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.     

本科教学中逻辑性课程《纳米材料》的主线设计探索

《纳米材料》课程主要讲解纳米材料的结构与性能之间关系的概念与理论,这种定位决定了纳米材料课应采用逻辑教学法.在这种方法下需找到课程逻辑起点,然后沿着起点设计出一条课程主线,建立课程理论体系,从而合理承接培养方案中的课程群.在《纳米材料》中,纳米结构就是逻辑起点,主线就是"结构与性能"的关系.故该门课程应按"结构和性能"这条主线展开.对现行纳米材料课程内容进行分析,大部分内容均可用主线串联起来.该方法为类似的逻辑性课程教学方法改革以及在课程章节内容之间建立逻辑关联提供借鉴.     

循环应力对储气库岩石微观结构及力学性质影响数值模拟

针对储气库循环注采过程中循环应力对储气库岩石产生疲劳损伤的问题。利用颗粒离散元法建立岩心真三轴数值模型,根据岩心室内试验标定数值模型参数,然后对数值模型进行多周期等幅值轴向循环应力加载,研究循环应力对储气库岩石微观结构及力学性质的影响。结果表明:循环应力加载过程中,模型内生成的无黏结接触数量和微裂缝数量逐渐增多,而生成位置受原始裂缝控制明显,模型孔隙度逐渐减小,且模型内无黏结接触数量、微裂缝数量和孔隙度的变化速率均呈递减趋势;相同应力水平下模型侧向应变和轴向应变均增大,但侧向应变占主导地位;模型弹性模量逐渐降低,而模型泊松比和损伤量逐渐增加,且模型弹性模量、泊松比和损伤量的变化速率均呈递减趋势。     

Two Innovative Coalition Formation Models for Dynamic Task Allocation in Disaster Rescues

This paper addresses the problem of multi-objective coalition formation for task allocation. In disaster rescue, due to the dynamics of environments, heterogeneity and complexity of tasks as well as limited available agents, it is hard for the single-objective and single (task)-to-single (agent) task allocation approaches to handle task allocation in such circumstances. To this end, two multi-objective coalition formation for task allocation models are proposed for disaster rescues in this paper. First, through coalition formation, the proposed models enable agents to cooperatively perform complex tasks that cannot be completed by single agent. In addition, through adjusting the weights of multiple task allocation objectives, the proposed models can employ the linear programming to generate more adaptive task allocation plans, which can satisfy different task allocation requirements in disaster rescue. Finally, through employing the multi-stage task allocation mechanism of the dynamic programming, the proposed models can handle the dynamics of tasks and agents in disaster environments. Experimental results indicate that the proposed models have good performance on coalition formation for task allocation in disaster environments, which can generate suitable task allocation plans according to various objectives of task allocation.     

肌肉自发振动过程中结合几率与化学反应速率的变化

定量分析肌球蛋白与肌动蛋白丝的结合几率及相关化学反应的速率常数,对于准确掌握肌肉收缩的内在机制具有非常重要的意义.以肌肉自发振动的实验结果为依据,从振动过程所满足的动力学方程出发,推导出结合几率与肌丝滑行速度及肌节长度之间的定量关系,并求得化学反应速率随肌肉收缩的速度变化而改变的数学规律.结果显示,结合几率的基准值由溶液中主要化学成分的浓度决定;结合几率的变化值与肌肉收缩的速度成正比,与肌节长度成反比;而化学反应速率随收缩速度按指数规律变化.上述结果与实验值基本一致.     

双壁钢套箱锁口围堰拼装施工

围堰是桥梁承台施工的大型临时结构设施,在水上桥梁施工过程中起到重要作用。无内支撑双壁钢套箱锁口围堰在承台施工中的运用较少,由于其使用条件的特殊性,本文结合港珠澳大桥围堰施工实例,简要介绍双壁钢套箱锁口围堰拼装的技术要点。     

木麻黄及2种相思海防林活立木应力波传播速度的影响因素分析

采用应力波技术分析海南岛海防林主要树种、胸径、不同气候分布区、活立木不同方位等因素对活立木应力波传播速度的影响。结果表明:(1)木麻黄应力波传播速度与胸径大小呈极显著正相关,其中S型曲线和倒函数曲线的相关性远好于直线的相关性,但二者之间的相关性主要适用于中小径级范围内,胸径大于16 cm后应力传播波速度基本稳定;(2)不同树种应力波传播速度具有一定的差异性,相同胸径条件下(DBH:12～16 cm),木麻黄Casuarina equisetifolia的应力波传播速度最大(4211.90 m·s-1),马占相思Acacia mangium次之(4025.17 m·s-1),大叶相思Acacia auriculiformis最小(3543.75 m·s-1),且DBH≥18 cm时,各径级木麻黄应力波传播速度也均大于马占相思,表明木麻黄的抗风性能良好;(3)不同气候分布区及活立木不同方位对木麻黄应力波传播速度无显著影响。研究结果对评价海防林不同树种的抗风性能具有重要意义。     

两阶段随机线性优化问题的等价形式

在极小极大两阶段随机线性优化问题中,往往只知道随机变量的概率分布所满足的一些条件,并不能精确求得。文章假设随机变量的一阶矩和二阶矩是已知的,将最坏情况下的条件风险值(CVaR)作为效用函数,基于矩理论和对偶理论,最终将概率分布由一阶矩和二阶矩描述的极小极大两阶段随机线性优化问题转换为可求解的半定优化问题。