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

The DArk Matter Particle Explorer mission

The DArk Matter Particle Explorer (DAMPE), one of the four scientific space science missions within the framework of the Strategic Pioneer Program on Space Science of the Chinese Academy of Sciences, is a general purpose high energy cosmic-ray and gamma-ray observatory, which was successfully launched on December 17th, 2015 from the Jiuquan Satellite Launch Center. The DAMPE scientific objectives include the study of galactic cosmic rays up to $\sim 10$ TeV and hundreds of TeV for electrons/gammas and nuclei respectively, and the search for dark matter signatures in their spectra. In this paper we illustrate the layout of the DAMPE instrument, and discuss the results of beam tests and calibrations performed on ground. Finally we present the expected performance in space and give an overview of the mission key scientific goals.Comment: 45 pages, including 29 figures and 6 tables. Published in Astropart. Phy

Direct detection of a break in the teraelectronvolt cosmic-ray spectrum of electrons and positrons

High energy cosmic ray electrons plus positrons (CREs), which lose energy quickly during their propagation, provide an ideal probe of Galactic high-energy processes and may enable the observation of phenomena such as dark-matter particle annihilation or decay. The CRE spectrum has been directly measured up to $\sim 2$ TeV in previous balloon- or space-borne experiments, and indirectly up to $\sim 5$ TeV by ground-based Cherenkov $\gamma$-ray telescope arrays. Evidence for a spectral break in the TeV energy range has been provided by indirect measurements of H.E.S.S., although the results were qualified by sizeable systematic uncertainties. Here we report a direct measurement of CREs in the energy range $25~{\rm GeV}-4.6~{\rm TeV}$ by the DArk Matter Particle Explorer (DAMPE) with unprecedentedly high energy resolution and low background. The majority of the spectrum can be properly fitted by a smoothly broken power-law model rather than a single power-law model. The direct detection of a spectral break at $E \sim0.9$ TeV confirms the evidence found by H.E.S.S., clarifies the behavior of the CRE spectrum at energies above 1 TeV and sheds light on the physical origin of the sub-TeV CREs.Comment: 18 pages, 6 figures, Nature in press, doi:10.1038/nature2447

Measurements of ψ(2S)\psi(2S) decays into Vector- Tensor final states

Decays of the $\psi(2S)$ into vector plus tensor meson final states have been studied with 14 million $\psi(2S)$ events collected with the BESII detector. Branching fractions of \psi(2S) \rt \omega f_{2}(1270), $\rho a_2(1320)$, $K^*(892)^0\bar{K}^*_2(1430)^0+c.c.$ and $\phi f_2^{\prime}(1525)$ are determined. They improve upon previous BESI results and confirm the violation of the "12%" rule for $\psi(2S)$ decays to VT channels with higher precision.Comment: 7 pages, 7 figures and 2 table

\psi(2S) Decays into \J plus Two Photons

Using \gamma \gamma J/\psi, J/\psi \ra e^+ e^- and $\mu^+ \mu^-$ events from a sample of $14.0\times 10^6$ \psip decays collected with the BESII detector, the branching fractions for \psip\ra \pi^0\J, \eta\J, and \psi(2S)\ar\gamma\chi_{c1},\gamma\chi_{c2}\ar\gamma\gamma\jpsi are measured to be B(\psip\ra \pi^0\J) = (1.43\pm0.14\pm0.13)\times 10^{-3}, B(\psip\ra \eta\J) = (2.98\pm0.09\pm0.23)%, B(\psi(2S)\ar\gamma\chi_{c1}\ar\gamma\gamma\jpsi) = (2.81\pm0.05\pm 0.23)%, and B(\psi(2S)\ar\gamma\chi_{c2}\ar\gamma\gamma\jpsi) = (1.62\pm0.04\pm 0.12)%.Comment: 7 pages, 6 figures. submitted to Phys. Rev.

Observation of a near-threshold enhancement in th p pbar mass spectrum from radiative J/psi-->gamma p pbar decays

We observe a narrow enhancement near 2mp in the invariant mass spectrum of ppbar pairs from radiative J/psi-->gamma ppbar decays. The enhancement can be fit with either an S- or P-wave Breit Wigner fuction. In the case of the S-wave fit, the peak mass is below the 2mp threshold and the full width is less than 30 MeV. These mass and width values are not consistent with the properties of any known meson resonance.Comment: 5 pages, 4 figures, submitted to Phys. Rev. Let

Temporal Structures in Positron Spectra and Charge-Sign Effects in Galactic Cosmic Rays

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4 ×106 positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5 σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5 σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere

Observation of χc1\chi_{c1} decays into vector meson pairs ϕϕ\phi\phi, ωω\omega\omega, and ωϕ\omega\phi

Decays of $\chi_{c1}$ to vector meson pairs $\phi\phi$, $\omega\omega$ and $\omega\phi$ are observed for the first time using $(106\pm4)\times 10^6$ \psip events accumulated at the BESIII detector at the BEPCII $e^+e^-$ collider. The branching fractions are measured to be $(4.4\pm 0.3\pm 0.5)\times 10^{-4}$, $(6.0\pm 0.3\pm 0.7)\times 10^{-4}$, and $(2.2\pm 0.6\pm 0.2)\times 10^{-5}$, for $\chi_{c1}\to \phi\phi$, $\omega\omega$, and $\omega\phi$, respectively. The observation of $\chi_{c1}$ decays into a pair of vector mesons $\phi\phi$, $\omega\omega$ and $\omega\phi$ indicates that the hadron helicity selection rule is significantly violated in $\chi_{cJ}$ decays. In addition, the measurement of $\chi_{cJ}\to \omega\phi$ gives the rate of doubly OZI-suppressed decay. Branching fractions for $\chi_{c0}$ and $\chi_{c2}$ decays into other vector meson pairs are also measured with improved precision.Comment: 4 pages, 2 figure