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A high-pressure pneumatic pilot-driven on/off valve (HPPV) that quickly switches an air inlet line on and off was designed to meet the requirements of a compressed air ejection device with high pressure, high flow rate, and continuous ejection. An HPPV multi-physics field simulation model was established using AMESim simulation software based on the bond graph modeling approach that considered mechanical, gas flow, pipe heat exchange, and pilot valve operation, and experiments were conducted to check the simulation model accuracy. The effects of real gas thermodynamics, pipeline heat exchange, and pilot valve operation on the simulation model accuracy and those of different initial parameter conditions on the dynamic characteristics of the HPPV were investigated in the validated simulation model. The results indicated that the tolerance between simulation and experiment was less than 7.3%, so the simulation model was realistic and reliable. In addition, among the different influencing factors, the pipeline heat transfer significantly affected the simulation model accuracy, and the tolerance between the simulation results without considering the pipeline heat exchange and the experimental results exceeded 10%. The real gas thermal effect slightly affected the simulation model accuracy, and the tolerance between the simulation results under the action of each gas state equation was less than 3%. The pilot valve operation affected only the opening and closing moments of the HPPV and had no effect on the simulation model accuracy. The dynamic characteristics of the HPPV were stable and reliable under different initial parameter conditions. [Display omitted] • The HPPV were designed and the performances of it was experimented to verify. • The simulation method in this paper can well predict the HPPV behaviors. • The factors affecting the modeling accuracy of HPPV were investigated. • The dynamic characteristics of the HPPV under different conditions are revealed. [ABSTRACT FROM AUTHOR]

The MutS2 homologues have been found widespread in most prokaryotes, which are involved in DNA repair and reactive oxygen species detoxification. The C-terminal small mutS-related (Smr) domain is critical for its endonucleolytic activity. However, the detailed catalytic mechanism is still unclear. In this study, we first investigated the in vivo role of drMutS2 in Deinococcus radiodurans, the most radiation-resistant organism exhibits the remarkable DNA repair capacity. mutS2 and recA mutS2 double knockout mutants were constructed because the phenotype was strongly masked by the predominant homologous recombination DNA repair pathway in this bacterium. Compared with the recA mutant, cells devoid of both genes showed increased sensitivity to ionizing radiation and oxidative agents, suggesting that drMutS2 is involved in RecA-independent mechanisms that enhance cellular resistance to oxidative stress-induced DNA damage. Moreover, the basal level of reductase activity and thiamine biosynthesis was induced in the absence of mutS2. To characterize its catalytic residues, the Smr domain was crystallized and soaked in buffer containing manganese ions. In contrast to native crystals, the space group of manganese-derivative crystals transformed from monoclinic to orthorhombic unexpectedly. This type of crystals showed improved diffraction resolution to 1.2 Å, which has the highest resolution of currently known Smr structures. Structural comparison revealed that three acidic amino-acid residues, which are all located in the α1 helix, changed the rotamer states after metal soaking. Mutational analysis of conserved residue glutamic acid 710 to alanine yielded a drMutS2 variant with impaired nuclease activity, and could only partially rescue the radiosensitive phenotype of the mutS2 null strain, indicating that glutamic acid 710 is the catalytic residue. [ABSTRACT FROM AUTHOR]

This paper extends the discontinuous deformation analysis (DDA) by using an additional evaluation of edge-to-edge contact, with the aim that it can be used to accurately model the failure behaviour of joints dominated by both cohesion and interface friction angle. The original DDA can deal well with the effects of interface friction angle. However, when cohesion exists, DDA results often show an inscrutable behaviour, i.e. a slope may be unstable even if the cohesion is much greater than the theoretical value required for its critical stability. After many detailed investigations and validations, joint contact treatment was found to be the key reason why the original DDA cannot simulate the cohesive material accurately, in which every edge-to-edge contact is treated as two vertex-to-edge contacts that may have different contact states associated with different cohesion treatments. In order to solve this problem, an additional contact type determination process for an edge-to-edge contact was added into the original computer code to avoid the unreasonable situation when two contact states exist in one joint. Several examples were performed to illustrate the accuracy of the modified code and a real landslide case was analysed by using the improved DDA to estimate the shear strength on the interface. Our results show that the improved DDA can simulate the failure of cohesive-frictional material accurately. [ABSTRACT FROM AUTHOR]

