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).     

Large scale communication networks—Design and analysis

The paper discusses the problem of design and analysis of large scale communication systems. An iterative process, composed of a minimum cost network design algorithm and a network performance algorithm, is presented for the solution of these problems. Computational considerations, using these algorithms, are discussed.     

An exploratory study of the influence of the IS function and organizational context on business process reengineering project initiatives

To help evaluate the risk of process reengineering failure and enhance the prospect of its success, three potential sources of influence on BPR initiatives and success are examined in this study. These include the innovative capacity of the organization, IS maturity and strategy-IS interface. It was found that while factors related to IT maturity and influence such as experience in mainframe and client/server computing may facilitate the decision to reengineer, they are not critical in the later stages of the initiative. On the other hand, factors having significant relationships beyond the initial decision include variables pertaining to innovative capacity of the organization and strategy-IS interface. These findings suggest that technical IT competence as a critical enabler is necessary but not sufficient for reengineering success. Based on study findings regarding the innovative capacity of the organization, guidelines for reengineering risk assessment are proposed. In addition, implications of the findings, limitations of the study and opportunities for further research are also discussed.     

Accounting, strategy and AMT investment

One strand in the current debate on AMT investment emphasises technical aspects of investment appraisal. Another calls for a broader focus on wider decision-making processes and strategic considerations. This paper seeks to merge both sets of concerns. It uses two empirical studies of AMT decisions in a number of companies. The first demonstrates specific linkages between manufacturing strategies and financial justifications. The second explores ways in which connections between finance and strategy are constructed and how they are understood and evaluated by decision-makers. We conclude that AMT proposals succeed by linking accounting information to strategic considerations throughout the investment decision process.