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81.
The statin drug Simvastatin is a HMG-CoA reductase inhibitor that has been widely used to lower blood lipid. However, the drug is clinically observed to reposition a significant suppressing potency on glioblastoma (GBM) by unexpectedly targeting diverse kinase pathways involved in GBM tumorigensis. Here, an inverse screening strategy is described to discover potential kinase targets of Simvastatin. Various human protein kinases implicated in GBM are enriched to define a druggable kinome; the binding behavior of Simvastatin to the kinome is profiled systematically via an integrative computational approach, from which most kinases have only low or moderate binding potency to Simvastatin, while only few are identified as promising kinase hits. It is revealed that Simvastatin can potentially interact with certain known targets or key regulators of GBM such as ErbB, c-Src and FGFR signaling pathways, but exhibit low affinity to the well-established GBM target of PI3K/Akt/mTOR pathway. Further assays determine that Simvastatin can inhibit kinase hits EGFR, MET, SRC and HER2 at nanomolar level, which are comparable with those of cognate kinase inhibitors. Structural analyses reveal that the sophisticated T790 M gatekeeper mutation can considerably reduce Simvastatin sensitivity to EGFR by inducing the ligand change between different binding modes. 相似文献
82.
Deepak Singh Kapkoti Shilpi Singh Sarfaraz Alam Feroz Khan Suaib Luqman 《Natural product research》2020,34(12):1735-1742
AbstractNovel Mannich base derivatives of glabridin were synthesized and their antiproliferative activity were performed along with our previously reported glabridin-chalcone hybrids molecules (GCHMs) against various human cell lines MDA-MB-231 (breast adenocarcinoma), HEK-293 (embryonic kidney cell line), K562 (leukemia), MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma), HepG2 (hepatocellular carcinoma) and WRL-68 (hepatic carcinoma). The result showed that the glabridin significantly reduced cell proliferation with IC50 ranges from 3.67 to 58.30?µM against all the tested cell lines. The remarkable reduction in antiproliferative activity 2’,4’-dimethoxyglabridin and GCHMs compounds with phenolic OH groups protected by methoxy (OCH3) groups suggested that the free OH groups are essential factor for the antiproliferative activity of glabridin and its derivatives. The Mannich base derivatives of glabridin showed moderate activity IC50 (2.20–>95.78?µM). Furthermore, in silico target identification analysis revealed that AKT1, DECR1 and NOS1 are the potential targets for glabridin and their derivatives. 相似文献
83.
Self-afline multiplicity scaling is investigated in the framework of a two-dimensional factorial mo-ment methodology using the concept of the Hurst exponent (H). Analyzing the experimental data of target evaporated fragments emitted in84Kr-AgBr interactions at 1.7 AGeV revealed that the best power law behav-ior is exhibited for H = 0.3 indicating a self-affine multiplicity fluctuation pattern. A signal of multifractality is also observed from knowledge of the anomalous fractal dimension dq extracted from the intermittency exponent aq of the anisotropic phase space scenario. 相似文献
84.
An infrared (IR) image synthesis method is proposed for the synthesis of a real IR background and modeled IR target, used as IR signatures, as well as a band-transformation between short wave IR (SWIR), middle wave IR (MWIR), and long wave IR (LWIR) in an IR imaging system simulation. IR target images are created by the RadThermIR software, an IR signature prediction software. Individual radiances for IR signatures, corresponding to the max/min temperatures of a real IR background and modeled IR target image, are calculated with Planck’s law. First, an IR background of an arbitrary wavelength band is transformed to one of the other wavelength bands with the temperature-radiance characteristics. And then, after adjusting the gray levels of the arbitrary IR target signatures based on their radiances for the wavelength band of the transformed IR background, these IR target and background signatures can be synthesized as one image for a specific wavelength band. The experimental results show that the modeled IR target images, such as a modeled helicopter and F16, can be synthesized on the IR background images of three IR wavelength bands. And we confirmed that IR background images of the three IR wavelength bands can diversely be synthesized with the modeled IR targets as the setting temperature of the target and background, the target distance, and the field of view (FOV) arbitrarily. 相似文献
85.
《Electrophoresis》2017,38(9-10):1260-1267
In this work, single‐piece fused silica capillaries with two different internal diameter segments featuring different inner surface roughness were prepared by new etching technology with supercritical water and used for volume coupling electrophoresis. The concept of separation and online pre‐concentration of analytes in high conductivity matrix is based on the online large‐volume sample pre‐concentration by the combination of transient isotachophoretic stacking and sweeping of charged proteins in micellar electrokinetic chromatography using non‐ionogenic surfactant. The modified surface roughness step helped to the significant narrowing of the zones of examined analytes. The sweeping and separating steps were accomplished simultaneously by the use of phosphate buffer (pH 7) containing ethanol, non‐ionogenic surfactant Brij 35, and polyethylene glycol (PEG 10000) after sample injection. Sample solution of a large volume (maximum 3.7 μL) dissolved in physiological saline solution was injected into the wider end of capillary with inlet inner diameter from 150, 185 or 218 μm. The calibration plots were linear (R 2 ∼ 0.9993) over a 0.060–1 μg/mL range for the proteins used, albumin and cytochrome c. The peak area RSDs from at least 20 independent measuremens were below 3.2%. This online pre‐concentration technique produced a more than 196‐fold increase in sensitivity, and it can be applied for detection of, e.g . the presence of albumin in urine (0.060 μg/mL). 相似文献
86.
Guillaume Jouvet Matthias Huss Heinz Blatter Marco Picasso Jacques Rappaz 《Journal of computational physics》2009,228(17):6426-6439
Due to climatic change, many Alpine glaciers have significantly retreated during the last century. In this study we perform the numerical simulation of the temporal and spatial change of Rhonegletscher, Swiss Alps, from 1874 to 2007, and from 2007 to 2100. 相似文献
87.
Samy Chammaa Dr. Bianca Sperl Anke G. Roth Aybike Yektaoglu Steffen Renner Dr. Thorsten Berg Prof. Dr. Christoph Arenz Prof. Dr. Athanassios Giannis Prof. Dr. Tudor I. Oprea Dr. Daniel Rauh Dr. Markus Kaiser Dr. Herbert Waldmann Prof. Dr. 《Angewandte Chemie (International ed. in English)》2010,49(21):3666-3670
88.
89.
Simple and robust digital holography for high-resolution imaging 总被引:2,自引:0,他引:2
Based on the point spread function of holographic system,the lateral resolution of digital holographic imaging system without any pre-magnification is studied.The expression of resolution limitation of holographic imaging system is thus presented.We investigate the possibilities to improve the lateral resolution.The simple experimental setup with an off-axis arrangement is built.By using a U.S.Air Force(USAF)test target as microscopic object,the recorded holograms are reconstructed digitally based on the principle of Fresnel diffraction.The lateral resolution of 2.76 μm without any pre-magnification is demonstrated experimentally,which matches the theoretical prediction well. 相似文献
90.
S. V. Zhamkochyan 《Journal of Contemporary Physics (Armenian Academy of Sciences)》2008,43(4):196-202
The time resolution of a new bunch-length detector based on the radio frequency (RF) scanning of the produced secondary electrons is calculated. A dedicated Monte-Carlo code by means of SIMION software is developed for accurate simulation of spread in the investigated secondary electrons transit times and image width. In calculation the initial energy distribution of electrons and the actual structure of accelerating and focusing electric fields were considered. It is shown that by using a thin-wire emission target a femtosecond time precision could be achieved using moderate applied voltages. 相似文献