Chestnut rose (Rosa roxburghii Tratt) is a fruit crop that contains unusually high levels of L-ascorbic acid (AsA;∼ 1300 mg 100 g-1 FW). To explore the mechanisms underlying AsA metabolism, we investigated the distribution and abundance of AsA during fruit development. We also analyzed gene expression patterns, enzyme activities, and content of metabolites related to AsA biosynthesis and recycling. AsA first accumulated during late fruit development and continued to accumulate during ripening, with the highest accumulation rate near fruit maturity. The redox state of AsA in fruit was also enhanced during late fruit development, while leaf and other tissues had much lower levels of AsA and the redox state of AsA was lower. In mature fruit, AsA was mainly distributed in the cytoplasm of the mesocarp. Correlation analysis suggested that the gene expression patterns, enzyme activities, and related metabolite concentrations involved in the L-galactose pathway showed relatively high correlations with the accumulation rate of AsA. The gene expression pattern and activity of dehydroascorbate reductase (DHAR, EC 1.8.5.1) correlated strongly with AsA concentration, possibly indicating the crucial role of DHAR in the accumulation of high levels of AsA in chestnut rose fruit. Over expression of DHAR in Arabidopsis significantly increased the reduced AsA content and redox state. This was more effective than over expression of the L-galactose pathway gene GDP-D-mannose-3,5-epimerase (EC 5.1.3.18). These findings will enhance understanding of the molecular mechanisms regulating accumulation of AsA in chestnut rose. [ABSTRACT FROM AUTHOR]

Abstract: Soil–rock mixtures (S–RM) which formed in the quaternary period are a type of extremely inhomogeneous and loose geomaterial with a certain percentage of rock blocks. They are composed of rock blocks with various sizes and high strength, fine grained soil and pores. The meso-failure mechanism and macro-physical and mechanical characteristics of S–RM are largely controlled by its rock block proportion and the granular distribution. As we know, when the rock blocks in the S–RM are larger, it is difficult to take an in-situ sample for an on-site test. In addition, it is difficult to obtain the granular distribution of rock blocks in S–RM by traditional sieving tests. This paper uses a new method called digital image processing (DIP) in which the rock blocks in S–RM samples are separated from the soil matrix, and the proportion and distribution of the rock blocks is obtained quantitatively. The results are used for the sample preparation of the large scale direct shear tests which provide a new method for the test study of S–RM. According to the results of large scale direct shear tests the rock block size proportion controls the deformation and fracture mechanism of the S–RM. The shape of the shear stress vs horizontal displacement curve and the vertical displacement vs horizontal displacement curve of the S–RM samples are different from that of general “soil” and “rock”. With the increment of the rock block proportion the shear band of the S–RM increases. When the rock block proportion lies in the range of 25–70%, the increment of the internal friction angle linearly increases with the increment of the rock block proportion. The cohesion of the S–RM decreases compared with that of the soil. When the rock block proportion is larger than 30%, however, there is only a little decrease in the cohesion with the increment of the rock block proportion. [Copyright &y& Elsevier]

Abstract: There is no doubt that the functional oligosaccharides have positive effects on human health, both in the prevention and in treatment of chronic diseases. Therefore, there is great interest in health benefits of the functional oligosaccharides. The functional oligosaccharides of various origins (viruses, bacteria, plants and fungi) have been used extensively both as pharmacological supplements, food ingredients, in processed food to aid weight control, to regulation of glucose control for diabetic patients and reducing serum lipid levels in hyperlipidemics and other some acute and chronic diseases. Keeping in view, the pharmacological importance of the functional oligosaccharides and its derivatives, this article discusses the potential of the functional oligosaccharides to modulate the gut flora, to affect different gastrointestinal activities and lipid metabolism, to enhance immunity, and to reduce diabetes, obesity and cardiovascular risk for further exploitation of health benefits of the functional oligosaccharides. [Copyright &y& Elsevier]

Abstract: Two kinds of rare earth zirconate (Sm0.5La0.5)2Zr2O7 and (Sm0.5La0.5)2(Zr0.8Ce0.2)2O7 ceramics were prepared by solid state reaction at 1600°C for 10h. The phase compositions and microstructures, thermophysical properties of these materials were investigated. XRD results revealed that single phase (Sm0.5La0.5)2Zr2O7 and (Sm0.5La0.5)2(Zr0.8Ce0.2)2O7 with pyrochlore structure were synthesized. The SEM results showed that the microstructures of these materials were dense and no other phases existed among the particles. With the temperature increasing, the thermal expansion coefficient (TEC) of the ceramic increased, while the thermal conductivity decreased. The thermal expansion coefficients of (Sm0.5La0.5)2Zr2O7 and (Sm0.5La0.5)2(Zr0.8Ce0.2)2O7 are lower than that of Sm2Zr2O7, the addition of CeO2 resulted in a higher thermal expansion coefficient of (Sm0.5La0.5)2(Zr0.8Ce0.2)2O7 than that of 8YSZ and (Sm0.5La0.5)2Zr2O7. However, the thermal expansion coefficient of (Sm0.5La0.5)2Zr2O7 is lower than that of 8YSZ, it still fulfills the basic requirement of thermal barrier coatings. The thermal conductivities of (Sm0.5La0.5)2Zr2O7 and (Sm0.5La0.5)2(Zr0.8Ce0.2)2O7 are much lower than that of Sm2Zr2O7 because of the phonon scattering resulted by the doping of La2O3 or CeO2, and the thermal conductivity of (Sm0.5La0.5)2(Zr0.8Ce0.2)2O7 is lower than of (Sm0.5La0.5)2Zr2O7. These results imply that (Sm0.5La0.5)2Zr2O7 and (Sm0.5La0.5)2(Zr0.8Ce0.2)2O7 have potentials to be used as novel candidate materials for thermal barrier coatings in the future. [Copyright &y& Elsevier]

