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In an effort to further translate these results into a practical clinical therapy, the ef cacy of prenylation inhibition-based antiviral therapy was evaluated in an in vivo animal model of HDV. This animal model combines an HBV transgenic mouse model26 with hydrodynamic transfection27 of the HDV genome into the tail vein of the mice. The HBV transgene helps supply a source of HBV HBsAg that is necessary for HDV particle formation, while the genome injection establishes highef ciency HDV replication in the mouse hepatocytes.28 This combination enables the production of infectious HDV particles in the mouse liver and their secretion into the blood. Single daily doses of two different farnesyltransferase inhibitors at 50 mg/kg/day were administered to such mice. These compounds were well tolerated, as there were no differences in measures of toxicity as compared to vehicle control. A dramatic effect on HDV viremia, however, was observed with both inhibitors achieving complete clearance of detectable viremia within one

Given the above discussion on possible control options, it is tempting to speculate on the simplest service model capable of meeting identi ed requirements. 16.5.1 Service Classes

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Eye Irritation. Because of the prospect of permanent blindness, ocular toxicity has long been a subject of both interest and concern. Although all regions of the eye are subject to systemic toxicity, usually chronic but sometimes acute, the tests of concern in this section are tests for irritancy of compounds applied topically to the eye. The tests used are all variations of the Draize test, and the preferred experimental animal is the albino rabbit. The test consists of placing the material to be tested directly into the conjunctival sac of one eye, with the other eye serving as the control. The lids are held together for a few seconds, and the material is left in the eye for at least 24 hours. After that time it may be rinsed out, but in any case, the eye is examined and graded after 1, 2, and 3 days. Grading is subjective and based on the appearance of the cornea, particularly as regards opacity; the iris, as regards both appearance and reaction to light; the conjunctiva, as regards redness and effects on blood vessels; and the eyelids, as regards swelling. Fluorescein dye may be used to assist visual examination because the dye is more readily absorbed by damaged tissues, which then uoresce when the eye is illuminated. Each end point in the evaluation is scored on a numerical scale, and chemicals are compared on this basis. In addition to the no-rinse test, some protocols also investigate the effect of rinsing the eye one minute after exposure to determine

We envisage a service model with just two service classes, one based on open-loop control for stream traf c and the other using closed-loop control for elastic traf c In this service model, ows destined for the rst class declare just a peak rate that is actively policed by packet spacing at the network ingress Measurement-based admission control would be used to ensure negligible data loss assuming bufferless multiplexing Although, in practice, a small buffer is necessary to account for the non uid nature of traf c, delay and delay variation remain very small Loss and delay performance are independent of any long-range dependence in the rate process of ows A low loss rate (10 9 , say) is compatible with a reasonable average link utilization (50%, say) if the peak rate of ows is not more than a small fraction of the 1 link bandwidth (100, say) [26, Chap.

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