Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis

Haploinsufficiency of Dll4, a vascular-specific Notch ligand, has shown that it is essential for embryonic vascular development and arteriogenesis. Mechanistically, it is unclear how the Dll4-mediated Notch pathway contributes to complex vascular processes that demand meticulous coordination of multiple signalling pathways. Here we show that Dll4-mediated Notch signalling has a unique role in regulating endothelial cell proliferation and differentiation. Neutralizing Dll4 with a Dll4-selective antibody rendered endothelial cells hyperproliferative, and caused defective cell fate specification or differentiation both in vitro and in vivo. In addition, blocking Dll4 inhibited tumour growth in several tumour models. Remarkably, antibodies against Dll4 and antibodies against vascular endothelial growth factor (VEGF) had paradoxically distinct effects on tumour vasculature. Our data also indicate that Dll4-mediated Notch signalling is crucial during active vascularization, but less important for normal vessel maintenance. Furthermore, unlike blocking Notch signalling globally, neutralizing Dll4 had no discernable impact on intestinal goblet cell differentiation, supporting the idea that Dll4-mediated Notch signalling is largely restricted to the vascular compartment. Therefore, targeting Dll4 might represent a broadly efficacious and well-tolerated approach for the treatment of solid tumours.     

肿瘤热疗用Fe3O4磁性纳米粒子的生物相容性研究

研究用于肿瘤热疗的自制Fe3O4磁性纳米粒子的生物相容性.采用MTT试验评价其浸提液体外细胞毒性;溶血试验评价其有无溶血作用;小鼠腹腔注射Fe3O4磁性纳米粒子无菌生理盐水混悬液以测定其LD50;微核试验评价其有无致畸、致突变作用等.MTT结果显示该材料对L-929细胞毒性为0~1级,均属对细胞无毒性范畴;溶血试验中Fe3O4磁性纳米粒子的溶血率为0.514%,远小于5%,表明实验用Fe3O4磁性纳米粒子无溶血作用;昆明小鼠腹腔注射该材料混悬液,其LD50为7.57g/kg体重,其95%的可信区间为6.18~9.27g/kg体重,属实际无毒范畴,且具有较广的安全值范围.微核试验结果表明该材料对小鼠骨髓微核形成率与阴性对照组相比无显著差异,而与阳性对照CTX组相比有显著差异,可以认为该材料无致畸或致突变作用.从实验目前的研究结果来看,自制的Fe3O4磁性纳米粒子具有良好的生物相容性,在肿瘤磁流体热疗方面具有良好的应用前景.     

A novel multi-functional cell-based microphysiometer

This paper presents a novel multi-functional microphysiometer for simultaneous measurements of several extracellular ion concentrations and action potential measurement in living cells based on MLAPS (multi-light addressable potentiometric sensor). In the microphysiometer, sorts of sensitive membranes are illuminated in parallel with n light sources at working frequencies, and the response amplitudes of each frequency component can be measured on-line by parallel processing algorithm. In the experiments, the relations of the extracellular environmental H⁺, Na⁺, K⁺, Ca²⁺ under the effects of western medicines (dilantin, phenobarbital sodium) and Chinese drugs (scutellaria, medlar, hemlock parsley) were analyzed, and the effects of several drugs were evaluated. Moreover, the action potential signals of different cell types (cardiac myocytes and neurons) could be measured and analyzed by LAPS. By detecting these parameters, the system can monitor the real-time process of the cell metabolism and action potential, observe the functional responses of different kinds of membrane-bound receptors, and evaluate the activities of drugs.     

代数曲线相交数的射影不变性

利用复分析的相关知识,证明了PC2中射影曲线F,G的相交数I(P,F,G)在射影变换之下是不变量,然后通过一个例子验证这个结论.     

“传承与教化”——图书馆的核心价值

阐述了"核心价值"一词的准确内涵,分析了图书馆核心价值的基本特性,介绍了关于图书馆核心价值的讨论,指出"传承与教化"就是图书馆的核心价值。     

多层电路结构微带天线的波概念迭代法分析

利用波概念迭代法结合传输线理论分析一种三层电路结构的超宽带微带贴片天线,通过与典型电磁场数值算法的计算复杂度对比,验证波概念迭代法在分析多层电路时计算效率高、计算速度快的优点;利用其计算该天线的回波损耗、方向图和增益等参数,通过与HFSS仿真结果对比,证明该方法在分析多层电路的正确性和有效性.     

质量互变规律在基础化学运动中的应用

从"物质的量"及"运动的量"的改变引起物质性质的改变的实例,说明了质量互变规律在化学中的应用,有助于理解、掌握化学运动的基本规律.     

A robust DNA mechanical device controlled by hybridization topology.

Controlled mechanical movement in molecular-scale devices has been realized in a variety of systems-catenanes and rotaxanes, chiroptical molecular switches, molecular ratchets and DNA-by exploiting conformational changes triggered by changes in redox potential or temperature, reversible binding of small molecules or ions, or irradiation. The incorporation of such devices into arrays could in principle lead to complex structural states suitable for nanorobotic applications, provided that individual devices can be addressed separately. But because the triggers commonly used tend to act equally on all the devices that are present, they will need to be localized very tightly. This could be readily achieved with devices that are controlled individually by separate and device-specific reagents. A trigger mechanism that allows such specific control is the reversible binding of DNA strands, thereby 'fuelling' conformational changes in a DNA machine. Here we improve upon the initial prototype system that uses this mechanism but generates by-products, by demonstrating a robust sequence-dependent rotary DNA device operating in a four-step cycle. We show that DNA strands control and fuel our device cycle by inducing the interconversion between two robust topological motifs, paranemic crossover (PX) DNA and its topoisomer JX2 DNA, in which one strand end is rotated relative to the other by 180 degrees. We expect that a wide range of analogous yet distinct rotary devices can be created by changing the control strands and the device sequences to which they bind.     

辉绿岩单轴及常规三轴压缩下力学特性试验研究

为了分析坚硬脆性岩石在单轴及常规三轴压缩条件下的强度和变形特性,通过在TAW-2000微机控制电液伺服试验机上对辉绿岩进行单轴及常规三轴压缩试验,主要分析辉绿岩在围压为1、3、5、10 MPa时基本物理力学参数的离散程度,其弹性模量的离散程度指标值较小,在0.27%～3.49%波动,能较好地表征辉绿岩的变形特性。试验结果表明:随着围压的增大,岩石峰值应变和残余应变均表现出显著的线性增长关系,可采用一次函数形式拟合,弹性模量、变形模量和泊松比均表现出较明显的非线性增长关系,可采用幂函数形式进行拟合,但并不会随着围压的增大而无限增大,而是趋于一个稳定值,这一规律为实际工程中不同地应力条件下准确选取弹性模量、泊松比等参数提供理论基础;随着围压的增大,岩石的峰值强度和残余强度均呈现出较显著的线性增长关系,可采用一次函数形式拟合,并计算出黏聚力和内摩擦角,为岩石工程设计时强度参数的选择提供参考依据。     

符号几何规划及其可行域修正算法

本文脱离了影响较广泛的文献１、２的思路，不依赖反向几何规划，直接讨论符号几何规划，不增变量个数和约束个数。利用集约化思想构造了一个可行城修正算法。本文还对文献２中的一个疏漏作了修改，增补了文献２的内容