The paper presents the results of observations of the sporadic Es layer during the period of meteorological disturbances in Kaliningrad in October 2017 and 2018 under quiet geomagnetic conditions. ...During the meteorological storms (October 29–30, 2017 and October 23–24, 2018), significant changes occurred in the dynamics of the Es-layer critical frequency. Observations of atmospheric and ionospheric disturbances in the Kaliningrad region show that the delay between the ionospheric response and the moment of maximum disturbances in atmospheric parameters is about 3 hours. These phenomena at the heights of the E-region might have been caused by propagation of acoustic-gravity waves generated by convective processes in the lower atmosphere during periods of a meteorological storm. Intensification of turbulent processes in the lower thermosphere leads to an increase in the atmospheric density and, accordingly, to higher recombination rates. This leads to a rapid decrease in the concentration of ions and, consequently, to a decrease in the critical frequency of the sporadic layer below the sensitivity threshold of ionosondes.
We derive an analytic expression for the composition of a ternary solid material nucleating from a quaternary liquid melt. The calculations are based on the two-component nucleation theory with ...realistic descriptions of the liquid and solid phases. We apply this theory to gold-catalyzed, nucleation limited vapor–liquid–solid growth of ternary III–V nanowires. We consider ternary gallium, indium, and aluminum arsenides and antimonides and discuss growth conditions for optimum composition control in these materials. Furthermore, we compare our calculations with the results of an equilibrium thermodynamic model.
In and Sn are the type of catalysts which do not introduce deep level electrical defects within the bandgap of Ge. However, Ge nanowires produced using these catalysts usually have a large diameter, ...a tapered morphology, and mixed crystalline and amorphous phases. In this study, we show that plasma-assisted vapor-liquid-solid (PA-VLS) method can be used to synthesize Ge nanowires. Moreover, at certain parameter domains, the sidewall deposition issues of this synthesis method can be avoided and long, thin tapering-free monocrystalline Ge nanowires can be obtained with In and Sn catalysts. We find two quite different parameter domains where Ge nanowire growth can occur via PA-VLS using In and Sn catalysts: i) a low temperature-low pressure domain, below ~ 235 °C at a GeH4 partial pressure of ~ 6 mTorr, where supersaturation in the catalyst occurs thanks to the low solubility of Ge in the catalysts, and ii) a high temperature-high pressure domain, at ~400 °C and a GeH4 partial pressure above ~ 20 mTorr, where supersaturation occurs thanks to the high GeH4 concentration. While growth at 235 °C results in tapered short wires, operating at 400 °C enables cylindrical nanowire growth. With the increase of growth temperature, the crystalline structure of the nanowires changes from multi-crystalline to mono-crystalline and their growth rate increases from ~0.3 nm/s to 5 nm/s. The cylindrical Ge nanowires grown at 400°C usually have a length of few microns and a radius of around 10 nm, which is well below the Bohr exciton radius in bulk Ge (24.3 nm). To explain the growth mechanism, a detailed growth model based on the key chemical reactions is provided.
Six new carotane sesquiterpenoids piltunines A-F (
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) together with known compounds (
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) were isolated from the marine-derived fungus
KMM 4668. Their structures were established using spectroscopic ...methods. The absolute configurations of
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were determined based on circular dichroism (CD) and nuclear Overhauser spectroscopy (NOESY) data as well as biogenetic considerations. The cytotoxic activity of some of the isolated compounds and their effects on regulation of reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages were examined.
A new model for the radial growth of self-catalyzed III-V nanowires on different substrates is presented, which describes the nanowire morphological evolution without any free parameters. The model ...takes into account the re-emission of group III atoms from a mask surface and the shadowing effect in directional deposition techniques such as molecular beam epitaxy. It is shown that radial growth is faster for larger pitches of regular nanowire arrays or lower surface density, and can be suppressed by increasing the V/III flux ratio or decreasing re-emission. The model describes quite well the data on the morphological evolution of Ga-catalyzed GaP and GaAs nanowires on different substrates, where the nanowire length increases linearly and the radius enlarges sub-linearly with time. The obtained analytical expressions and numerical data should be useful for morphological control over different III-V nanowires in a wide range of growth conditions.
Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches ...to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.
Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab ...would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer.
