Activity of Oritavancin and Its Synergy with Other Antibiotics against Mycobacterium abscessus Infection In Vitro and In Vivo

Background: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. Methods: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC₅₀ of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time–kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. Results: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. Conclusions: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.     

Interface crack between two elastic layers

A semi-infinite interface crack between two infinite isotropic elastic layers under general edge loading conditions is considered. The problem can be solved analytically except for a single real scalar independent of loading, which is then extracted from the numerical solution for one particular loading combination. Two applications of the basic solution are made which illustrate its utility: interface cracking driven by residual stress in a thin film on a substrate, and an analysis of a test specimen proposed recently for measuring interface toughness.

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Résumé On considère une fissure d'interface semi-infinie entre deux couches infinies élastiques et isotropes soumises à des conditions générales de sollicitations sur leurs bords. Le problème peut être solutionné par voie analytique, à l'exception d'un scalaire réel simple, indépendant de la charge, qui est extrait de la solution numérique relative à une combinaison particulière des sollicitations.On procède à deux applications de la solution de base qui illustrent son utilité: l'une est relative à une fissure d'interface soumise aux tensions résiduelles dans un film mince déposé sur un substrat. L'autre est l'analyse d'une éprouvette d'essai proposée récemment pour mesurer la ténacité de l'interface.

     

2001年羊毛价格预测

分析了影响羊毛价格的因素，如其它纺织纤维的市场价格，当前的国际经济形势、商品价格、汇率等，预测了2001年19.5um及其以下的超细羊毛、20-23um羊毛、24dum以及更粗的羊毛的价格走势。     

闸坝与生态

闸坝建设与生态保护问题,已经引发了社会各界的广泛关注.如何正确处理闸坝与生态的关系,做到人与自然和谐相处,是当前迫切需要解决的问题.     

Synthesis, Characterization and Antitumor Activity of Lanthanum(Ⅲ) Complex with Demethylcantharidate

A novel complex of lanthanum(Ⅲ) with demethylcantharidate group (DCA), Na[La(DCA)2(H2O)], was synthesized in aqueous solution and characterized by elemental analysis, molar conductance, IR, UV, 1H-NMR spectra and TG-DTA. The results suggest that lanthanum ion is seven-coordinated. Six oxygen atoms are from carboxyl groups and cyclic ethers of two DCA ligand, and on oxygen is from a H2O. The antitumor activities of the complex against HL-60 human leukemia, BGC-823 human gastric carcinoma, Bel-7402 human hepatic carcinoma, Hela human cervical carcinoma were investigated with MTT or SRB assays. Na[La(DCA)2(H2O)] exhibits stronger inhibition against certain kinds of cancer cells than Na2DCA in vitro.     

EFFECTS OF HEXASULFOBUTYLATED C60 ON THE GASTRIC CIRCULAR MUSCLE OF GUINEA PIG

The effects of hexasulfobutylated (FC₄S), the fullerene derivative on the contraction of smooth muscle were tested pharmacologically on the circular muscle of stomach of guinea pigs. The effects of monomalonic acid C₆₀ (MMA C₆₀) on the same preparations were compared. The effects of those compounds on the taenia coli, portal vein and vas deferens of guinea pigs were also tested. The FC₄S did, while MMA C₆₀ did not elicit contracture of the circular muscle of stomach and taenia coli. Both FC₄S and MMA C₆₀ did not elicit contraction on the portal vein and on the vas deferens of the guinea pig. Prazosin (0.5 μM) or propranolol (0.5 μM) did not alter the FC₄S elicit contracture of the circular muscle of stomach. However, atropine (0.01, 0.1 and 1 μM), tetrodotoxin (0.1 μM) or low calcium medium decreased reversibly the FC₄S elicited contracture of the circular muscle of stomach. The effect of FC₄S on the contracture of the gastric muscles was also tested using various muscarinic receptor subtype antagonists. 4-DAMP (1 μM), muscarinic M3 receptor antagonist, and tropicamide (1 μM), muscarinic M4 receptor antagonist, did not alter the contracture elicited by FC₄S. Pirenzepine (0.1 μM), muscarinic M1 receptor antagonist, and methoctramine (0.25 μM), muscarinic M2 receptor antagonist, significantly decreased the FC₄S elicited contracture of the circular muscle. Atropine (1 μM) or tetrodotoxin (0.1 μM) completely blocked the FC₄S elicited contracture of the circular muscle of stomach. It is concluded that FC₄S elicited contracture of the circular muscle of stomach. The effect may be due to FC₄S acts on the cholinergic cells existed in the gastric muscle and indirectly activating the tetrodotoxin dependent releasing of the transmitters from the cells, then, activating the muscarinice M1, M2 receptors in the muscle eliciting the contractures.     

喷射FRP-混凝土界面的黏结滑移模型研究

为研究喷射FRP-混凝土界面黏结滑移关系,对5个试件进行了双面剪切试验以及数值模拟,分析其界面破坏模式、界面受剪承载力、加载端荷载滑移曲线、界面黏结滑移关系等力学性能指标,并对纤维体积率、喷射FRP厚度等影响因素展开了研究。最后在试验和数值模拟的基础上,建立了喷射FRP-混凝土界面黏结滑移本构模型,并将模型计算结果与试验结果进行对比。研究表明：纤维体积率和喷射FRP厚度对界面黏结性能影响较大;论文所建的界面有限元模型可较为准确地模拟喷射FRP-混凝土界面的黏结力学性能;提出的指数型理论计算模型具有较高的准确度及一定的安全裕度,可用于实际工程中分析喷射FRP-混凝土界面黏结力学性能。论文研究成果可为喷射FRP加固技术的应用推广提供理论基础。     

T6处理对 ZL105A 铸造铝合金组织和性能的影响

对ZL105A铸造铝合金进行了T6处理。研究了铸态和经T6处理后该合金的显微组织、力学性能和拉伸试样断口形貌。结果表明,T6处理后,ZL105A合金组织更细小、均匀,硬度、抗拉强度大幅度提高,断后伸长率降低。     

轧制中间热处理温度对Ni7W/Ni12W/Ni7W复合基带组织及织构的影响

采用压延辅助双轴织构技术制备了涂层导体用Ni7W/Ni12W/Ni7W复合基带。复合基带轧制形变过程加入3次不同温度的轧制中间热处理优化其形变组织。采用X射线衍射及背散射电子衍射技术分析了复合基带轧制过程中表面及截面的形变及回复组织,以此探索轧制中间热处理温度对Ni7W/Ni12W/Ni7W复合基带形变及立方织构形成过程的影响机制。结果显示,经600S°C/60Smin轧制中间热处理后的复合基带在较低的再结晶温度下获得了95% (<10°)的高立方织构含量。晶体取向分布图表明该中间热处理温度下复合基带回复及初始再结晶组织中立方取向的晶粒含量都更高;不同取向间点对点的晶体取向差分析证实了立方取向晶粒较大的晶界角,这使立方取向在回复及初始再结晶过程具有高的界面迁移率,从而促进了后续再结晶过程强立方织构的形成。     

Analysis of the mechanism and failure mode of landslides subjected to transient seepage in a Piedmont region of Nanjing area

Bulletin of Engineering Geology and the Environment - The landslide mechanism and failure mode of the gently sloping Piedmont region are analyzed in Fangshan and Zhutoushan hills in the...