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971.
The Discovery of Potent Nonstructural Protein 5A (NS5A) Inhibitors with a Unique Resistance Profile—Part 2 下载免费PDF全文
Florian Wakenhut Thien Duc Tran Dr. Chris Pickford Stephen Shaw Dr. Mike Westby Caroline Smith‐Burchnell Lesa Watson Michael Paradowski Dr. Jared Milbank David Stonehouse Dr. Kathy Cheung Dr. Robert Wybrow Dr. Felice Daverio Dr. Samuel Crook Keith Statham Dr. David Leese Dr. Darren Stead Fiona Adam Duncan Hay Dr. Lee R. Roberts Jean‐Yves Chiva Carly Nichols Dr. David C. Blakemore Gilles H. Goetz Dr. Ye Che Iain Gardner Satish Dayal Dr. Andrew Pike Rob Webster Dr. David C. Pryde 《ChemMedChem》2014,9(7):1387-1396
In ongoing studies towards novel hepatitis C virus (HCV) therapeutics, inhibitors of nonstructural protein 5A (NS5A) were evaluated. Specifically, starting from previously reported lead compounds, peripheral substitution patterns of a series of biaryl‐linked pyrrolidine NS5A replication complex inhibitors were probed and structure–activity relationships were elucidated. Using molecular modelling and a supercritical fluid chromatographic (SFC) technique, intramolecular H‐bonding and peripheral functional group topology were evaluated as key determinants of activity and membrane permeability. The novel compounds exhibited retained potency as compared with the lead compounds, and also showed promising results against a panel of resistance viruses. Together, the results of the study take us a step closer towards understanding the potency of daclatasvir, a clinical candidate upon which the compounds were based, and to designing improved analogues as second‐generation antiviral agents targeting NS5A. 相似文献
972.
Orosco Adam 《精细化工原料及中间体》2014,(4)
正本发明涉及到操作蒸馏塔分离乙醇混合物的过程,乙醇混合物含有乙醇和醋酸,该过程回收的乙醇含醋酸量小于700wppm。蒸馏塔的操作条件可以根据加料组分变化。具体说,过程提供了具有低醋酸浓 相似文献
973.
In the batch emulsion copolymerization of styrene and α-tert-butoxy-ω-vinylbenzyl-polyglycidol macromonomer, carried out at macromonomer concentrations exceeding the critical micelle concentration (cmc), particles are formed by a two-step coagulative nucleation mechanism. This mechanism leaves its mark on morphology of particle interface, rate of polymerization and on molecular weight distribution of the obtained polymer. AFM studies revealed that the interface of particles is composed of objects with dimensions close to dimensions of the primary particles. Compartmentalization of styrene in the macromonomer micelles leads to the higher initial rate of styrene conversion than in the similar macromonomer free homopolymerization of styrene. The initial polymerization in the monomer-swollen macromonomer micelles, similar to the microemulsion polymerization, is responsible for the formation of the highest molecular weight component. In the mature particles there are two different polymerization loci: the interfacial layer and the core. This leads to bimodal molecular weight distribution of the formed polymer. 相似文献
974.
Michael Adam Cekdar Vakifahmetoglu Paolo Colombo Michaela Wilhelm Georg Grathwohl 《Journal of the American Ceramic Society》2014,97(3):959-966
By direct foaming of a Pt‐containing polysiloxane precursor, macroporous ceramics were generated by pyrolysis at 1400°C under nitrogen or argon. The growth of nanowires was induced via a vapor–liquid–solid mechanism in which the Pt particles acted as deposition site for the decomposition gases released upon pyrolyzing the preceramic polymer. SEM, HR‐SEM, TEM/EDX, and XRD investigations revealed that pyrolysis under argon atmosphere leads to short SiC nanowires of only a few micrometers length and under nitrogen atmosphere Si3N4 nanowires evolved, with length of several 10 μm. In both cases the tips of the nanowires mainly consisted of PtSi. In contrast to samples pyrolyzed at 600°C, the components after higher temperature pyrolysis showed moderate‐specific surface areas of 55–67 m2/g. In CO oxidation experiments, a good catalytic activity was found for the Pt silicide particles, suggesting that despite their relatively large size, their location at the tips of the nanowires affords them good reactivity. 相似文献
975.
Mohammed Noushad Ismail Ab Rahman Noor Sheeraz Che Zulkifli Adam Husein Dasmawati Mohamad 《Ceramics International》2014
This study aimed to obtain nanosilica with desirable characteristics from an agricultural biomass waste using an organic acid. The effect of the feed rate of the precipitant and the mixing speed on the morphology and characteristics of nanosilica from rice husk for use as fillers in dental nanocomposites has been explored. The feed rate showed considerable effects on the agglomeration and the size of the silica nanoparticles. At a feed rate of 0.2 ml/min, the particles were bigger and highly agglomerated with a mean particle size of 261 nm. The mean particle sizes for the feed rates of 1 ml/min and 5 ml/min were 213 nm and 174 nm, respectively, exhibiting a decrease in the mean particle size with increasing feed rate. The shape of the silica nanoparticles depended on the mixing speed and it was possible to obtain spherical, dense, low surface area silica particles suitable for use in the fabrication of dental nanocomposites using this simple technique. 相似文献
976.
