Elastic Wave Diffraction at Cracks in Anisotropic Materials

Ultrasonic inspection is used to confirm that there are no defects of concern in various regions of a nuclear reactor primary circuit. All materials are naturally anisotropic, but if the grains are small relative to the ultrasonic wavelength and are also randomly oriented, then the material will appear as homogeneous and isotropic as in ferritic steel. The ultrasonic wavelength is chosen as a compromise between resolution of defect size and acoustic noise from grain boundaries. In austenitic steel, the wavelength chosen will typically be smaller than the grain size, at least in one direction. The grains are not randomly oriented but exhibit macroscopic patterns which depend on the welding process, and the material is neither homogeneous nor isotropic

Crystal Structure of the PIM2 Kinase in Complex with an Organoruthenium Inhibitor

BACKGROUND: The serine/threonine kinase PIM2 is highly expressed in human leukemia and lymphomas and has been shown to positively regulate survival and proliferation of tumor cells. Its diverse ATP site makes PIM2 a promising target for the development of anticancer agents. To date our knowledge of catalytic domain structures of the PIM kinase family is limited to PIM1 which has been extensively studied and which shares about 50% sequence identity with PIM2. PRINCIPAL FINDINGS: Here we determined the crystal structure of PIM2 in complex with an organoruthenium complex (inhibition in sub-nanomolar level). Due to its extraordinary shape complementarity this stable organometallic compound is a highly potent inhibitor of PIM kinases. SIGNIFICANCE: The structure of PIM2 revealed several differences to PIM1 which may be explored further to generate isoform selective inhibitors. It has also demonstrated how an organometallic inhibitor can be adapted to the binding site of protein kinases to generate highly potent inhibitors. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

A Computational Approach to Finding Novel Targets for Existing Drugs

Repositioning existing drugs for new therapeutic uses is an efficient approach to drug discovery. We have developed a computational drug repositioning pipeline to perform large-scale molecular docking of small molecule drugs against protein drug targets, in order to map the drug-target interaction space and find novel interactions. Our method emphasizes removing false positive interaction predictions using criteria from known interaction docking, consensus scoring, and specificity. In all, our database contains 252 human protein drug targets that we classify as reliable-for-docking as well as 4621 approved and experimental small molecule drugs from DrugBank. These were cross-docked, then filtered through stringent scoring criteria to select top drug-target interactions. In particular, we used MAPK14 and the kinase inhibitor BIM-8 as examples where our stringent thresholds enriched the predicted drug-target interactions with known interactions up to 20 times compared to standard score thresholds. We validated nilotinib as a potent MAPK14 inhibitor in vitro (IC50 40 nM), suggesting a potential use for this drug in treating inflammatory diseases. The published literature indicated experimental evidence for 31 of the top predicted interactions, highlighting the promising nature of our approach. Novel interactions discovered may lead to the drug being repositioned as a therapeutic treatment for its off-target's associated disease, added insight into the drug's mechanism of action, and added insight into the drug's side effects

Measurements of absolute hadronic branching fractions of Λc+\Lambda_{c}^{+} baryon

Using $567\rm{pb}^{-1}$ of $e^+e^-$ collisions recorded at $\sqrt{s}=4.599\rm{GeV}$ with the BESIII detector, we report first measurements of absolute hadronic branching fractions of Cabibbo-favored decays of the $\Lambda_{c}^{+}$ baryon with a double-tag technique. A global least-square fitter is utilized to improve the measured precision. Among the measurements for twelve $\Lambda_{c}^{+}$ decay modes, the branching fraction for $\Lambda_{c}^{+} \rightarrow pK^-\pi^+$ is determined to be $(5.84\pm0.27\pm0.23)\%$, where the first uncertainty is statistical and the second is systematic. In addition, the measurements of the branching fractions of the other eleven Cabbibo-favored hadronic decay modes are significantly improved

Observation of e+e−→ωχc1,2e^+e^- \rightarrow \omega \chi_{c1,2} near s\sqrt{s} = 4.42 and 4.6 GeV

