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C-C chemokine receptor 2 (CCR2) is a key driver of monocyte/macrophage trafficking to sites of inflammation and has long been considered a target for intervention in autoimmune disease. However, systemic administration of CCR2 antagonists is associated with marked increases in CCL2, a CCR2 ligand, in the blood. This heretofore unexplained phenomenon complicates interpretation of in vivo responses to CCR2 antagonism. We report that CCL2 elevation after pharmacological CCR2 blockade is due to interruption in a balance between CCL2 secretion by a variety of cells and its uptake by constitutive internalization and recycling of CCR2. We observed this phenomenon in response to structurally diverse CCR2 antagonists in wild-type mice, and also found substantially higher CCL2 plasma levels in mice lacking the CCR2 gene. Our findings suggest that CCL2 is cleared from blood in a CCR2-dependent but G protein (Gαi, Gαs or Gαq/11)--independent manner. This constitutive internalization is rapid: on a given monocyte, the entire cell surface CCR2 population is turned over in <30 minutes. We also found that constitutive receptor internalization/recycling and ligand uptake are not universal across monocyte-expressed chemokine receptors. For example, CXCR4 does not internalize constitutively. In summary, we describe a mechanism that explains the numerous preclinical and clinical reports of increased CCL2 plasma levels following in vivo administration of CCR2 antagonists. These findings suggest that constitutive CCL2 secretion by monocytes and other cell types is counteracted by constant uptake and internalization by CCR2-expressing cells. The effectiveness of CCR2 antagonists in disease settings may be dependent upon this critical equilibrium. [ABSTRACT FROM AUTHOR]

Palladium-catalyzed allylic C−H silylation was performed with use of hexamethyldisilane as the silyl source. These C−H functionalization reactions occur only in the presence of hypervalent iodine reagents or other strong oxidants and proceed with excellent regioselectivity, providing the linear allylic isomer of the allylsilane products. In demonstrating the first oxidative allylic C−H silylation of alkenes, this study marks an important advance for the catalytic C−H functionalization method. [ABSTRACT FROM AUTHOR]

The semi-arid Loess Plateau is a central zone of Chinese rain-fed farming. Drought and soil erosion are the two major obstacles to restrict economic development in this semi-arid Loess Plateau. The traditional conservation agriculture and runoff agriculture have been developed for several decades, which have reduced water and soil loss and improved rainwater utilization efficiency to a certain extent. However, its regulative role in rainwater is very much limited, and problems of agriculture production, such as severe seasonal drought and water shortage, low agriculture productivity, fragile ecological environment, and low yield-invest ratio, are still going on. Supplemental irrigation of harvested rainwater is an important form of rainfall regulation and utilization on the basis of sophisticated technologies and theories of conservation agriculture and runoff agriculture, which not only promotes fulfilling rainfall harvesting in spatial location like the conservation agriculture and runoff agriculture measure but also gets at true rainfall harvesting in time distribution by principle of superposition and also decreases invalid evaporation for rainfall runoff. Agriculture productivity will be highly increased by using rainwater harvesting for supplemental irrigation. It not only brings about the integration of ecological reconstruction with economic development, but also provides a new approach to the agriculture sustainable development and overcomes two of the biggest obstacles (drought and soil erosion). It is suggested that this technology will become a strategic measure and comprehensive development model in semi-arid Loess Plateau of China. [ABSTRACT FROM AUTHOR]

ABSTRACTObjective:Baseline clinical and health-related quality of life (HRQoL) data from a phase 2, multi-site, international, randomized, controlled trial were analyzed to: (1) characterize the health status of patients with relapsing-remitting multiple sclerosis (RRMS), (2) explore cross-sectional relationships between HRQoL and clinical measures, and (3) evaluate differences in HRQoL scores for subsequent validation as minimally important differences (MID). Clinical Trial Registration: www.clinicaltrials.gov, NCT00207727.Research design and methods:Baseline clinical and HRQoL data were selected and analyzed. HRQoL questionnaires included the Short Form-36 (SF-36), Fatigue Severity Scale (FSS), a Patient Assessment of multiple sclerosis (MS) Impact (PAMSI), and MS-specific symptom scales for Bladder and Bowel Control, Cognition, and Sexual Satisfaction. Standard summary statistics described the population while Pearson and Spearman correlations evaluated the baseline association between HRQoL and clinical measures. Cross-sectional estimates of MID in HRQoL scores were derived using several clinical anchors, the PAMSI, and two tests: Tukey multiple comparisons and adjacent mean difference.Results: Patients (n  249) had a mean age of 39.0 (Standard deviation, SD  10.5), 70 were female, 63 resided in Europe, and 96 were Caucasian. Baseline median Expanded Disability Severity Scale (EDSS) was 2.5 (range  0.0–6.5); median disease duration was 1.9 years (range  0.1–33.6). The worst baseline mean (normalized) SF-36 scores were for General Health (39.9), Role Physical (40.4), Physical Functioning (41.0), and Vitality (42.7). The worst MS symptom mean scores were for Cognition (6.3) and FSS (4.4). Fatigue scores indicated substantial burden and were consistent with SF-36 Vitality results. Baseline HRQoL scores (SF-36, FSS, MS symptom scales) correlated most with EDSS, Multiple Sclerosis Functional Composite (MSFC), age and disease duration. Lesion count and pre-baseline relapse rate had no meaningful association with HRQoL or other clinical measures. The MID for several HRQoL measures are proposed for confirmation in longitudinal patient datasets.Conclusion: Clinical and HRQoL assessments documented health impairments in physical functioning, fatigue, and cognition among these RRMS patients with relatively short disease duration. HRQoL data varied with clinical measures and contributed new information regarding disease burden. The association between clinical and HRQoL measures was limited to cross-sectional analysis and requires confirmation in longitudinal datasets. These findings reflect an ambulatory, early-stage RRMS population that was mostly European in location or descent. The PAMSI also requires further validation as a measure of patient health status. [ABSTRACT FROM AUTHOR]

