Spread of Salmonella enterica in the body during systemic infection: unravelling host and pathogen determinants.

Salmonella enterica causes a range of life-threatening diseases in humans and animals worldwide. Current treatments for S. enterica infections are not sufficiently effective, and there is a need to develop new vaccines and therapeutics. An understanding of how S. enterica spreads in tissues has very important implications for targeting bacteria with vaccine-induced immune responses and antimicrobial drugs. Development of new control strategies would benefit from a more sophisticated evaluation of bacterial location, spatiotemporal patterns of spread and distribution in the tissues, and sites of microbial persistence. We review here recent studies of S. enterica serovar Typhimurium (S. Typhimurium) infections in mice, an established model of systemic typhoid fever in humans, which suggest that continuous bacterial spread to new infection foci and host phagocytes is an essential trait in the virulence of S. enterica during systemic infections. We further highlight how infections within host tissues are truly heterogeneous processes despite the fact that they are caused by the expansion of a genetically homogeneous microbial population. We conclude by discussing how understanding the within-host quantitative, spatial and temporal dynamics of S. enterica infections might aid the development of novel targeted preventative measures and drug regimens.

Dynamics of spread of Salmonella enterica in the systemic compartment.

Traditional microbiological and immunological tools, combined with modern imaging, and molecular and mathematical approaches, have revealed the dispersive nature of Salmonella infections. Bacterial escape from infected cells, spread in the tissues and attempts to restrain this process by the host give rise to fascinating scenarios that underpin the pathogenesis of salmonelloses.

Dynamics of spread of Salmonella enterica in the systemic compartment

Traditional microbiological and immunological tools, combined with modern imaging, and molecular and mathematical approaches, have revealed the dispersive nature of Salmonella infections. Bacterial escape from infected cells, spread in the tissues and attempts to restrain this process by the host give rise to fascinating scenarios that underpin the pathogenesis of salmonelloses. © 2013 Institut Pasteur.

Caspase-3-dependent phagocyte death during systemic Salmonella enterica serovar Typhimurium infection of mice.

Growth of Salmonella enterica in mammalian tissues results from continuous spread of bacteria to new host cells. Our previous work indicated that infective S. enterica are liberated from host cells via stochastic necrotic burst independently of intracellular bacterial numbers. Here we report that liver phagocytes can undergo apoptotic caspase-3-mediated cell death in vivo, with apoptosis being a rare event, more prevalent in heavily infected cells. The density-dependent apoptotic cell death is likely to constitute an alternative mechanism of bacterial spread as part of a bet-hedging strategy, ensuring an ongoing protective intracellular environment in which some bacteria can grow and persist.

The challenge of cancer control in Africa.

While the world is focused on controlling the spread of diseases such as HIV and malaria in the developing world, another approaching epidemic has been largely overlooked. The World Heath Organization predicts that there will be 16 million new cancer cases per year in 2020 and 70% of these will be in the developing world. Many of these cancers are preventable, or treatable when detected early enough. Establishing effective, affordable and workable cancer control plans in African countries is one step in the right direction toward limiting this epidemic.

Friction of sliding surfaces carrying adsorbed lubricant layers

In concentrated contacts the behaviour of lubricants is much modified by the high local pressures: changes can arise both from molecular ordering within the very thin film lubricant layers present at the interface as well as from the deposition on the component surfaces of more solid-like polymeric boundary layers. These 'third bodies' separating the solid surfaces may have rheological or mechanical properties very different from those observed in the bulk. Classical elasto-hydrodynamic theory considers the entrapped lubricant to exhibit a piezo-viscous behaviour while the conventional picture of more solid boundary lubricant layers views their shear strength r as being linearly dependent on local pressure p, so that T = TO + ap where TO and a are constants. If TO is relatively small, then the coefficient of friction \i = T Ip ~ a and so Amonton's laws are recovered. However, the properties of adsorbed or deposited surface films, or indeed other third bodies such as debris layers, may be more complex than this. A preliminary study has looked quantitatively at the influence of the pressure dependence of the shear strength of any surface layer on the overall friction coefficient of a contact which is made up of an array of asperities whose height varies in a Gaussian manner. Individual contact points may be elastic or plastic. The analysis results in plots of coefficient of friction versus the service or load parameter PIH&NRa where P is the nominal pressure on the contact, HS the hardness of the deforming surface, N the asperity density, R the mean radius of curvature of the asperities, and a is the standard deviation of their height distribution. In principle, any variation oft withp can be incorporated into the model; however, in this initial study we have used data on colloidal suspensions from the group at the Ecole Centrale de Lyon as well as examining the effect of functional relationships of somewhat greater complexity than a simple linear form. Results of the analysis indicate that variations in fj. are possible as the load is varied which depend on the statistical spread of behaviour at individual asperity contacts. The value of this analysis is that it attempts to combine the behaviour of films on the molecular scale with the topography of real engineering surfaces and so give an indication of the effects at the full-size or macro-scale that can be achieved by chemical or molecular surface engineering.

