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; Drach, J C; Kitaoka, S; Konno, T Broad-spectrum antiviral activities of neplanocin-A, 3-deazaneplanocin-A, and their 50 -nor derivatives Antimicrob Agents Chemother 1989, 33, 1291 1297 124 Tseng, C K H; Marquez, V E; Fuller, R W; Goldstein, B M; Haines, D R; Mcpherson, H; Parsons, J L; Shannon, W M; Arnett, G; Hollingshead, M; Driscoll, J S Synthesis of 3-deazaneplanocin-A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities J Med Chem 1989, 32, 1442 1446 125 Smee, D F; Alaghamandan, H A; Cottam, H B; Jolley, W B; Robins, R K Antiviral activity of the novel immune modulator 7-thia-8-oxoguanosine J Biol Response Mod 1990, 9, 24 32 126 Smee, D F; Alaghamandan, H A; Jin, A; Sharma, B S.

Numerical inversion can easily be applied with Eqs. (17.29) and (17.30). However, since the time-domain formulas (17.27) and (17.28) involve single convolution integrals, numerical computation of Eqs. (17.27) and (17.28) in the time domain is also a feasible alternative. Moreover, if the underlying distributions have special structure, then the integrals in Eqs. (17.27) and (17.28) can be calculated analytically. For example, analytical integration can easily be done when all holding-time distributions are hyperexponential. In Duf eld and Whitt [15, Section 3] we give a numerical example illustrating how the two approximations compare to the exact conditional mean for a single source with four levels. 17.6 THE VALUE OF INFORMATION

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Extraction methods include lipid solvents, acids and bases, concentrated urea solutions, and solubilization and precipitation of the proteins They tend to underestimate the extent of covalent binding because even covalent bonds may be broken by the rigorous procedures used Newer methods involving dialysis against detergents and separation of adducted proteins will probably prove more appropriate Blood proteins, such as hemoglobin, may be used in tests of human exposure because blood is readily and safely accessible For example, the exposure of mice to ethylene oxide or dimethylnitrosamine was estimated by measuring alkylated residues in hemoglobin The method was subsequently extended to people exposed occupationally to ethylene oxide by measuring N-3-(2-hydroxyethyl) histidine residues in hemoglobin Similarly methyl cysteine residues in hemoglobin can be used as a measure of methylation.

We can use the source model to investigate the value of information. We can consider how prediction is improved when we condition rst, on, only the level and, second, on both level and age. The reference case is the steady-state mean M

DNA-RNA adducts can also be measured in various ways, including rigorous extraction, separation, and precipitation following administration of labeled compounds in vivo, or use of antibodies raised to chemically modi ed DNA or RNA Although many compounds of different chemical classes have been shown to bind covalently when activated by microsomal preparations in vitro (eg, a atoxin, ipomeanol, stilbene, vinyl chloride), these observations have not been developed into routine testing procedures Such procedures could be useful in predicting toxic potential Immunotoxicity Immunotoxicology comprises two distinct types of toxic effects: the involvement of the immune system in mediating the toxic effect of a chemical and the toxic effects of chemicals on the immune system The former is shown, for.

; Jolley, W B Roles of interferon and natural killer cells in the antiviral activity of 7-thia-8-oxoguanosine against Semliki Forest virus infections in mice Antiviral Res 1990, 13, 91 102 127 Smee, D F; Huffman, J H; Gessaman, A C; Huggins, J W; Sidwell, R W Prophylactic and therapeutic activities of 7-thia-8-oxoguanosine against Punta Toro virus infections in mice Antiviral Res 1991, 15, 229 239 128 Smee, D F; Alaghamandan, H A; Gilbert, J; Burger, R A; Jin, A; Sharma, B S; Ramasamy, K; Revankar, G R; Cottam, H B; Jolley, W B; Robins, R K Immunoenhancing properties and antiviral activity of 7-deazaguanosine in mice Antimicrob Agents Chemother 1991, 35, 152 157 129 Smee, D F; Alaghamandan, H A; Ramasamy, K; Revankar, G R.

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example, in tests for cutaneous sensitization, whereas the latter is shown in impairment of the ability to resist infection. Tests for immunotoxicity are not required by all regulatory agencies, but it is an area of great interest, both in the fundamental mechanisms of immune function and in the design of tests to measure impairment of immune function. Both of these aspects are discussed in detail in 19.

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