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which can be complicated to use. Then we will discover a way to simplify the description of the overall cascade by taking into account special characteristics of some of its parts. This will lead us to a standard cascade, composed of unilateral modules separated by interconnects (e.g., cables) that have well-controlled impedances. The unilateral modules, usually active, have negligible reverse transmission. The passive cables are well matched at the standard impedance (e.g., 50 ) of the cascade interfaces; these are the impedances used in characterizing the modules. It is common to specify the desired performance of each module plus allowed variations from that ideal. The desired performance includes a gain and standard interface impedances. The allowed variations are given by a gain tolerance and the required degree of input and output impedance matches, expressed as maximum SWRs or, equivalently, return losses or re ection coef cient magnitudes (see Appendix F.2). These are the parameters required for determination of the performance of the standard cascade. We will also nd ways to t bilateral modules into this scheme. We will also consider the case where the modules are speci ed in terms of their performance with various nonstandard interface impedances (e.g., 2000 j 500 ), and we will discover how to characterize cascades of these modules. For cases where it may be desirable to include these nonstandard cascades as parts of a standard cascade, we will determine how to describe them in those terms. Finally, we will study the use of sensitivities in analyzing cascade performance. Many varieties of power gains are described in Appendix G. If all interfaces were at standard impedance levels (e.g., 50 everywhere), these gains would all be the same, but the usually unintended mismatches lead to differing values for gain, depending on the de nitions employed.

a/2

Rectifiers or inverters use thyristors which need a temporal reference allowing switching to take place at predetermined times. This temporal reference comes from the three-phase voltage system. If the voltage almost reaches zero during a fault, the reference disappears which may lead to disturbances upon re-initialization of the process.

theme here is that additional model complexity should be introduced only if it is useful. In this respect, a constructively simple approach is fundamentally different from a simplistic approach that involves adopting simplicity naively and precludes any further model development. Note that this approach to modelling in a particular instance is the reverse of the overall approach just discussed. This reversing of directions is not inconsistent. The craft skills required to use the process effectively in a particular instance are developed within the overall approach outlined earlier in this chapter. Usually additional model complexity proves useful (constructive) because it:

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that hostile environment This drug misoprostol (Fig 11) is indicated for reducing the propensity for NSAID-induced ulcers in patients in high-risk populations such as the elderly on high-dose chronic anti-in ammatory regimes or individuals with a previous history of ulcers The drug is also used off-label as an adjunct to the arbotifacient mifepristone (RU-486) that is discussed in the chapter on steroids Misoprostol is virtually the only prostaglandin-derived drug to have achieved much of a market in spite of the enormous expenditure of time and money devoted to the eld in both the private and public sectors Research of NSAIDs had pretty much run its course by the 1990s The close mechanistic connection between activity and the side effect seemed to preclude the likelihood of nding a drug that would divorce those properties.

There was something that he did not like about them It was not that the diamonds were bad; quite the opposite, he said that they were too nice Each diamond was clear in color and free of any aws He muttered and said that it was not what he had expected..

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Earlier discussions in this volume have noted that more detailed experiments on enzymes have time and again led to the nding that they exist in subcategories Such ndings also sometimes led to the discovery of new classes of drugs This has recently also been the case with NSAIDs Research on the DNA that codes for the synthesis of COX led to the discovery that this enzyme too existed in two forms32 These were designated COX-1 and COX-2, forsaking in this case the use of Greek letters It was found within a short time that COX-1 is the main enzyme responsible for maintaining the gastric mucosa, and both it and COX-2 were involved in prostaglandin production at most other sites33 A drug that was selective for COX-2 would at least in theory have anti-in ammatory activity without the attendant effect on the gastric mucosa.

It might be noted in passing that some quite recent research has led to the identi cation of yet another variation of this enzyme That subcategory, COX-3, is said to act at only the analgesic and fever-causing sites This would account for the activity of drugs such as acetaminophen, which are devoid of anti-in ammatory activity34 The structural lead for the class of drugs that are selective for COX-2 actually came from a quite unexpected source that traced back almost half a century35 Very few practical sources of steroids were available when the sex steroids were discovered in the 1930s As noted in the chapter on steroids, this led to the development of the nonsteroid estrogens The nonsteroid estrogen antagonists comprised a further extension of that research The announcement by a group at Richardson Merrell that one of those compounds, MRL-41 (Fig.

310 160 310 220 310 275 255 300 200 325 145 300 85 275

12), showed good antifertility activity in rats led a number of competitors to launch their own programs based on that structural lead Although it was known by then that a steroid oral contraceptive was in the late stages of development, it was thought that a nonsteroid might.

Then, using equation [9.12], this vector is the solution of equation X Q = 0, and, using equation [9.11], it is less than or equal to , component per component. Hence the sum of its components is nite. Normalizing it (i.e. dividing it by this sum), we obtain , a distribution solution. But the distribution solution is unique, so = = . The normalizing equation can be written as:

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