Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter antigens for control of C. jejuni in poultry

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.

Dynamic compressive response of composite square honeycombs

Carbon fibre-epoxy composite square honeycombs, and the parent composite material, were tested in quasi-static compression at a strain rate of 10 -3 s -1 and in dynamic compression at strain rates of 10 3-10 4 s -1 using an instrumented Kolsky bar arrangement. Taken together, these tests provide an assessment of the potential of this composite topology for use as a lightweight sandwich core. The honeycombs had two relative densities, 0.12 and 0.24, and two material orientations, ±45° and 0/90° with respect to the prismatic, loading direction of the honeycomb. Honeycomb manufacture was by slotting, assembling and bonding together carbon fibre/epoxy woven plies of composite sheets of 2 × 2 twill weave construction. The peak value of wall stress in the honeycombs was about one third that of the parent material, for all strain rates. An elastic finite element analysis was used to trace the source of this knock-down in strength: a stress concentration exists at the root of the slots and leads to premature failure by microbuckling. Shock-wave effects were evident at impact velocities exceeding 50 ms -1 for the honeycomb of relative density 0.12. This was traced to stubbing of the buckled cell walls against the face of the Kolsky bar. © 2011 Elsevier Ltd. All rights reserved.

Human muscle spindles act as forward sensory models.

Modern theories of motor control incorporate forward models that combine sensory information and motor commands to predict future sensory states. Such models circumvent unavoidable neural delays associated with on-line feedback control. Here we show that signals in human muscle spindle afferents during unconstrained wrist and finger movements predict future kinematic states of their parent muscle. Specifically, we show that the discharges of type Ia afferents are best correlated with the velocity of length changes in their parent muscles approximately 100-160 ms in the future and that their discharges vary depending on motor sequences in a way that cannot be explained by the state of their parent muscle alone. We therefore conclude that muscle spindles can act as "forward sensory models": they are affected both by the current state of their parent muscle and by efferent (fusimotor) control, and their discharges represent future kinematic states. If this conjecture is correct, then sensorimotor learning implies learning how to control not only the skeletal muscles but also the fusimotor system.

Change propagation analysis in complex technical systems

Understanding how and why changes propagate during engineering design is critical because most products and systems emerge from predecessors and not through clean sheet design. This paper applies change propagation analysis methods and extends prior reasoning through examination of a large data set from industry including 41,500 change requests, spanning 8 years during the design of a complex sensor system. Different methods are used to analyze the data and the results are compared to each other and evaluated in the context of previous findings. In particular the networks of connected parent, child and sibling changes are resolved over time and mapped to 46 subsystem areas. A normalized change propagation index (CPI) is then developed, showing the relative strength of each area on the absorber-multiplier spectrum between -1 and +1. Multipliers send out more changes than they receive and are good candidates for more focused change management. Another interesting finding is the quantitative confirmation of the "ripple" change pattern. Unlike the earlier prediction, however, it was found that the peak of cyclical change activity occurred late in the program driven by systems integration and functional testing. Patterns emerged from the data and offer clear implications for technical change management approaches in system design. Copyright © 2007 by ASME.