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Traf c engineering for a multiservice network handling both stream and elastic traf c is still a largely unexplored eld. In this section we suggest how it may be possible to generalize the methods and tools developed over the years for dimensioning the telephone network. 16.6.1 Provisioning for Stream Traf c

It is necessary, however, to pay close attention to the skin at the point of application because local effects may be as important as systemic ones.

To determine the network capacity required to meet a target blocking probability for stream ows, it is necessary to make assumptions about the arrival process of new demands, their rate, and their duration For illustration purposes, we consider a simple traf c model consisting of one link receiving traf c from a very large population of users Details and more general models may be found in Roberts et al [26] for example First assume that it is possible to identify m distinct homogeneous classes, ows of each class having a common rate distribution Flows from class i arrive according to a Poisson process of intensity li (requests per second) and have an expected duration of 1=mi seconds Their peak rate is pi .

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Antisense oligonucleotides containing modi ed residues have been employed: modi ed phosphorothioate oligonucleotides in which the C-5 atoms of uridines and cytidines were replaced by propynyl groups caused a signi cant inhibition of DENV-2.272 The antisense oligomer AVI-4020, which contains morpholino backbone, was shown to cross the BBB in infected animals. This drug is currently in a Phase I/II clinical trial for WNV infection.273 There have been a number of infectious clones and subgenomic replicons reported in the literature including those of YFV, JEV, DENV (types 2 and 4), tickborne encephalitis virus (TBEV), and WNV.274,275 (See references cited in a review by Shi.252) These reverse genetics systems, full-length infectious cDNA clones, and replicon systems could be utilized to develop cell-based HTS assays to screen chemical libraries for the identi cation of future novel inhibitors.252,253,276,277 3.6 INHIBITORS OF ALPHAVIRUSES

Twenty-Eight- to Ninety-Day Inhalation Tests. Inhalation studies are indicated whenever the route of exposure is expected to be through the lungs. Animals are commonly exposed for 6 to 8 hours each day, 5 days each week, in chambers of the type previously discussed. Even in those cases where the animals are maintained in the inhalation chambers during nonexposure hours, food is always removed during exposure. Nevertheless, exposure tends to be in part dermal and, due to grooming of the fur, in part oral. Environmental and biologic parameters are the same as those for other subchronic tests, as are the routine end points to be measured before, during, and after the test period. Particular attention must be paid, however, to effects on the tissues of the nasal cavity and the lungs because these are the areas of maximum exposure. If the test material is particulate, consideration must be given to the particle size and its inhalation potential. Particles of 4 microns in size are considered to be inhalable; larger particles will be cleared from the respiratory tract by ciliary action and subsequently swallowed (oral exposure) or expelled by sneezing or expectoration.

For a xed (fairly large) link capacity c, the impact of a ow of class i on the probability of data loss can be summarized in a single gure, the effective bandwidth: the effective bandwidth ei is such that the P probability of data loss is negligible (less than a target value) as long as ni ei c, where ni is the number of class i ows in progress Although measurement-based admission control does not rely on the identi cation of the different classes (a new ow is denied access if its peak rate is greater than a real-time estimate of available bandwidth), for dimensioning purposes we can P assume a ow of class j will be blocked if ni ei > c ej With this blocking condition and the assumption of Poisson arrivals, the distribution of the ni has a wellknown product form enabling computation of the blocking probability.

Note that blocking probabilities and data loss rates are insensitive to the distribution of ow duration A reasonable approximation for the blocking probability of a ow with peak rate pi when c is large with respect to the ei is given by Bi % where a P ei li =mi , d P pi E a=d; c=d ; d 16:1.

Chronic tests are those conducted over a signi cant part of the life span of the test animal. The duration of a chronic study is generally one year or more. Typically rat and dog are the preferred species; for carcinogenicity studies, rats and mice are used.

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