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.     

基于语料库分析中性名词的演变

语言是文化的载体,其变化可以反映特定的社会文化现象。文章以spokesperson、police officer为研究对象,按照历时方法分析英语中性名词渐增的使用频率及其原因。作者发现: (1)在女权运动影响下,女性主义者对语言进行了“中性化”的改写,由于性别平等意识深入人心,这种改写被整个社会普遍接受;(2)女性主义翻译观鼓励使用中性名词,这对其使用也起到了推动作用。     

牛顿-莱布尼兹公式在与路径无关的曲线积分中的应用

在现有高等数学教材中,对于一元函数的定积分有牛顿-莱布尼兹公式,而对于与积分路径无关的曲线积分,没有给出对应的公式.根据与积分路径无关的曲线积分的充要条件(e)P/(e)y=(e)Q/(e)x,经过严谨的数学推导,得出与路径无关的曲线积分的牛顿-莱布尼兹公式:∫(x2,y2)(x1y1)Pdx+ Qdy=∫(x2,y2)(x1y1)du(x,y)=u(x2,y2)-u(x1,y1).最后,通过实例验证,无论是对与积分路径无关的曲线积分的计算题还是证明题,所给出的公式都是有效的、实用的.     

Test for Heteroscedasticity in Partially Linear Regression Models

Testing heteroscedasticity determines whether the regression model can predict the dependent variable consistently across all values of the explanatory variables. Since the proposed tests could not detect heteroscedasticity in all cases, more precisely in heavy-tailed distributions, the authors established new comprehensive test statistic based on Levene's test. The authors built the asymptotic normality of the test statistic under the null hypothesis of homoscedasticity based on the recent theory of analysis of variance for the infinite factors level. The proposed test uses the residuals from a regression model fit of the mean function with Levene's test to assess homogeneity of variance. Simulation studies show that our test yields better than other methods in almost all cases even if the variance is a nonlinear function. Finally, the proposed method is implemented through a real data-set.     

隐喻型术语的修辞特征研究 ——以经济学英文术语为例

无论是术语命名、术语整理还是术语规范都离不开术语分类,术语的分类研究有助于分析和描述某一类术语的共性特征,昭示其特殊性,使相关研究更具针对性和应用性。基于这一认识,文章以经济学英文术语为例,从结构形式、构词能力以及表情色彩等三方面来描述隐喻型术语这一特殊类别术语的修辞特征,并探讨这些修辞特征对此类术语认知与交际的意义。     

破除“西部意识”:西部高等教育全面振兴的思路与策略

全面振兴西部高等教育是推进新时代西部大开发的重要方面,是《中国教育现代化2035》重点部署的十大战略任务的重要内容。西部高等教育振兴已取得很大成绩,但全面振兴仍在路上,其面临的真正约束是“西部意识”的思想约束。因此,西部高等教育的全面振兴,需要破除“西部意识”,突破思想约束。要坚持追求卓越,切实提高西部高等教育定位站位,确立西部高等教育志存高远、对标一流的发展意识,激发不懈奋斗、追求卓越的精神动力。要坚持问题导向,深化改革,通过建构信息化时代西部高等教育发展新生态、加快推进西部高等教育思想观念更新、强化西部高等教育振兴的制度供给、增强西部高等教育自主发展能力等举措,全面增强自我“造血”功能,推动西部高等教育全面振兴,加快实现教育现代化。     

非线性光机械系统中的弱力探测

从理论上研究了包含光学参量放大器的非线性腔光机械系统的弱力探测性能.一方面,发现通过调节光学参量放大器的非线性增益以及输入光场与腔场之间的有效失谐,可以减小压缩正交中约14 dB的量子噪声,从而将弱力探测灵敏度提高2倍以上.另一方面,分析了非线性腔结合零差测量产生的反作用噪声相消现象并且实现量子非破坏测量的方法.     

安徒生与王尔德童话拯救模式的比较研究

在施救者与被救者、被救者困境与拯救目标、拯救结果等三个方面，安徒生与王尔德的童话在拯救模式上存在鲜明的差异。安徒生童话中要拯救的是有深入交流的“那个人”，拯救目标涉及到个体的生死、罪行和毁灭，拯救结果具有神圣和美好的特质；而王尔德笔下的被救者则是匿名的一个社会或特指的一类人，在拯救目标层面王尔德更关注社会性的功利、财产福祉以及日常道德问题，拯救结果更倾向为悲剧。拯救模式的差异与两位作者所处的不同基督教文化有着密切关系。