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The toluene solvate crystal of the titled highly congested aromatic ketone-ester compound has been subjected to crystal structural analysis from the viewpoints of the clarification of distribution feature of effective non-classical hydrogen bonds and the retention and perturbation of the symmetric nature. The two independent molecules of the title naphthalene derivative, which bears two aroyl groups at the adjacent inner positions and two benzoyloxy groups at the neighboring β-positions, and one disordered solvent toluene molecule are incorporated in the asymmetric unit of P21/c (Z′= 2). In the packing of the solvate crystal, the solvent toluene molecule plays the multi roles of hydrogen donor/acceptor for C–H…π non-classical hydrogen bonds and hydrogen donor for C–H…O = C ones. On the other hand, the role of other benzene rings of the parts of the title compound molecules is confined. The 4-methylbenzoyl groups situated at the molecular inner positions mainly play the role of the hydrogen donor of C–H…π non-classical hydrogen bond. The benzoyloxy groups that extend outward from the molecular body mainly act as the hydrogen acceptors of C–H…O and C–H…π non-classical hydrogen bonds. The naphthalene ring moderately contributes as the hydrogen acceptor for C–H…π non-classical hydrogen bonds and as the hydrogen donor for C–H…O non-classical hydrogen bonds. The roles of the toluene molecule are not limited to a simple filler for the void among the major constituent molecules but proved to position at the pseudo-centrosymmetric center of the counter-configurated pair of molecules of the independent major component compounds to concentrate the effective non-classical hydrogen bonds.

Background:Opioid and benzodiazepine use and abuse is a national healthcare crisis to which patients with cancer are particularly vulnerable. Long-term use and risk factors for opioid and benzodiazepine use in patients with breast cancer is poorly characterized.Methods:We conducted a retrospective population-based study of patients with breast cancer diagnosed between 2008 and 2015 undergoing curative-intent treatment identified through the SEER-Medicare linked database. Primary outcomes were new persistent opioid use and new persistent benzodiazepine use. Factors associated with new opioid and benzodiazepine use were investigated by univariate and multivariable logistic regression.Results:Among opioid-naïve patients, new opioid use was observed in 22,418 (67.4%). Of this group, 611 (2.7%) developed persistent opioid use at 3 months and 157 (0.7%) at 6 months after treatment. Risk factors for persistent use at 3 and 6 months included stage III disease (odds ratio [OR], 2.16; 95% CI, 1.49–3.12, and OR, 3.48; 95% CI, 1.58–7.67), surgery plus chemotherapy (OR, 1.44; 95% CI, 1.10–1.88, and OR, 2.28; 95% CI, 1.40–3.71), surgery plus chemoradiation therapy (OR, 1.47; 95% CI, 1.10–1.96, and OR, 2.34; 95% CI, 1.38–3.96), and initial tramadol use (OR, 2.66; 95% CI, 2.05–3.46, and OR, 3.12; 95% CI, 1.93–5.04). Among benzodiazepine-naïve patients, new benzodiazepine use was observed in 955 (10.3%), and 111 (11.6%) developed new persistent use at 3 months. Tamoxifen use was statistically significantly associated with new persistent benzodiazepine use at 3 months.Conclusions:A large percentage of patients receiving curative-intent treatment of breast cancer were prescribed new opioids; however, only a small number developed new persistent opioid use. In contrast, a smaller proportion of patients received a new benzodiazepine prescription; however, new persistent use after completion of treatment was more likely and particularly related to concurrent treatment with tamoxifen.

Molecular drivers are increasingly identified as therapeutic targets for non-small cell lung cancer (NSCLC). This review focuses on the role of ROS1 inhibitors in treating relapsed/metastatic ROS-1 altered (ROS1+) NSCLC. Four FDA-approved drugs have significant activity against ROS1+ NSCLC: crizotinib, ciritinib, lorlatinib, and entrectinib. Each drug yields an overall response rates exceeding 60% with ciritinib, lorlatinib, and entrectinib possessing intracranial activity. The drugs have manageable toxicity profiles. ROS1 alterations are rare molecular drivers of NSCLC that can be effectively treated with a variety of ROS1-targetd drugs. New agents are being identified that may treat resistance mutations.

