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This work led to the perhaps surprising nding that the mother of all NSAIDs, aspirin, in fact quite effectively inhibited the action of the cyclooxygenase (COX) enzyme, sometimes called prostaglandin synthetase Interference with the action of the enzyme in effect reduced levels of thromboxanes and other pro-in amatory prostaglandins30 This nding was not con ned to aspirin; all other known NSAIDS, it was found, in fact owed their activity to inhibition of the COX enzyme The use of the singular for the latter substance re ects the state of knowledge at that time More detailed research later showed that the ubiquitous products of the arachidonic acid cascade play bene cial as well as injurious roles One of the latter functions helped explain the most prominent side effect of NSAIDs as a class, that is, their propensity to lead to the development of gastric and duodenal ulcers.

Figure 4.3 The minimum cost and mean cost as a function of generation when the subjective cost function was used (our judgment as to how close the song associated with a chromosome came to the actual tune of Mary Had a Little Lamb ).

convey the more restricted neurobiological definition. We do not, for example, see a kind of encapsulated arrogance in the case of Leonard, the librarian.

This starts with the fact that the stomach is amply supplied with highly acidic juices that contain enzymes such as peptidases and proteases, a combination that is required for digesting proteins The specialized layer of cells and mucus that line the interior of that organ in effect protects its own proteinaceous structure from those digestive juices Prostaglandins, it was found, play a very direct role in maintaining that protective layer; this is especially important in secretion and maintenance of the mucus layer Inhibition of the COX enzyme decreases levels of prostaglandins and thus the very necessary protective layer The very mechanism by which NSAIDs act at the same time accounts for their salient side effect The stomach irritating and ulcerogenic activity of this class thus turns out to be a simple extension of their mode of action31 Locally administered prostaglandins could at least in theory overcome that side effect.

(1.18)

Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: The Pediatric OCD Treatment Study (POTS) randomized controlled trial Journal of the American Medical Association, 292, 1969 1976 Pegalow, C H, Macklin, E A, Moser, F G, & Names, N M (2002) Longitudinal changes in brain magnetic resonance imaging ndings in children with sickle cell disease Blood, 99, 3014 3018 Pelham, W E, & Fabiano, G A (2008) Evidence-based psychosocial treatments for attention-de cit/hyperactivity disorder Journal of Clinical Child and Adolescent Psychology, 37, 184 214 Pelham, W E, Fabiano, G A, & Massetti, G M (2005) Evidence-based assessment of attention de cit hyperactivity disorder in children and adolescents Journal of Clinical Child and Adolescent Psychology, 34, 449 476 Pelham, W E, Gnagy, E M, Greiner, A R, Hoza, B, Hinshaw, S P, Swanson, J M.

1. Richard Barovick, Outsourcing Export Financing, World Trade (October 2003), pp. 58 59. 2. John Harney, Staking a Claim to Excellence with Offshore Outsourcing, OutsourcingOffshore.com (March 2003). 3. Kathleen Goolsby, Truckloads of Treasures, Outsourcing Journal (February 2002). 4. Kim S. Nash, Sears: The Return on Returns, Baseline (January 17, 2003). 5. Leslie Hansen Harps, Making Dollars and Sense Out of Logistics, Inbound Logistics (March 2002). 6. Kit Davis, Blue Christmas RIS News (January 2002). 7. Kim S. Nash, Getting It Back, Baseline News (January 2003). 8. Jeffrey Schwartz, The Art of the Deal, VARBusiness (May 26, 2003), pp. 57 59. 9. The Value of Utility Service Options, Computer Finance (February 2003), pp. 2 4. 10. AMR Warns of Negative Impact of Utility Computing Model, MultiMedia Futures (August 8, 2003), pp. 6 7. 11. Much of this discussion has been derived from an online case study of the Kohler API outsourcing relationship at www.apioutsourcing.com/cs_kohler.asp. 12. Amazon Unit to Offer Outsourced Web Stores, Computergram Weekly (June 11, 2003). 13. Lee Copeland, Borders Turns to Amazon for Outsourcing, Computerworld (April 16, 2001). 14. Amazon.com Launches New Services Subsidiary, Material Handling Management (August 2003). 15. Michael Fitzgerald, Amazon Finds Profits in Outsourcing, CIO (October 15, 2002). 16. Linda Rosencrance, Amazon Outsources Additional Data Center to Equinix, Computerworld (July 23, 2003). 17. Transformational Outsourcing, InfoWorld (January 3, 2003). 18. Accenture and BC Hydro in Agreement Valued at Nearly $1 Billion, News Release (February 2003). 19. BC Hydro and Accenture Plan to Offer Services to Utilities Throughout North America, Creative Resistance (July 18, 2002). 20. Wesley Bertch, Why Offshore Outsourcing Failed Us, Network Computing (October 16, 2003), pp. 65 68.

The compounds in the natural series are, however, too quickly destroyed in the stomach to be of any use Chemists at G D Searle were able to synthesize a congener that survived.