55 resultados para mutation load

em Cambridge University Engineering Department Publications Database


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Campylobacter jejuni is a zoonotic bacterial pathogen of worldwide importance. It is estimated that 460,000 human infections occur in the United Kingdom per annum and these involve acute enteritis and may be complicated by severe systemic sequelae. Such infections are frequently associated with the consumption of contaminated poultry meat and strategies to control C. jejuni in poultry are expected to limit pathogen entry into the food chain and the incidence of human disease. Toward this aim, a total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium ΔaroA vaccine expressing the C. jejuni amino acid binding protein CjaA as a plasmid-borne fusion to the C-terminus of fragment C of tetanus toxin. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4 log10 colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA. Protection was not observed using a vaccine strain containing the empty plasmid. Vaccination with recombinant CjaA subcutaneously at the same intervals significantly reduced the caecal load of C. jejuni at three and four weeks post-challenge. Taken together these data imply that responses directed against CjaA, rather than competitive or cross-protective effects mediated by the carrier, confer protection. The impact of varying parameters on the efficacy of the S. Typhimurium ΔaroA vaccine expressing TetC-CjaA was also tested. Delaying the age at primary vaccination had little impact on protection or humoral responses to CjaA. The use of the parent strain as carrier or changing the attenuating mutation of the carrier to ΔspaS or ΔssaU enhanced the protective effect, consistent with increased invasion and persistence of the vaccine strains relative to the ΔaroA mutant. Expression in the ΔaroA strain of a TetC fusion to Peb1A, but not TetC fusions to GlnH or ChuA, elicited protection against intestinal colonisation by C. jejuni that was comparable to that observed with the TetC-CjaA fusion. Our data are rendered highly relevant by use of the target host in large numbers and support the potential of CjaA- and Peb1A-based vaccines for control of C. jejuni in poultry. © 2009 Elsevier Ltd. All rights reserved.

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A full-scale experimental study on the structural performance of load-bearing wall panels made of cold-formed steel frames and boards is presented. Six different types of C-channel stud, a total of 20 panels with one middle stud and 10 panels with two middle studs were tested under vertical compression until failure. For panels, the main variables considered are screw spacing (300 mm, 400 mm, or 600 mm) in the middle stud, board type (oriented strand board - OSB, cement particle board - CPB, or calcium silicate board - CSB), board number (no sheathing, one-side sheathing, or two-side sheathing), and loading type (1, 3, or 4-point loading). The measured load capacity of studs and panels agrees well with analytical prediction. Due to the restraint by rivet connections between stud and track, the effective length factor for the middle stud and the side stud in a frame (unsheathed panel) is reduced to 0.90 and 0.84, respectively. The load carrying capacity of a stud increases significantly whenever one- or two-side sheathing is used, although the latter is significantly more effective. It is also dependent upon the type of board used. Whereas panels with either OSB or CPB boards have nearly identical load carrying capacity, panels with CSB boards are considerably weaker. Screw spacing affects the load carrying capacity of a stud. When the screw spacing on the middle stud in panels with one-side sheathing is reduced from 600 mm to 300 mm, its load carrying capacity increases by 14.5 %, 20.6% and 94.2% for OSB, CPB and CSB, respectively.