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The aim of developmental and reproductive testing is to examine the potential for a compound to interfere with the ability of an organism to reproduce. This includes testing to assess reproductive risk to mature adults as well as the developing individual at various stages of life, from conception to sexual maturity. Traditionally animal studies have been conducted in three segments : (I) in adults, treatment during a pre-mating period and optionally continuation for the female through implantation or lactation; (II) in pregnant animals treatment during the major period of organogenesis; and (III) treatment of pregnant/lactating animals from the completion of organogenesis through lactation (peri- and postnatal study). Although guidelines addressing treatment regimens have been rather similar throughout the world, required end points measured in adults and developing organisms have varied. International harmonization of guidelines has demonstrated the need for exibility in testing for reproductive and developmental toxicity, and toxicologists are now often challenged to design unique studies to examine potential effects on all the parameters considered in the classical segment I, II, and III studies. In adults, these include development of mature egg and

H5N1 from Hong Kong A/HK/156/1997 H9N2 from Hong Kong A/HK/1074/1999 H7N2 from Virginia H5N1 from Hong Kong A/HK/213/2003; H9N2 from Hong Kong; H7N7 from Netherlands H5N1 from Asia; H7N3 from Canada

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We have in mind two problems: rst, we want to do capacity planning and, second, we want to do real-time connection-admission control and congestion control In both cases, we want to determine whether any candidate capacity is adequate to meet the aggregate demand associated with a set of sources In both cases, we represent the aggregate demand simply as the sum of the bandwidth requirements of all sources In forming this sum, we regard the bandwidth processes of the different sources as probabilistically independent The performance analysis for capacity planning is coarser, involving a longer time scale, so that it may be appropriate to do a steady-state analysis However, when we consider connection-admission control and congestion control, we suggest focusing on a shorter time scale We are still concerned with the relatively long time scale of connections, or scene times in video, instead of the shorter time scales.

sperm, fertilization, implantation, delivery of offspring (parturition), and lactation. In the developing organism, these include early embryonic development, major organ formation, fetal development and growth, and postnatal growth including behavioral assessments and attainment of full reproductive function. These evaluations are usually best carried out in several separate studies.

of cells or bursts, but admission control and congestion control are suf ciently shortterm that we propose focusing on the transient behavior of the aggregate demand process In fact, even for capacity planning the transient analysis plays an important role The transient analysis determines how long it takes to recover from rare congestion events One application we have in mind is that of networks carrying rate-adaptive traf c In this case the bandwidth process could represent the ideal demand of a source, even though it is able to function when allocated somewhat less bandwidth So from the point of view of quality, excursion of aggregate bandwidth demand above available supply may be acceptable in the short-term, but one would want to dimension the link so that such excursions are suf ciently short-lived.

Since viral replication closely mimics the host cell s replication machinery, selective drugs should target speci c viral events in order to avoid unwanted side effects. Therefore, the complexity inherent in antiviral drug discovery requires interdisciplinary approaches. The toolbox needed for such approaches is outlined in the rst major theme of the new NIH Roadmap initiative: New Pathways to Discovery (see http://nihroadmap.nih.gov/). It is anticipated that advances in genomics and proteomics (for NIAID bioinformatics resource centers, see http://www.niaid.nih.gov/dmid/genomes) should be able to provide new pathways to discover vital targets for rational drug design. Characterization of the targets followed by generation of novel combinatorial chemical libraries coupled with screening assays in high-throughput format should accelerate the discovery of novel potent and selective antiviral agents.

In this or other contexts, if the recovery time from overload is relatively long, then we may elect to provide extra capacity (or reduce demand) so that overload becomes less likely However, we do not focus speci cally on actual design and control here; see Duf eld and Whitt [14] for some speci c examples Our main contribution here is to show how the transient analysis for design and control can be done The remainder of this chapter is devoted to showing how to do transient analysis with the source traf c model We suggest focusing on the future time-dependent mean conditional on the present state The present state of each level process consists of the level and age (elapsed holding time in that level).

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