Biological evaluation of 2-methylpyrimidine derivatives as active pan Bcr-Abl inhibitors

We designed a series of 2-methylpyrimidine derivatives as new BCR-ABL inhibitors using scaffold-hopping strategy.These synthetic compounds exhibited significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I mutant.Compound 7u showed very potent kinase inhibitory activities against Bcr-Abl WT,Bcr-Abl E255K,Bcr-Abl Q252H,Bcr-Abl G250E and Bcr-Abl T315I,with IC50 values of 0.13 nM,0.17 nM,0.24 nM,0.19 nM and 0.65μM,respectively.This compound also displayed anti-proliferation activity against K562 cell line with an IC50 value of 1.1 nM,thus representing a new lead for further optimization.     

分子信标探针荧光法测定慢性粒细胞性白血病相关基因

根据慢性粒细胞性白血病(CML)相关基因b3a2序列设计了一种带有荧光基团和淬灭基团的凸环结构探针(分子信标,MB),研究其与互补目标DNA杂交前后的荧光变化行为,建立了b3a2基因检测的新方法.在最适条件下,得到杂交后溶液荧光强度与本底荧光强度的比值(S/B)和目标DNA 的浓度呈线性关系,r=0.9973,线性范围4.0×10-9～3.2×10-8 mol/L.该方法为实际样品的检测奠定了基础.     

CML模型的时空混沌

提出了一类新的耦合映射格点（ＣＭＬ）模型．数值实验表明这类新的ＣＭＬ模型对于强弱耦合系统均能有效研究其时空复杂性，揭示了非线性、耗散、色散相互作用的非常丰富的时空Ｐａｔｅｒｎ行为     

时空Chaos研究中的CML模型

通过对有关差分格式的稳定性分析，我们提出了一类新的格点耦合映射（ＣＭＬ）模型。数值试验表明：我们提出的ＣＭＬ模型是一类有效的研究时空复杂性的模型，特别是对于强耦合系统。     

UPLC-Q-TOF/MS在烘焙食品中羧甲基赖氨酸和羧乙基赖氨酸检测中的应用

建立了烘焙食品中羧甲基赖氨酸(CML)和羧乙基赖氨酸(CEL)的UPLC-Q-TOF/MS检测方法。烘焙食品经脱脂、还原、沉淀蛋白、酸水解释放出CML和CEL,使用FMOC-Cl柱前衍生和HLB小柱固相萃取净化后,采用UPLC-Q-TOF/MS检测。CML和CEL在1~700 ng/m L浓度范围内均呈良好的线性关系,线性回归系数r0.999。CML和CEL的检出限均为0.1 mg/kg;回收率为94.4%~108.3%;相对标准偏差(RSD,n=6)为0.4%~6.2%。该方法定性、定量准确,灵敏度高,能很好地应用于烘焙食品中CML和CEL的检测。     

Analysis of advanced glycation endproducts in dairy products by isotope dilution liquid chromatography–electrospray tandem mass spectrometry. The particular case of carboxymethyllysine

A fully validated multiple-transition recording isotope dilution liquid chromatography–electrospray tandem mass spectrometry (LC–MS/MS) method for the simultaneous quantitative determination of N^?-carboxymethyllysine (CML) and lysine in dairy products is described. Internal standards were [N-1′,2′-¹³C₂]CML and [1,2,3,4,5,6-¹³C₆-2,6-¹⁵N₂]lysine, and the method was validated by evaluating the selectivity, linearity, precision (repeatability and reproducibility) and trueness, using both powder and liquid products. For liquid dairy products, the repeatability and reproducibility was 2.79% and 11.0%, while 4.85% and 4.92% were determined for powder dairy products, respectively. The trueness of the method ranged from −9.6% to −3.6% for powder and from −0.99% to 6.8% for liquid dairy products. The limit of detection for CML was estimated to be 8 ng CML per mg protein while the limit of quantification was 27 ng CML per mg protein. The method encompasses a proteolytic cleavage mediated by enzymatic digestion to reach a complete release of the amino acids prior to a sample cleanup based on solid phase extraction, and followed by LC–MS/MS analysis of CML and lysine residues. To ensure a suitable performance of the enzymatic digestion, CML measurements were compared to values obtained with an acid hydrolysis-mediated proteolysis. Finally, the method was employed for the analysis of CML in various dairy products. The values compare well to the data available in the literature when similar methods were used, even if some discrepancies were observed upon comparison with the results obtained by other techniques such as enzyme-linked immunosorbent assay and GC–MS.     

CML模型和湍流的非线性

本文在现有耦合映射格点(CML)动力系统模型的基础上,提出了能够同时模拟对流项和扩散项的强弱耦合系统的CML模型,分析了这类模型的特点和结构.数值试验表明,这类CML模型能够有效地研究时空复杂性,利用数值模拟的结果对湍流的物理机制作了初步的阐释.     

Detection of BCR- ABL Gene Rearrangement by RT/PCR Technology and Its Mechanism in the Generation and Development of Chronic Myeloid Leukemia

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Study on random and coherence states using a family of CML models

A family of coupled map lattice (CML) models has been developed to simulate the interaction of convection, diffusion and dispersion in both weakly and strongly coupled cases. With variation of parameters, the models can simulate those systems of convection dominating, diffusion dominating, and dispersion dominating states. Not only coherent and turbulent properties as well as their interrelations, but also the transitional state between any modes with local coupling and global coupling are analysed to demonstrate the essential characteristics of any state. Numerical results show that the models are capable of simulating both layered coupling and stochastic mechanism, and thus can be conveniently used to analyse an initiative and driven coupled system. Results of numerical simulation also lead us to understand whether or not turbulence coherent structure is formed by modulation of wave packet. Finally, the duality of wave and particle characters of turbulence is illustrated in the numerical simulation.