Virulent Salmonella enterica infections can be exacerbated by concomitant infection of the host with a live attenuated S. enterica vaccine via Toll-like receptor 4-dependent interleukin-10 production with the involvement of both TRIF and MyD88.

During systemic disease in mice, Salmonella enterica grows intracellularly within discrete foci of infection in the spleen and liver. In concomitant infections, foci containing different S. enterica strains are spatially separated. We have investigated whether functional interactions between bacterial populations within the same host can occur despite the known spatial separation of the foci and independence of growth of salmonellae residing in different foci. In this study we have demonstrated that bacterial numbers of virulent S. enterica serovar Typhimurium C5 strain in mouse tissues can be increased by the presence of the attenuated aroA S. Typhimurium SL3261 vaccine strain in the same tissue. Disease exacerbation does not require simultaneous coinjection of the attenuated bacteria. SL3261 can be administered up to 48 hr after or 24 hr before the administration of C5 and still determine higher tissue numbers of the virulent bacteria. This indicates that intravenous administration of a S. enterica vaccine strain could potentially exacerbate an established infection with wild-type bacteria. These data also suggest that the severity of an infection with a virulent S. enterica strain can be increased by the prior administration of a live attenuated vaccine strain if infection occurs within 48 hr of vaccination. Exacerbation of the growth of C5 requires Toll-like receptor 4-dependent interleukin-10 production with the involvement of both Toll/interleukin-1 receptor-domain-containing adaptor inducing interferon-beta and myeloid differentiation factor 88.

Modelling within-host spatiotemporal dynamics of invasive bacterial disease

Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single bacterial population. They are also currently poorly understood. Here, we report on the application of sophisticated experimental approaches to map spatiotemporal population dynamics of bacteria during an infection. We analyzed heterogeneous traits of simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic tagged strains [WITS]) in wild-type and gene-targeted mice. WITS are phenotypically identical but can be distinguished and enumerated by quantitative PCR, making it possible, using probabilistic models, to estimate bacterial death rate based on the disappearance of strains through time. This multidisciplinary approach allowed us to establish the timing, relative occurrence, and immune control of key infection parameters in a true host-pathogen combination. Our analyses support a model in which shortly after infection, concomitant death and rapid bacterial replication lead to the establishment of independent bacterial subpopulations in different organs, a process controlled by host antimicrobial mechanisms. Later, decreased microbial mortality leads to an exponential increase in the number of bacteria that spread locally, with subsequent mixing of bacteria between organs via bacteraemia and further stochastic selection. This approach provides us with an unprecedented outlook on the pathogenesis of S. enterica infections, illustrating the complex spatial and stochastic effects that drive an infectious disease. The application of the novel method that we present in appropriate and diverse host-pathogen combinations, together with modelling of the data that result, will facilitate a comprehensive view of the spatial and stochastic nature of within-host dynamics. © 2008 Grant et al.

Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections.

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

Large strain field near a crack tip in a rubber sheet

The distribution of stress-strain near a crack tip in a rubber sheet is investigated by employing the constitutive relation given by Gao (1997). It is shown that the crack tip field is composed of two shrinking sectors and one expanding sector. The stress state near the crack tip is in uniaxial tension. The analytical solutions are obtained for both expanding and shrinking sectors.

Strain Rate-Dependent Compressive Deformation Behavior of Nd-Based Bulk Metallic Glass

Compressive deformation behavior of the Nd60Fe20Co10Al10 bulk metallic glass was characterized over a wide strain rate range (6.0 x 10(-4) to 1.0x10(3) s(-1)) at room temperature. Fracture stress was found to increase and fracture strain decrease with increasing applied strain rate. Serrated flow and a large number of shear bands were observed at the quasi-static strain rate (6.0 x 10(-4)s(-1)). The results suggest that the appearance of a large number of shear bands is probably associated with flow serration observed during compression; and both shear banding and flow serration are a strain accommodation and stress relaxation process. At dynamic strain rates (1.0 x 10(3) s(-1)), the rate of shear band nucleation is not sufficient to accommodate the applied strain rate and thus causes an early fracture of the test sample. The fracture behavior of the Nd60Fe20Co10Al10 bulk metallic glass is sensitive to strain rate.

Finite Element Solutions for Plane Strain Mode I Crack with Strain Grading Effect

In this paper, a new phenomenological theory with strain gradient effects is proposed to account for the size dependence of plastic deformation at micro- and submicro-length scales. The theory fits within the framework of general couple stress theory and three rotational degrees of freedom omega(i) are introduced in addition to the conventional three translational degrees of freedom mu(i). omega(i) is called micro-rotation and is the sum of material rotation plus the particles' relative rotation. While the new theory is used to analyze the crack tip field or the indentation problems, the stretch gradient is considered through a new hardening law. The key features of the theory are that the rotation gradient influences the material character through the interaction between the Cauchy stresses and the couple stresses; the term of stretch gradient is represented as an internal variable to increase the tangent modulus. In fact the present new strain gradient theory is the combination of the strain gradient theory proposed by Chen and Wang (Int. J. Plast., in press) and the hardening law given by Chen and Wang (Acta Mater. 48 (2000a) 3997). In this paper we focus on the finite element method to investigate material fracture for an elastic-power law hardening solid. With remotely imposed classical K fields, the full field solutions are obtained numerically. It is found that the size of the strain gradient dominance zone is characterized by the intrinsic material length l(1). Outside the strain gradient dominance zone, the computed stress field tends to be a classical plasticity field and then K field. The singularity of stresses ahead of the crack tip is higher than that of the classical field and tends to the square root singularity, which has important consequences for crack growth in materials by decohesion at the atomic scale. (C) 2002 Elsevier Science Ltd. All rights reserved.