Based on data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies $\sqrt{s} >$ 4.4 GeV, the processes $e^+e^- \rightarrow \omega \chi_{c1,2}$ are observed for the first time. With an integrated luminosity of $1074 pb^{-1}$ near $\sqrt{s} =$ 4.42 GeV, a significant $\omega \chi_{c2}$ signal is found, and the cross section is measured to be (20.9 \pm 3.2 \pm 2.5)\pb. With $567 pb^{-1}$ near $\sqrt{s} =$ 4.6 GeV, a clear $\omega \chi_{c1}$ signal is seen, and the cross section is measured to be (9.5 \pm 2.1 \pm 1.3) \pb, while evidence is found for an $\omega \chi_{c2}$ signal. The first errors are statistical and the second are systematic. Due to low luminosity or low cross section at other energies, no significant signals are observed. In the $\omega \chi_{c2}$ cross section, an enhancement is seen around $\sqrt{s} =$ 4.42 GeV. Fitting the cross section with a coherent sum of the $\psi(4415)$ Breit-Wigner function and a phase space term, the branching fraction $\mathcal{B}(\psi(4415)\to\omega\chi_{c2})$ is obtained to be of the order of $10^{-3}$.Comment: 7 pages, 3 figure

Improved measurement of the absolute branching fraction of D+→Kˉ0μ+νμD^{+}\rightarrow \bar K^0 \mu^{+}\nu_{\mu}

By analyzing 2.93 fb$^{-1}$ of data collected at $\sqrt s=3.773$ GeV with the BESIII detector, we measure the absolute branching fraction ${\mathcal B}(D^{+}\rightarrow\bar K^0\mu^{+}\nu_{\mu})=(8.72 \pm 0.07_{\rm stat.} \pm 0.18_{\rm sys.})\%$, which is consistent with previous measurements within uncertainties but with significantly improved precision. Combining the Particle Data Group values of ${\mathcal B}(D^0\to K^-\mu^+\nu_\mu)$, ${\mathcal B}(D^{+}\rightarrow\bar K^0 e^{+}\nu_{e})$, and the lifetimes of the $D^0$ and $D^+$ mesons with the value of ${\mathcal B}(D^{+}\rightarrow\bar K^0 \mu^{+}\nu_{\mu})$ measured in this work, we determine the following ratios of partial widths: $\Gamma(D^0\to K^-\mu^+\nu_\mu)/\Gamma(D^{+}\rightarrow\bar K^0\mu^{+}\nu_{\mu})=0.963\pm0.044$ and $\Gamma(D^{+}\rightarrow\bar K^0 \mu^{+}\nu_{\mu})/\Gamma(D^{+}\rightarrow\bar K^0 e^{+}\nu_{e})=0.988\pm0.033$.Comment: 9 pages; 8 figure

Determination of the number of J/ψJ/\psi events with inclusive J/ψJ/\psi decays

A measurement of the number of $J/\psi$ events collected with the BESIII detector in 2009 and 2012 is performed using inclusive decays of the $J/\psi$ . The number of $J/\psi$ events taken in 2009 is recalculated to be $(223.7\pm1.4)\times 10^6$, which is in good agreement with the previous measurement, but with significantly improved precision due to improvements in the BESIII software. The number of $J/\psi$ events taken in 2012 is determined to be $(1086.9\pm 6.0)\times 10^6$. In total, the number of $J/\psi$ events collected with the BESIII detector is measured to be $(1310.6\pm 7.0)\times 10^6$, where the uncertainty is dominated by systematic effects and the statistical uncertainty is negligible.Comment: 10 pages, 6 figure

Observation of hch_{c} radiative decay hc→γη′h_{c} \rightarrow \gamma \eta' and evidence for hc→γηh_{c} \rightarrow \gamma \eta

A search for radiative decays of the $P$-wave spin singlet charmonium resonance $h_c$ is performed based on $4.48 \times 10^{8}$ $\psi'$ events collected with the BESIII detector operating at the BEPCII storage ring. Events of the reaction channels $h_{c} \rightarrow \gamma \eta'$ and $\gamma \eta$ are observed with a statistical significance of $8.4 \sigma$ and $4.0 \sigma$, respectively, for the first time. The branching fractions of $h_{c} \rightarrow \gamma \eta'$ and $h_{c} \rightarrow \gamma \eta$ are measured to be $\mathcal{B}(h_{c} \rightarrow \gamma \eta')=(1.52 \pm 0.27 \pm 0.29)\times10^{-3}$ and $\mathcal{B}(h_{c} \rightarrow \gamma \eta)=(4.7 \pm 1.5 \pm 1.4)\times10^{-4}$, respectively, where the first errors are statistical and the second are systematic uncertainties.Comment: 7 pages, 2 figure