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Antiviral Drug Discovery for Emerging Diseases and Bioterrorism Threats. Edited by Paul F. Torrence Copyright # 2005 John Wiley & Sons, Inc.

antigen Type I reactions include immediate asthmatic responses to allergen, allergic rhinitis (hay fever), atopic dermatitis (eczema), and acute urticaria (hives) The most severe form is systemic anaphylaxis (eg, in response to a bee sting), which results in anaphylactic shock, and potentially death Type II hypersensitivity is the result of antibody-mediated cytotoxicity that occurs when antibodies respond to cell surface antigens Antibodies bound to antigen on the cell surface activate the complement system and/or macrophages, leading to lysis of the target cell Frequently blood cells are the targets, as in the case of an incompatible blood transfusion or Rh blood incompatibility between mother and child The basement membrane of the kidney or lung may also be a target Autoimmune diseases can result from drug treatments with penicillin, quinidine, quinine, or acetaminophen.

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The rst indication that the Weibull distribution might be a good model is obtained by plotting the standardized skewness versus the coef cient of variation for both models and datasets and observing that the points of the datasets are clustered around the Weibull distribution. Figure 15.5(a) demonstrates this for eight complete datasets, Fig. 15.5(b) for eight hour periods of the external AT&T dataset from 18 November to 8 December 1995, and Fig. 15.5(c) for one hour periods of all Web requests of the external AT&T dataset from 18 November to 8 December 1995. The arrival processes are by no means stationary. Indeed, Fig. 15.6(a) shows how the number of Web connections changes over time for the CMU trace from 29 June. Each point represents the number of Web connections that arrived within a 15 minute interval. For the longer external AT&T trace from 18 November, Fig. 15.6(b) shows how many Web connections arrived within each four hour time period. These graphs show clear time of day and day of week dependencies. Nevertheless, we will show in this section that the Weibull distribution provides a good t for the connection interarrival times of TCP connections over all different measurement periods. We start by rst examining the distribution of all connection

Apparently these drugs interact with the cell membrane such that the immune system detects foreign antigens on the cell surface This type of autoimmune disease may also have unknown etiologies Type III reactions are the result of antigen-antibody (IgG) complexes that accumulate in tissues or the circulation, activate macrophages and the complement system, and trigger the in ux of granulocytes and lymphocytes (in ammation) This is sometimes referred to as the Arthrus reaction and includes postinfection sequelae such as rheumatic heart disease Farmer s lung, a pneumonitis caused by molds has been attributed to both type III and type IV, and some of the late phase response (4 6 hours after exposure) in asthmatics may be the result of Arthrus-type reactions Unlike the preceding three types, type IV, or delayed-type hypersensitivity (DTH), involves T cells and macrophages, not antibodies.

Fig. 15.6 (a) Time of day effects for Web traf c in June 1995 CMU dataset. (b) Time of day and day of week effects for Web traf c in external AT&T dataset.

coinfection can dramatically increase both the severity and rate of progression of the liver disease10 HDV affects $15 million of HBV-infected individuals worldwide11 and in the United States the prevalence of HDV has been estimated to be around 70,000 individuals12 To date, effective medical therapy has been lacking HDV is a single-stranded RNA virus with a 17 kb circular genome The viral genome codes for only two proteins known as small and large delta antigens (SHDAg and LHDAg, respectively) These proteins are identical except that the large delta antigen contains an extra 19 amino acids at its carboxyl terminus This extension is the result of a speci c RNA editing event that occurs during replication of the genome13 The complete HDV viral particle consists of a complex of the viral genome, both delta antigen isoforms, all encapsulated by a lipid envelope.

requests, then distinguishing between the application types, next considering application-speci c arrivals over time periods of various length, and nally we present time-dependent models for only a subset of the sources. While one might argue that we are planning to present the most useful models last (after all, arrivals are dependent on the time of day), we choose this order to familiarize the reader with the data and some graphical tools. 15.5.3 All Interarrival Times

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