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.     

城市公共空间与大众健康--19世纪英国城市公园发展的启示

在城市发展和改造过程中,英国近代城市先后着手进行城市公共空间———公园建设,从而掀起了一场造园运动。这场运动既是英国城市发展的必然结果,同时也是解决城市环境问题、提高大众健康水平的需要。而公园等公共空间的建设,为居民提供了一个锻炼与休闲的空间,有利于提高居民的健康水平。健康的人居环境,为各阶层民众提供了聚会的场所,体现了社会成员和谐相处的精神,成为英国资本主义成熟的重要表现之一。     

简论知识经济时代创新人才的继续教育培训模式

随着以科技创新为主要特征的知识经济时代的来临 ,继续教育要适应现代社会发展的需要 ,培养具有创新意识、创新能力的高素质人才 ,必须在教育观念、培养目标、教学内容、教学方法、教学手段、师资队伍等方面进行改革和创新 ,探索出适应知识经济时代需要的创新人才继续教育培训模式。     

载波相位平滑GPS伪码伪距的研究

分析了全球定位系统接收机可获取的观测量。给出了载波相位平滑伪码伪距的一个递归算法结构。讨论了平滑算法初值的设定和构造伪距前向预测值，并对各种情况进行了统计分析。文中还给出了平滑算法的性能评估，结论表明载波相位平滑技术可大大改善伪距观测精度。改善程度与该算法中的权重因子和递归时间密切相关     

顾客价值创新:战略分析的基点

传统的战略分析是以竞争为基点的。其目的是如何比竞争对手做得更好。在这种思维指导下 ,企业经营往往产生竞争激烈、市场不敏感、反应性行为、缺乏创新等后果。在复杂多变的环境中 ,战略分析应转移到顾客价值创新上来。顾客价值创新战略通过为顾客提供完全新型或得到重大改进的价值而使企业经营与竞争无关。顾客价值创新战略与竞争基点战略在战略导向、对竞争的认知及态度、企业本身实力的认识等具有明显不同的特征 ;进行顾客价值创新可以按照顾客价值创新循环机制进行 ,这一循环机制以顾客消费流程分析为起点 ,由创新机会认别、资源需求分析及价值创新实施等环节构成。     

一般Gauss－Markov模型下一般可估函数的线性充分性和线性完全性

发展了Ｂａｋｓａｌａｒｙ和Ｄｒｙｇａｓ提出的一般Ｇａｕｓｓ－Ｍａｒｋｏｖ模型中线性充分性、最小充分性和完全性的概念，用Ｒａｏ的最小二乘统一理论，给出了这些概念的刻划定理。     

庄子哲学的历史渊源

庄子哲学思想产生于楚国独特的历史土壤。楚国历史悠久的天文学,为庄子的朴素唯物的天道观提供了科学基础;楚人是《易经》与阴阳家的鼻祖,其辩证的思维方式,为庄子哲学提供了“切玉刀”;楚国在长期而独特的历史道路中成长的民族精神,为庄子哲学提供了丰厚的精神营养。     

Robust confidence interval for a residual standard deviation

The residual standard deviation of a general linear model provides information about predictive accuracy that is not revealed by the multiple correlation or regression coefficients. The classic confidence interval for a residual standard deviation is hypersensitive to minor violations of the normality assumption and its robustness does not improve with increasing sample size. An approximate confidence interval for the residual standard deviation is proposed and shown to be robust to moderate violations of the normality assumption with robustness to extreme non-normality that improves with increasing sample size.     

Uncertainty Analysis for Computer Model Projections of Hurricane Losses

Projecting losses associated with hurricanes is a complex and difficult undertaking that is wrought with uncertainties. Hurricane Charley, which struck southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting damages from these storms. Due to shifts in the track and the rapid intensification of the storm, real-time estimates grew from 2 to 3 billion dollars in losses late on August 12 to a peak of 50 billion dollars for a brief time as the storm appeared to be headed for the Tampa Bay area. The storm hit the resort areas of Charlotte Harbor near Punta Gorda and then went on to Orlando in the central part of the state, with early poststorm estimates converging on a damage estimate in the 28 to 31 billion dollars range. Comparable damage to central Florida had not been seen since Hurricane Donna in 1960. The Florida Commission on Hurricane Loss Projection Methodology (FCHLPM) has recognized the role of computer models in projecting losses from hurricanes. The FCHLPM established a professional team to perform onsite (confidential) audits of computer models developed by several different companies in the United States that seek to have their models approved for use in insurance rate filings in Florida. The team's members represent the fields of actuarial science, computer science, meteorology, statistics, and wind and structural engineering. An important part of the auditing process requires uncertainty and sensitivity analyses to be performed with the applicant's proprietary model. To influence future such analyses, an uncertainty and sensitivity analysis has been completed for loss projections arising from use of a Holland B parameter hurricane wind field model. Uncertainty analysis quantifies the expected percentage reduction in the uncertainty of wind speed and loss that is attributable to each of the input variables.