Abstract: Al-doped ZnO (ZnO:Al) thin films were grown on glass substrates by sol–gel method, which were characterized by X-ray diffraction, electrical measurements and ultra-violet photoluminescence spectrometry. It is found that all the thin films have a preferential c-axis orientation. With increase of Al doping, the peak position of the (002) plane is shifted to the low 2θ values. A minimum resistivity of 6.2×10−4 Ωcm is obtained for the film doped with 1.5mol% Al. The band gap is found to broaden with increasing dopant concentration. It is found from the PL measurement that near band edge (NBE) emission and deep-level (DL) emissions are observed in pure ZnO thin films. However, when Al was doped into thin films, the DL emissions of the thin films were depressed. As the concentration of Al increases, the peak of NBE emission has a blueshift to region of higher photon energy, which is coincident with those values calculated by the linear fit from the transmittance data. [Copyright &y& Elsevier]

Abstract: A rare earth zirconate (Dy2Zr2O7) ceramic for thermal barrier coatings (TBCs) was synthesized by solid state reaction at 1600 °C for 10 h. The phase composition, microstructure, thermophysical properties of the material were investigated. XRD results revealed that single phase Dy2Zr2O7 with fluorite structure was synthesized and the SEM showed that the microstructure of the product was dense and no other phases existed among the particles. With the temperature increasing, the thermal expansion coefficient (TEC) of the ceramic increased, while the thermal conductivity decreased. The thermophysical results indicated that TEC of the ceramic was slightly higher than that of conventional Y2O3-8wt.%ZrO2 (8YSZ) and the thermal conductivity of the ceramic was much lower than that of 8YSZ. The lower thermal conductivity of Dy2Zr2O7 was mainly attributed to more oxygen vacancies and larger atomic weight of substitutional atom. These results imply that Dy2Zr2O7 can be explored as the candidate material for the ceramic layer in TBCs system. [Copyright &y& Elsevier]

The RecQ helicases belong to an important family of highly conserved DNA helicases that play a key role in chromosomal maintenance, and their defects have been shown to lead to several disorders and cancer in humans. In this work, the conformational and functional properties of the Escherichia coli RecQ helicase have been determined using a wide array of biochemical and biophysical techniques. The results obtained clearly indicate that E. coli RecQ helicase is monomeric in solution up to a concentration of 20 µM and in a temperature range between 4 and 37 °C. Furthermore, these properties are not affected by the presence of ATP, which is strictly required for the unwinding and translocating activity of the protein, or by its nonhydrolyzable analogue 5'-adenylyl-β,γ-imidodiphosphate. Consistent with the structural properties, functional analysis shows that both DNA unwinding activity and singlestranded DNA-stimulated ATPase specific activity were independent of RecQ concentration. The monomeric state was further confirmed by the ATPase-deficient mutants of RecQ protein. The rate of unwinding was unchanged when the wild type RecQ helicase was mixed with the ATPase-deficient mutants, indicating that nonprotein-protein interactions were involved in the unwinding processes. Taken together, these results indicate that RecQ helicase functions as a monomer and provide new data on the structural and functional properties of RecQ helicase that may help elucidate its mechanism action. [ABSTRACT FROM AUTHOR]

Dense TiB/Ti composites were fabricated by Self-propagating High Temperature Synthesis connected with Pseudo Hot Isostatic Pressing (SHS/PHIP). Tads, Tc and combustion velocities of the TiB–xTi system decrease with increasing the amount of Ti. The synthesized TiB–Ti cermets mainly consisted of TiB and Ti phases, but TiB2 phase existed in some products with lower content of metal. Needle-like, rod-like or plate-like TiB grains formed in the microstructure of synthesized TiB–xTi composites. The size of the TiB grains decreased with an increasing amount of metal addition. The hardness and relative density of the synthesized materials are all beyond HRA82 and 94%, respectively. The introduction of Ti into TiB–xTi cermets resulted in a drastic increase in the bending strength, tensile strength, compression strength, fracture toughness and the maximum values were obtained with the addition of 40 wt.%Ti. [Copyright &y& Elsevier]

