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Indeed, it is known that the response time performance of a shared resource is optimized on using the shortest remaining processing time (SRPT) rst scheduling discipline: a controller is assumed to know the remaining volume of data of all documents to be transferred and devotes link capacity exclusively to the smallest; if a new arrival concerns a document whose size is less than that of the document in service, the latter is preempted; any preempted transfer resumes service where it left off, as soon as its remaining volume is again smaller than that of any other pending request The performance of SRPT was studied by Schrage and Miller [30] They derive expressions for the response time R p of a document of size p under an assumption of Poisson arrivals and general service time distribution Figure 16.

a practical antiviral therapy. As detailed below, this hypothesis has now been successfully tested rst using the VLP model system, then with complete infectious virions in a cell culture model, and nally most recently in an animal model of HDV infection.

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2 shows a numerical evaluation of their formulas for exponential and in nite variance Pareto distributed document sizes, respectively Link load is 2, as in the example of Fig 3 161 The p axis, in units of the mean document size, is on a log scale to capture the heavy tail particularly of the Pareto distribution The normalized response time R p =p is considerably less than that of perfectly fair sharing (ie, the processor sharing model), equal here to 3 for all values of p It is interesting to note that, in this system, the response time for medium to large documents improves on passing from short-range to long-range dependent processes Implementation of SRPT in the case of a single link would, of course, be very complex and the appropriate extension of this principle to a network remains unclear.

2 times the previous dose The starting dose should be slightly below the estimated LD50 If no information is available to estimate the LD50, the starting dose is 175 mg/kg A computer program was developed by the US EPA to simplify both the experimental phase of the test and the calculation of the LD50 and con dence intervals For all three guidelines, selection of a starting dose close to the actual LD50 should decrease the number of animals necessary, reduce study duration, and decrease the amount of test substance needed Therefore it is desirable that all information on the test substance be made available to the testing laboratory for consideration prior to.

However, it does provide a clear illustration that fairness, or weighted fairness, is not necessarily a useful objective in bandwidth sharing In particular, both users and network provider stand to gain by employing a ow control protocol that discriminates in favor of short documents The processor sharing model illustrates how performance can deteriorate suddenly as offered load r increases through 1: if link bandwidth c is high, throughput performance is good even when r is close to 1 For heavier loads,.

The discovery that the oncogene Ras is farnesylated and that this prenylation enables both Ras localization to the plasma membrane and Ras-mediated tranformation20 has opened up a ourishing eld of research on prenyltransferase inhibitors. For example, BZA-5B was developed as a speci c inhibitor of farnesyltransferase.21 BZA-5B was shown to inhibit prenylation of the oncoprotein H-RasV12 and abrogate its prenylation-mediated transformation of Rat-1 cells.21,22. BZA-5B was thus a logical choice for evaluating the effect of pharmacologically inhibiting prenylation of another farnesylated protein namely, large delta antigen. Treatment of HDV VLP-producing cells with BZA-5B showed a substantial inhibition of VLP formation at 10 mM concentration of drug and a complete inhibition at 50 mM.23 Surprisingly, minimal cytotoxic effects were observed at any of these concentrations. Indeed, cells can be grown for several generations in BZA-5B without signi cant effects.23 These results demonstrated that prenylation inhibitors (PIs) are valid candidates for preventing HDV particle production. It was important to show, however, that the same effect can be exerted by other types of PIs (i.e., the observed antiviral effect was truly a result of farnesyltransferase inhibition and not related to some other feature of BZA-5B) and to extend this strategy to the inhibition of complete, genome-containing, infectious HDV particles. For these purposes a cell culture system that is capable of producing such infectious particles was utilized and treated with FTI-277,24 a farnesyltransferase inhibitor that is structurally very different from BZA-5B. Dose-dependent inhibition of HDV infectious particle formation at micromolar concentrations of FTI-277 was observed25 (Figure 11.2a). Furthermore, similar ef cacies were achieved against another HDV genotype that is associated with particularly severe clinical disease.25

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