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Core fucosylation of N-glycans is catalyzed by fucosyltransferase 8 and is associated with various types of cancer. Most reported fucosyltransferase inhibitors contain non-drug-like features, such as charged groups. New starting points for the development of inhibitors of fucosyltransferase 8 using a fragment-based strategy are presented. Firstly, we discuss the potential of a new putative binding site of fucosyltransferase 8 that, according to a molecular dynamics (MD) simulation, is made accessible by a significant motion of the SH3 domain. This might enable the design of completely new inhibitor types for fucosyltransferase 8. Secondly, we have performed a docking study targeting the donor binding site of fucosyltransferase 8, and this yielded two fragments that were linked and trimmed in silico. The resulting ligand was synthesized. Saturation transfer difference (STD) NMR confirmed binding of the ligand featuring a pyrazole core that mimics the guanine moiety. This ligand represents the first low-molecular-weight compound for the development of inhibitors of fucosyltransferase 8 with drug-like properties.  相似文献   
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Slag is by‐product of iron‐making industry and is commonly used in concrete working; however, the application of such inorganic material as an additive in the polymer composites field is quite new and has not yet been really explored. The current investigation reports the potential of virgin slag, strong polar acid activated slag and organic treated slag as reinforcement, fire and thermal resistance additive for rubberized, unsaturated polyester (R‐UPE) composites. The slag was subjected to three pretreatments, the first was mechanical (comminution) to reduce the particle size, the second was chemical activation by strong polar acid namely H2SO4, and the third was coating by organic stearic acid. The effectiveness of chemical activation and coating of the slag was followed by EDX and infrared attenuated total reflectance (ATR‐IR). The potential of activated and coated slag as reinforcement for rubberized, unsaturated polyester resin was evaluated and compared to the sample with pristine slag. The fabricated composites were evaluated with respect to their mechanical mechanical behavior. Thermal behavior was inspected using behavior using differential scanning calorimeter (DSC), dynamic mechanical analysis (DMA) was investigated. Fire resistance of the R‐UPE containing slag was performed by direct exposure of the sample to torch. It has been found that the activated slag has improved the concerned properties. The observed findings were related to the role of activated and coated to interact with the R‐UPE matrix via polar–polar interaction due to the development of surface functional groups after chemical activation. J. VINYL ADDIT. TECHNOL., 26:173–179, 2020. © 2019 Society of Plastics Engineers  相似文献   
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Software Quality Journal - Today, many tools exist that attempt to find possible vulnerabilities in Android applications, e.g., FlowDroid, Fortify, or AppScan. However, all these tools aim to...  相似文献   
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Cells respond to mechanical forces by deforming in accordance with viscoelastic solid behavior. Studies of microscale cell deformation observed by high speed video microscopy have elucidated a new cell behavior in which sufficiently rapid mechanical compression of cells can lead to transient cell volume loss and then recovery. This work has discovered that the resulting volume exchange between the cell interior and the surrounding fluid can be utilized for efficient, convective delivery of large macromolecules (2000 kDa) to the cell interior. However, many fundamental questions remain about this cell behavior, including the range of deformation time scales that result in cell volume loss and the physiological effects experienced by the cell. In this study, a relationship is established between cell viscoelastic properties and the inertial forces imposed on the cell that serves as a predictor of cell volume loss across human cell types. It is determined that cells maintain nuclear envelope integrity and demonstrate low protein loss after the volume exchange process. These results define a highly controlled cell volume exchange mechanism for intracellular delivery of large macromolecules that maintains cell viability and function for invaluable downstream research and clinical applications.  相似文献   
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In this study we developed an immunofluorescence method to detect pea protein in meat products. Pea protein has a high nutritional value but in sensitive individuals it may be responsible for causing allergic reactions. We produced model meat products with various additions of pea protein and flour; the detection limit (LOD) of the method for pea flour was 0.5% addition, and for pea protein it was 0.001% addition. The repeatabilities and reproducibilities for samples both positive and negative for pea protein were all 100%. In a blind test with model products and commercial samples, there was no statistically significant difference (p > 0.05) between the declared concentrations of pea protein and flour and the immunofluorescence method results. Sensitivity was 1.06 and specificity was 1.00. These results show that the immunofluorescence method is suitable for the detection of pea protein in meat products.  相似文献   
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