Sustainable TGF-β1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-β1 signaling remains unclear. In this study, we revealed that dietary folate restriction promoted the resolution of liver fibrosis in mice with nonalcoholic steatohepatitis. In activated hepatic stellate cells, folate shifted toward mitochondrial metabolism to sustain TGF-β1 signaling. Mechanistically, nontargeted metabolomics screening identified that a-linolenic acid (ALA) is exhausted by mitochondrial folate metabolism in activated hepatic stellate cells. Knocking down serine hydroxymethyltransferase 2 increases the bioconversion of ALA to docosahexaenoic acid, which inhibits TGF-β1 signaling. Finally, blocking mitochondrial folate metabolism promoted liver fibrosis resolution in nonalcoholic steatohepatitis mice. In conclusion, mitochondrial folate metabolism/ALA exhaustion/TGF-βR1 reproduction is a feedforward signaling to sustain profibrotic TGF-β1 signaling, and targeting mitochondrial folate metabolism is a promising strategy to enforce liver fibrosis resolution. [ABSTRACT FROM AUTHOR]

Pharmacological inhibition of the Nod-like receptor family protein 3 (NLRP3) inflammasome contributes to the treatment of numerous inflammation-related diseases, making it a desirable drug target. Spirodalesol, derived from the ascomycete fungus Daldinia eschscholzii, has been reported to inhibit NLRP3 inflammasome activation. Based on the structure of spirodalesol, we synthesized and screened a series of analogs to find a more potent inhibitor. Analog compound 8A was iden-tified as the most potent selective inhibitor for NLRP3 inflammasome assembly, but 8A did not inhibit the priming phase of the inflammasome. Specifically, while 8A did not reduce NLRP3 oligomerization, we found that it inhibited the oligomerization of adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), as ASC speck formation was significantly reduced. Also, 8A interrupted the assembly of the NLRP3 inflammasome complex and inhibited the activation of caspase-1. Subsequently, we used a cellular thermal shift assay and microscale thermophoresis assay to demonstrate that 8A interacts directly with ASC, both in vitro and ex vivo. Further, 8A alleviated lipopolysaccharide-induced endotoxemia, as well as monosodium urate-induced peritonitis and gouty arthritis in mice by suppressing NLRP3 inflammasome activation. Thus, 8A was identified as a promising ASC inhibitor to treat inflammasome-driven diseases. [ABSTRACT FROM AUTHOR]

Abstract: Large-area films of colloidal photonic crystals (PCs) were prepared by self-assembly technique. The films contain ordered PC domains separated by cracks. The size of the domains and cracks can be controlled by the drying process. The angular dependence of the stop-band was studied by changing the angle of incidence θ between the beam and the (111) direction, from 0° to 60°. The observed stop-bands are almost independent of the density of cracks. It is seen that as the angle increases the stop-band shifts to shorter wavelengths. We demonstrate that the photoluminescence emission spectra depend on the PC domain size and on the concentration of cracks. For a film with small density of cracks, we observed light channeling through cracks probably due to light inhibition. [Copyright &y& Elsevier]

Abstract: A field experiment on rain-fed spring wheat (Triticum aestivum) was conducted at the Haiyuan Experimental Station (36°34′N, 105°39′E), in a semiarid region of China, during 2001–2003. According to the experimental design, the CO2 concentration increased by 90μmolmol−1 (from 360 to 450μmolmol−1), while the mean daily temperature, during the whole growth stage, increased 0.8°C (from 14.3 to 15.1°C) and 1.8°C (from 14.3 to 16.1°C). The results showed that the combination of a 450μmolmol−1 CO2 concentration and a 0.8°C temperature increase stimulated rain-fed spring wheat yield by ∼5.3%. The combination of a 450μmolmol−1 CO2 concentration and a 1.8°C temperature increase, however, reduced wheat yield by ∼5.7%. This combined effect on wheat yield presents an image of the climatic result of global changes over the next 30 years in semiarid regions of China. As an agronomic practice, supplemental irrigation of 30mm may compensate for any loss of yield caused by climatic changes in the future. Furthermore, 60 and 90mm supplemental irrigation improved wheat yield 3.8 and 10.1%, respectively. Consequently, in this region, supplemental irrigation (from 30 to 90mm) may play a crucial role in maintaining rain-fed spring wheat yield affected by global climatic changes. [Copyright &y& Elsevier]

