表面粗糙度的激光在线测量

为了克服现有方法在表面粗糙度测量范围和抗震动等方面的不足,分析了最近发展起来的几种动态表面粗糙度测量方法的优缺点,提出采用被测表面激光反射图的暗区比来实现运动表面粗糙度的实时测量。该方法的测量范围可达３０倍跨度,即可测量的表面粗糙度为０．０５μｍ到１．６μｍ或０．４μｍ到１２．５μｍ。分析了试样的运动速度和初试平均光强对暗区比的影响,该方法的测量结果与Ｔｅｌｙｅｒ－ｓｏｆｔ表面形貌测量仪的测量结果很吻合。     

强电场下部分极化反转对铁电复合物ε2的贡献

建立起适合厚片材料测试的非线性介电测试系统和相应的数据处理方法;测得了在不同场强和温度下ＰＺＴ／Ｐ［ＶＤＦ（７７）ＴｒＦＥ（２３）］０３ 型铁电复合物厚片的二阶非线性介电系数;根据Ｙａｍａｄａ 模型拟合（一阶） 介电系数的电场和温度依赖关系得到了退极化场系数Ｌｚ,并由此计算了在各电场和温度下作用于陶瓷粒子的局域场;结果说明在介电系数测试过程中,未预极化复合物试样的二阶非线性介电系数起源于分散相陶瓷粒子在局域场作用下发生的部分极化反转．     

Effects of La3+ and Gd3+ on Ca2+ influx in rat hepatoma H-35 cells

Effects of La³⁺ and Gd³⁺ on Ca²⁺ influx were investigated in rat hepatoma H-35 cells by measuring the initial rate of⁴⁵Ca²⁺ uptake. It was found that the maximum initial rate of Ca²⁺ uptake was increased six-to ten-fold at low concentrations of La³⁺ and Gd³⁺. Kinetic analyses by measuring the initial rate of Ca²⁺ influx at different external Ca²⁺ concentrations indicated the existence of two intracellular exchangeable components in the basal Ca²⁺ system, with low and high affinities for Ca²⁺, and only one class of Ca²⁺ binding sites was observed in the La³⁺-or Gd³⁺-treated cells. For high affinity, La³⁺ and Gd³⁺ increased both kinetic parametersK _m andV _max of basai Ca²⁺ influx. La³⁺ and Gd³⁺ compete directly with Ca²⁺ for Ca²⁺ binding site for low affinity. The kinetics is competitive.     

基于荧光(或磷光)猝灭的氧传感器的研制(Ⅰ)——指示剂的合成及筛选

金属有机络合物被波长合适的光激发可发射荧光或磷光,这种发射光能被氧气猝灭,现合成了13种金属有机络合物,详尽地研究了它们的光谱特性及氧猝灭特性,总结了关联氧浓度（分压）和发射光强度关系的数学模型,从中筛选了两种灵敏度高、测量范围宽、光学稳定性好的氧感应指示剂,即[Ru(bathophen)3](ClO4)2和Pt（TFPP）,用[Ru(bathophen)3](ClO4)2-Cab-O-Sil-Silicone膜和Pt(TFPP)-Silicone膜进行猝灭实验,证明改进的Stern-Volmer方程计算结果与猝灭数据非常一致,可以作为传感器的标定方程。     

Endothelial epsins as regulators and potential therapeutic targets of tumor angiogenesis

VEGF-driven tumor angiogenesis has been validated as a central target in several tumor types deserving of continuous and further considerations to improve the efficacy and selectivity of the current therapeutic paradigms. Epsins, a family of endocytic clathrin adaptors, have been implicated in regulating endothelial cell VEGFR2 signaling, where its inactivation leads to nonproductive leaky neo-angiogenesis and, therefore, impedes tumor development and progression. Targeting endothelial epsins is of special significance due to its lack of affecting other angiogenic-signaling pathways or disrupting normal quiescent vessels, suggesting a selective modulation of tumor angiogenesis. This review highlights seminal findings on the critical role of endothelial epsins in tumor angiogenesis and their underlying molecular events, as well as strategies to prohibit the normal function of endogenous endothelial epsins that capitalize on these newly understood mechanisms.     

Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥ 4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival.     

Multiple regions within 8q24 independently affect risk for prostate cancer

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.     

Essential role for oncogenic Ras in tumour maintenance.

Advanced malignancy in tumours represents the phenotypic endpoint of successive genetic lesions that affect the function and regulation of oncogenes and tumour-suppressor genes. The established tumour is maintained through complex and poorly understood host-tumour interactions that guide processes such as angiogenesis and immune sequestration. The many different genetic alterations that accompany tumour genesis raise questions as to whether experimental cancer-promoting mutations remain relevant during tumour maintenance. Here we show that melanoma genesis and maintenance are strictly dependent upon expression of H-RasV12G in a doxycycline-inducible H-Ras12G mouse melanoma model null for the tumour suppressor INK4a. Withdrawal of doxycycline and H-RasV12G down-regulation resulted in clinical and histological regression of primary and explanted tumours. The initial stages of regression involved marked apoptosis in the tumour cells and host-derived endothelial cells. Although the regulation of vascular endothelial growth factor (VEGF) was found to be Ras-dependent in vitro, the failure of persistent endogenous and enforced VEGF expression to sustain tumour viability indicates that the tumour-maintaining actions of activated Ras extend beyond the regulation of VEGF expression in vivo. Our results provide genetic evidence that H-RasV12G is important in both the genesis and maintenance of solid tumours.     

Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels, which are densely localized in nerve terminals. Because neurotransmitter release is proportional to the fourth power of calcium concentration, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins, and recent evidence indicates feedback regulation of P/Q-type channels by calcium. Although calcium-dependent inactivation of L-type channels is well documented, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the alpha1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.