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71.
Manuel G. Ricardo Ameena M. Ali Jacek Plewka Ewa Surmiak Beata Labuzek Constantinos G. Neochoritis Jack Atmaj Lukasz Skalniak Ran Zhang Tad A. Holak Matthew Groves Daniel G. Rivera Alexander Dmling 《Angewandte Chemie (International ed. in English)》2020,59(13):5235-5241
Stapled peptides are chemical entities in‐between biologics and small molecules, which have proven to be the solution to high affinity protein–protein interaction antagonism, while keeping control over pharmacological performance such as stability and membrane penetration. We demonstrate that the multicomponent reaction‐based stapling is an effective strategy for the development of α‐helical peptides with highly potent dual antagonistic action of MDM2 and MDMX binding p53. Such a potent inhibitory activity of p53‐MDM2/X interactions was assessed by fluorescence polarization, microscale thermophoresis, and 2D NMR, while several cocrystal structures with MDM2 were obtained. This MCR stapling protocol proved efficient and versatile in terms of diversity generation at the staple, as evidenced by the incorporation of both exo‐ and endo‐cyclic hydrophobic moieties at the side chain cross‐linkers. The interaction of the Ugi‐staple fragments with the target protein was demonstrated by crystallography. 相似文献
72.
Meng Su Feifei Qin Zeying Zhang Bingda Chen Qi Pan Zhandong Huang Zheren Cai Zhipeng Zhao Xiaotian Hu Dominique Derome Jan Carmeliet Yanlin Song 《Angewandte Chemie (International ed. in English)》2020,59(34):14234-14240
A key issue of micro/nano devices is how to integrate micro/nanostructures with specified chemical components onto various curved surfaces. Hydrodynamic printing of micro/nanostructures on three‐dimensional curved surfaces is achieved with a strategy that combines template‐induced hydrodynamic printing and self‐assembly of nanoparticles (NPs). Non‐lithography flexible wall‐shaped templates are replicated with microscale features by dicing a trench‐shaped silicon wafer. Arising from the capillary pumped function between the template and curved substrates, NPs in the colloidal suspension self‐assemble into close‐packed micro/nanostructures without a gravity effect. Theoretical analysis with the lattice Boltzmann model reveals the fundamental principles of the hydrodynamic assembly process. Spiral linear structures achieved by two kinds of fluorescent NPs show non‐interfering photoluminescence properties, while the waveguide and photoluminescence are confirmed in 3D curved space. The printed multiconstituent micro/nanostructures with single‐NP resolution may serve as a general platform for optoelectronics beyond flat surfaces. 相似文献
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Wave-activity relation containing wave-basic flow interaction based on decomposition of general potential vorticity 下载免费PDF全文
On the basis of the general potential vorticity theorem(GPV),a new wave-activity relation is derived in an ageostrophic and nonhydrostatic dynamic framework.Whe... 相似文献
75.
Kunqian Mu Kaiwen Jiang Yue Wang Zihan Zhao Song Cang Kaishun Bi Qing Li Ran Liu 《Molecules (Basel, Switzerland)》2022,27(3)
β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing drug stability. As a bioactive molecule, the metabolism of β-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of β-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient β-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of β-cyclodextrin after oral administration in rats. Results showed that β-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of β-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact β-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that β-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO2 and H2O. Results proved that β-cyclodextrin, with relative low accumulation in the body, had good safety. The results will assist further study of the design and safety evaluation of adjuvant β-cyclodextrin and promote its clinical development. 相似文献
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We demonstrated a femtosecond mode-locked Er:Zr F4-Ba F2-La F3-Al F3-Na F(Er:ZBLAN)fiber laser at 2.8μm based on the nonlinear polarization rotation technique.The laser generated an average output power of 317 m W with a repetition rate of 107 MHz and pulse duration as short as 131 fs.To the best of our knowledge,this is the shortest pulse generated directly from a mid-infrared mode-locked Er:ZBLAN fiber laser to date.Numerical simulation and experimental results confirm that reducing the gain fiber length is an effective way to shorten the mode-locked pulse duration in the Er:ZBLAN fiber laser.The work takes an important step towards sub-100-fs mid-infrared pulse generation from mode-locked Er:ZBLAN fiber lasers. 相似文献
78.
Meccanica - In this paper, we develop a framework of time optimization path planning for robotic manipulators surrounded by static obstacles. Our approach is based on the recursive dynamics method... 相似文献
79.
本文研究了含非完整界面的功能梯度压电复合材料的Ⅲ型裂纹问题.此裂纹垂直于非完整界面,采用弹簧型力电耦合界面模型模拟非完整界面.界面两侧材料的性质,如弹性模量、压电常数和介电常数均假定呈指数函数形式且沿着裂纹方向变化.运用积分变换法将裂纹面条件转换为奇异积分方程,并使用Gauss-Chebyshev方法对其进行数值求解.根据算例结果讨论了一些退化问题并分析了裂纹尖端强度因子与材料的非均匀系数和非完整界面参数的关系. 相似文献
80.
The development of display technology has continuously increased the requirements for image resolution. However, the imaging systems of many cameras are limited by their physical conditions, and the image resolution is often restrictive. Recently, several models based on deep convolutional neural network (CNN) have gained significant performance for image super-resolution (SR), while extensive memory consumption and computation overhead hinder practical applications. For this purpose, we present a lightweight network that automatically searches dense connection (ASDCN) for image super-resolution (SR), which effectively reduces redundancy in dense connection and focuses on more valuable features. We employ neural architecture search (NAS) to model the searching of dense connections. Qualitative and quantitative experiments on five public datasets show that our derived model achieves superior performance over the state-of-the-art models. 相似文献