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991.
本文介绍了铼钠克G—SPEED开放式数控系统的功能、特点以及G—SPEED数控系统往现代模具及零部件加工中的应用方法与技巧。包括在CNC自动车床上的应用、在加工小心及磨床上的应用、在鞋揎机上的应用、在四轴及五轴加工、在高光加工上的应用。 相似文献
992.
基于企业对模具设计与制造人才的需求,结合高职院校模具专业学生的特点及就业分析,模拟实际工作过程,改革课程建设,完成了《冲压模具设计》课程“教学做”一体化教学设计方案。实践表明,教学效果得到显著改善,提高了学生的基本职业素养和岗位基本技能。 相似文献
993.
Target Hopping as a Useful Tool for the Identification of Novel EphA2 Protein–Protein Antagonists 下载免费PDF全文
Dr. Daniele Pala Dr. Simonetta Russo Dr. Riccardo Castelli Dr. Iftiin Hassan‐Mohamed Dr. Carmine Giorgio Dr. Alessio Lodola 《ChemMedChem》2014,9(1):67-72
Lithocholic acid (LCA), a physiological ligand for the nuclear receptor FXR and the G‐protein‐coupled receptor TGR5, has been recently described as an antagonist of the EphA2 receptor, a key member of the ephrin signalling system involved in tumour growth. Given the ability of LCA to recognize FXR, TGR5, and EphA2 receptors, we hypothesized that the structural requirements for a small molecule to bind each of these receptors might be similar. We therefore selected a set of commercially available FXR or TGR5 ligands and tested them for their ability to inhibit EphA2 by targeting the EphA2‐ephrin‐A1 interface. Among the selected compounds, the stilbene carboxylic acid GW4064 was identified as an effective antagonist of EphA2, being able to block EphA2 activation in prostate carcinoma cells, in the micromolar range. This finding proposes the “target hopping” approach as a new effective strategy to discover new protein–protein interaction inhibitors. 相似文献
994.
Structure‐Guided Design of Thiazolidine Derivatives as Mycobacterium tuberculosis Pantothenate Synthetase Inhibitors 下载免费PDF全文
Parthiban Brindha Devi Ganesh Samala Jonnalagadda Padma Sridevi Shalini Saxena Mallika Alvala Elena G. Salina Prof. Dharmarajan Sriram Prof. Perumal Yogeeswari 《ChemMedChem》2014,9(11):2538-2547
The pantothenate biosynthetic pathway is essential for the persistent growth and virulence of Mycobacterium tuberculosis (Mtb) and one of the enzymes in the pathway, pantothenate synthetase (PS, EC: 6.3.2.1), encoded by the panC gene, has become an appropriate target for new therapeutics to treat tuberculosis. Herein, we report nanomolar thiazolidine inhibitors of Mtb PS developed by a rational inhibitor design approach. The thiazolidine compounds were discovered by using energy‐based pharmacophore modelling and subsequent in vitro screening, which resulted in compounds with a half maximal inhibitory concentration (IC50) value of (1.12±0.12) μM . These compounds were subsequently optimised by a combination of modelling and synthetic chemistry. Hit expansion of the lead by chemical synthesis led to an improved inhibitor with an IC50 value of 350 nM and an Mtb minimum inhibitory concentration (MIC) of 1.55 μM . Some of these compounds also showed good activity against dormant Mtb cells. 相似文献
995.
Structural and Biochemical Studies of Actin in Complex with Synthetic Macrolide Tail Analogues 下载免费PDF全文
Dr. Jose H. Pereira Dr. Chutima Petchprayoon Dr. Alexander C. Hoepker Dr. Nigel W. Moriarty Dr. Sarah J. Fink Dr. Giuseppe Cecere Prof. Ian Paterson Prof. Paul D. Adams Prof. Gerard Marriott 《ChemMedChem》2014,9(10):2286-2293
The actin filament‐binding and filament‐severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF‐01 and GC‐04) are shown to bind to G‐actin with dissociation constants of (285±33) and (132±13) nM , respectively. The crystal structures of actin complexes with GC‐04, SF‐01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region to the SD1/SD3 cleft on the upper protomer, which displaces loop‐D from the lower protomer on the same half‐filament. With previous studies showing that the GC‐04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F‐actin would make them more effective at severing filaments compared with plasma gelsolin. Structure‐based analyses are used to suggest more reactive or targetable forms of GC‐04 and SF‐01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis. 相似文献
996.
Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood‐Stage Antimalarial Compounds 下载免费PDF全文
Dr. Sandeep Sundriyal Dr. Nicholas A. Malmquist Dr. Joachim Caron Scott Blundell Dr. Feng Liu Xin Chen Nitipol Srimongkolpithak Prof. Jian Jin Prof. Susan A. Charman Prof. Artur Scherf Dr. Matthew J. Fuchter 《ChemMedChem》2014,9(10):2360-2373
Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1‐benzyl‐4‐piperidyl)[6,7‐dimethoxy‐2‐(4‐methyl‐1,4‐diazepin‐1‐yl)‐4‐quinazolinyl]amine (BIX01294; 1 ), a known human G9a inhibitor, together with its dose‐dependent effects on histone methylation in the malarial parasite. This work describes our initial medicinal chemistry efforts to optimise the diaminoquinazoline chemotype for antimalarial activity. A variety of analogues were designed by substituting the 2 and 4 positions of the quinazoline core, and these molecules were tested against Plasmodium falciparum (3D7 strain). Several analogues with IC50 values as low as 18.5 nM and with low mammalian cell toxicity (HepG2) were identified. Certain pharmacophoric features required for antimalarial activity were found to be analogous to the previously published SAR of these analogues for G9a inhibition, thereby suggesting potential similarities between the malarial and human HKMT targets of this chemotype. Physiochemical, in vitro activity, and in vitro metabolism studies were also performed for a select set of potent analogues to evaluate their potential as antimalarial leads. 相似文献
997.