We report here a low-temperature, solution-processed high-k dielectric, which can be used effectively to achieve high-performance, low-voltage organic field-effect transistors (OFETs). A CuPc device based on the solution-processed dielectric possessed a mobility of 0.15 cm² V-1 s-1 under a voltage of only -2V, which is more than one order of magnitude higher than that obtained on traditional 300 nm SiO2 under -40V. Detailed studies by atomic force microscopy and grazing incidence x- ray diffraction reveal that the high performance can be attributed to the crystallized interconnected rod-like structure of CuPc molecules in the initial growth on ATO. Pentacene and rubrene single crystal FETs on the solution-processed dielectric also exhibit higher performance than those on 300 nm SiO2. Our findings suggest that the low-temperature, solution-processed high-k dielectric can be a plausible choice for fabrication of high-performance low-voltage OFETS, and also provide some clues in designing effective high-k dielectrics. [ABSTRACT FROM AUTHOR]

Tibetans form a population which has resided on the Qinghai–Tibetan plateau for thousands of years, and are reported to have less hemoglobin than Han Chinese lowlanders who have migrated to the plateau. However, for various altitudes, detailed comparisons of hemoglobin in the two ethnic groups has not been reported. We investigated the hypothesis that the effects of altitude, age, and gender on hemoglobin concentration would differ between Han and Tibetan residents of the plateau. Hematological parameters for both genders were determined in healthy Tibetan adults ( n=3,000) and children ( n=332), and healthy Han Chinese adults ( n=2,612) and children ( n=275), aged 5–60 years living at four different altitudes (mean altitude of 2,664, 3,813, 4,525, and 5,200 m). Hemoglobin values increased with altitude for all ages in both ethnic groups and in both genders. The gain in hemoglobin with altitude had the rank order: Han males > Han females > Tibetan males and females. Even before puberty, Han children had more hemoglobin than Tibetan children. An effect of age on hemoglobin was seen at the time of puberty in men, but not in women. A positive correlation was found between hemoglobin concentration and age in adult Han males and females, but not in Tibetan males, and only at the higher altitudes, in Tibetan females. In both Tibetans and Hans, males had higher hemoglobin values than females at each altitude, but the gender differences increased with altitude in Han, whereas it either decreased or did not change in Tibetans. Examination of hemoglobin levels by histogram showed non-Gaussian distributions: Tibetan men and women had skewing to higher values, whereas Han men and women had skewing in the opposite direction. We conclude that increasing age and the effect of gender in Tibetans are associated with different hemoglobin responses to altitude than in Han, and we speculate that genetic influences may be involved. [ABSTRACT FROM AUTHOR]

Particle-in-cell (PIC) simulations are used to study the nonlinear process of stimulated Raman scattering (SRS) excited by a rotated polarized laser interacting with underdense plasmas. The influence of the rotating frequency on linear SRS growth rate is theoretically analyzed and the long-term nonlinear SRS behavior excited by the rotated polarized pump is illustrated by the PIC simulations. Our results show that the evolution of reflectivity, plasma wave and electron energy distribution in the nonlinear stage is quite different from that in the linear stage, which is principally caused by the mitigation of electron trapping. Furthermore, our fluid theory and simulations have demonstrated that opposite to the suppression of Raman backscattering, Raman forward scattering becomes stronger with increasing rotating frequency. The above nonlinear effects are valid in the regime of and a plasma length of hundreds of microns for the key role of the kinetic effect. [ABSTRACT FROM AUTHOR]

