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991.
Hua Y Dagan S Wickramasekara S Boday DJ Wysocki VH 《Journal of mass spectrometry : JMS》2010,45(12):1394-1401
Chemically modified silicon nanoparticles were applied for the laser desorption/negative ionization of small acids. A series of substituted sulfonic acids and fatty acids was studied. Compared to desorption ionization on porous silicon (DIOS) and other matrix-less laser desorption/ionization techniques, silicon nanoparticle-assisted laser desorption/ionization (SPALDI) mass spectrometry allows for the analysis of acids in the negative ion mode without the observation of multimers or cation adducts. Using SPALDI, detection limits of many acids reached levels down to 50 pmol/μl. SPALDI of fatty acids with unmodified silicon nanoparticles was compared to SPALDI using the fluoroalkyl silylated silicon powder, with the unmodified particles showing better sensitivity for fatty acids, but with more low-mass background due to impurities and surfactants in the untreated silicon powder. The fatty acids exhibited a size-dependent response in both SPALDI and unmodified SPALDI, showing a signal intensity increase with the chain length of the fatty acids (C12-C18), leveling off at chain lengths of C18-C22. The size effect may be due to the crystallization of long chain fatty acids on the silicon. This hypothesis was further explored and supported by SPALDI of several, similar sized, unsaturated fatty acids with various crystallinities. Fatty acids in milk lipids and tick nymph samples were directly detected and their concentration ratios were determined by SPALDI mass spectrometry without complicated and time-consuming purification and esterification required in the traditional analysis of fatty acids by gas chromatography (GC). These results suggest that SPALDI mass spectrometry has the potential application in fast screening for small acids in crude samples with minimal sample preparation. 相似文献
992.
随着DNA G-四链体结构的发现和现代分子生物学技术对其与癌症关系的揭示,DNA G-四链体逐渐成为抗肿瘤药物研究的新靶点。c-myc启动区 G-四链体由于在细胞生长、增殖、凋亡、衰老及肿瘤形成等过程中的重要作用,成为DNA G-四链体中最受关注的序列之一。本文旨在对c-myc启动区 G-四链体的结构及靶向c-myc G-四链体的小分子配体的研究进展进行综述。首先,介绍c-myc G-四链体的生物学意义;其次,对几种常用的c-myc G-四链体的结构进行解析;最后,对以c-myc为靶点的小分子配体的研究进展及其与G-四链体的作用模式进行综述,并对目前以c-myc G-四链体为靶点、已经走向临床实验的CX-3543的开发与作用机制进行介绍。 相似文献
993.
本文比较动态增强磁共振成像(DCE-MRI)与16层螺旋CT(MSCT)对小肾癌诊断及术前评估中的价值.选取64例疑似小肾癌患者作为研究对象,均接受DCE-MRI与MSCT检查.以术后病理结果为参照,比较DCE-MRI和MSCT检查对小肾癌诊断及术前评估的灵敏度、特异度和准确度,并分析这两种检查的参数与Fuhrman分... 相似文献
994.
Stefan Saretz Gabriele Basset Liridona Useini Markus Laube Jens Pietzsch Dijana Dra
a Danijela Maksimovi-Ivani Johannes Trambauer Harald Steiner Evamarie Hey-Hawkins 《Molecules (Basel, Switzerland)》2021,26(10)
All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research. 相似文献
995.
Hongbo Zhang Yu Xia Chunqiu Yu Huijie Du Jinchang Liu Hui Li Shihui Huang Qihua Zhu Yungen Xu Yi Zou 《Molecules (Basel, Switzerland)》2021,26(11)
Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study. 相似文献
996.
997.
W. Zielenkiewicz 《Journal of Thermal Analysis and Calorimetry》2008,92(1):105-108
The work describes the development in calorimetric studies on the aggregation process of simple globular proteins solutions
induced by the presence of electrolytes. It also provides information on theoretical models and experimental methods applied
to the examination of those processes. 相似文献
998.
999.
基于分形的捷联惯组历次测试数据混合插值算法 总被引:2,自引:2,他引:0
针对捷联惯组历次测试数据小样本、非等间隔、非线性的问题,提出了一种基于分形插值的三次混合插值算法.通过第一次分形插值保证原始测试数据的变化趋势;通过第二次样条函数插值保证了插值的准确性,实现原始测试数据等间隔化;通过第三次分段线性插值,扩大样本容量,同时保证了原有测试序列的统计特性不变.实例分析表明,该算法很好的实现了对捷联惯组历次测试数据的等间隔处理和样本容量扩大,为捷联惯组历次测试数据小样本建模分析提供良好的基础. 相似文献
1000.
V. Yu. Novokshenov 《Regular and Chaotic Dynamics》2008,13(5):424-430
An asymptotic solution of the KdV equation with small dispersion is studied for the case of smooth hump-like initial condition
with monotonically decreasing slopes. Despite the well-known approaches by Lax-Levermore and Gurevich-Pitaevskii, a new way
of constructing the asymptotics is proposed using the inverse scattering transform together with the dressing chain technique
developed by A. Shabat [1]. It provides the Whitham-type approximaton of the leading term by solving the dressing chain through
a finite-gap asymptotic ansatz. This yields the Whitham equations on the Riemann invariants together with hodograph transform
which solves these equations explicitly. Thus we reproduce an uniform in x asymptotics consisting of smooth solution of the Hopf equation outside the oscillating domain and a slowly modulated cnoidal
wave within the domain. Finally, the dressing chain technique provides the proof of an asymptotic estimate for the leading
term.
相似文献