Molecular drivers are increasingly identified as therapeutic targets for non-small cell lung cancer (NSCLC). This review focuses on the role of ROS1 inhibitors in treating relapsed/metastatic ROS-1 altered (ROS1+) NSCLC.Four FDA-approved drugs have significant activity against ROS1+ NSCLC: crizotinib, ciritinib, lorlatinib, and entrectinib. Each drug yields an overall response rates exceeding 60% with ciritinib, lorlatinib, and entrectinib possessing intracranial activity. The drugs have manageable toxicity profiles. ROS1 alterations are rare molecular drivers of NSCLC that can be effectively treated with a variety of ROS1-targetd drugs. New agents are being identified that may treat resistance mutations.

A tritium imaging plate technique (TIPT) in combination with an electron-probe microscopic analysis (EPMA) were applied to examine tritium (T) retention characteristics in individual dust particles collected in the Joint European Torus with the ITER-like Wall (JET-ILW) after the first campaign in 2011–2012.A lot of carbon (C)-dominated dust particles were found, which would be pre-existing carbon deposits in the JET-C or released carbon particles from the remaining carbon-fiber components in the JET-ILW. Most of T was retained at the surface of and/or in the C-dominated dust particles. The retention in tungsten, beryllium and other metal-dominated dust particles is relatively lower by a factor of 10–100 in comparison with that in the C-dominated particles.

The optimized superconducting stellarator device Wendelstein 7-X (with major radius , minor radius , and plasma volume) restarted operation after the assembly of a graphite heat shield and 10 inertially cooled island divertor modules. This paper reports on the results from the first high-performance plasma operation. Glow discharge conditioning and ECRH conditioning discharges in helium turned out to be important for density and edge radiation control. Plasma densities of with central electron temperatures were routinely achieved with hydrogen gas fueling, frequently terminated by a radiative collapse. In a first stage, plasma densities up to were reached with hydrogen pellet injection and helium gas fueling. Here, the ions are indirectly heated, and at a central density of a temperature of with was transiently accomplished, which corresponds to with a peak diamagnetic energy of and volume-averaged normalized plasma pressure . The routine access to high plasma densities was opened with boronization of the first wall. After boronization, the oxygen impurity content was reduced by a factor of 10, the carbon impurity content by a factor of 5. The reduced (edge) plasma radiation level gives routinely access to higher densities without radiation collapse, e.g. well above line integrated density and central temperatures at moderate ECRH power. Both X2 and O2 mode ECRH schemes were successfully applied. Core turbulence was measured with a phase contrast imaging diagnostic and suppression of turbulence during pellet injection was observed.

Summary Deep learning has the potential to estimate velocity models directly from shot gathers, which would reduce the turn-around time of seismic inversion. Our study addresses two challenges in implementing deep learning techniques for seismic inversion: the practical generation of a large amount of training data and the search for the best neural network architecture. First, we propose a flexible system which parametrically generates velocity models to create a large-scale, complex and fully synthetic training dataset, without using a target subsurface model. Using this system, we created 300,000 synthetic velocity models for our experiments. Second, we employ neural architecture search techniques to design a suitable neural network using Optuna, an automatic hyperparameter optimisation framework. We incorporated the residual network into an encoder–decoder model and optimised its architecture. Thus, we obtained an optimal neural network model consisting of more than 100 hidden layers. We evaluated our model using the Marmousi2 model and the 1994 Amoco statics test dataset. The model demonstrated comprehensible estimations of the benchmark velocity models.

Density control is crucial for maintaining stable confined plasma. Divertor pumping, where neutral particles are compressed and exhausted in the divertor region, was developed for this task for the Large Helical Device. In this study, neutral particle pressure, which is related to recycling, was systematically scanned in the magnetic configuration by changing the magnetic axis position. High neutral particle pressure and compression were obtained in the divertor for a high plasma electron density and the inner magnetic axis configuration. Density control using divertor pumping with gas puffing was applied to electron cyclotron heated plasma in the inner magnetic axis configuration, which provides high neutral particle compression and exhaust in the divertor. Stable plasma density and electron temperature were maintained with divertor pumping. A heat analysis shows that divertor pumping did not affect edge electron heat conductivity, but it led to low electron heat conductivity in the core caused by electron-internal-transport-barrier-like formation.

In this text, the Japanese composer highlights the elements that guide his research around the sound. In particular, he focuses on the acoustic implications of “resonance”, the principle through which he operates on the matter of sound. Besides, he takes into consideration the works developed with the artist Shiro Takatani, with whom he has created hybrid works between installation and theatre.