Martensitic transformation under impact with high strain rate

This paper deals with the quantitative prediction of the volume fraction of martensitic transformation in a austenitic steel that undergoes impact with high strain rate. The coupling relations between strain, stress, strain rate, transformation rate and transformed fraction were derived from the OTC model and modified Bodner-Partom equations, where the impact process was considered as an adiabatic and no entropy-increased process (pressure less than or equal to 20GPa). The one-dimensional results were found to model and predict various experimental results obtained on 304 stainless steel under impact with high strain rate.

Analysis of Dislocation-Induced Strain Field in an Idealized Wafer-Bonded Microstructure

The localized dislocation at the interface induces uneven strain distribution in two wafer-bonded layers. Because of the different elastic properties of two bonding layers and this uneven strain distribution, the bilayered microstructure deflects and deflection relaxes the strains. Depending on the microstructure dimensions, elastic properties and lattice parameters, the contribution of deflection to strain field can be very significant. The interface condition also plays an important role in relaxing strain. Two models capable of describing different interface conditions are used for the analysis and offer a more comprehensive study on the dislocation-induced strain field in a wafer-bonded bilayered microstructure. The combined effect of microstructure dimensions and interface condition on the strain is presented and compared.

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.

Interface crack problems with strain gradient effects

In this paper, the strain gradient theory proposed by Chen and Wang (2001 a, 2002b) is used to analyze an interface crack tip field at micron scales. Numerical results show that at a distance much larger than the dislocation spacing the classical continuum plasticity is applicable; but the stress level with the strain gradient effect is significantly higher than that in classical plasticity immediately ahead of the crack tip. The singularity of stresses in the strain gradient theory is higher than that in HRR field and it slightly exceeds or equals to the square root singularity and has no relation with the material hardening exponents. Several kinds of interface crack fields are calculated and compared. The interface crack tip field between an elastic-plastic material and a rigid substrate is different from that between two elastic-plastic solids. This study provides explanations for the crack growth in materials by decohesion at the atomic scale.

Microstructure, strain fields and flow stress in deformed metal matrix composites

An experimental study of local orientations around whiskers in deformed metal matrix composites has been used to determine the strain gradients existing in the material following tensile deformation. These strain fields have been represented as arrays of geometrically necessary dislocations, and the material flow stress predicted using a standard dislocation hardening model. Whilst the correlation between this and the measured flow stress is reasonable, the experimentally determined strain gradients are lower by a factor of 5-10 than values obtained in previous estimates made using continuum plasticity finite element models. The local orientations around the whiskers contain a large amount of detailed information about the strain patterns in the material, and a novel approach is made to representing some of this information and to correlating it with microstructural observations. © 1998 Acta Metallurgica Inc. Published by Elsevier Science Ltd. All rights reserved.

Crack Tip Field and J-Integral with Strain Gradient Effect

The mode I plane strain crack tip field with strain gradient effects is presented in this paper based on a simplified strain gradient theory within the framework proposed by Acharya and Bassani. The theory retains the essential structure of the incremental version of the conventional J_2 deformation theory No higher-order stress is introduced and no extra boundary value conditions beyond the conventional ones are required. The strain gradient effects are considered in the constitutive relation only through the instantaneous tangent modulus. The strain gradient measures are included into the tangent modulus as internal parameters. Therefore the boundary value problem is the same as that in the conventional theory Two typical crack Problems are studied: (a) the crack tip field under the small scale yielding condition induced by a linear elastic mode-I K-field and (b) the complete field for a compact tension specimen. The calculated results clearly show that the stress level near the crack tip with strain gradient effects is considerable higher than that in the classical theory The singularity of the strain field near the crack tip is nearly equal to the square-root singularity and the singularity of the stress field is slightly greater than it. Consequently, the J-integral is no longer path independent and increases monotonically as the radius of the calculated circular contour decreases.

Strain Rate Dependence of Plastic Flow in Ce-based Bulk Metallic Glass During Nanoindentation

The strain rate dependence of plastic deformation of Ce60Al15CU10Ni15 bulk metallic glass was studied by nanoindentation. Even though the ratio of room temperature to the glass transition temperature was very high (0.72) for this alloy, the plastic deformation was dominated by shear banding under nanoindentation. The alloy exhibited a critical loading rate dependent serrated flow feature. That is, with increasing loading rate, the alloy exhibited a transition from less prominent serrated flow to pronounced serrated flow during continuous loading but from serrated to smoother flow during stepped loading.

Mode I and Mode II Crack Tip Asymptotic Fields with Strain Gradient Effects

The strain gradient effect becomes significant when the size of fracture process zone around a crack tip is comparable to the intrinsic material length l, typically of the order of microns. Using the new strain gradient deformation theory given by Chen and Wang, the asymptotic fields near a crack tip in an elastic-plastic material with strain gradient effects are investigated. It is established that the dominant strain field is irrotational. For mode I plane stress crack tip asymptotic field, the stress asymptotic field and the couple stress asymptotic field can not exist simultaneously. In the stress dominated asymptotic field, the angular distributions of stresses are consistent with the classical plane stress HRR field; In the couple stress dominated asymptotic field, the angular distributions of couple stresses are consistent with that obtained by Huang et al. For mode II plane stress and plane strain crack tip asymptotic fields, only the stress-dominated asymptotic fields exist. The couple stress asymptotic field is less singular than the stress asymptotic fields. The stress asymptotic fields are the same as mode II plane stress and plane strain HRR fields, respectively. The increase in stresses is not observed in strain gradient plasticity for mode I and mode II, because the present theory is based only on the rotational gradient of deformation and the crack tip asymptotic fields are irrotational and dominated by the stretching gradient.