Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

外源性H2S通过调节β-位淀粉样前体蛋白裂解酶1表达对PC12细胞APP／Aβ代谢的影响

目的观察外源性硫化氢对嗜铬细胞瘤细胞β-位淀粉样前体蛋白裂解酶1（BACE1）的调节作用,进而探讨其对淀粉样前体蛋白／β-位淀粉样蛋白代谢途径的影响。方法用硫氢化钠作外源性H2s供体,实验设空白对照组、NaHs50μmol／L组、NaHS100μmol／L组和NariS200μmol／L组,按分组浓度处理PC12细胞24h后,RT-PCR和Western blot法检测细胞内BACE1 mRNA及蛋白表达,并用Western blot法继而检测APP代谢过程中关键蛋白APP、C99、C83表达变化,EusA法检测细胞培养液中AB40和AB42水平。结果NaHS在实验浓度范围内从基因与蛋白两个水平上呈剂量依赖性下调BACE1表达,并下调C99、Ap40和Ap42蛋白表达,上调C83蛋白,各NaHS组分别与对照组比较,差别均有统计学意义（P〈0．05）,而对APP蛋白表达没有影响,各组间比较差别无显著性（P〉0．05）。结论外源性H2s具有通过调节PC12细胞BACE1表达下调APP／Aβ代谢的作用。     

压力传感器的硅玻静电键合

针对MEMS压力传感器封装关键技术,从结构仿真和工艺参数等方面研究了一款压力传感器的硅玻静电键合问题,旨在减小封接对压力传感器芯片输出性能的影响。设计并制作键合装置,进而完成实验,最终优化键合温度,电压等参数值,验证最佳温度350~C,理想电压范围500～900V。     

胰岛素信号通路PI3K／Akt对海马神经元β-淀粉样前体蛋白裂解酶1mRNA水平的影晌

目的通过胰岛素和磷脂酰肌醇-3激酶（P13K）抑制剂渥曼青霉素（wortmannin）对P13K／丝氨酸苏氨酸蛋白激酶（P13K／Akt）信号通路的激活和抑制作用,观察P13K／Akt信号通路对海马神经元β-淀粉样前体蛋白裂解酶1（BACEl）mRNA水平表达的影响。方法20只sD大鼠随机分为空白对照组、假手术组、胰岛素组和渥曼青霉素组,海马立体定向注射胰岛素和P13K抑制剂渥曼青霉素。逆转录一聚合酶链反应（RT-PCR）检测P13K／Akt信号传导下游蛋白Akt以及BACEImRNA水平。结果注射胰岛素的海马P13K信号通路下游信号分子：AktmRNA表达上调（分别较空白和阴性对照组P=0．047,P=0．002）,而BACElmRNA表达下调（分别较空白和阴性对照组P=0．004,P=0．01）。渥曼青霉素组的P13K下游信号分子AktmRNA表达明显被抑制（分别较空白和阴性对照组P=0．002,P=0．039）,同时BACEImRNA的表达较对照组上调（分别较空白和阴性对照组P=0．039,P=0．018）。结论胰岛素信号通路P13K／AM可以调节BACEl的转录水平参与阿尔茨海默病的发病机制。     

Germline-specific dgcr8 knockout in zebrafish using a BACK approach

Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development. Our findings establish that Cre/loxP-mediated tissue-specific gene knockout could be achieved using this BACK strategy and that canonical microRNAs play important roles in early embryonic development in zebrafish.     

A Flexible Functional Form Approach To Mortality Modeling: Do We Need Additional Cohort Dummies?

The increasing amount of attention paid to longevity risk and funding for old age has created the need for precise mortality models and accurate future mortality forecasts. Orthogonal polynomials have been widely used in technical fields and there have also been applications in mortality modeling. In this paper we adopt a flexible functional form approach using two‐dimensional Legendre orthogonal polynomials to fit and forecast mortality rates. Unlike some of the existing mortality models in the literature, the model we propose does not impose any restrictions on the age, time or cohort structure of the data and thus allows for different model designs for different countries' mortality experience. We conduct an empirical study using male mortality data from a range of developed countries and explore the possibility of using age–time effects to capture cohort effects in the underlying mortality data. It is found that, for some countries, cohort dummies still need to be incorporated into the model. Moreover, when comparing the proposed model with well‐known mortality models in the literature, we find that our model provides comparable fitting but with a much smaller number of parameters. Based on 5‐year‐ahead mortality forecasts, it can be concluded that the proposed model improves the overall accuracy of the future mortality projection. Copyright © 2016 John Wiley & Sons, Ltd.     

PPAR γ partial agonist, KR-62776, inhibits adipocyte differentiation via activation of ERK

Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2 in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological responses of the ligands. Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009     

实物期权视角的CAPM有效性检验

实物期权对资产定价的非线性影响会导致本质为线性定价的CAPM模型失效.本文以沪深A股2000-2014年间1503家上市公司为样本,利用市值规模、账面市值比、资本支出和总资产回报四个企业特征变量作为实物期权的代理变量,分别对个股贝塔和预期超额收益率进行实物期权调整,给出了经实物期权调整后CAPM有效的证据;而且,较之市值规模和账面市值比,资本支出和总资产回报更加能够反映实物期权对CAPM有效性的影响.此外,实物期权调整对CAPM有效性的影响对处于生命周期早期阶段的企业、高科技行业以及对股权分置改革和次贷危机后的子样本更为明显.     

基于奇异谱分析的我国航空客运量集成预测模型

针对时间序列包含噪声以及单一模型可能存在预测表现不稳定的问题,本文提出了一个基于奇异谱分析(SSA)的集成预测模型,并将其运用于我国年度航空客运量的预测中.首先,采用SSA方法对原始时间序列进行分解和重构,得到一个剔除噪声的时间序列,然后将其作为单整自回归移动平均模型(ARIMA)、支持向量回归模型(SVR)、Holt-Winters方法(HW)等单一模型的输入并进行预测,接着再采用加权平均集成预测方法(WA)将三种单一模型的预测结果进行综合集成.通过与各单一模型、基于经验模态分解方法(EMD)的模型以及简单平均集成预测方法(SA)的预测结果进行对比发现,本文所建模型具有较高的预测精度和较稳定的预测表现.最后,采用本文的模型对我国2014-2016年年度航空客运量进行了预测.