The effect of relative humidity (RH) on the adhesion of particles colliding with a hard surface was studied for submicron particles of liquid oleic acid, solid ammonium sulfate, and solid polystyrene latex (PSL). For this purpose, a three-arm impactor was designed and constructed. The three arms consisted of one impactor having an uncoated impaction plate (i.e., a rebound arm), one impactor having a viscous-liquid-coated impaction plate (i.e., a capture arm), and one impactor having no impaction plate (i.e., a null arm). The particle number concentrations downstream of each arm were measured by condensation particle counters (CPCs). Data were analyzed to obtain the particle rebound fraction. Use of ambient upstage pressure allowed measurements from 5 to 95% RH at the impaction plate. Particle rebound depended strongly on RH, even for non-hygroscopic PSL particles. The rebound fraction for PSL particles dropped monotonically from nearly unity at 50% RH to 0.4 at 95% RH. For ammonium sulfate, the rebound fraction dropped from nearly unity at 25% RH to 0.5 at 70% RH. The decreased rebound at higher RH was explained by the formation of a water meniscus. The resulting capillary forces inhibited particle detachment. A model, taking into account the impact kinetic energy compared to the contact adhesion energy arising from van der Waals and capillary forces, captured the observations well. The reduced rebound arising from increased adhesion at high RH, independent of particle water content, potentially confounds a recent assumption that non-rebounding atmospheric particles are liquid.
Copyright 2014 American Association for Aerosol Research 相似文献
977.
Ewa
widerska Justyna Strycharz Adam Wrblewski Piotr Czarny Janusz Szemraj Jzef Drzewoski Agnieszka
liwiska 《International journal of molecular sciences》2021,22(14)
Background: Due to its prominence in the regulation of metabolism and inflammation, adipose tissue is a major target to investigate alterations in insulin action. This hormone activates PI3K/AKT pathway which is essential for glucose homeostasis, cell differentiation, and proliferation in insulin-sensitive tissues, like adipose tissue. The aim of this work was to evaluate the impact of chronic and intermittent high glucose on the expression of biomolecules of insulin signaling pathway during the differentiation and maturation of human visceral preadipocytes. Methods: Human visceral preadipocytes (HPA-V) cells were treated with high glucose (30 mM)during the proliferation and/or differentiation and/or maturation stage. The level of mRNA (by Real-Time PCR) and protein (by Elisa tests) expression of IRS1, PI3K, PTEN, AKT2, and GLUT4 was examined after each culture stage. Furthermore, we investigated whether miR-29a-3p, miR-143-3p, miR-152-3p, miR-186-5p, miR-370-3p, and miR-374b-5p may affect the expression of biomolecules of the insulin signaling pathway. Results: Both chronic and intermittent hyperglycemia affects insulin signaling in visceral pre/adipocytes by upregulation of analyzed PI3K/AKT pathway molecules. Both mRNA and protein expression level is more dependent on stage-specific events than the length of the period of high glucose exposure. What is more, miRs expression changes seem to be involved in PI3K/AKT expression regulation in response to hyperglycemic stimulation. 相似文献
978.
轮胎翻新是废旧轮胎的一种利用手段。在轮胎翻新过程中,旧轮胎胎面花纹是通过覆盖一层胎面胶料进行修复的。翻新轮胎性能的完善以及其价格比新轮胎低使其被相当频繁地使用,但安装翻新轮胎的汽车经常发生车祸。在轮胎翻新时,关于翻新轮胎性能如何影响交通安全方面的信息非常重要。在给定路况条件下,轮胎的制动性能、抓着性能和行驶操纵性能等方面的知识令人关注。 相似文献
979.
Martha Tsigkari Adam Davis Francis Aish Specialist Modelling Group Foster + Partners 《Architectural Design》2011,81(4):54-57
Mathematics in design is most often associated with its visual manifestation in geometrical surfaces and elements. The finely tuned ambient qualities of a space, necessary for environmental performance, may not be so apparent, but can involve the application of many branches of mathematics. Martha Tsigkari, Adam Davis and Francis Aish of Foster + Partners' Specialist Modelling Group bring this to the fore by describing how at Al Raha Beach development in Abu Dhabi and the City of Justice in Madrid environmental considerations were interpreted through analytical numerical data. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
980.
Jakub Adam Koza Iwao Mogi Margitta Uhlemann Annett Gebert 《Electrochimica acta》2010,55(22):6533-6541
The effects of a uniform magnetic field on the early stages of Ag, Fe and CoFe alloys electrocrystallisation have been investigated. It was found for Fe and CoFe alloys, irrespective of the applied parameters, that early stages of the layer growth can be characterised by a nucleation and 3D diffusion controlled growth. The influence of the deposition parameters on the nucleation behaviour was studied on the basis of the Sharifker-Mostany (SM) model. A modification to the existing model has been proposed in order to model alloy systems. It is reported that a magnetic field superposed parallel to the electrode surface has a significant influence on the early stages of Fe and CoFe alloys growth. The growth of the nuclei is enhanced by the Lorentz-force-driven convection, while the nucleation processes remain unaffected. The hydrodynamic origin of these phenomena is confirmed by independent rotating disk electrode (RDE) investigations. Moreover, the proposed mechanism of a magnetic field influence on the 3D diffusion controlled growth is supported by a microscopic investigation of Ag deposits. It was found that Ag deposits obtained without a magnetic field superposition are characterised by a relatively large number of small 3D growth centres, whereas the deposits obtained in a field show fewer 3D centres but their size is greatly increased. 相似文献