Sunghoon Park Soohyun Kim Gun-Joo Sun Wan In Lee Kyoung Kook Kim Chongmu Lee 《Nanoscale research letters》2014,9(1):638
TeO2-nanostructured sensors are seldom reported compared to other metal oxide semiconductor materials such as ZnO, In2O3, TiO2, Ga2O3, etc. TeO2/CuO core-shell nanorods were fabricated by thermal evaporation of Te powder followed by sputter deposition of CuO. Scanning electron microscopy and X-ray diffraction showed that each nanorod consisted of a single crystal TeO2 core and a polycrystalline CuO shell with a thickness of approximately 7 nm. The TeO2/CuO core-shell one-dimensional (1D) nanostructures exhibited a bamboo leaf-like morphology. The core-shell nanorods were 100 to 300 nm in diameter and up to 30 μm in length. The multiple networked TeO2/CuO core-shell nanorod sensor showed responses of 142% to 425% to 0.5- to 10-ppm NO2 at 150°C. These responses were stronger than or comparable to those of many other metal oxide nanostructures, suggesting that TeO2 is also a promising sensor material. The responses of the core-shell nanorods were 1.2 to 2.1 times higher than those of pristine TeO2 nanorods over the same NO2 concentration range. The underlying mechanism for the enhanced NO2 sensing properties of the core-shell nanorod sensor can be explained by the potential barrier-controlled carrier transport mechanism.
PACS
61.46. + w; 07.07.Df; 73.22.-f 相似文献998.
Earthworms can ‘biotransform’ or ‘biodegrade’ chemical contaminants, rendering them harmless in their bodies, and can bioaccumulate them in their tissues. They ‘absorb’ the dissolved chemicals through their moist ‘body wall’ due to the interstitial water and also ingest by ‘mouth’ while soil passes through the gut. Since the advent of the nanotechnology era, the environmental sink has been continuously receiving engineered nanomaterials as well as their derivatives. Our current understanding of the potential impact of nanomaterials and their natural scavenger is limited. In the present investigation, we studied the cellular uptake of ZnO nanoparticles (NPs) by coelomocytes especially by chloragocytes of Eisenia fetida and their role as nanoscavenger. Results from exposure to 100- and 50-nm ZnO NPs indicate that coelomocytes of the earthworm E. fetida show no significant DNA damage at a dose lower than 3 mg/l and have the potential ability to uptake ZnO NPs from the soil ecosystem and transform them into microparticles. 相似文献
999.
Hyung Won Lee Suek Joo Choi Sung Hoon Park Jong-Ki Jeon Sang-Chul Jung Sang Chai Kim Young-Kwon Park 《Nanoscale research letters》2014,9(1):376
The catalytic co-pyrolysis of a seaweed biomass, Laminaria japonica, and a typical polymer material, polypropylene, was studied for the first time. A mesoporous material Al-SBA-15 was used as a catalyst. Pyrolysis experiments were conducted using a fixed-bed reactor and pyrolysis gas chromatography/mass spectrometry (Py-GC/MS). BET surface area, N2 adsorption-desorption isotherms, and NH3 temperature programmed desorption were measured to examine the catalyst characteristics. When only L. japonica was pyrolyzed, catalytic reforming slightly increased the gas yield and decreased the oil yield. The H2O content in bio-oil was increased by catalytic reforming from 42.03 to 50.32 wt% due to the dehydration reaction occurring on the acid sites inside the large pores of Al-SBA-15. Acids, oxygenates, mono-aromatics, poly aromatic hydrocarbons, and phenolics were the main components of the bio-oil obtained from the pyrolysis of L. japonica. Upon catalytic reforming over Al-SBA-15, the main oxygenate species 1,4-anhydro-d-galactitol and 1,5-anhydro-d-manitol were completely removed. When L. japonica was co-pyrolyzed with polypropylene, the H2O content in bio-oil was decreased dramatically (8.93 wt% in the case of catalytic co-pyrolysis), contributing to the improvement of the oil quality. A huge increase in the content of gasoline-range and diesel-range hydrocarbons in bio-oil was the most remarkable change that resulted from the co-pyrolysis with polypropylene, suggesting its potential as a transport fuel. The content of mono-aromatics with high economic value was also increased significantly by catalytic co-pyrolysis. 相似文献
1000.
Fengzhen Lv Jing Zhang Cunxu Gao Li Ma Daqiang Gao Shiming Zhou Desheng Xue 《Nanoscale research letters》2014,9(1):266
We report a novel epitaxial growth of EuTiO3 films on SrTiO3(001) substrate by hydrothermal method. The morphological, structural, chemical, and magnetic properties of these epitaxial EuTiO3 films were examined by scanning electron microscopy, transmission electron microscopy, high-resolution X-ray diffractometry, X-ray photoelectron spectroscopy, and superconducting quantum interference device magnetometry, respectively. As-grown EuTiO3 films with a perovskite structure were found to show an out-of-plane lattice shrinkage and room-temperature ferromagnetism, possibly resulting from an existence of Eu3+. Postannealing at 1,000°C could reduce the amount of Eu3+, relax the out-of-plane lattice shrinkage, and impact the magnetic properties of the films.