In order to acquire 3D information for reconstruction of vanished historical structure, grasp of 3D shape of such structure was attempted by using an ancient picture. Generally, 3D information of a structure is acquired by photogrammetric theory which requires two or more pictures. This paper clarifies that the geometrical information of the structure was obtained only from an ancient picture, and 3D information was acquired. This kind of method was applied for an ancient picture of the Old Imperial Theatre. The Old Imperial Theatre in the picture is constituted by two-point perspective. Therefore, estimated value of focal length of camera, length of camera to the Old Imperial Theatre and some parameters were calculated by estimation of field angle, using body height as an index of length and some geometrical information. Consequently, 3D coordinate of 120 measurement points on the surface of the Old Imperial Theatre were calculated respectively, and 3DCG modeling of the Old Imperial Theatre was realized.

Summary What is known and objective In Japan, although topiroxostat, a selective xanthine oxidoreductase inhibitor, has been used for the treatment of patients with hyperuricemia including gout, no published randomized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported. The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout. Methods We conducted an exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study in Japanese hyperuricemic patients with or without gout. The study arms were placebo and topiroxostat 40, 60, 80 or 120 mg/day. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit. Results and discussion One hundred and eighty-seven eligible patients were randomized and 186 received at least one dose of the study drug. The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day (P < 0·001, Jonckheere–Terpstra test). The mean per cent change in serum urate level from baseline at the final visit was −30·8% in the 120-mg group and 1·6% with placebo, with a between-group difference of −32·4% ([95% confidence interval, −38·9% to −25·9%]; P < 0·001). Incidences of overall adverse events (AEs) in the topiroxostat groups were comparable to those in the placebo group; however, the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group. The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups. What is new and conclusions A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout. Further clinical studies aimed at evaluating the long-term safety and clinical efficacy are warranted.

We have been developing a conduction cooled 3T HTS(REBCO)-MRI system. The prototype system of 100 mm DSV (diameter spherical volume) was designed and made.The MRI image of a mouse fetus (25 mm long) was obtained successfully with 2.9 T under a power supply driven operation. However, the HTS(ReBCO)-MRI magnet still had a considerable magnetic field fluctuation for clear MRI imaging due to a long-lasting attenuation of screening current induced on the superconducting tapes. To solve this problem, we introduced a power supply system consists of a exciter power supply and a small trimming current supply, which compensates the magnetic field deviation due to the screening current, in parallel. We measured and evaluated the magnetic field stability of a commercial 3T-LTS-MRI magnet under both the power supply driven operation with proposed system and the persistent current operation. The availability of the power supply system was discussed using an experimental HTS-MRI system.

A new temperature controlled material probe was designed for the exposure of W samples to He plasma in the LHD (Large Helical Device). TEM (Transmission Electron Microscopy) analysis allowed the study of the impact of He irradiation under high temperatures (up to 600 °C) on W microstructure: bubbles and dislocation loops are formed at the surface. A heavily damaged layer rich in both damages is formed at the very surface layer whose thickness increases with the incident fluence; beyond this layer, bubbles are observed much deeper than expected, rising concerns about the consequences for the material properties conservation. Nano-indentation measurements showed that the hardness of exposed tungsten indeed increases as the dislocation loops are formed and large bubbles appear in the material.

Petroleum in the Surma basin, NE Bangladesh (part of the Bengal Basin) ranges from waxy crude oils to condensates. The origin and source rocks of these hydrocarbons were investigated based on the distributions of saturated and aromatic hydrocarbons in 20 oil samples from seven oil and gas fields. The relative compositions of pristane, phytane and adjacent n-alkanes suggest that the source rock was deposited in a non-marine setting. The abundance and similar distribution of biphenyls, cadalene and bicadinanes in most of the crude oils and condensates indicates a significant supply of higher-plant derived organic matter to the source rocks. Maturity levels of the crude oils and condensates from the Surma basin correspond to calculated vitrinite reflectance (Rc) values of 1.0–1.3%, indicating hydrocarbon expulsion from the source rock at a comparatively high maturity level. The Rc values of oils from the Titas field in the southern margin of the Surma basin are relatively low (0.8–1.0%). Some oils were severely biodegraded. The similar distribution of diamondoid hydrocarbons in both biodegraded and non-biodegraded oils indicated similar types of source rocks and similar maturity levels to those of oils from the Surma basin. The Oligocene Jenam Shale and/or underlying non-marine deposits located at greater depths may be potential source rocks. The diversity of the petroleum in the Surma basin was likely due to evaporative fractionation, resulting in residual waxy oils and lighter condensates which subsequently underwent tertiary migration and re-accumulation. Evaporative fractionation due to modification of the reservoir structure occurred during and after the Pliocene, when large-scale tectonic deformation occurred in and around the Bengal Basin.

