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Moss, B. Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox. Nature 2004, 428, 182 185. Stittelaar, K. J.; Kuiken, T.; de Swart, R. L.; van Amerongen, G.; Vos, H. W.; Niesters, H. G.; van Schalkwijk, P.; van der Kwast, T.; Wyatt, L. S.; Moss, B.; Osterhaus, A. D. Safety of modi ed vaccinia virus Ankara (MVA) in immune-suppressed macaques. Vaccine 2001, 19, 3700 3709. Tartaglia, J.; Cox, W. I.; Taylor. J.; Perkus. K.; Riviere, M.; Meignier, B.; Paoletti, E. Highly attenuated poxvirus vectors. AIDS Res. Hum. Retroviruses 1992, 8(8), 1445 1447. Danzig, R.; Berkowsky, P. B. Why should we be concerned about biological warfare JAMA 1997, 278, 431 432. Pearson, G. S. The complementary role of environmental and security biological control regimes in the 21st century. JAMA 1997, 278, 369 372. Inglesby, T. V.; Henderson, D. A.; Bartlett, J. G.; Ascher, M. S.; Eitzen, E.; Friedlander, A. M.; Hauer, J.; McDade, J.; Osterholm, M. T.; O Toole, T.; Parker, G.; Perl, T. M.; Russell, P. K.; Tonat, K. Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA 1999, 281, 1735 1745. Henderson, D. A. The looming threat of bioterrorism. Science 1999, 283, 1279 1282. Fenner, F.; Henderson, D. A.; Arita, I.; Jezek, Z.; Ladnyi, I. D. Smallpox and Its Eradication. World Health Organization, Geneva, 1988. Brandt, T. A; Jacobs, B. L. Both carboxy- and amino-terminal domains of the vaccinia virus interferon resistance gene, E3L, are required for pathogenesis in a mouse model. J. Virol. 2001, 75, 850 856. Saunders, L. R.; Barber, G. N. The dsRNA binding protein family: critical roles, diverse cellular functions. FASEB 2003, 17, 961 983.

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These substances come primarily from three sources: (1) combustion sources that burn fossil fuel for heating and power, or exhaust emissions from transportation vehicles that use gasoline or diesel fuels; (2) industrial processes; and (3) mining and drilling The principal pollutants from combustion are y ash, smoke, sulfur, and nitrogen oxides, as well as CO and CO2 Combustion of coal and oil, both of which contain signi cant amounts of sulfur, yields large quantities of sulfur oxides One effect of the production of sulfur oxides is the formation of acidic deposition, including acid rain Nitrogen oxides are formed by thermal oxidation of atmospheric nitrogen at high temperatures; thus almost any combustion process will produce nitrogen oxides Carbon monoxide is a product of incomplete combustion; the more ef cient the combustion, the higher is the ratio of CO2 to CO.

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Transportation sources, particularly automobiles, are a major source of air pollution and include smoke, lead particles from tetraethyl lead additives, CO, nitrogen oxides, and hydrocarbons Since the mid-1960s there has been signi cant progress in reducing exhaust emissions, particularly with the use of low-lead or no-lead gasoline as well as.

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Steroid and thyroid hormones are typically distributed throughout the body while bound to serum-binding proteins such as sex hormone-binding globulin, corticosteroid-binding globulin, thyroxine-binding globulin (transthyretin), and albumin. Most steroid and thyroid hormones (>95%) are present in the blood reversibly bound to proteins. This bound hormone is not available for cell entry where it may interact with nuclear receptors or undergo inactivation/elimination reactions. Rather, the bound hormone serves as a reservoir from which hormone can be liberated (free hormone) for cell entry. Some xenobiotics can compete with hormones for binding to the blood proteins. As a result the circulating hormone reservoir can be depleted and free hormone becomes limited. A variety of phenolic compounds, including hydroxylated metabolites of polychlorinated biphenyls (PCBs), chlorophenols, chlorophenoxy acids, and nitrophenols, have been shown to interfere with thyroxine binding to thyroxine-binding globulin during in vitro experiments. In some instances compounds that displace thyroxine from the binding protein also have been shown to decrease circulating thyroxine levels in exposed animal models or in humans. In vitro experiments also have revealed that testosterone and 17 -estradiol can be displaced from sex hormone-binding globulin by some chemicals such as 4-nonylphenol, 4-tert-octylphenol, bisphenol A, O-hydroxybiphenyl, and pyrethroid insecticides. However, it is not clear whether these chemicals would signi cantly displace sex steroids from the binding globulin at concentrations typically measured in human blood.

Fig. 14.6 Relative frequency of unweighted le size distributions of TCP runs with Pareto (a) with a 1.05 and (b) with a 1.95; (c) exponential distribution.

Canadian Blood Services and Department of Pathology and Laboratory Medicine, University of British Columbia

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