Functional and physical communication between oncoproteins and tumor suppressors

The discovery of oncogenes (c-onc’s) and tumor suppressors (TS’s) has led to the concept that cancer arises from defects in each of these classes of genes or their products. More recently, it has been appreciated that c-onc and TS proteins often affect one another’s functions. Within this context, I review the two classical TS’s, p53 and the retinoblastoma protein, and the consequences of their inactivation. The various forms of genomic instability (GI) that underly the high mutation rates of transformed cells are then discussed. Particular emphasis is placed upon the concept that GI is not only an integral part of the transformed state but is a prerequisite. Increased oxidative DNA damage, and/or an inabiliy to repair it, can lead to GI. The review then discusses recent observations showing that loss of the TS protein peroxiredoxin 1 (prdx1) and increased expression of the c-onc protein c-Myc, each leads to increased oxidative DNA damage. The critical nature of the c-onc-TS interaction is underscored by that occurring between prdx1 and c-Myc, with the former protein regulating the production of DNA-damaging reactive oxygen species by the latter. The intimate association between these proteins and others serves as a paradigm for the exquisite balancing act that c-onc’s and TS’s must maintain in order to properly control normal DNA replication and cellular proliferation while simultaneously minimizing the acquisition of potentially neoplastic mutations. Received 10 May 2005; received after revision 3 July 2005; accepted 19 July 2005     

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     

《史记·律书》律数匡正：—兼论先秦管律

《史记·律书》有“黄钟长八寸七分一，宫”的一组律数，至迟从唐代起，人们就把它看作一组弦律数据，并以为原数据甚误而不可解，从而校正勘误。本文经过严格推算后指出：１．该组律数不是弦律。而是管律；２．该组律数的原数据基本上没有错，尤其是“黄钟长八寸七分一”是完全正确的黄钟管长，由于历代校勘家不辨弦律与管律之别，书“七”字改为“十”字，从而认为《律书》中这段文字“误七句、衍二字”，历代的校改本质上是错误的；３．在历代传抄翻刻《史记》的过程中，律数原数据中有三律的律位与数值被窜乱。在更正被窜乱了的这三律之后，作者对原数据小作校正，并补正了原数据中遗漏和误植的二律数值，恢复了《史记》所载的先秦管律的本来面目。     

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。