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Traditionally the basis for the determination of toxicity has been administration of the test compound, in vivo, to one or more species of experimental animal, followed by examination for clinical signs of toxicity and/or mortality in acute tests. In addition pathological examination for tissue abnormalities is also performed, especially in tests of longer duration. The results of these tests are then used by a variety of extrapolation

It does, however, lead to an imprecision in the nature of the offered service and in the basis of charging, which may prove unacceptable as the multiservice networking market gains maturity In the present chapter, we have sought to establish a more rigorous basis for network engineering where quality of service guarantees are real and veri able..

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91 Talon, J; Horvath, C M; Polley, R; Basler, C F; Muster, T; Palese, P; Garcia-Sastre, A Activation of interferon regulatory factor 3 is inhibited by the in uenza A virus NS1 protein J Virol 2000, 74(17), 7989 7996 92 Donelan, N R; Basler, C F; Garcia-Sastre, A A Recombinant in uenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice J Virol 2003, 77(24), 13257 13266 93 Dauber, B; Heins, G; Wolff, T The in uenza B virus nonstructural NS1 protein is essential for ef cient viral growth and antagonizes beta interferon induction J Virol 2004 78(4), 1865 1872 94 Taubenberger, J K; Reid, A H; Janczewski, T A; Fanning, T G.

This leads us to ignore the advantages of considering an aggregation as a single traf c entity and to require that individual stream and elastic ows be recognized for the purposes of admission control and routing. In other words, transparency, throughput, and accessibility are guaranteed on an individual ow basis, not for the aggregate. Of course, it remains useful to aggregate traf c within the network and ows of like characteristics can share buffers and links without the need to maintain detailed state information. 16.3 OPEN-LOOP CONTROL

techniques to estimate hazard to humans. These tests are summarized in the remainder of this section. While these tests offer many advantages and are widely used, they suffer from a number of disadvantages: they require the use of animals, whose numbers are often deemed unnecessary by both animal rights and animal welfare advocates; they are extremely expensive to conduct, and they are time-consuming. As a result they have been supplemented by many specialized in vitro tests, some of which are summarized in Section 21.6, and research is ongoing to further develop tests with fewer disadvantages.

In this and the next section we discuss traf c control options and their potential for realizing quality of service guarantees. Here we consider open-loop, or preventive, traf c control based on the notion of ``traf c contract'': a user requests a communication described in terms of a set of traf c parameters and the network performs admission control, accepting the communication only if quality of service requirements can be satis ed. Either ingress policing or service rate enforcement by scheduling in network nodes is then necessary to avoid performance degradation due to ows that do not conform to their declared traf c descriptor. 16.3.1 Multiplexing Performance

Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish in uenza virus Philos Trans R Soc London B Biol Sci 2001, 356(1416), 1829 1839 95 Geiss, G K; Salvatore, M; Tumpey, T M; Carter, V S; Wang, X; Basler, C F; Taubenberger, J K; Bumgarner, R E; Palese, P; Katze, M; Garcia-Sastre, A Cellular transcriptional pro ling in in uenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic in uenza Proc Natl Acad Sci USA 2002, 99(16), 10736 10741 96 Schlender, J; Bossert, B; Buchholz, U; Conzelmann, K K Bovine respiratory syncytial virus nonstructural proteins NS1 and NS2 cooperatively antagonize a/b interferoninduced antiviral response J Virol.

Acute toxicity test methods measure the adverse effects that occur within a short time after administration of a single dose of a test substance This testing is performed principally in rodents and is usually done early in the development of a new chemical or product to provide information on its potential toxicity This information is used to protect individuals who are working with the new material and to develop safe handling procedures for transport and disposal The information gained also serves as the basis for hazard classi cation and labeling of chemicals in commerce Acute toxicity data can help identify the mode of toxic action of a substance and may provide information on doses associated with target-organ toxicity and lethality that can be used in setting dose levels for repeated-dose studies This information may also be extrapolated for use in the diagnosis and treatment of toxic reactions in humans.

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