Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons

Many have hypothesized that cell death in Parkinsons disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP⁺ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP⁺ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, –8, –6 and –7. A time-course study indicated that activation of caspase-2 and –8 occurred upstream of caspase-6 and caspase-7. Upon MPP⁺ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.Received 20 September 2004; received after revision 5 November 2004; accepted 22 November 2004     

高校图书馆大规模馆藏精准迁移模式探讨--以华北电力大学图书馆为例

书库藏书迁移的运作主要在于精心准备和周密筹划。详细介绍了华北电力大学图书馆利用汇文文献信息服务系统的强大分析功能并结合Excel软件的使用技巧,实现大规模馆藏迁移精准排架工作的经验。     

Correcting the January optimism effect

Each month, various professional forecasters give forecasts for next year's real gross domestic product (GDP) growth and unemployment. January is a special month, when the forecast horizon moves to the following calendar year. Instead of deleting the January data when analyzing forecast updates, I propose a periodic version of a test regression for weak-form efficiency. An application of this periodic model for many forecasts across a range of countries shows that in January GDP forecast updates are positive, whereas the forecast updates for unemployment are negative. I document that this January optimism about the new calendar year is detrimental to forecast accuracy. To empirically analyze Okun's law, I also propose a periodic test regression, and its application provides more support for this law.     

Intermittent demand forecasting in the Enterprise: Empirical verification

Forecasting methods are often valued by means of simulation studies. For intermittent demand items there are often very few non–zero observations, so it is hard to check any assumptions, because statistical information is often too weak to determine, for example, distribution of a variable. Therefore, it seems important to verify the forecasting methods on the basis of real data. The main aim of the article is an empirical verification of several forecasting methods applicable in case of intermittent demand. Some items are sold only in specific subperiods (in given month in each year, for example), but most forecasting methods (such as Croston's method) give non–zero forecasts for all periods. For example, summer work clothes should have non–zero forecasts only for summer months and many methods will usually provide non–zero forecasts for all months under consideration. This was the motivation for proposing and testing a new forecasting technique which can be applicable to seasonal items. In the article six methods were applied to construct separate forecasting systems: Croston's, SBA (Syntetos–Boylan Approximation), TSB (Teunter, Syntetos, Babai), MA (Moving Average), SES (Simple Exponential Smoothing) and SESAP (Simple Exponential Smoothing for Analogous subPeriods). The latter method (SESAP) is an author's proposal dedicated for companies facing the problem of seasonal items. By analogous subperiods the same subperiods in each year are understood, for example, the same months in each year. A data set from the real company was used to apply all the above forecasting procedures. That data set contained monthly time series for about nine thousand products. The forecasts accuracy was tested by means of both parametric and non–parametric measures. The scaled mean and the scaled root mean squared error were used to check biasedness and efficiency. Also, the mean absolute scaled error and the shares of best forecasts were estimated. The general conclusion is that in the analyzed company a forecasting system should be based on two forecasting methods: TSB and SESAP, but the latter method should be applied only to seasonal items (products sold only in specific subperiods). It also turned out that Croston's and SBA methods work worse than much simpler methods, such as SES or MA. The presented analysis might be helpful for enterprises facing the problem of forecasting intermittent items (and seasonal intermittent items as well).     

Taming theory with thought experiments: Understanding and scientific progress

I claim that one way thought experiments contribute to scientific progress is by increasing scientific understanding. Understanding does not have a currently accepted characterization in the philosophical literature, but I argue that we already have ways to test for it. For instance, current pedagogical practice often requires that students demonstrate being in either or both of the following two states: 1) Having grasped the meaning of some relevant theory, concept, law or model, 2) Being able to apply that theory, concept, law or model fruitfully to new instances. Three thought experiments are presented which have been important historically in helping us pass these tests, and two others that cause us to fail. Then I use this operationalization of understanding to clarify the relationships between scientific thought experiments, the understanding they produce, and the progress they enable. I conclude that while no specific instance of understanding (thus conceived) is necessary for scientific progress, understanding in general is.     

阿罗不可能性定理和社会选择的无矛盾性问题

2017年2月21日,国际著名数理经济学家、1972年度诺贝尔(Nobel)经济学奖获得者阿罗(K.J.Arrow)于美国辞世。谨作此文,以纪念他在社会选择理论,特别是其中将有关数学应用于研究经济学领域发现的"阿罗不可能性定理"作出的重大贡献。     

基于SHPB试验的高速铁路CRTSⅡ型CA砂浆动态性能

采用分离式霍普金森压杆(Split Hopkinson Pressure Bar,SHPB)试验研究了高速铁路CRTS II型水泥乳化沥青砂浆(CA砂浆)的动态力学性能,并建立了CRTS II型CA砂浆的动态本构关系模型.结果表明:随着应变率的增大,CRTS II型CA砂浆峰值强度逐渐增加,但增加速率随应变率的增大而减小,当应变率从44.17增加至54.79 s-1和从54.79增加至108.47 s-1时,峰值强度分别增加了初始峰值强度的52.28%和7.5%,弹性模量随应变率的变化规律性较差;应变率越大,破坏时的贯通裂纹越多,碎裂程度越大;CRTS II型CA砂浆的比能量吸收随着应变率的增大而增大.所建立的动态本构模型拟合曲线与试验曲线具有较好的一致性.     

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。     

基于人眼状态识别的驾驶员疲劳检测方法研究

提出一种基于眼睛状态识别的驾驶员疲劳状态检测的方法。首先通过建立肤色模型分割出人脸区域,再利用搜索连通域的方法实现眼睛区域的定位;然后计算出眼睛区域的垂直积分投影曲线,提取并比较曲线的特征参数,从而识别眼睛的状态;最后以眼睛闭合时间比率为测量标准实现对驾驶员疲劳程度的检测。实验表明,该方法简单、有效、实时性较好,疲劳检测的正确率较高。     

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。