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Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1–3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4–7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation.Serial femtosecond crystallography reveals the structural dynamics of photosystem II during the S-state transitions that produce dioxygen, providing insight into electron transfer, water insertion, proton release and O–O bond formation on sub-microsecond timescales. [ABSTRACT FROM AUTHOR]

In this study, a real-time tsunami estimation method was developed using the linear superposition of Green's functions, which account for nonlinear tsunami effects around coastal areas. To this end, first, the nonlinear effects associated with the inundation and bottom friction and advection terms in a nonlinear long-wave model were investigated, focusing on large tsunamis around Urado Bay in Kochi Prefecture, Japan, which is at risk of future damage from tsunamis produced by the Nankai Trough earthquake. The results indicate that the effects of advection play a more significant role than those of the inundation and bottom friction in terms of accurately estimating near-shore tsunami propagation. Then, based on these results, Green's functions were modified to account for the linearly approximated effects of the advection terms. By applying the developed method to tsunamis around Urado Bay, it was demonstrated that accurate estimations of the water surface level and flow velocity changes could be quickly obtained at any location around the bay. The developed method can be applied to real-time tsunami inundation forecasting and off-shore evacuation simulations of vessels to support optimal evacuation decisions. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of a new oral rinse containing sodium hyaluronate and other functional ingredients in reducing xerostomia‐associated symptoms. Materials and Methods: In this 8‐week, double‐blind crossover study, xerostomia subjects used all three of GUM®HYDRAL™ Oral Rinse, placebo rinse, and Biotene® Oral Rinse as active control. Visual Analog Scale, a dry mouth questionnaire, Oral Health Impact Profile‐14, unstimulated saliva flow rate (USFR), and Revised Oral Assessment Guide (ROAG) were assessed before and after 2 weeks of treatments. Results: Thirty‐seven patients completed all three treatment modalities. Subjective measurements were significantly decreased by test product and active control; however, no significant difference was observed between the treatments. Test product and active control demonstrated a significant increase in USFR over 0.2 ml/min, a normal threshold of hyposalivation. Both test product and active control improved a total score of ROAG, whereas the effectiveness of the test product was significantly better than that of other two treatments. Conclusions: The new oral rinse may be beneficial to improve the quality of life of xerostomia patients as dry mouth symptoms were reduced for both subjective and objective measurements. Test oral rinse was found to be more effective than placebo or active control for some of the objective measurements. [ABSTRACT FROM AUTHOR]

Patients with uncommon EGFR-mutated non-small-cell lung cancer (NSCLC) demonstrated lower clinical efficacy of first-generation EGFR-tyrosine kinase inhibitors compared with patients harboring common EGFR-mutated NSCLC. The US FDA has approved afatinib for uncommon EGFR mutation positive NSCLC based on the pooled analysis in the first- or second-line setting. Osimertinib has limited evidence in the small sample sizes of phase 2 studies in any-line settings. The aim of the present single-arm, multicenter, phase 2 study is to evaluate the efficacy of osimertinib for previously untreated NSCLC. The primary end point is to assess the overall response to osimertinib. The secondary end points include disease control rate, progression-free survival, duration of time-to-treatment failure, overall survival and safety. Clinical trial registration: jRCTs071200002. [ABSTRACT FROM AUTHOR]

The development of a new atom-economical In[(OTf).sub.3]-catalyzed synthesis of ring-condensed heteroaromatic compounds via a domino intramolecular nucleophilic attack/intermolecular cycloaddition/dehydration reaction is reported. The synthesis used readily available ortho-alkynylanilines and ortho-alkynylbenzaldehydes as starting materials.

Background: Desmoplastic malignant pleural mesothelioma (DMM) is rare histological subtype of diffuse malignant pleural mesothelioma (MPM), accounting for 5-10 % of cases. It has a poor prognosis, with direct invasion of the chest wall or lungs and distant metastases. Its pathological characteristics include dense collagen fibers in a storiform pattern. Its pretreatment pathological diagnosis is difficult, with fibrous pleuritis and reactive mesothelial hyperplasia as potential differential diagnoses.Case Presentation: We retrospectively reviewed the medical charts of patients with MPM from 1996 to 2012. Among 60 patients with MPM, four patients with the desmoplastic subtype were identified and their clinical characteristics, including asbestos exposure, treatment, and prognosis, were reviewed. All of the patients with DMM were men, with a median age of 69 years (range: 63-74 years). All four patients had been exposed to asbestos. The definitive diagnosis was made histologically and the International Mesothelioma Interest Group classification was advanced (III/IV: 2/3) in all four patients. Three patients were treated with chemotherapy (two with cisplatin/pemetrexed and one with cisplatin/gemcitabine) and one patient underwent surgery. The median survival time in the patients with DMM was 3.8 months (range: 0.9-11.5 months), compared with 10.5 months in patients with other subtypes of MPM in our institution.Conclusions: DMM continues to have a poor prognosis. It is important to recognize this variant and distinguish it from pleural plaques, non-specific reactive pleural fibrosis, pleurisy, and other lung diseases. [ABSTRACT FROM AUTHOR]