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exponential size distribution and an arrival rate of 1; ows of class i have sharing 3 parameter ji, where fj1 ; j2 g f1; 2g From the gure we note that the sharing parameters ensure effective discrimination for the transfer time of short documents but that throughput for both classes tends to the limit c 1 r as document size increases The limiting large object throughput is explained by the fact that, whatever its sharing parameter ji, a very long transfer utilizes all the bandwidth except that required by other users, equal on average to cr Results for hyperexponential distributions (not reported here) show that discrimination is more effective as the document size distribution variability increases.

of protease inhibitors lopinavir and ritonavir for HIV treatment) might result in a favorable response when administered early.203,209 A summary of early clinical treatments of SARS can be found in a review by Fujii et al.207 Several types of IFN have been used clinically for viral infections; therefore, testing IFNs in vitro and in vivo would potentially lead to the discovery of drugs immediately available for this new disease. However, IFN activity could be speciesand cell-speci c; therefore, not all of the models are appropriate for evaluation.201, 202,204,210 As always, in vivo studies might be more predictable for the clinical ef cacy in humans.204 In macaques, it was shown that pegylated IFN-a protected type 1 pneumocytes against SARS-CoV infection.211 Other than monkeys, potential animal models for general drug evaluation are SARS virus infection in cats, ferrets, hamsters, and mice.212,213 The genomic sequence of the SARS-CoV has been published. The initial characterization of the viral genome showed this new virus is not closely related to any of the previously known CoVs,214 218 but distantly resembles group 2 CoVs.216,217,219,220 The initial products after translation of the SARS-CoV genome are autoproteolytically processed primarily by the main protease (Mpro, also called the 3C-like protease, 3CLpro) to release a number of nonstructural proteins, including the RNA-dependent RNA polymerase221 (RdRp) and the NTPase/helicase.218,222 These enzymes are attractive targets for HTS and drug design.223,224 Models of SARS-CoV Mpro have been constructed based on the crystal structures for group 1 viruses, that is, human coronavirus (HCoV) strain 229E and transmissible gastroenteritis virus (TGEV, a porcine CoV).225 229 Studies with these models suggested AG7088225,230 30 (an inhibitor of HRV 3Cpro) and L-700,417231 31 (an inhibitor of HIV protease) might be good starting points for drug

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This method calls for testing animals sequentially at one of four doses: 5, 50, 300, or 2000 mg/kg body weight The test begins with a sighting study in which animals are tested, one at a time, at doses selected from the set doses Once clear signs of toxicity appear, additional animals (females, or the more sensitive sex) are dosed at that level for a total of ve animals Subsequent groups of animals may receive doses at higher or lower levels, if necessary, depending on the outcome of the previous group Decision criteria based on the number of animals surviving or showing evident toxicity provide for classi cation decisions The acute toxic class method (guideline OECD 423) aims to identify the appropriate hazard and labeling classi cation and provides a range for lethality rather than a point estimate of the LD50.

It is likely therefore that for a heavy-tailed distribution most document transfers will see an improvement in throughput with an increasing weight, although the improvement is less than proportional and still tends to disappear for exceptionally long documents Note that throughput of large objects is not affected by the rate assigned to the transfer of short objects, which start and nish within the transfer time of the former Overall throughput can therefore be improved by giving priority to short objects.

Groups of three animals (females, or the more sensitive sex) receive one of four or ve doses: 5, 50, 300, 2000 and if necessary 5000 mg/kg body weight Depending on the survival or mortality of the rst group of animals, three or more animals may receive the same or a higher or lower dose The number of animals that survive or die determines the classi cation decisions The up-and-down procedure (Guideline OECD 425) employs sequential dosing, using only a single animal at each step, the dosage depending on whether the previously dosed animal lives or dies The test provides a point estimate of lethality and con dence intervals, and can be used to evaluate lethality up to 5000 mg/kg The main test incorporates elements of range nding and uses a exible stopping point A sequential limit test uses up to ve animals Default dose spacing is 3.

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