In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine–carboplatin), PD-L1 expression at baseline (combined positive score CPS ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Eligibility criteria included age at least 18 years, centrally confirmed triple-negative breast cancer; at least one measurable lesion; provision of a newly obtained tumour sample for determination of triple-negative breast cancer status and PD-L1 status by immunohistochemistry at a central laboratory; an Eastern Cooperative Oncology Group performance status score 0 or 1; and adequate organ function. The sponsor, investigators, other study site staff (except for the unmasked pharmacist), and patients were masked to pembrolizumab versus saline placebo administration. In addition, the sponsor, the investigators, other study site staff, and patients were masked to patient-level tumour PD-L1 biomarker results. Dual primary efficacy endpoints were progression-free survival and overall survival assessed in the PD-L1 CPS of 10 or more, CPS of 1 or more, and intention-to-treat populations. The definitive assessment of progression-free survival was done at this interim analysis; follow-up to assess overall survival is continuing. For progression-free survival, a hierarchical testing strategy was used, such that testing was done first in patients with CPS of 10 or more (prespecified statistical criterion was α=0·00411 at this interim analysis), then in patients with CPS of 1 or more (α=0·00111 at this interim analysis, with partial alpha from progression-free survival in patients with CPS of 10 or more passed over), and finally in the intention-to-treat population (α=0·00111 at this interim analysis). This study is registered with ClinicalTrials.gov, NCT02819518, and is ongoing.
Between Jan 9, 2017, and June 12, 2018, of 1372 patients screened, 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab–chemotherapy group and 281 patients in the placebo–chemotherapy group. At the second interim analysis (data cutoff, Dec 11, 2019), median follow-up was 25·9 months (IQR 22·8–29·9) in the pembrolizumab–chemotherapy group and 26·3 months (22·7–29·7) in the placebo–chemotherapy group. Among patients with CPS of 10 or more, median progression-free survival was 9·7 months with pembrolizumab–chemotherapy and 5·6 months with placebo–chemotherapy (hazard ratio HR for progression or death, 0·65, 95% CI 0·49–0·86; one-sided p=0·0012 primary objective met). Median progression-free survival was 7·6 and 5·6 months (HR, 0·74, 0·61–0·90; one-sided p=0·0014 not significant) among patients with CPS of 1 or more and 7·5 and 5·6 months (HR, 0·82, 0·69–0·97 not tested) among the intention-to-treat population. The pembrolizumab treatment effect increased with PD-L1 enrichment. Grade 3–5 treatment-related adverse event rates were 68% in the pembrolizumab–chemotherapy group and 67% in the placebo–chemotherapy group, including death in <1% in the pembrolizumab–chemotherapy group and 0% in the placebo–chemotherapy group.
Pembrolizumab–chemotherapy showed a significant and clinically meaningful improvement in progression-free survival versus placebo–chemotherapy among patients with metastatic triple-negative breast cancer with CPS of 10 or more. These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic triple-negative breast cancer.
Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
GaN nanowires grown on metal substrates have attracted increasing interest for a wide range of applications. Herein, we report GaN nanowires grown by plasma-assisted molecular beam epitaxy on thin ...polycrystalline ZrN buffer layers, sputtered onto Si(111) substrates. The nanowire orientation was studied by X-ray diffraction and scanning electron microscopy, and then described within a model as a function of the Ga beam angle, nanowire tilt angle, and substrate rotation. We show that vertically aligned nanowires grow faster than inclined nanowires, which leads to an interesting effect of geometrical selection of the nanowire orientation in the directional molecular beam epitaxy technique. After a given growth time, this effect depends on the nanowire surface density. At low density, the nanowires continue to grow with random orientations as nucleated. At high density, the effect of preferential growth induced by the unidirectional supply of the material in MBE starts to dominate. Faster growing nanowires with smaller tilt angles shadow more inclined nanowires that grow slower. This helps to obtain more regular ensembles of vertically oriented GaN nanowires despite their random position induced by the metallic grains at nucleation. The obtained dense ensembles of vertically aligned GaN nanowires on ZrN/Si(111) surfaces are highly relevant for device applications. Importantly, our results are not specific for GaN nanowires on ZrN buffers, and should be relevant for any nanowires that are epitaxially linked to the randomly oriented surface grains in the directional molecular beam epitaxy.