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These data imply that vaccinia virus infection leads to the activation of these host responses to which the virus must respond in order to maintain ef cient replication An alternative approach to preparing safer vaccine strains of vaccinia virus is to prepare replication competent strains that are attenuated for pathogenesis Targets for attenuation include viral genes known to be involved in blocking the cellular immune or antiviral response Viruses containing mutations in the vaccinia virus E3L gene are candidates for such vaccine vectors 1 Mutations in E3L render the virus attenuated but yield a virus that is otherwise fully replication competent in cells-in-culture These viruses are drastically reduced in terms of pathogenesis in mouse model systems102 and since these viruses do not disseminate from the site of infection, the major complications associated with wild-type virus vaccination should be greatly reduced, if not completely eliminated.

On processors where the replacement algorithm is a run-time option, this is con gured using a CP15 con guration register setting in the base port; it is very important to ensure that this is con gured appropriately..

2 y ( x1 )2 + ( y1 )2 = d1 x 2 y ( x2 )2 + ( y2 )2 = d2 x 2 ( x3 )2 + ( y3 )2 = d3 x y

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where ( , ) is the position we want to compute, (xi ,yi ) is the position of the ith xy reference, and di is the distance of the ith reference node to the unknown node. In this case, we have three quadratic equation with two unknowns, which can be solved, theoretically, into one solution. In real-world applications, the distance estimation inaccuracies as well as the inaccurate position information of the reference nodes make it dif cult to compute the position. As depicted in Figure 11.7a, the circles do not intersect into only one point, resulting in an in nite set of possible solutions. Furthermore, when a larger number of reference points are available, we can use the multilateration to compute the nodes position. In this case, an overdetermined system of equations, where we have more equations than unknowns, must be solved. Figure 11.8 depicts this case. Usually, overdetermined systems do not have a unique

Given the importance of dsRNA and possibly Z-DNA (or Z-RNA) in controlling viral replication, the E3L gene, in many ways, is the optimal target for developing attenuated vaccinia virus strains and as a possible target for novel anti-poxvirus compounds The future holds great promise in these regards with many directions of research being conducted One day, the foreseen threat of smallpox as a bioterror agent that could once again wreak havoc on the human population may be a peril of the past..

Since ARM processors generally only handle word-aligned memory operations, accessing non-single-byte quantities that are not aligned to a word boundary is not as fast as accessing ones that are. The Mem::Copy() method is very heavily optimized, using a special twister algorithm to copy unaligned data using aligned memory access cycles. This makes it about three times faster than a conventional implementation of memcpy() for both unaligned copies and for copies in which the source is not aligned with the destination. Similarly, particularly on ARM926EJ platforms, the memory interface does not generate burst accesses for cache missing STM or LDM instructions that are not aligned to a 16 byte boundary. The Mem:: methods include code to alleviate these problems, and their performance is very close to the theoretical maximum. In some situations you may choose to modify your code to place important members of structures in aligned locations. Packing structs can help to save memory but may signi cantly reduce the available memory bandwidth on these processors. ARM926EJ is a very popular core at the

Figure 11.7. A more realistic model of the trilateration: (a) The inconsistencies of the positions and distances generate a system with in nite solutions. (b) The residual value, as the sum of the squared differences between the estimated and computed distances.

time of writing and can be found in many mobile phones. ARM926EJ cache lines are eight words long, so to be aligned, an address must be divisible by 32.

1 Jacobs, B L; Langland, J O When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA Virology 1996, 219, 339 349 2 Moss, B Poxviridae and their replication In Virology, 2nd Ed, Fields, BN; Knipe, D M (eds) Raven Press, New York, 1990, pp 2079 2111, 3 Colby, C; Jurale, C; Kates, J R Mechanism of synthesis of vaccinia virus doublestranded ribonucleic acid in vivo and in vitro J Virol 1971, 7, 71 76 4 Boone, R F; Parr, R P; Moss, B Intermolecular duplexes formed from polyadenylated vaccinia virus RNA J Virol 1979, 30, 365 374 5 Bayliss, C D; Condit, R C Temperature-sensitive mutants in the vaccinia virus A18R gene increase double-stranded RNA synthesis as a result of aberrant viral transcription Virology 1993, 194, 254 262 6 Simpson, D.

Figure 11.8. Multilateration: similar to the trilateration, but more than three references can be used and an overdetermined system is solved. A method to solve this system includes the least squares method.

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