Alzheimer's disease,neuropeptides, neuropeptidase,and amyloid-beta peptide metabolism

Amyloid-beta peptide (Abeta), the pathogenic agent of Alzheimer's disease (AD), is a physiological metabolite in the brain. We have focused our attention and effort on elucidating the unresolved aspect of Abeta metabolism: proteolytic degradation. Among a number of Abeta-degrading enzyme candidates, we used a novel in vivo paradigm to identify a member of the neutral endopeptidase family, neprilysin, as the major Abeta catabolic enzyme. Neprilysin deficiency results in defects in the metabolism of endogenous Abeta 40 and 42 in a gene dose-dependent manner. Our observations suggest that even partial down-regulation of neprilysin activity, which could be caused by aging, can contribute to AD development by promoting Abeta accumulation. Moreover, we discuss the fact that an aging-dependent decline of neprilysin activity, which leads to elevation of Abeta concentrations in the brain, is a natural process that precedes AD pathology. In this Perspective, we hypothesize that neprilysin down-regulation has a role in sporadic AD (SAD) pathogenesis, and we propose that this knowledge be used for developing preventive and therapeutic strategies through use of a G protein-coupled receptor (GPCR).     

Does Intercultural Education Lead to More Cultural Homogeneity and Tolerance?

Intercultural education is often assumed to lead to more tolerance towards other cultures. It may also entail an acculturation process that will lead to more cultural homogeneity. The European School system provides an interesting experiment in intercultural and multilingual education, which can help us answer these questions. A value survey among European Schools alumni showed that a "European School effect" does indeed seem to exist. Students staying longer at a European School and entering the European Schools system at a younger age form a somewhat more culturally homogenous group. There are also strong indications that European Schools' alumni are much more tolerant towards people from other nations and cultures than their average compatriots. However, it is not completely possible to rule out the possibility that this is caused by a sampling effect.     

A Methodology for Seismic Risk Analysis of Nuclear Power Plants

This methodology begins by quantifying the fragility of all key components and structures in the plant. By means of the logic encoded in the plant event trees and fault trees, the component fragilities are combined to form fragilities for the occurrence of plant damage states or release categories. Combining these, in turn, with the seismicity curves yields the frequencies of those states or releases. Uncertainty is explicitly included at each step of the process.     

How Close Is Close Enough: Public Perceptions of the Risks of Industrial Facilities

Public opinion poll data have consistently shown that the proportion of respondents who are willing to have a nuclear power plant in their own community is smaller than the proportion who agree that more nuclear plants should be built in this country. Respondents' judgments of the minimum safe distance from each of eight hazardous facilities confirmed that this finding results from perceived risk gradients that differ by facility (e.g., nuclear vs. natural gas power plants) and social group (e.g., chemical engineers vs. environmentalists) but are relatively stable over time. Ratings of the facilities on thirteen perceived risk dimensions were used to determine whether any of the dimensions could explain the distance data. Because the rank order of the facilities with respect to acceptable distance was very similar to the rank order on a number of the perceived risk dimensions, it is difficult to determine which of the latter is the critical determinant of acceptable distance if, indeed, there is only one. There were, however, a number of reversals of rank order that indicate that the respondents had a differentiated view of technological risk. Finally, data from this and other studies were interpreted as suggesting that perceived lack of any other form of personal control over risk exposure may be an important factor in stimulating public opposition to the siting of hazardous facilities.     

U.K. competition policy evaluated

This paper surveys the application of U.K. monopoly policy and examines its general impact on industrial structure and market processes. It considers the effects of the Competition Act 1980 in relation to U.K. monopoly control and concludes that unless further measures are introduced, competitive pressures are likely to be weakened over the longer term.     

Biologically Motivated Cancer Risk Models

A two-stage dose response model is proposed for use in cancer risk assessment. The model assumes that transformation probabilities and cellular dynamics are exposure- and time-dependent.     

Mlonte Carlo Techniques for Quantitative Uncertainty Analysis in Public Health Risk Assessments

Most public health risk assessments assume and combine a series of average, conservative, and worst-case values to derive a conservative point estimate of risk. This procedure has major limitations. This paper demonstrates a new methodology for extended uncertainty analyses in public health risk assessments using Monte Carlo techniques. The extended method begins as do some conventional methods--with the preparation of a spreadsheet to estimate exposure and risk. This method, however, continues by modeling key inputs as random variables described by probability density functions (PDFs). Overall, the technique provides a quantitative way to estimate the probability distributions for exposure and health risks within the validity of the model used. As an example, this paper presents a simplified case study for children playing in soils contaminated with benzene and benzo(a)pyrene (BaP).     

Some quantitative concepts of value and utility from a utilitarian point of view

This paper clarifies and interprets some basic quantitative concepts of value, utility and utility function from a utilitarian point of view. First, I discuss the question as to whether value is objective or subjective. I hold that value is subjective and statistical in nature (although from the various subjective values of a certain object a norm can usually be obtained). Second, I emphasize the distinction between use value and exchange value in relation to utility. Third, I propose a law of diminishing incremental interest, which refers to the incremental (marginal) utility of money. Fourth, I identify the utility of money with the von Neumann-Morgenstern utility. Fifth, I question the necessity of the usual normalization of utility functions and the restricted linear transformation (and the consequent concept of strategic equivalence). Sixth, I discuss in detail the terminal values and utilities of a utility function from a philosophical rather than mathematical point of view, particularly the boundedness of a utility function and the magnitudes of V ₀ and U ₀. Finally, I conclude that, in order to be able to have interpersonal comparisons of utility, utility should have the same dimension as value rather than no dimension, and the normalization problem should be reconsidered in the light of terminal values and utilities.     

Retrospective on the utility theory of von Neumann and Morgenstern

This article offers an exegesis of the passages in von Neumann and Morgenstern (1944, 1947, 1953) that discuss their conception of utility. It is occasioned by two factors. First, as we approach the semicentennial of the publication of Theory of Games and Economic Behavior, its immense impact on economic thought in the intervening years encourages serious reflection on its authors' ideas. Second, misleading statements about the theory continue to appear. The article will have accomplished its purpose if it helps others appreciate the genius and spirit of the theory of utility fashioned by John von Neumann and Oskar Morgenstern.