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It is customary to consider bandwidth sharing under the assumption that the number of contending ows remains xed (or changes incrementally, when it is a question of studying convergence properties) The sharing objective is then essentially one of fairness: a single isolated link shared by n ows should allocate (1=n)th of its bandwidth to each This fairness objective can be generalized to account for a weight ji attributed to each ow i, the bandwidth allocated to ow i then being proportional P to ji = all flows jj The ji might typically relate to different tariff options In a network the generalization of the simple notion of fairness is max min fairness [3]: allocated rates are as equal as possible, subject only to constraints imposed by the capacity of network links and the ow's own peak rate limitation.

Z-DNA binding domain of vaccinia virulence factor E3L,186,187 DNA synthesis processivity factor (A20),188,189 vaccinia core protein protease,190 and vacciniaencoded protein kinases (B1 and F10) and H1 phosphatase.191,192 For a list of selected poxvirus enzymes that could be potential drug targets, see a review by Harrison et al.193

For the previously listed reasons, there has been a concerted effort in recent years to modify the concept of acute toxicity testing as it is embodied in the regulations of many countries and to substitute more meaningful methods that use fewer experimental animals. The article by Zbinden and Flury-Roversi is an excellent summary of the

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The max-min fair allocation is unique and such that no ow rate l, say, can be increased without having to decrease that of another ow whose allocation is already less than or equal to l Max-min fairness can be achieved exactly by centralized or distributed algorithms, which calculate the explicit rate of each ow However, most practical algorithms sacri ce the ideal objective in favor of simplicity of implementation [1] The simplest rate sharing algorithms are based on individual ows reacting to binary congestion signals Fair sharing of a single link can be achieved by allowing rates to increase linearly in the absence of congestion and decrease exponentially as soon as congestion occurs [6].

Table 21.4 Factors Causing Variation in LD50 Values Species Strain Age Weight Gender Health Nutrition Gut contents Route of administration Housing Temperature Time of day Season Human error

3.4 INHIBITORS OF SEVERE ACUTE RESPIRATORY SYNDROME (SARS) Recognizing the potentially high mortality and morbidity associated with SARS, in May 2003, NIAID convened a colloquium entitled SARS: Developing a Research Response to help identify research needs in SARS research clinical research, epidemiology, diagnostic, therapeutics, and vaccines and to help coordinate international research efforts.194 There are four areas being considered as SARS therapeutic research priorities: (1) drug screening (high throughput screening (HTS) assay and assay of existing compounds), (2) antiviral drug design (identi cation of viral targets, structural models of viral targets, design and synthesis of candidates), (3) immunomodulation and other therapies, and (4) preclinical (nonhuman primate and small-animal models) and clinical studies. In order to help accelerate the discovery of new leads for effective SARS countermeasures, NIAID offers a SARS Chip free to researchers for microarray analysis (see http:// www.niaid.nih.gov). A number of research initiatives and funding opportunities are also published on this website. In the area of drug screening, NIAID is participating in a project to screen compounds for in vitro activity against SARS associated coronavirus (SARS-CoV). The project was initiated in a collaborative effort with USAMRIID195 and continued with two domestic institutions under NIAID contracts. At this writing, NIAID is still actively accepting compounds (synthetic compounds and natural products) for screening against SARS-CoV under a con dentiality agreement (see http://www.niaid-aacf.org and http://www.niaid.nih.gov/dmid/ viral). Barnard and co-workers reported that b-D-N 4-hydroxycytidine 26 showed in vitro activity by both cytopathic effect (CPE) inhibition and virus yield reduction assays.196 Calpain inhibitors, such as calpain inhibitor VI 27, also were active in the same study. Combined with the data reported in other studies, it appeared that

It has recently been pointed out that max-min fairness is not necessarily a desirable rate sharing objective and that one should rather aim to maximize overall utility, where the utility of each ow is a certain nondecreasing function of its allocated rate [15, 18] General bandwidth sharing objectives and algorithms are further discussed in Massoulie and Roberts [21] Distributed bandwidth sharing algorithms and associated mechanisms need to be robust to noncooperative user behavior A particularly promising solution is to perform bandwidth sharing by implementing per ow, fair queueing The feasibility of this approach is discussed by Suter et al [29], where it is demonstrated that an appropriate choice of packets to be rejected in case of congestion (namely, packets at the front of the longest queues) considerably improves both fairness and ef ciency 1642 Randomly Varying Traf c.

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