The RecQ helicase family is highly conserved from bacteria to men and plays a conserved role in the preservation of genome integrity. Its deficiency in human cells leads to a marked genomic instability that is associated with premature aging and cancer. To determine the thermodynamic parameters for the interaction of Escherichia coli RecQ helicase with DNA, equilibrium binding studies have been performed using the thermodynamic rigorous fluorescence titration technique. Steady-state fluorescence anisotropy measurements of fluorescein-labeled oligonucleotides revealed that RecQ helicase bound to DNA with an apparent binding stoichiometry of 1 protein monomer/10 nucleotides. This stoichiometry was not altered in the presence of AMPPNP (adenosine 5'-(β,γ-imido) triphosphate) or ADP. Analyses of RecQ helicase interactions with oligonucleotides of different lengths over a wide range of pH, NaCl, and nucleic acid concentrations indicate that the RecQ helicase has a single strong DNA binding site with an association constant at 25 °C of K = 6.7 ± 0.95 × 106 M-6 and a cooperativity parameter of ω = 25.5 ± 1.2. Both single-stranded DNA and double-stranded DNA bind competitively to the same site. The intrinsic affinities are salt-dependent, and the formation of DNA-helicase complex is accompanied by a net release of 3-4 ions. Allosteric effects of nucleotide cofactors on RecQ binding to DNA were observed only for single-stranded DNA in the presence of 1.5 mM AMPPNP, whereas both AMPPNP and ADP had no detectable effect on doublestranded DNA binding over a large range of nucleotide cofactor concentrations. [ABSTRACT FROM AUTHOR]

Antibodies blocking the PD-1/PD-L1 pathway have achieved great success. However, some disadvantages of antibodies have been found, which limit their clinical applications. Peptide antagonists are alternatives to antibodies in PD-1/PD-L1 blockage, but successful studies in this area are limited. A PD-1 targeting peptide, P-F4, was identified using phage display. P-F4 bound PD-1 with an affinity of 0.119 μM, inhibited PD-1/PD-L1 interaction at the cellular level and modulated T cell activity in vitro. We have overcome the poor solubility and rapid degradation problems of this peptide by packaging P-F4 in nanoparticles. In vivo experiments demonstrated that P-F4 nanoparticles could strongly inhibit tumor growth in a CT26 mouse model. Further research revealed that treatment of P-F4 nanoparticles increased CD8+T cells and reduced Tregs in the tumor microenvironment and tumor-draining lymph nodes. It was shown that treatment of P-F4 nanoparticles also increased lymphocytic activities, including proliferation, cytokine secretion and cytolytic activity. Moreover, computer modeling suggested that the P-F4 binding site to PD-1 overlaps with the PD-L1 binding surface. In this study, a peptide candidate for cancer immunotherapy was provided, and its working mechanisms were studied. [ABSTRACT FROM AUTHOR]

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: A novel preparation method to synthesize TiO2/SnO2 nanocrystalline sol under mild conditions was presented. Ti(OC4H9)4 used as a precursor was hydrolyzed in the rutile SnO2 nanocrystalline sol, and in-situ formed TiO2/SnO2 nanocrystalline sol. The crystal structure, morphology and photocatalysis performance of samples were investigated. The results show that the additional rutile SnO2 nano grains serve as heterogeneous crystal nucleus and exhibite the inducing effect on TiO2 grains growth, thus leading to the changes in crystalline phase and particle morphology. In addition, the photoluminescence (PL) spectra analysis indicates that TiO2/SnO2 composite structure induces a better charge separation, and thus the photocatalytic activity of TiO2/SnO2 sol is increased significantly compared with TiO2 sol. [Copyright &y& Elsevier]

Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design. [ABSTRACT FROM AUTHOR]

• Potential fatigue crack detection method for high pressure manifold joints based on strain analysis. • The strain distribution of non-threaded part under different internal pressures was analyzed. • The regular variation of strain concentration coefficient in non-threaded part was studied. There is a high stress concentration at the connection threads of high-pressure manifolds. Under the action of internal pressure(P int) and rapid vibration, the root of the thread is prone to fatigue cracking. To study the variation in the damage of a high-pressure manifold with connection threading, this paper first analyzed the strain of the manifold with different P int and with or without defects at different positions on the outer wall shaft. The potential fatigue crack damage of a high-pressure manifold of a hydraulic fracturing truck was monitored and analyzed by strain testing technology. The variation of the strain signals of defected and defect-free high-pressure pipe fittings were compared. The damage stress concentration point of the connection thread of the high-pressure manifold was analyzed. When there is a crack at the root of the thread, results show that there is a large difference in strain in the axial direction of the crack compared to the strain in threading thread without a crack. Meanwhile, the strain concentration coefficients of different stress concentration points change regularly. In this paper, the damage state of the thread is analyzed by strain monitoring. The results can provide a theoretical and practical basis for the prediction of root cracks in connection threads. [ABSTRACT FROM AUTHOR]