Summary What is known and objective There are no clinical reports that have compared topiroxostat, a selective xanthine oxidase inhibitor, with allopurinol in serum urate-lowering efficacy. The aim of this study was to compare the efficacy and safety of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout. Methods A phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study conducted in Japan. Patients who had inadequate serum urate levels (a gout patient: serum urate level ≥416·4 μmol/L; an asymptomatic hyperuricemic patient with specific complications (urinary lithiasis, hypertension, hyperlipidemia and/or diabetes): serum urate level ≥475·8 μmol/L; and an asymptomatic hyperuricemic patient with no specific complications: serum urate level ≥535·3 μmol/L) were randomized to topiroxostat 120 mg/day or allopurinol 200 mg/day, with an equal allocation ratio, for 16 weeks. To prevent the onset of gouty arthritis by rapid serum urate reduction, these doses were increased in a stepwise manner. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit. Results and discussion Overall, 206 patients were randomly assigned to topiroxostat and allopurinol. Two hundred and three patients (allopurinol: n = 105, topiroxostat: n = 98) received at least one dose of the study drug and had their serum urate level assessed at least once. The baseline characteristics were comparable between groups. The mean age of patients was 53·0 ± 11·4 years and 99% of patients were male. The primary efficacy endpoint was −34·3 ± 11·1% in the allopurinol group (n = 105) and −36·3 ± 12·7% in the topiroxostat group (n = 98). Non-inferiority of the serum urate-lowering efficacy of topiroxostat to allopurinol was proved by the predefined non-inferiority margin (95% confidence interval, −5·3 to 1·3%). The overall incidences of adverse events and adverse drug reactions were similar between both groups. What is new and conclusion Topiroxostat 120 mg/day provides non-inferior serum urate reduction compared with allopurinol 200 mg/day and is well tolerated in Japanese hyperuricemic patients with or without gout.

A core density collapse (CDC) phenomenon is a rapid collapse events observed in super dense core (SDC) plasma with internal diffusion barrier (IDB) in the Large Helical Device (LHD). By CDC, the central beta is decreased by up to 50%. The collapse starts from the edge region of the plasma. CDCs appear with plasma parameters where the high–n ballooning modes are unstable at ϱ ∼ 0.8. With less collisional conditions, m = 1 type oscillations are observed with similar beta profile. The origin of the m = 1 oscillations is not clarified (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Edge cooling experiments with a tracer-encapsulated solid pellet in the large helical device (LHD) show a significant rise in core electron temperature (the maximum rise is around 1 keV) as well as in many tokamaks. This experimental result indicates the possible presence of the nonlocality of electron heat transport in plasmas where turbulence as a cause of anomalous transport dominates. The nonlocal electron temperature rise in the LHD takes place in almost the same parametric domain (e.g. in a low density) as in the tokamaks. Meanwhile, the experimental results of LHD show some new aspects of nonlocal electron temperature rise, for example the delay in the nonlocal rise of core electron temperature relative to the pellet penetration time increases with the increase both in the collisionality in the core plasma and the electron temperature gradient scale length in the outer region of the plasma.

To investigate the relationship of dental status to food diversity among older Japanese.A community-based cross-sectional study conducted in the town of Tosa, Kochi Prefecture, Japan.The study participants were 252 Japanese (84 men and 168 women, average age 81.2 years) and dentate participants were classified into three groups: 1-9 teeth, 10-19 teeth and 20 or more teeth. Food diversity was assessed as a validated measure of dietary quality using the 11-item Food Diversity Score Kyoto (FDSK-11), which evaluates frequency of consumption of 11 main food groups. Multivariable analysis of the differences in FDSK-11 score ranging from 0 to 11, with a higher score indicating greater food diversity, among the three dental status groups was conducted using general linear models. All the performed analyses were stratified by gender.There was no association between dental status and food diversity score in models for men. In contrast, women with ≤ 9 teeth and with 10-19 teeth had significantly lower FDSK-11 scores than women with ≥ 20 teeth after adjusting for confounders (p0.001 and p = 0.009, respectively). Additionally, there was a trend toward lower scores for FDSK-11 with fewer teeth (p = 0.001).A less varied diet, as indicated by low FDSK-11 score, was observed in female participants with fewer teeth. Tooth loss was associated with poor diet quality among older Japanese women.

