km (3 sigma) and 10 m/s (3 sigma),
respectively.Comment: Accepted by the Astrophysical Journal Supplemen
Discovery of delayed spin-up behavior following two large glitches in the Crab pulsar, and the statistics of such processes
Glitches correspond to sudden jumps of rotation frequency () and its
derivative () of pulsars, the origin of which remains not well
understood yet, partly because the jump processes of most glitches are not well
time-resolved. There are three large glitches of the Crab pulsar, detected in
1989, 1996 and 2017, which were found to have delayed spin-up processes before
the normal recovery processes. Here we report two additional glitches of the
Crab pulsar occurred in 2004 and 2011 for which we discovered delayed spin up
processes, and present refined parameters of the largest glitch occurred in
2017. The initial rising time of the glitch is determined as hour. We
also carried out a statistical study of these five glitches with observed
spin-up processes. The two glitches occurred in 2004 and 2011 have delayed
spin-up time scales () of \,days and \,days,
respectively. We find that the vs. relation
of these five glitches is similar to those with no detected delayed spin-up
process, indicating that they are similar to the others in nature except that
they have larger amplitudes. For these five glitches, the amplitudes of the
delayed spin-up process () and recovery process
(), their time scales (, ), and
permanent changes in spin frequency () and total frequency
step () have positive correlations. From these
correlations, we suggest that the delayed spin-up processes are common for all
glitches, but are too short and thus difficult to be detected for most
glitches.Comment: 25 pages, 8 figure
Measurement of proton electromagnetic form factors in in the energy region 2.00-3.08 GeV
The process of is studied at 22 center-of-mass
energy points () from 2.00 to 3.08 GeV, exploiting 688.5~pb of
data collected with the BESIII detector operating at the BEPCII collider. The
Born cross section~() of is
measured with the energy-scan technique and it is found to be consistent with
previously published data, but with much improved accuracy. In addition, the
electromagnetic form-factor ratio () and the value of the
effective (), electric () and magnetic () form
factors are measured by studying the helicity angle of the proton at 16
center-of-mass energy points. and are determined with
high accuracy, providing uncertainties comparable to data in the space-like
region, and is measured for the first time. We reach unprecedented
accuracy, and precision results in the time-like region provide information to
improve our understanding of the proton inner structure and to test theoretical
models which depend on non-perturbative Quantum Chromodynamics
New measurement of via neutron capture on hydrogen at Daya Bay
This article reports an improved independent measurement of neutrino mixing
angle at the Daya Bay Reactor Neutrino Experiment. Electron
antineutrinos were identified by inverse -decays with the emitted
neutron captured by hydrogen, yielding a data-set with principally distinct
uncertainties from that with neutrons captured by gadolinium. With the final
two of eight antineutrino detectors installed, this study used 621 days of data
including the previously reported 217-day data set with six detectors. The
dominant statistical uncertainty was reduced by 49%. Intensive studies of the
cosmogenic muon-induced Li and fast neutron backgrounds and the
neutron-capture energy selection efficiency, resulted in a reduction of the
systematic uncertainty by 26%. The deficit in the detected number of
antineutrinos at the far detectors relative to the expected number based on the
near detectors yielded in the
three-neutrino-oscillation framework. The combination of this result with the
gadolinium-capture result is also reported.Comment: 26 pages, 23 figure
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