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Androgen Receptor Chemicals that bind to the androgen receptor in an antagonistic fashion include the pharmaceuticals spironolactone, cimetidine, cyperoterone acetate, and hydroxy utamide Environmental chemicals that have been shown to act as androgen receptor antagonists include the metabolites of the agricultural fungicide vinclozolin, the DDT metabolite p, p -DDE, some hydroxylated PCBs, and the organophosphate insecticide fenitrothion The consequence of androgen receptor antagonism is typically considered demasculinization (loss of male traits) Demasculinizing effects of antiandrogens in laboratory animal studies have included reductions in the size of the ventral prostate and seminal vesicle weights along with deformities of the penis Glucocorticoid Receptor Some drugs (ie, mifepristone) elicit antagonistic activity toward the glucocorticoid receptor This property has been associated with adverse side effects of some drugs and also has been capitalized upon therapeutically for the modulation of the glucocorticoid receptor.

The result in each case is a time series of one million data points; using such extremely long series increases the reliability of statistical measurements of selfsimilarity Although most of the runs reported here were done with a 2-server=32client bottleneck con guration (Fig 141), other con gurations were tested including performance runs with the number of clients varying from 1 to 132 The bottleneck link was varied from 15 Mb=s up to OC-3 levels, and buffer sizes were varied in the range of 1 128 kB Non-bottleneck links were set at 10 Mb=s and the latency of each link was set to 15 ms The maximum segment size was xed at 1 kB for the runs reported here.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, and Veterans Administration Medical Center

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Antiglucocorticoids typically are steroidal compounds that are capable of binding to the receptors but are relatively ineffective in activating the receptor As such, these compounds are typically mixed agonists/antagonists (see below) Glucocorticoid receptor antagonists can adversely affect growth, development, and other glucocorticoid-regulated processes (Table 171) Little is known of the ability of environmental chemicals to function as glucocorticoid receptor antagonists Mixed Agonists/Antagonists Chemicals often can function as either a receptor agonist or antagonist depending on the level of endogenous hormone A weak agonist may bind to a receptor and stimulate some low-level receptor-mediated activity in the absence of the endogenous hormone However, in the presence of the hormone, binding of the xenobiotic to the receptor may prevent binding of the endogenous hormone, and if the xenobiotic is a much weaker activator of receptor-mediated activity, then the net effect is loss of activity.

For any reasonable assignment to bandwidth, buffer size, mean le request size, and other system parameters, it was found that by adjusting either the number of clients or the mean of the idle time distribution di appropriately, any intended level of network contention could be achieved..

Thus, in the presence of the endogenous hormone, the xenobiotic functions as a receptor antagonist Whether a weak xeno-agonist functions as an agonist or antagonist depends on (1) the concentration of the xeno-agonist, (2) the binding af nity of the xeno-agonist to the receptor, (3) the concentration of the endogenous hormone to the receptor, and (4) the binding af nity of the endogenous hormone to the receptor These compounds are classi ed mixed agonists/antagonists..

14.4 14.4.1

Although a wide selection of antibiotics exists for treating bacterial infections, our arsenal of effective antiviral agents is more limited. This is a challenge for treating many acute and chronic viral infections of traditional medical importance. The challenge is even greater when considering viral bioterror threats. Vaccines have been the classic bulwarks against viral diseases, but such an approach has a variety of important limitations when planning for biodefense against a viral agent employed as a weapon. For one, vaccines traditionally take several years to develop and test. Thus, they may not be available to counter an immediate threat. Second, they require an a priori knowledge of the speci c viral agent to be targeted information that may not be forthcoming. Finally, with current technology and distributed knowledge base it may be relatively easy for an individual to purposely engineer a virus capable of eluding the epitopes targeted by a given vaccine. To address these gaps in our biodefense strategy, ideally, one would like to have a drug preferably orally available and with low side effects with potential for broad-spectrum antiviral activity. This might allow its administration even before a precise identi cation of the speci c threat is made in the eld. Perhaps most critical for confronting viral bioweapons in the near-term, however, is that such a drug be

An important characteristic of our proposed mechanism for traf c self-similarity is that the sizes of les being transferred are drawn from a heavy-tailed distribution. A distribution is heavy tailed if P X > x $ x a as x 3 I;

Effects of receptor agonists or antagonists on endocrine related processes are often described as being either organizational or activational. An organizational effect of an endocrine toxicant is one that typically results from neonatal or prenatal exposure during which time hormones are directing various irreversible aspects of development.

Antiviral Drug Discovery for Emerging Diseases and Bioterrorism Threats. Edited by Paul F. Torrence Copyright # 2005 John Wiley & Sons, Inc.

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