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This in essence deprives the enzyme of fresh glutarate starting material for conversion to mevalonate.19 Lovastatin was the rst of the statins to be introduced into clinical practice (Fig. 9). This fermentation product differs from the lead compound, mevastatin, by the presence of an additional methyl group in one of the fused rings.20 A second fermentation of mevastatin with a different organism introduces an additional hydroxyl group into the same ring.21 The resulting compound, pravastatin, is one of the more prominent of the currently available statins. Partial synthesis gained a very prominent role in the history of antibiotics leading for example to the modi ed cephalosporins. A similar strategy led to the new statin simvastatin. This compound is prepared by replacing the ester side chain present in the other statins with one that has an additional methyl group.22 These fermentation-derived statins share a mevalonic acid-like fragment attached to an all-carbon, six-membered fused-ring portion, called a decalin. This portion of the molecule is possibly involved in transport of the drug to the site of action; it probably also plays a role in tting the molecule on the HMG-CoA binding site. Research in several competing rms concentrated on compounds that were prepared by synthesis in the laboratories of organic chemists instead of fermentation-derived products. This work revealed that fragments that differed widely from the decalin would ful ll the same functions as the decalin. The results from

Since the social planner takes an overall view of network welfare, let us label his problem as X SYSTEM : maximize u i .x i / c.x/ ; subject to x D x 1 C C x n

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The patterns literature with the most impact in the past four years has focused on concrete patterns and pattern languages, often derived from object-oriented application frameworks [John97]. Looking ahead, we expect that future work in the pattern community will expand upon this tradition. For example, the next generation of object-oriented applications and frameworks will embody patterns explicitly. Patterns will also continue to be used to document the form and content of frameworks [SFJ96]. Other key topics and domains that will benefit from concrete pattern mining include the following: Distributed objects. Many patterns associated with middleware and applications for concurrent and networked objects have been documented during the past decade [SC99] [Lea99a], including those in this book. A key next step is to document the patterns for distributed objects, extending earlier work to focus on distribution topics, such as remote service location [JK00] and partitioning, naming and directory services, load balancing, dependability, and security. An increasing number of distributed object computing systems, for example, must provide high levels of dependability to client programs and end-users. With the adoption

The new infrastructure conducted static analysis of the code to verify that it complied with the two coding standards that the architect selected for immediate implementation. It also checked whether code complied with other coding standards, even though the team was not yet required to follow them. Additionally, the con gured infrastructure automatically generated and executed unit test cases for the application. The data collected included the number of rule violations reported by the static analysis tool, the number of code revisions, and the number of failed tests reported by the dynamic analysis tool. The collected data was stored in a reporting system. The reports allowed developers to quickly identify and

to be functioning in the low-average to average range of nonverbal ability/reasoning (see Table 133) These scores are consistent with his previous evaluation In order to assess higher-order executive functions, Demetric was administered the Tower subtest of the Neuropsychological Assessment (NEPSY) On this task, he was required to move three colored balls to target positions on three pegs in a prescribed number of moves In addition, there were rules and time constraints that increase task dif culty and necessitate planning/forethought Demetric scored within the borderline range on this task, suggesting that he has poor planning/sequencing reasoning skills Assessment of linguistic functioning was conducted in order to evaluate expressive and receptive language development Analysis of Demetric s performance indicates that, at the present time, his expressive and receptive language development continue to be signi cantly below nonverbal intellectual expectancy.

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