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31.
Electrochemical impedance spectroscopy (EIS), anodic polarization and scanning electron microscopy techniques were used to investigate the damage mechanism in the transpassive potential region of AISI ...  相似文献   
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Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.  相似文献   
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Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.  相似文献   
35.
Based on the phase transformation theories, especially the T0 concept of bainite transformation, alloy optimisation of bainitic steel with carbides has been carried out aiming at the produce of plastic mould with large cross-section. The effect of manganese and silicon on proeutectoid ferrite and bainite transformation is explored by dilatometric analysis, XRD and different microscopy techniques. The results show that after the alloy optimisation, the transformation of proeutectoid ferrite is suppressed and when the cooling rate is lower than 0·1°C?s??1, the new lower bainite transformation appears by decreasing carbon capacity of austenite and promoting carbide precipitation. Industrial production proves that the optimised alloy SDP1 can meet the demand for the plastic mould with the thickness of 1050?mm.  相似文献   
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Removal by absorptive ceramic membranes can simultaneously absorb and separate metal ions from water. Alumina/yttria‐stabilized zirconia (Al2O3/YSZ) hollow‐fiber membranes, fabricated using phase inversion and sintering process, were deposited with iron oxide by an in‐situ hydrothermal process. The results showed that α‐Fe2O3 was produced and incorporated across the membranes. A reduction in flux was recorded with the deposition of α‐Fe2O3. However, it improved the adsorption capacity for heavy metal adsorption. The adsorption‐separation test demonstrated that the optimized membrane is able to completely remove Pb(II) ions after two hours.  相似文献   
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The copper and cobalt oxides composites coatings on aluminum substrates have been successfully synthesized via sol-gel method using nitrate-based sol precursors. The composites were characterized by X-ray Diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), and UV–Vis–NIR spectrophotometry. The sol-gel reactions were discussed and Molecular Dynamics (MD) simulation was integrated into the study to predict molecules assembly properties. The XRD analyses revealed that the CuO and the Co3O4 composites were formed after the annealing process with the average difference of the calculated lattice parameters compared to ICDDs was 1.17%. The surface electronic structure was mainly consisted of tetrahedral Cu(I), octahedral Cu(II), tetrahedral Co(II), octahedral Co(III) as well as surface, sub-surface and lattice oxygen O?. The XRD, XPS and MD simulation results showed that there was minimal (or possibly non-existing) indication of copper-cobalt mixed phase oxides formations. FESEM and AFM surveys revealed that the coating had a porous surface composed of interlinked nanoparticles in the range of ~?10 to ~?40?nm. UV–Vis–NIR reflectance spectra showed that the sol precursors concentration and the dip-drying cycle significantly influenced the absorptance value with optimum absorptance (α) of 88.7% exhibited by coating synthesized using sol concentration of 0.1?M and 10 dip-drying cycles. High absorptance value and simplicity in the synthesis process render the coatings to be very promising candidates for solar selective absorber (SSA) applications.  相似文献   
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