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In order to study the processing adaptability and influencing factors of discharge-induced combustion with function electrode for difficult-to-machine materials, contrast experiments between conventional electric discharge machining (EDM) with cylindrical electrode and combustion machining with function electrode are carried out. Four typical difficult-to-machine materials, i. e. nickel-base superalloy GH4169, die steel Cr12, titanium alloy TC4 and titanium-aluminum alloy TAC-2 are selected in the contrast experiments. The results show that the efficiencies of combustion machining for GH4169 is 112 mm³/min, for Cr12 is 92.28 mm³/min, for TC4 is 347.7 mm³/min and for TAC-2 is 152.5 mm³/ min, which are 37.3, 13.5, 58.7, 13.7 times than those of conventional EDM respectively under the same conditions. With the augmentation of metal activity, the burning intensity and combustion hot melting increase and the combustion effect also becomes more apparent. The characteristics of oxidation layer covering on machining surface plays a significant role in improving alloy material processing efficiency. Some factors determine the relative wear of the electrode, which include the weakened phenomenon on anti-plating of inner ejection liquid, the improvement of ablation processing efficiency, the characteristic of the oxide layer, etc. [ABSTRACT FROM AUTHOR]

Electrospark surface strengthening of titanium alloys is done by flexible rotating copper electrode with high-frequency pulse power supply. Then the oxygen and other elements from the air could react with titanium under the condition of high temperature and pressure caused by discharge. Experimental results show that the surface hardness of titanium alloy is improved by 237%--399% with reference to the substrate, and the thickness of the strengthened layer reaches a range of 21***157 µm. Through energy dispersive spectrometer (EDS) and X-ray diffraction (XRD) analysis, it is shown that titanium oxides and other strengthening matter such as titanium and copper/zinc alloys are generated on the titanium surface. In addition, obvious mechanical scraping and coating traces exist on the strengthening surface, but there are no significant traditional discharge erosion concave pits. At the same time, single pulse discharge energy is dispersed, thus the surface roughness value increases a little and is controllable. Besides, the strengthened layer has an improved ability of anti-corrosion in the mixed solution of hydrofluoric acid and nitric acid, and the enhanced layer has a high corrosion resistance. Point and surface wear tests show that the surface abrasion performance of the strengthened layer is improved significantly relative to the substrate surface. Good abrasion resistance, good corrosion resistance, and good quality of titanium alloy surface are obtained after being hardened. [ABSTRACT FROM AUTHOR]

JAK2 has been considered as an important target for the development of anti-cancer agents. In this study, considering the flexibility of its binding site, an integrated strategy combining Bayesian categorization modeling and ensemble docking was established. Four representative crystal structures were selected for ensemble docking by the hierarchical clustering of 34 crystal structures according to the volume overlaps of each structure. A retrospective virtual screening was performed to validate this integrated strategy. As the preliminary filtration, the Bayesian model enhanced the ratio of actives by reducing the large amount of decoys. After docking the remaining compounds, the comparison between the ensemble and individual results showed that the enrichment of ensemble docking improved significantly. The results of analysis on conformational changes of two top ranked active inhibitors when docking into different proteins indicated that compounds with flexible conformations well fitted the different binding site shapes were more likely to be potential JAK2 inhibitors. This high efficient strategy will facilitate virtual screening for novel JAK2 inhibitors and could be even applied in drug discovery against other targets. [ABSTRACT FROM AUTHOR]

Sodium-dependent glucose cotransporters (SGLTs) play an important role in glucose reabsorption in the kidney and have been identified as promising targets to treat diabetes. Because of the side effects like glucose and galactose malabsorption by targeting SGLT1, highly selective SGLT2 inhibitors are more promising in the treatment of diabetes. To understand the mechanism of selectivity, we conducted selectivity-based three-dimensional quantitative structure-activity relationship studies to highlight the structure requirements for highly selective SGLT2 inhibitors. The best comparative molecular field analysis and comparative molecular similarity indices analysis models showed the noncross-validated coefficient ( r2) of 0.967 and 0.943, respectively. The predicted correlation coefficients ( r2pred) of 0.974 and 0.938 validated the reliability and predictability of these models. Besides, homology models of SGLT2 and SGLT1 were also constructed to investigate the selective mechanism from structure-based perspective. Molecular dynamics simulation and binding free energy calculation were performed on the systems of a potent and selective compound interacting with SGLT2 and SGLT1 to compare the different binding modes. The simulation results showed that the stretch of the methylthio group on Met241 had an essential effect on the different binding modes between SGLT1 and SGLT2, which was consistent with the three-dimensional quantitative structure-activity relationship analysis. Hydrogen bond analysis and binding free energy calculation revealed that SGLT2 binding complex was more stable and favorable than SGLT1 complex, which was highly correlated with the experimental results. Our obtained results give useful information for the investigation of the inhibitors' selectivity between SGLT2 and SGLT1 and will help for further development of highly selective SGLT2 inhibitors. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Highlights: [•] We developed CoMFA, CoMSIA and Topomer CoMFA models for a series of ALK inhibitors. [•] Topomer Search was utilized for virtual screening to obtain suitable fragments. [•] Novel compounds were generated by molecular fragment replacement. [•] Novel compounds were evaluated by 3D-QSAR models prediction and docking analysis. [•] A set of novel derivatives with predicted activities were designed. [Copyright &y& Elsevier]

Aluminum bronze coatings were prepared on the as-cast substrate of the same material by electro-spark deposition (ESD), and the coatings were treated by ultrasonic surface rolling (USR). The effects of USR on the microstructural, mechanical, and tribological properties of the ESD coatings were investigated. The microstructure, phase composition, nanoindentation, microhardness, surface residual stress, and tribological properties of the coatings were experimentally determined and characterized in detail. The USR treatment with different static pressures (1.0 MPa, 2.5 MPa, 4.0 MPa) was employed to reveal the mechanism of microstructure evolution and surface modification. The results showed that the original columnar crystal structure of the coatings treated by USR was deflected, elongated, and even broken, resulting in the grain refinement of the coatings. The hole defects were healed after USR2.5 treatment. The phase composition of the coatings changed from β′ (Cu3Al) phase to α (Cu) and κ (Fe3Al) phase because of the heat released at USR. The nanohardness, static creep resistance, and microhardness of the ESD coatings were effectively promoted by USR. The nano-hardness of the ESD coating after USR4.0 treatment (4.4 GPa) was 1.38 times and 2.2 times that of the ESD coating and the as-cast alloy respectively, and the creep displacement (5.193 nm) was 27.2% and 18.5% that of the ESD coating and the as-cast alloy respectively. The residual tensile stress of the ESD coatings was eliminated after USR treatment and converted into the residual compressive stress. The surface residual stress of the ESD coating after USR2.5 was −337.16 MPa. After USR2.5 treatment, the wear loss of ESD coating reduced by about 1/2, which was attributed to the healing of hole defects, residual compressive stress, and the increase of the hardness. • The mechanical and tribological properties of ESD coating were improved by USR. • Influence of USR under difference static pressure on the ESD coatings was evaluated. • The hole defects in the coatings were healed and the grains were refined by USR. • The β′ phase transformed into α phase and κ phase under the heat released during USR treatment. • The tribological behaviors of different samples were compared and analyzed. [ABSTRACT FROM AUTHOR]