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1. Reverse mutations in Escherichia coli. This test is similar to the Ames test and depends on reversion of tryptophane mutants, which cannot synthesize this amino acid, to the wild type, which can. The S-9 fraction from the liver of induced rats

^ De s is the diagonal matrix with diagonal elements ^ Dejj s ^ ^ 1 gje s sm Gj 1 gj s ; 2 m G s s j 17:37

can also be used as an activating system in this test. Other E. coli reverse mutation tests utilize nicotinic acid and arginine mutants. 2. Forward mutations in S. typhimurium. One such assay, dependent on the appearance of a mutation conferring resistance to 8-azaguanine in a histidine revertant strain, has been developed and is said to be as sensitive as the reverse-mutation tests 3. Forward mutations in E. coli. These mutations depend on mutation of galactose nonfermenting E. coli to galactose fermenting E. coli or the change from 5methyltryptophane to 5-methyltryptophane resistance. 4. DNA repair. Polymerase-de cient, and thus DNA repair-de cient, E. coli has provided the basis for a test that depends on the fact that the growth of a de cient strain is inhibited more by a DNA-damaging agent than is that of a repaircompetent strain. The recombinant assay using Bacillus subtilis is conducted in much the same way because recombinant de cient strains are more sensitive to DNA-damaging agents.

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^ ^ gj s is the level-j holding-time LST, and gje s is the LST of its stationary-excess cdf in Eq. (17.33). Proof. Modify the proof of Theorem 17.4.1, inserting Pjl Gje t for Hjl tjx and c Gje t for Gjc tjx . j Consider the on=off source in Section 17.4. Paralleling Eq. (17.18), it suf ces to calculate only P12 t . Its Laplace transform is ^ ^ g s 1 g2 s ^ : P12 s 1e ^ ^ s 1 g1 s g2 s 17:38

Treatment of aerosolized cowpox virus infection in mice with aerosolized cidofovir Antiviral Res 2002, 54, 129 142 155 Roy, C J; Baker, R; Washburn, K; Bray, M Aerosolized cidofovir is retained in the respiratory tract and protects mice against intranasal cowpox virus challenge Antimicrob Agents Chemother 2003, 47, 2933 2937 156 Smee, D F; Bailey, K W; Wong, M H; Sidwell, R W Intranasal treatment of cowpox virus respiratory infections in mice with cidofovir Antiviral Res 2000, 47, 171 177 157 Smee, D F; Bailey, K W; Sidwell, R W Treatment of lethal vaccinia virus respiratory infections in mice with cidofovir Antiviral Chem Chemother 2001, 12, 71 76 158 Smee, D F; Bailey, K W; Wong, M H; Sidwell, R W Effects of cidofovir on the pathogenesis of a lethal vaccinia virus respiratory infection in mice Antiviral Res.

Example 17.6.2. To show the value of knowing the age, consider an on=off source with holding-time complementary cdf's

Mammalian Cell Mutation The development of cell culture techniques that permit both survival and replication have led to many advances in cell biology, including the use of certain of these cell lines for detection of mutagens Although such cells, if derived from mammals, would seem ideal for testing for toxicity toward mammals, there are several problems Primary cells, which generally resemble those of the tissue of origin, are dif cult to culture and have poor cloning ability Because of these dif culties, certain established cell lines are usually used These cells, such as Chinese hamster ovary cells and mouse lymphoma cells, clone readily and do not become senescent with passage through many cell generations Unfortunately, they have little metabolic activity toward xenobiotics and thus do not readily activate toxicants Moreover they usually show chromosome changes, such as aneuploidy (ie.

2001, 52, 55 62 159 Smee, D F; Bailey, K W; Sidwell, R W Comparative effects of cidofovir and cyclic HPMPC on lethal cowpox and vaccinia virus respiratory infections in mice Chemotherapy 2003, 49, 126 131 160 Smee, D F; Sidwell, R W; Kefauver, D; Bray, M; Huggins, J W Characterization of wild-type and cidofovir-resistant strains of camelpox, cowpox, monkeypox, and vaccinia viruses Antimicrob Agents Chemother 2002, 46, 1329 1335 161 Quenelle, D C; Collins, D J; Kern, E R Ef cacy of multiple- or single-dose cidofovir against vaccinia and cowpox virus infections in mice Antimicrob Agents Chemother 2003, 47, 3275 3280 162 Quenelle, D C; Collins, D J; Kern, E R Cutaneous infections of mice with vaccinia or cowpox viruses and ef cacy of cidofovir Antiviral Res 2004, 63, 33 40 163 Smee, D F; Bailey, K W.

c G1 t 0:01e 0:01t 0:1e 0:1t 0:89e t ; c G2 t e t ;

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