Comparison of Analysis and Spectral Nudging Techniques for Dynamical Downscaling with the WRF Model over China

To overcome the problem that the horizontal resolution of global climate models may be too low to resolve features which are important at the regional or local scales, dynamical downscaling has been extensively used. However, dynamical downscaling results generally drift away from large-scale driving fields. The nudging technique can be used to balance the performance of dynamical downscaling at large and small scales, but the performances of the two nudging techniques (analysis nudging and spectral nudging) are debated. Moreover, dynamical downscaling is now performed at the convection-permitting scale to reduce the parameterization uncertainty and obtain the finer resolution. To compare the performances of the two nudging techniques in this study, three sensitivity experiments (with no nudging, analysis nudging, and spectral nudging) covering a period of two months with a grid spacing of 6 km over continental China are conducted to downscale the 1-degree National Centers for Environmental Prediction (NCEP) dataset with the Weather Research and Forecasting (WRF) model. Compared with observations, the results show that both of the nudging experiments decrease the bias of conventional meteorological elements near the surface and at different heights during the process of dynamical downscaling. However, spectral nudging outperforms analysis nudging for predicting precipitation, and analysis nudging outperforms spectral nudging for the simulation of air humidity and wind speed

Origin of two types of rhyolites in the Tarim Large Igneous Province: Consequences of incubation and melting of a mantle plume

The Early Permian Tarim Large Igneous Province (LIP) in northwestern China contains a large area of silicic volcanics (similar to 48,000 km(2)) which are spatially and temporally associated with mafic-ultramafic rocks. In order to understand the behavior of crust above a mantle plume, selected rhyolitic samples are investigated in terms of U-Pb zircon dating, geochemical and isotopic analyses. The Tarim rhyolites have high A/CNK ratios (= molar Al2O3/CaO + Na2O + K2O), Fe#, Ga/Al ratios, concentrations of high field strength elements (HFSEs) such as Zr and Nb, and rare earth elements (REEs), along with high zircon saturation temperatures (872-940 degrees C), typical of aluminous A-type granitoids. Two contrasting rock types have been recognized. The low Nb-Ta type rhyolites are mainly associated with the first phase of the Tarim flood basalt magmatism at similar to 290 Ma. They are characterized by negative Nb-Ta anomalies, low epsilon(Nd)(t) and epsilon(Hf)(t) values, and high Sr-87/Sr-88(t) and delta(18) O-zircon values, consistent with a derivation from continental crustal source. The high Nb-Ta type rhyolites and their plutonic equivalents are associated with the second episode of Tarim magmatism (283-272 Ma). They are characterized by small negative to positive Nb-Ta anomalies, oceanic island basalt (0113)-like trace element ratios, low Sr-87/Sr-88(t) and high epsilon(Nd)(t) and epsilon(Hf)(t) values. These high Nb-Ta rhyolites are best interpreted as hybrid products of crystal fractionation of mafic magmas, coupled with crustal assimilation. The temporal and compositional evolution of the Tarim rhyolites reflects various extents of thermal and mass exchange between mantle-derived basaltic magma and crustal material above a mantle plume. When the plume head rises to the base of the Tarim craton, it first melts enriched components in the lithospheric mantle (similar to 290 Ma), part of which may have ponded near the crust-mantle boundary and induced crustal anatexis leading to the formation of the low Nb-Ta type rhyolites. At similar to 280 Ma, large magma chambers and plumbing systems were formed due to increasing magma supply rate during decompression melting of the mantle plume. This led to the formation of a mafic-ultramafic and felsic association of which the high Nb-Ta type rhyolites are a part. (C) 2014 Elsevier B.V. All right reservedGeochemistry & GeophysicsMineralogySCI(E)[email protected],SI59-7220

