Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD

The type III receptor tyrosine kinase FLT3 is frequently mutated in acute myeloid leukemia. Oncogenic FLT3 mutants display constitutive activity leading to aberrant cell proliferation and survival. Phosphorylation on several critical tyrosine residues is known to be essential for FLT3 signaling. Among these tyrosine residues, Y842 is located in the so-called activation loop. The position of this tyrosine residue is well conserved in all receptor tyrosine kinases. It has been reported that phosphorylation of the activation loop tyrosine is critical for catalytic activity for some but not all receptor tyrosine kinases. The role of Y842 residue in FLT3 signaling has not yet been studied. In this report, we show that Y842 is not important for FLT3 activation or ubiquitination but plays a critical role in regulating signaling downstream of the receptor as well as controlling receptor stability. We found that mutation of Y842 in the FLT3-ITD oncogenic mutant background reduced cell viability and increased apoptosis. Furthermore, the introduction of the Y842 mutation in the FLT3-ITD background led to a dramatic reduction in in vitro colony forming capacity. Additionally, mice injected with cells expressing FLT3-ITD/Y842F displayed a significant delay in tumor formation, compared to FLT3-ITD expressing cells. Microarray analysis comparing gene expression regulated by FLT3-ITD versus FLT3-ITD/Y842F demonstrated that mutation of Y842 causes suppression of anti-apoptotic genes. Furthermore, we showed that cells expressing FLT3-ITD/Y842F display impaired activity of the RAS/ERK pathway due to reduced interaction between FLT3 and SHP2 leading to reduced SHP2 activation. Thus, we suggest that Y842 is critical for FLT3-mediated RAS/ERK signaling and cellular transformation.     

功能化聚丙烯酸酯乳液的表面改性及产物性能

丙烯酸酯单体添加量达到70%时,加入γ-甲基丙烯酰氧基丙基三甲氧基硅烷(KH570)与剩余单体发生共聚制备表面SiOH功能化聚丙烯酸酯乳液(PAES),产物与正硅酯乙酯(TEOS)发生溶胶-凝胶反应,制备PAES/SiO2杂合乳液.透射电镜分析显示,乳胶粒表面被一层无机硅覆盖.傅里叶变换红外光谱结果表明,KH570与丙...     

喷雾干燥-碳热还原法制备介孔球形LiFePO4/C正极材料

以聚乙二醇(PEG)为辅助模板剂和碳源,以廉价的三价铁为铁源,采用喷雾干燥-碳热还原法制备了LiFePO4/C正极材料,并对该材料的微观结构及PEG添加量、焙烧温度等对材料结构和性能的影响进行了表征和研究.结果表明:制得的LiFePO4/C材料呈介孔结构,具有漂亮的差级球状形貌、高的比表面积和容量、优异的循环性;PEG...     

单臂氮氧自由基-抗磁金属Cd(Ⅱ)配合物的合成、结构和磁性研究

采用吡啶取代的单臂氮氧自由基与抗磁金属Cd(Ⅱ)进行配位,得到了一个新的单核配合物[Cd(1M4Py)3(OCN)2·2H2O](其中IM4Py=2-(4'-吡啶基)-4,4,5,5-四甲基咪唑啉-1-氧基自由基).单晶X-射线衍射结果表明,配合物属四方晶系,I4(1)/a空间群;晶胞参数a=1 443 9(3)nm,...     

配置500 MPa钢筋的混凝土梁裂缝试验研究

为研究配置500 MPa纵向热轧带肋钢筋的混凝土梁的裂缝特征及评估相关规范裂缝计算公式的适用性,进行了22根钢筋混凝土梁受弯性能试验,得到22个平均裂缝间距和92组裂缝宽度数据,相应的钢筋应力范围在201~482MPa,这些试验数据可反映钢筋应力较高情况下受弯构件的裂缝开展特点.试验结果表明,按规范GB50010—2002公式计算的平均裂缝间距、平均裂缝宽度和最大裂缝宽度比试验值普遍偏大,二者之比的均值分别为1.127,1.557和1.535.根据试验结果,提出配置500 MPa带肋钢筋的混凝土梁的裂缝宽度计算公式修正建议,并给出梁侧面钢筋处和受拉边缘的平均裂缝宽度的换算关系式,建议公式的计算值和试验值符合较好.     

中亚热带优势灌木根系对土壤抗剪切力的影响

在浙江南部的山体滑坡、泥石流易发区,对中亚热带常绿阔叶林中3种优势灌木植物(檵木、麂角杜鹃和香港黄檀)根系进行野外和室内剪切测试,探讨了灌木植物根系增强土壤抗剪切强度的作用。结果表明:须根相对丰富的植物能明显提高表层土壤的抗剪强度;根系抗拉力和抗剪力均与根径呈幂函数正相关关系;檵木和麂角杜鹃根系抗拉强度与根径呈幂函数负相关关系,而香港黄檀根系抗拉强度与根径无明显相关性;细根或比粗根更有利于土壤加固和抗剪强度的提高。     

如何看待人工智能的发展

人工智能本质上是对人类智能的功能模拟。虽然在某些方面的表现比人类智能更优秀,但是由于其固有的复杂性和技术的局限性,所以充其量只不过是人类智能的延伸,最终在整体上是不能代替人类智能的。     

阴阳直径等分圆的和谐美

用阴阳直径等分圆得到的圆形图案,有简单、对称、和谐之美。     

Skin collagen fiber-based radar absorbing materials

By using skin collagen fiber (CF) as raw material,Schiff base structure containing CF (Sa-CF) was synthesized through CF-salicylaldehyde reaction.Then a novel radar absorbing material (Fe-Sa-CF) was prepared by chelating reaction between Sa-CF and Fe 3+.The coaxial transmission and reflection method was used to analyze the complex permittivity and complex magnetic permeability of these CF-based materials,and the radar cross section (RCS) method was used to investigate their radar absorbing properties in the frequency range of 1.0-18.0 GHz.Experimental results indicated that the conductivity of CF increased from initial 1.08×10-11 to 2.86×10-6 S/cm after being transferred into Fe-Sa-CF,and its dielectric loss tangent (tanδ) in the frequency range of 1.0-17.0 GHz also increased.These facts suggest that the Fe-Sa-CF is electric-loss type radar absorbing material.In the frequency range of 3.0-18.0 GHz,Sa-CF (1.0 mm in thickness) exhibited somewhat radar absorbing property with maximum radar reflection loss (RL) of-4.73 dB.As for Fe-Sa-CF,the absorbing bandwidth was broadened,and the absorbing intensity significantly increased in the frequency range of 1.0-18.0 GHz where a maximum radar RL of-9.23 dB was observed.In addition,the radar absorbing intensity of Fe-Sa-CF can be further improved by increasing membrane thickness.When the thickness reached to 2.0 mm,the RL values of Fe-Sa-CF were-15.0-18.0 dB in the frequency range of 7.0-18.0 GHz.Consequently,a kind of novel radar absorbing material can be prepared by chemical modification of collagen fiber,which is characterized by thin thickness,low density,broad absorption bandwidth and high absorption intensity.     

Interpretation of the architectural design methods

文章结合笔者近年来的工作实践,从建筑设计因素入手,分析和阐述了建筑设计的几种方法,并提出了自己的一些看法.