The use of 3D printing technology for manufacturing construction materials is gaining popularity, however, only a few studies have reported the fire behavior of such parts. In this research, the fire properties of 3D printed polylactide acid (PLA) parts with varying infill densities along with the tensile properties were analysed. The results from the fire tests showed that increasing the infill density increased the fuel load, which sustained combustion. Hence, the peak heat release rate and total heat release increased with an increment in infill density percentage. It was also observed that the increasing infill density had no effect on the flammability rating of the parts due to the constant shell thickness used for all the parts. In addition, the tensile strength and ductility of the parts increased with density as a porous part is more susceptible to failure than a solid homogeneous part. • Higher infill density increases the amount of material in the part. • Increasing infill density increases fuel load and flammability. • Flammability rating of 3D printed parts depend on shell thickness. • Ductility of 3D printed parts increases with infill density. • Higher infill density improves tensile strength. [ABSTRACT FROM AUTHOR]

Intrarenal interleukin-15 (IL-15) plays a major role controlling epithelial survival and polarization both in physiological and pathologic conditions. Herein, we confirmed that human renal cell carcinomas (RCCs) express a membrane-bound IL-15 isoform displaying an unusual molecular weight of 27 kDa. Its stimulation with soluble IL-15 receptor α chain (s-IL-15Rα) triggers epithelial-mesenchymal transition (EMT) process as shown by the down-regulation of E-cadherin and zona occludens 1 and the up-regulation of vimentin and N-cadherin and promotes the migratory and invasive properties of RCC. S-IL-15Rα treatment triggered the Src/PI3K/Akt/GSK-3β pathway and promoted β-catenin nuclei translocation. Deactivation of this pathway by using Src-specific inhibitor PP2, PI3K inhibitor LY294002, and AKT inhibitor MK2206 hampered β-catenin nuclei translocation and suppressed EMT, migration, and invasion of RCC. S-IL-15Rα treatment also enhanced Src-dependent phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (Erk1/2). FAK knockdown significantly decreased the migration and invasion of RCC, which suggest that Src-FAK signaling was involved in s-IL-15Rα-favored migration and invasion of RCC. At the same time, inhibitors of Erk1/2 also significantly decreased the migration and invasion of RCC but could not reverse s-IL-15Rα-induced EMT. Taken together, our results reveal that Src-dependent PI3K/Akt/GSK3b/β-catenin pathway is required for s-IL-15Ra-dependent induction of EMT in RCC, while Src-FAK and Src-Erk1/2 signaling were involved in s-IL-15Rα-promoted migration and invasion properties of RCC. Our study provides a better understanding of IL-15 signaling in RCC tumor progression, which may lead to novel targeted therapies and provide some suggestions when using IL-15 in clinic. [ABSTRACT FROM AUTHOR]

Background Pharmacogenetic (PG) algorithms were proposed to predict warfarin therapeutic dose more accurately. However, the clinical efficacy of the strategy over the standard treatment was not consistently proven. Methods We conducted a meta-analysis of the published randomized controlled trials (RCTs) comparing PG algorithm-based warfarin dosing (PG group) with clinical or standard protocols (STD group). The PUBMED, EMBASE, Cochrane Library and Web of Science databases were searched up to June 2014. Results A total of 10 RCTs were retrieved for the meta-analysis with the inclusion of 2,601 participants. Primary analysis showed both major bleeding (2.65% versus 4.75%; RR: 0.57, 95% CI: 0.37-0.90, P = 0.02) and thromboembolic events (0.59% versus 1.88%; RR: 0.38, 95% CI: 0.17-0.85, P = 0.02) were significantly lower in PG than in STD group. There was a trend towards increased percentage of time in therapeutic range (%TTR) [mean difference (MD): 4.65, 95% CI: 0.01-9.29, P = 0.05] in PG group, but no difference was observed for over-anticoagulation (INR > 4). Subgroup analyses showed significant reduction of both major bleeding and thromboembolic events in PG group when the follow-up time was more than 1 month. After stratified by different PG algorithms, significant major bleeding reduction could be found in PG group when warfarin indication or co-medication of amiodarone was integrated in the algorithms. Conclusion PG algorithm-guided warfarin anticoagulation is beneficial for the reduction of both major bleeding and thromboembolic events compared with standard dosing strategy. The benefits may be prominent in patients with longer follow-up time, or guided by refined PG algorithms. Highlights • We conducted a meta-analysis to evaluate PG algorithm-based warfarin dosing. • Risks for major bleeding and thromboembolic events were lower in PG-guided group. • The benefits of PG algorithm were prominent in patients with longer follow-up time. • Refined PG algorithm based warfarin dosing was more beneficial for patients. [ABSTRACT FROM AUTHOR]