Engineering the Mechanics of Heterogeneous Soft Crystals

This work demonstrates how the geometric and topological characteristics of substructures within heterogeneous materials can be employed to tailor the mechanical responses of soft crystals under large strains. The large deformation mechanical behaviors of elastomeric composites possessing long-range crystalline order are examined using both experiments on 3D-printed prototype materials and precisely matched numerical simulations. The deformation mechanisms at small and large strains are elucidated for six sets of morphologies: dispersed particles on each of the simple cubic, body-centered cubic or face-centered cubic lattices, and their bi-continuous counterparts. Comparison of results for the six types of morphologies reveals that the topological connectivity of dissimilar domains is of critical importance for tailoring the macroscopic mechanical properties and the mechanical anisotropy

Leptospira santorosai serovar shermani detergent extract induces an increase in fibronectin production through a toll-like receptor 2-mediated pathway

Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-κB, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition

Upconversion Nanomaterials: Synthesis, Mechanism, and Applications in Sensing

Upconversion is an optical process that involves the conversion of lower-energy photons into higher-energy photons. It has been extensively studied since mid-1960s and widely applied in optical devices. Over the past decade, high-quality rare earth-doped upconversion nanoparticles have been successfully synthesized with the rapid development of nanotechnology and are becoming more prominent in biological sciences. The synthesis methods are usually phase-based processes, such as thermal decomposition, hydrothermal reaction, and ionic liquids-based synthesis. The main difference between upconversion nanoparticles and other nanomaterials is that they can emit visible light under near infrared irradiation. The near infrared irradiation leads to low autofluorescence, less scattering and absorption, and deep penetration in biological samples. In this review, the synthesis of upconversion nanoparticles and the mechanisms of upconversion process will be discussed, followed by their applications in different areas, especially in the biological field for biosensing

Paclitaxel Enhances the Innate Immunity by Promoting NLRP3 Inflammasome Activation in Macrophages

Microtubules play critical roles in regulating the activation of NLRP3 inflammasome and microtubule-destabilizing agents such as colchicine have been shown to suppress the activation of this inflammasome. However, it remains largely unknown whether paclitaxel, a microtubule-stabilizing agent being used in cancer therapy, has any influences on NLRP3 inflammasome activation. Here we showed that paclitaxel pre-treatment greatly enhanced ATP- or nigericin-induced NLRP3 inflammasome activation as indicated by increased release of cleaved caspase-1 and mature IL-1β, enhanced formation of ASC speck, and increased gasdermin D cleavage and pyroptosis. Paclitaxel time- and dose-dependently induced α-tubulin acetylation in LPS-primed murine and human macrophages and further increased ATP- or nigericin-induced α-tubulin acetylation. Such increased α-tubulin acetylation was significantly suppressed either by resveratrol or NAD+ (coenzyme required for deacetylase activity of SIRT2), or by genetic knockdown of MEC-17 (gene encoding α-tubulin acetyltransferase 1). Concurrently, the paclitaxel-mediated enhancement of NLRP3 inflammasome activation was significantly suppressed by resveratrol, NAD+, or MEC-17 knockdown, indicating the involvement of paclitaxel-induced α-tubulin acetylation in the augmentation of NLRP3 inflammasome activation. Similar to paclitaxel, epothilone B that is another microtubule-stabilizing agent also induced α-tubulin acetylation and increased NLRP3 inflammasome activation in macrophages in response to ATP treatment. Consistent with the in vitro results, intraperitoneal administration of paclitaxel significantly increased serum IL-1β levels, reduced bacterial burden, dampened infiltration of inflammatory cells in the liver, and improved animal survival in a mouse model of bacterial infection. Collectively, our data indicate that paclitaxel potentiated NLRP3 inflammasome activation by inducing α-tubulin acetylation and thereby conferred enhanced antibacterial innate responses, suggesting its potential application against pathogenic infections beyond its use as a chemotherapeutic agent

Maternal exposure to ambient air pollution and congenital heart defects in China

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China.Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤1 µm (PM1), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes.Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m3] increase in PM1 was associated with 1.09-fold ([95% confidence interval, 1.01-1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed.Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings

Polycatechol Nanoparticle MRI Contrast Agents

Amphiphilic triblock copolymers containing Fe III -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles ( SMN and CMN , respectively) are described as new T 1 -weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fl uids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic fi eld strengths. Interestingly, shape-dependent behavior is observed in terms of the particles\u2019 interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN . These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London