Dedicated experiments focusing on the influence of lower hybrid waves (LHWs) on edge-localized modes (ELMs) were first performed during the 2012 experimental campaign of EAST, via modulating the input power of LHWs in the high-confinement-mode (H-mode) plasma mainly sustained by ion cyclotron resonant heating. Natural ELMs are effectively mitigated (ELM frequency increases, while its intensity decreases dramatically) as the LHW is applied, observed over a fairly wide range of plasma current or edge safety factor. By scanning the modulation frequency (fm) of LHW injected power in a target plasma dominated by the so-called small ELMs, we conclude that large ELMs with markedly larger amplitudes and lower frequencies are reproduced at low modulation frequencies (fm < 100 Hz). Analysis of the evolution of edge extreme ultraviolet radiation signals further indicates that plasma fluctuations at the pedestal region indistinctively respond to rapid modulation (fm ⩾ 100 Hz) of LHW injected power. This is proposed as the mechanism responsible for the observed fm dependence of the mitigation effect induced by LHWs on large ELMs. In addition, a critical threshold of LHW input power PLHW is estimated as , beyond which the impact of applied LHWs on ELM behaviours can be achieved. Finally, Langmuir probe measurements suggest that, rather than the concentration of free energy into a narrowband quasi-coherent precursor commonly observed growing until the ELM crash, the continuous development of broadband turbulence during the ELM-absent phase with the application of LHWs might contribute to the avoidance of ELM crashes. These results present new insights into existing experiments, and also provide some foundations and references for the next-step research about exploring in more depth and improving this new attractive method to effectively control the ELM-induced very large transient heat and particle flux. [ABSTRACT FROM AUTHOR]

Two enhanced-recycling H-mode regimes, named low-enhanced-recycling (LER) and high-enhanced-recycling (HER) H-mode regimes, with edge coherent modes, have been achieved by lower hybrid current drive and ion cyclotron resonance heating with lithium-wall conditioning in the EAST superconducting tokamak. In the LER H-mode regime, the density and radiation increase during the ELM-free phase until the onset of edge-localized modes (ELMs), while in the HER H-mode regime, the density and radiation are well controlled without the presence of ELMs. Both LER and HER H-modes exhibit a low-frequency (frequency <100 kHz) edge quasi-coherent mode (ECM) with an initial frequency chirping down phase, following the L–H transition. In addition, an electromagnetic high-frequency coherent mode (HFM) with frequency >170 kHz appears shortly (<1 ms) after the transition during HER H-modes. Both ECM and HFM propagate in the electron diamagnetic drift direction in the lab frame with a low poloidal wavelength and may be responsible for enhanced recycling during the ELM-free phase. These two enhanced-recycling H-mode regimes may have significant implications for long-pulse high-performance operations in future fusion experiments. [ABSTRACT FROM AUTHOR]

Bipolar resistive-switching memories were demonstrated based on a Ag/ZnS/ITO stack structure, where the electrolyte layer is made into a double-layer structure composed of a Ag-nanoclusters-embedded ZnS layer and a pure ZnS layer. The introduction of Ag-nanoclusters results in thicker Ag conducting filaments (CFs) formed in ZnS–Ag than in ZnS. This difference in CFs’ size between two sub-layers makes the resistive switching localized in the ZnS sub-layer. By reducing its thickness, the switching region is reduced and the degree of localization is enhanced. Therefore, compared with the single-layer ZnS memory, the double-layer device shows improved switching uniformity, reduced forming/switching voltages and better endurance. [ABSTRACT FROM AUTHOR]

The turbulence and flows at the plasma edge during the L–I–H, L–I–L and single-step L–H transitions have been measured directly using two reciprocating Langmuir probe systems at the outer midplane with several newly designed probe arrays in the EAST superconducting tokamak. The E × B velocity, turbulence level and turbulent Reynolds stress at ∼1 cm inside the separatrix ramp-up in the last ∼20 ms preceding the single-step L–H transition, but remain nearly constant near the separatrix, indicating an increase in the radial gradients at the plasma edge. The kinetic energy transfer rate from the edge turbulence to the E × B flows is significantly enhanced only in the last ∼10 ms and peaks just prior to the L–H transition. The E × B velocity measured inside the separatrix, which is typically in the electron diamagnetic drift direction in the L-mode, decays towards the ion diamagnetic drift direction in response to fluctuation suppression at the onset of the single-step L–H, L–I–L as well as L–I–H transitions. One important distinction between the L–I–H and the L–I–L transitions has been observed, with respect to the evolution of the edge pressure gradient and mean E × B flow during the I-phase. Both of them ramp up gradually during the L–I–H transition, but change little during the L–I–L transition, which may indicate that a gradual buildup of the edge pedestal and mean E × B flow during the I-phase leads to the final transition into the H-mode. In addition, the transition data in EAST strongly suggest that the divertor pumping capability is an important ingredient in determining the transition behaviour and power threshold. [ABSTRACT FROM AUTHOR]