A repetitive pellet injector has been developed and pellet refuelling experiments have been launched on the Large Helical Device (LHD) in a new regime characterized by high density steady state operation. In order to suppress the disturbance to the core plasma as much as possible, we employ relatively small and slow pellets. The size and velocity of the pellets are typically 2.5?mm in diameter and 250?m?s?1, respectively. The pellets were injected into neutral beam heated plasmas with repetition frequency of 10?Hz. The density rise per pellet is 1.5 ? 1019?m?3 and the pellet penetration depth, which is normalized by the plasma minor radius, is typically less than 0.5. Quasi-steady-state operation was achieved at plasma parameters of , Te = Ti = 1.0?keV. Repetitive pellet fuelling showed improved energy confinement compared with massive gas puff fuelling in the high density regime in common with previous transient pellet injection experiments, and it can sustain such an improved confinement property.

Steady state divertor operation with high performance plasmas (ne ~ 0.7 × 1019 cm−3, Ti ~ 2 keV) was demonstrated for half an hour in the Large Helical Device (LHD), the superconducting helical device (R = 3.6–3.9 m, a = 0.6 m, B = 3 T, l/m = 2/10). The high performance plasmas have been sustained with an averaged heating power of 680 kW and achieved an injected energy of 1.3 GJ. This required both advanced technological integration of heating systems and divertor heat flux control. In particular, optimization of divertor heat flux distribution along the divertor leg trace on divertor plates and real-time magnetic axis sweeping (R = 3.67–3.7 m) have allowed LHD to access a steady state regime with a margin of safety for the actively cooled divertor plates. The distribution of divertor heat load along the traces was investigated with calorimetric measurements and it was found that there was a localized heat load connected with the loss of high-energy ions produced by ion cyclotron radio frequency near-fields. Orbit analysis shows that the behaviour of high-energy ions is qualitatively in good agreement with the experimental result. Long-pulse discharges were terminated by radiation collapse due to penetration of metallic flakes into the plasma.

Magnetic configurations of LHD are characterized by the presence of chaotic magnetic field, the so-called ergodic layer, surrounding the core plasma. H-mode-like discharges have been obtained at an outwardly shifted configuration of Rax = 4.00 m with a thick ergodic layer, where the ι/2π = 1 position is located in the middle of the ergodic layer. A clear density rise and a reduction of magnetic fluctuation were observed. ELM-like Hα bursts also appeared with a radial propagation of density bursts. These H-mode-like discharges can be triggered by changing PNBI(

Self-sustained detachment has been obtained in the Large Helical Device (LHD). Strong hydrogen gas puffing of ~200 Pa m3 s−1 after a density feedback phase detaches the plasma from the divertor plates with high reproducibility. High electron density of over 1 × 1020 m−3 is sustained without gas puffing until the heating beam stops and a high-density flat top for 2 s has been demonstrated. Throughout the self-sustained detachment phase, the minor radius of the hot plasma column shrinks to ~90% of the last-closed-flux-surface, which corresponds to the rational surface. This new state has been named the 'Serpens mode', for self-regulated plasma edge 'neath the last-closed-flux-surface. Global energy confinement of the Serpens mode is compared with the international stellarator scaling 1995 (ISS95) and the recently established scaling for high-density LHD plasmas (HD scaling), where shrinking confinement volume and shallow penetration of the heating beams are taken into account. Although the energy confinement of the Serpens mode seems deteriorated compared with ISS95, as in the case of high-density attached plasmas, it is consistent with the HD scaling. This suggests that the energy confinement properties of detached plasmas in LHD are similar to those in high-density attached plasmas.

In the Large Helical Device (LHD), two different divertor configurations, i.e. helical divertor (HD) and local island divertor (LID), are utilized to control the edge plasma. The HD with two X-points is an intrinsic divertor for heliotron devices, accompanied with a relatively thick ergodic layer outside the confinement region. Edge and divertor plasma behavior from low density to high density regimes is presented, referring to the divertor detachment. The effect of the ergodic layer on the edge transport is also discussed. On the other hand, the LID is an advanced divertor concept which realizes a high pumping efficiency by the combination of an externally induced magnetic island and a closed pumping system. Experimental results to confirm the fundamental divertor performance of the LID are presented.