Waterlogging usually leads plant cells to shift their metabolism towards anaerobic fermentation pathways due to the hypoxia stress. The roles of two different levels of waterlogging treatments (water level was kept on the base of hypocotyls and on the base of the first true leaf) in induction of fermentation in waterlogged roots of cucumber line ‘Zaoer-N’ (waterlogging tolerant line) were examined. Root activities, numbers of dead cells, transcripts of genes encoding pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH), and activities of the PDC, ADH, and LDH enzymes, concentrations of acetaldehyde, alcohol and lactate were quantified during 48 h of waterlogging, and 48 h of subsequent recovery. The results showed that PDC , ADH , and LDH transcripts, activities of PDC, ADH and LDH, and concentrations of acetaldehyde, alcohol and lactate were upregulated or increased during waterlogging, and decreased with recovery time prolonged. The results revealed that waterlogging up to the base of first true leaf responded more severe than waterlogging up to the base of hypocotyls in root activity and numbers of dead cells, which were mainly caused by alcohol fermentation. [ABSTRACT FROM AUTHOR]

Purpose Psychogenic non-epileptic seizures (PNES) are paroxysmal behaviors that resemble epileptic seizures but lack abnormal electrical activity. Some neuroimaging studies have reported that PNES exhibits aberrant functional connectivity in specific brain networks. Thus, advanced neuroimaging technologies may aid clinical diagnosis and treatment of PNES. Methods We investigated changes in brain functional connectivity in 18 patients with PNES and 20 healthy controls. Functional connectivity density mapping (FCDM), a voxelwise data-driven technique, was employed to compute local and global FCD maps. Then, short-range and long-range FCD values were calculated and group analyses performed between patents with PNES and healthy controls. A correlation analysis with clinical variables was also performed. Results We found that patients with PNES showed abnormal FCD regions mainly in the frontal cortex, sensorimotor cortex, cingulate gyrus, insula and occipital cortex. Seed-voxel correlation analyses also showed disrupted functional connectivity between these regions. In addition, the occipital cortex FCD correlated with duration of disease. Conclusion The present results support the hypothesis that patients with PNES are associated with altered attention, sensorimotor and emotion systems. Furthermore, correlations between altered regions in the occipital cortex and duration of disease may reflect an adaptation in these patients for long-term hypervigilance and increased response to external stimuli. This study adds new knowledge to our understanding of the pathophysiological mechanisms underlying PNES. [ABSTRACT FROM AUTHOR]

Few layers graphene nanosheets (GS) are obtained by the reduction of graphite oxide (GO) via Lithium aluminium tetrahydride (LiAlH4) and Phosphorus tribromide (PBr3) as the deoxidizer. The LiFePO4/GS composite is prepared using a solution phase method followed by a calcination process with only 2 h at 600 °C. The effect of the GS content in LiFePO4/GS on the morphology and electrochemical performance of LiFePO4 particles is extensively investigated. Results show that the optimized amount of GS in LiFePO4/GS is 5%. The primary particle size of LiFePO4/5%GS is 100~150 nm which are wrapped and connected homogeneously and loosely by GS with ~4 layers. The GS can restrict the growth of LiFePO4particle and construct an effective conductive network LiFePO4/GS composite, which all can enhance the conductivity of LiFePO4 particle. The LiFePO4/5%GS composite delivers a capacity of 155.4 mAhg-1 at 0.2 C, which is much higher than pure LiFePO4 (125.3 mAhg-1). Even at high rate of 5 C, a specific capacity of 124.3 mAhg-1 is achievable, with no obvious capacity fading after 100 cycles. [ABSTRACT FROM AUTHOR]

Making the decision between self-renewal and differentiation of adult stem cells is critical for tissue repair and homeostasis. Here we show that the apoptotic adaptor Fas-associated death domain (FADD) regulates the fate decisions of muscle satellite cells (SCs). FADD phosphorylation was specifically induced in cycling SCs, which was high in metaphase and declined in later anaphase. Furthermore, phosphorylated FADD at Ser-191 accumulated in the uncommitted cycling SCs and was asymmetrically localized in the self-renewing daughter SCs. SCs containing a phosphoryl-mimicking mutation at Ser-191 of FADD (FADD-D) expressed higher levels of stem-like markers and reduced commitment-associated markers. Moreover, a phosphoryl-mimicking mutation at Ser-191 of FADD suppressed SC activation and differentiation, which promoted the cycling SCs into a reversible quiescent state. Therefore, these data indicate that FADD regulates the fate determination of cycling SCs. [ABSTRACT FROM AUTHOR]

