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51.
Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
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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53.
This paper discusses the compressive performance of perforated brick masonry after fire exposure. Compressive strength tests of the mortar, clay perforated brick, and perforated brick masonry specimens were performed in accordance with ISO834 fire tests of different durations. The temperature distribution of the masonry materials and specimens was simulated using the finite element software ABAQUS, with the thermal parameters of masonry materials recommended by European standard Eurocode 6 and related literature. The compressive strength reduction factors of mortar and clay perforated brick exposed to different fire durations were calculated via the layered method suggested by European standard Eurocode 1. In addition, the compressive strength reduction factors after cooldown were obtained from the experimental data of the masonry materials, and by considering further reductions in the compressive strength after cooling from high temperatures. Experimental data of the masonry specimens were compared with the numerical results obtained using the reduction factors proposed in this work. The comparison revealed an overall acceptable approximation. Thus, the method presented in this paper can be used to evaluate the residual capacity of masonry structures after fire. 相似文献
54.
Hwang Seongil Park Sang Hyun Jin Maolin Kang Sang Hoon 《Intelligent Service Robotics》2021,14(3):471-484
Intelligent Service Robotics - A robust control designed for multiple degrees-of-freedom (DOF) robot manipulators performing complex tasks requiring frequent physical interaction with unknown... 相似文献
55.
Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
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
56.
Shanquan Chen Sicong Wei Fei Jin Shanming Ke Xierong Zeng Lang Chen Chuanwei Huang 《Ceramics International》2018,44(12):13695-13698
From the perspectives of scientific researches and practical applications, it is desirable to explore high operating temperature ferromagnetic films. The effect of biaxial strain on magnetic properties of (110)-oriented La0.7Sr0.3MnO3 films was studied. High quality La0.7Sr0.3MnO3 films were grown on (110)-oriented perovskite single crystal substrates using pulsed laser deposition, varying substrate-induced misfit strains from ??2.27–0.75%. A remarkable enhancement of Curie temperature has been achieved for (110)-oriented La0.7Sr0.3MnO3 films clamped with small misfit strains (i.e., grown on LAST (110)). The enhanced Curie temperature of (110)-oriented La0.7Sr0.3MnO3 films could be attributed to the misfit strain between the films and the underlying substrates and may have technological implication for applications at high temperature environments. 相似文献
57.
Jin Huandong 《中国油气》2018,(2)
This paper analyzes the status quo and progress of overseas oil and gas business cooperation built by Chinese oil enterprises in 2017. With the slow recovery of the oil and gas industries as a whole, the overseas oil and gas business of Chinese oil enterprises has continued to grow in size, and all-round cooperation progress was made along the Belt and Road. Breakthroughs were made in oil and gas cooperation between China and the United States. In the meantime, new features have emerged in the overseas cooperation of Chinese enterprises, and a pattern of diversified investors has basically taken shape. 相似文献
58.
Li Lei Limin Li Shasha Wang Gaoyang Zhao Yoshifumi Oshima Yang Ren Lei Zhao Lihua Jin Yao Wang Chengshan Li Pingxiang Zhang 《Journal of the European Ceramic Society》2018,38(14):4694-4700
Highly (100)-oriented Ce1-x(Y0.2Zr0.8)xOδ (CYZO) films were prepared on biaxially textured NiW substrates by a chemical solution deposition approach using metal inorganic salts as starting materials. It has been found that both the preferential orientation and surface roughness of CYZO films decrease gradually with increasing of the doping percentage of Y3+ and Zr4+ ions. The epitaxial growth relationship of (220)CYZO//(200)NiW and [00?l]CYZO//[001]NiW was demonstrated by XRD texture measurement as well as atomic resolution STEM observation. XRD, Raman and XPS spectra results indicate that Y3+ and Zr4+ ions were indeed introduced into CeO2 lattice to substitute Ce4+ ions and form cubic fluorite CYZO solid solution. Moreover, CeO2 buffer layer can be endowed a strong enough capability to prevent element diffusion through co-doping of yttrium and zirconium, provided that an optimal doping ratio of them is adopted. This will provide a new approach to fabricating strong-barrier single buffer layer for coated conductor. 相似文献
59.
60.
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