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 ($\nu$) and its derivative ($\dot{\nu}$) 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 $<0.48$ 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 ($\tau_{1}$) of $1.7\pm0.8$\,days and $1.6\pm0.4$\,days, respectively. We find that the $\Delta{\nu}$ vs. $|\Delta{\dot\nu}|$ 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 ($|\Delta{\nu}_{\rm d1}|$) and recovery process ($\Delta{\nu}_{\rm d2}$), their time scales ($\tau_{1}$, $\tau_{2}$), and permanent changes in spin frequency ($\Delta{\nu}_{\rm p}$) and total frequency step ($\Delta{\nu}_{\rm g}$) 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 e+e−→ppˉe^+e^- \to p\bar{p} in the energy region 2.00-3.08 GeV

The process of $e^+e^- \rightarrow p\bar{p}$ is studied at 22 center-of-mass energy points ($\sqrt{s}$) from 2.00 to 3.08 GeV, exploiting 688.5~pb$^{-1}$ of data collected with the BESIII detector operating at the BEPCII collider. The Born cross section~($\sigma_{p\bar{p}}$) of $e^+e^- \rightarrow p\bar{p}$ 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 ($|G_{E}/G_{M}|$) and the value of the effective ($|G_{\rm{eff}}|$), electric ($|G_E|$) and magnetic ($|G_M|$) form factors are measured by studying the helicity angle of the proton at 16 center-of-mass energy points. $|G_{E}/G_{M}|$ and $|G_M|$ are determined with high accuracy, providing uncertainties comparable to data in the space-like region, and $|G_E|$ 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