A novel hybrid material silica gel chemically modified by diethylenetriaminemethylenephosphonic acid GH-D-P has been developed and characterized. The results of the adsorption thermodynamics and kinetics of the as-synthesized GH-D-P for Au(III) showed that this high efficient inorganic-organic hybrid adsorbent had good adsorption capacity for Au(III), and the best interpretation for the experimental data was given by the Langmuir isotherm equation, the maximum adsorption capacity for Au(III) is 357.14mg/g at 35 °C. Moreover, the study indicated the adsorption kinetics of GH-D-P could be modeled by the pseudo-second-order rate equation wonderfully, and the adsorption thermodynamic parameters ΔG, ΔH and ΔS were -20.43 kJ mol-1 9.17 kJ mo1-1, and 96.24J K-1 mol-1, respectively. Therefore, the high adsorption capacity make this hybrid material have significant potential for Au(III) uptake from aqueous solutions using adsorption method. [ABSTRACT FROM AUTHOR]

Mature B cells (BCs) express CD23 and B cell receptors. Whether activation of CD23 and B cell receptors has different effects on BC activities is unclear. This study aims to investigate the mechanism by which the specific antigen immunotherapy regulates the activation of BCs in the skewed Th2 responses. Mice were sensitized to ovalbumin. The specific antigen vaccination (SAV) at graded doses was employed to modulate the activities of BCs in which the expression of IL-10, IgE, matrix metalloproteinase-9 (MMP9), CD23, and serum soluble CD23 by BCs was evaluated. The immune regulatory effect of BCs primed by lower or higher SAV doses was observed with an adoptive transfer mouse experiment. SAV activated CD23 to produce IL-10 in BCs at lower doses. The higher doses of SAV increased the expression of MMP9 in BCs that reduced the amounts of CD23 in BCs and increased the serum levels of soluble CD23, which was abrogated by the pretreatment with MMP9 inhibitor. Adoptively transfer with BCs primed by lower doses of SAV inhibited the ongoing antigen-specific Th2 responses whereas the BCs primed by higher doses of SAV exacerbated the ongoing Th2 responses. Exposure to specific antigens at optimal doses can activate BCs to produce IL-10 to suppress the skewed antigen-specific Th2 responses. The antigen doses of SAV higher than the optimal doses may promote the production of soluble CD23 to exacerbate the ongoing immune responses. [ABSTRACT FROM AUTHOR]

Celestial navigation system (CNS) and inertial navigation system (INS) are traditional autonomous integrated navigation methods. CNS is generally used to correct the cumulative error of the gyroscope in INS. The cumulative error of the accelerometer in INS cannot be corrected. As a new type of autonomous navigation method, the X-ray pulsar navigation system (XNAV) can correct the cumulative error of the accelerometer. This study proposes an integrated navigation method based on a combination of single x-ray pulsar navigation (SXPN), INS, and CNS. The method constructs a virtual accelerometer (VA) by coordinate system transformation, then compensates the error of the virtual accelerometer by using single X-ray pulsar navigation method, and then estimates the position, velocity, and angle errors by Kalman filtering method. The proposed method is an improvement of the SXPN navigation method of Q. Xu et al. in 2018. These improvements are twofold, that is, the positioning has high accuracy and is stable. A method was proposed to correct the error of the accelerometer and then analysis and simulation to support our guess is provided. This navigation method not only can correct the zero-order error of the accelerometer but also the first-order error that few scholars have studied. Simulations show that the proposed method reduces the total position error in three directions. In comparison with the method of adding the pulsar arrival time directly to the observation equation, our proposed method not only has higher precision, but it can also alleviate the jitter of the velocity position and attitude curve. [ABSTRACT FROM AUTHOR]

Celestial navigation system (CNS) and inertial navigation system (INS) are traditional autonomous integrated navigation methods. CNS is generally used to correct the cumulative error of the gyroscope in INS. The cumulative error of the accelerometer in INS cannot be corrected. As a new type of autonomous navigation method, the X-ray pulsar navigation system (XNAV) can correct the cumulative error of the accelerometer. This study proposes an integrated navigation method based on a combination of single x-ray pulsar navigation (SXPN), INS, and CNS. The method constructs a virtual accelerometer (VA) by coordinate system transformation, then compensates the error of the virtual accelerometer by using single X-ray pulsar navigation method, and then estimates the position, velocity, and angle errors by Kalman filtering method. The proposed method is an improvement of the SXPN navigation method of Q. Xu et al. in 2018. These improvements are twofold, that is, the positioning has high accuracy and is stable. A method was proposed to correct the error of the accelerometer and then analysis and simulation to support our guess is provided. This navigation method not only can correct the zero-order error of the accelerometer but also the first-order error that few scholars have studied. Simulations show that the proposed method reduces the total position error in three directions. In comparison with the method of adding the pulsar arrival time directly to the observation equation, our proposed method not only has higher precision, but it can also alleviate the jitter of the velocity position and attitude curve. [ABSTRACT FROM AUTHOR]