Artesunate potentiates antibiotics by inactivating heme-harbouring bacterial nitric oxide synthase and catalase

<p>Abstract</p> <p>Background</p> <p>A current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics. It is urgent to work out a practical solution to combat the multidrug resistant bacterial pathogens.</p> <p>Findings</p> <p>Oxidative stress-acclimatized bacteria thrive in rifampicin by generating antibiotic-detoxifying nitric oxide (NO), which can be repressed by artesunate or an inhibitor of nitric oxide synthase (NOS). Suppressed bacterial proliferation correlates with mitigated NO production upon the combined treatment of bacteria by artesunate with antibiotics. Detection of the heme-artesunate conjugate and accordingly declined activities of heme-harbouring bacterial NOS and catalase indicates that artesunate renders bacteria susceptible to antibiotics by alkylating the prosthetic heme group of hemo-enzymes.</p> <p>Conclusions</p> <p>By compromising NO-mediated protection from antibiotics and triggering harmful hydrogen peroxide burst, artesunate may serve as a promising antibiotic synergist for killing the multidrug resistant pathogenic bacteria.</p

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

A New Look at the Scalar Meson f0(500)f_0(500) via D+→π+π−ℓ+νℓD^+\to \pi^+\pi^-\ell^+\nu_\ell Decays

Using $2.93~\mathrm{fb}^{-1}$ of $e^+e^-$ collision data collected with the BESIII detector at the center-of-mass energy of 3.773 GeV, we investigate the semileptonic decays $D^+\to \pi^+\pi^- \ell^+\nu_\ell$ ($\ell=e$ and $\mu$). The $D^+\to f_0(500)\mu^+\nu_\mu$ decay is observed for the first time. By analyzing simultaneously the differential decay rates of $D^+\to f_0(500) \mu^+\nu_\mu$ and $D^+\to f_0(500) e^+\nu_e$ in different $\ell^+\nu_\ell$ four-momentum transfer intervals, the product of the relevant hadronic form factor $f^{f_0}_{+}(0)$ and the magnitude of the $c\to d$ Cabibbo-Kobayashi-Maskawa matrix element $|V_{cd}|$ is determined to be $f_{+}^{f_0} (0)|V_{cd}|=0.0787\pm0.0060_{\rm stat}\pm0.0033_{\rm syst}$ for the first time. With the input of $|V_{cd}|$ from the global fit in the standard model, we determine $f_{+}^{f_0} (0)=0.350\pm0.027_{\rm stat}\pm0.015_{\rm syst}$. The absolute branching fractions of $D^+\to f_0(500)_{(\pi^+\pi^-)}\mu^+\nu_\mu$ and $D^+\to \rho^0_{(\pi^+\pi^-)} \mu^+\nu_\mu$ are determined as $(0.72\pm0.13_{\rm stat}\pm0.10_{\rm syst})\times10^{-3}$ and $(1.64\pm0.13_{\rm stat}\pm0.11_{\rm syst})\times 10^{-3}$. Combining these results with those of previous BESIII measurements on their semielectronic counterparts from the same data sample, we test lepton flavor universality by measuring the branching fraction ratios ${\mathcal B}_{D^+\to \rho^0 \mu^+\nu_\mu}/{\mathcal B}_{D^+\to \rho^0 e^+\nu_e}=0.88\pm0.10$ and ${\mathcal B}_{D^+\to f_0(500) \mu^+\nu_\mu}/{\mathcal B}_{D^+\to f_0(500) e^+\nu_e}=1.14\pm0.28$, which are compatible with the standard model expectation.Comment: Supplemental Materials added in this versio

First observation of the decay Λc+→nKS0π+π0\Lambda^+_c\to nK^{0}_{S}\pi^+\pi^0

Based on 4.5 fb$^{-1}$ of $e^{+}e^{-}$ collision data accumulated at center-of-mass energies between $4599.53$ MeV and $4698.82$ MeV with the BESIII detector, the decay $\Lambda_{c}^{+}\to nK_{S}^{0}\pi^+\pi^0$ is observed for the first time with a significance of $9.2\sigma$. The branching fraction is measured to be $(0.85\pm0.13\pm0.03)\%$, where the first uncertainty is statistical and the second systematic, which differs from the theoretical prediction based on isospin by 4.4$\sigma$. This indicates that there may be resonant contributions or some unknown dynamics in this decay

Improved measurements of the Dalitz decays η/η′→γe+e−\eta/\eta'\rightarrow\gamma e^{+}e^{-}

Based on a data sample of 10 billion $J/\psi$ events collected with the BESIII detector, improved measurements of the Dalitz decays $\eta/\eta'\rightarrow\gamma e^+e^-$ are performed, where the $\eta$ and $\eta'$ are produced through the radiative decays $J/\psi\rightarrow\gamma \eta/\eta'$. The branching fractions of $\eta\rightarrow\gamma e^+e^-$ and $\eta'\rightarrow\gamma e^+e^-$ are measured to be $(7.07 \pm 0.05 \pm 0.23)\times10^{-3}$ and $(4.83\pm0.07\pm0.14)\times10^{-4}$, respectively. Within the single pole model, the parameter of electromagnetic transition form factor for $\eta\rightarrow\gamma e^+e^-$ is determined to be $\Lambda_{\eta}=(0.749 \pm 0.027 \pm 0.007)~ {\rm GeV}/c^{2}$. Within the multi-pole model, we extract the electromagnetic transition form factors for $\eta'\rightarrow\gamma e^+e^-$ to be $\Lambda_{\eta'} = (0.802 \pm 0.007\pm 0.008)~ {\rm GeV}/c^{2}$ and $\gamma_{\eta'} = (0.113\pm0.010\pm0.002)~ {\rm GeV}/c^{2}$. The results are consistent with both theoretical predictions and previous measurements. The characteristic sizes of the interaction regions for the $\eta$ and $\eta'$ are calculated to be $(0.645 \pm 0.023 \pm 0.007 )~ {\rm fm}$ and $(0.596 \pm 0.005 \pm 0.006)~ {\rm fm}$, respectively. In addition, we search for the dark photon in $\eta/\eta^\prime\rightarrow\gamma e^{+}e^{-}$, and the upper limits of the branching fractions as a function of the dark photon are given at 90\% confidence level