Estimation of Metabolic Rate Constants in PBPK‐Models from Liver Slice Experiments: What Are the Experimental Needs?

A mechanistic model is presented describing the clearance of a compound in a precision-cut liver slice that is incubated in a culture medium. The problem of estimating metabolic rate constants in PBPK models from liver slice experiments is discussed using identifiability analysis. From the identifiability problem analysis, it appears that in addition to the clearance, the compound's free fraction in the slice and the diffusion rate of the exchange of the compound between culture medium and liver slice should be identified. In addition, knowledge of the culture medium volume, the slice volume, the compound's free fraction, and octanol-water-based partition between medium and slice is presupposed. The formal solution for identification is discussed from the perspective of experimental practice. A formally necessary condition for identification is the sampling of parent compound in liver slice or culture medium. However, due to experimental limitations and errors, sampling the parent compound in the slice together with additional sampling of metabolite pooled from the medium and the slice is required for identification in practice. Moreover, it appears that identification results are unreliable when the value of the intrinsic clearance exceeds the value of the diffusion coefficient, a condition to be verified a posteriori.     

广谱存在论与传统本体论的比较

系统地比较了哲学史上3种典型的本体论(物质本体论、理念本体论、心灵本体论)与广谱存在论的联系与区别,剖析了传统本体论的理论基础和主要特征,阐明了广谱存在论的相关观点。     

An Existential Approach to Risk Perception

Existential, or existential-phenomenological philosophical approaches to the social psychology of risk perception provide a novel framework for understanding issues that are common to all humanity, such as fear of death, freedom and responsibility, isolation and meaninglessness, as these anxieties are a function of existing, or being-in-the-world. These fundamental anxieties can be related theoretically to the ways people perceive risks within social and cultural milieus, and can also be used practically within case studies, as demonstrated in the three examples presented, which examine perceptions of climate change, food-related risks, and environmental awareness via a mixture of quantitative and qualitative techniques. The discussion focuses on the possible insights that can be gained from taking an existential perspective on risk perception, and relates notions of contemporary technologically-oriented societies to the existential challenges faced by individuals and societies in the contemporary world.     

析恩格斯晚年的一个重要观点

恩格斯晚年曾对《共产党宣言》何以这样冠名有一个追忆性的说明 ;在另一地方他又明确讲到“三十年不曾使用”共产主义一词的事。这两段话虽然是在不同时间、地点、情况下说的 ,却有着密切的联系 ,后一段话恰恰是解答为什么会有前段话的说明的根据     

釜山亚运反思北京奥运展望

第十四届釜山亚运会 ,中国代表团以绝对优势 ,位于亚洲各国之首 ,但是与世界体育强国相比较 ,还有一定的差距。本文通过对釜山亚运会的反思 ,具体分析我国的优势项目与不足之处 ,在今后的 6年中 ,全面改进 ,才能使中国军团在北京奥运会再创佳绩。     

文化与河流

文化与河流的关系十分特殊，文化既源于河流，又反过来改造河流。文章重点阐述了文化如何由源于河流到改造河流，如何由被动地改造河流到主动地改造河流的过程。     

What to Do at Low Doses: A Bounding Approach for Economic Analysis

To quantify the health benefits of environmental policies, economists generally require estimates of the reduced probability of illness or death. For policies that reduce exposure to carcinogenic substances, these estimates traditionally have been obtained through the linear extrapolation of experimental dose-response data to low-exposure scenarios as described in the U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment (1986). In response to evolving scientific knowledge, EPA proposed revisions to the guidelines in 1996. Under the proposed revisions, dose-response relationships would not be estimated for carcinogens thought to exhibit nonlinear modes of action. Such a change in cancer-risk assessment methods and outputs will likely have serious consequences for how benefit-cost analyses of policies aimed at reducing cancer risks are conducted. Any tendency for reduced quantification of effects in environmental risk assessments, such as those contemplated in the revisions to EPA's cancer-risk assessment guidelines, impedes the ability of economic analysts to respond to increasing calls for benefit-cost analysis. This article examines the implications for benefit-cost analysis of carcinogenic exposures of the proposed changes to the 1986 Guidelines and proposes an approach for bounding dose-response relationships when no biologically based models are available. In spite of the more limited quantitative information provided in a carcinogen risk assessment under the proposed revisions to the guidelines, we argue that reasonable bounds on dose-response relationships can be estimated for low-level exposures to nonlinear carcinogens. This approach yields estimates of reduced illness for use in a benefit-cost analysis while incorporating evidence of nonlinearities in the dose-response relationship. As an illustration, the bounding approach is applied to the case of chloroform exposure.     

乐教与儒者的宗教情怀

乐教是理解儒家精神不可忽视的重要方面。乐教扎根于“亲亲”之情,具体体现为与“忧患意识”有别,而与“安”“乐”相协调一致的“怛”和“哀”“悲”之情。此情实质上是超越的天道内化为人的心性而落实下来的生命意义与价值得以呈现的方式。儒者虽深知人生之哀、悲,但以乐入手,解悟和转化现实的人生与宇宙,是一大特色。如此,宗教情怀转化为现实的人生关怀,成为特有的礼乐文明的核心内涵。     

Social Stratification and the Division of Household Labor in Japan: The Effect of Wives' Work on the Division of Labor among Dual-earner Families

Abstract:  This article explores the relationship between social stratification and the division of household labor by examining how the contribution to housework by husbands in dual-earner families varies across the Japanese social stratification structure. First, I review previous studies concerning the determinants of husbands' participation in housework and construct four hypotheses regarding the relative resources explanation, the time constraints explanation, the ideology/sex role explanation, and the alternative manpower explanation. Second, I examine the empirical support for these hypotheses in dual-earner couples and the effect of social stratification on husband's participation in housework, which has not been studied thus far. Third, I investigate the effect of social stratification in more detail. According to the results of TOBIT regressions and other supplementary analyses, the principal findings are as follows:

• 1) 

  the relative resources explanation is not supported;