Contrasting code performances for computational aeroacoustics of jets

The numerical propagation of subcritical Tollmein-Schlichting (T-S), inviscid vortical and cut-on acoustic waves is explored. For the former case, the performances of the very different NEAT, NTS, HYDRA, FLUXp and OSMIS3D codes is studied. A modest/coarse hexahedral computational grid that starkly shows differences between the different codes and schemes used in them is employed. For the same order of discretization the five codes show similar results. The unstructured codes are found to propagate vortical and acoustic waves well on triangular cell meshes but not the T-S wave. The above code contrasting exercise is then carried out using implicit LES or Smagorinsky LES for and Ma = 0.9 plane jet on modest 0.5 million cell grids moving to circa 5 million cell grids. For this case, even on the coarse grid, for all codes results were generally encouraging. In general, the spread in computational results is less than the spread of the measurements. Interestingly, the finer grid turbulence intensity levels are slightly more under-predicted than those of the coarse grid. This difference is attributed to the numerical dispersion error having a favourable coarse grid influence. For a non-isothermal jet, HYDRA and NTS also give encouraging results. Peak turbulence values along the jet centreline are in better agreement with measurements than for the isothermal jets. Copyright © 2006 by University of Wales.

Re-examination of the coefficient of determination (r2) using road materials engineering case studies

The analysis of scientific data is integral to materials engineering and science. The correlation between measured variables is often quantified by estimating the coefficient of determination or the r2 value. This is the recognised procedure for determining linear relationships. The authors review the derivation of the r2 value and derive an associated quantity, termed the relative deviation (RD), which is the ratio of the root mean square of the deviations about the fitted line to the root mean square of the deviations about the y bar line expressed as a percentage. The relative deviation has an advantage over the coefficient of determination in that it has greater numerical sensitivity to changes in the spread of data about the fitted line, especially when the scatter is small. In addition, the relative deviation is able to define, in percentage terms, the reduction in scatter when different independent variables are correlated with a common dependent variable. Four case studies in the materials field (aggregate crushing value, Atterberg limits, permeability and creep of asphalt) from work carried out at the Queensland Main Roads Department are presented to show the use of the new parameter RD.

Determination of the rheological parameters of self-compacting concrete matrix using slump flow test

The classification of a concrete mixture as self-compacting (SCC) is performed by a series of empirical characterization tests that have been designed to assess not only the flowability of the mixture but also its segregation resistance and filling ability. The objective of the present work is to correlate the rheological parameters of SCC matrix, yield stress and plastic viscosity, to slump flow measurements. The focus of the slump flow test investigation was centered on the fully yielded flow regime and an empirical model relating the yield stress to material and flow parameters is proposed. Our experimental data revealed that the time for a spread of 500 mm which is used in engineering practice as reference for measurement parameters, is an arbitrary choice. Our findings indicate that the non-dimensional final spread is linearly related to the non-dimensional yield-stress. Finally, there are strong indications that the non-dimensional viscosity of the mixture is associated with the non-dimensional final spread as well as the stopping time of the slump flow; this experimental data set suggests an exponential decay of the final spread and stopping time with viscosity. © Appl. Rheol.

Numerical study of the impact of process variations on the motional resistance of weakly coupled MEMS resonators

This paper presents a numerical study of the impact of process-induced variations on the achievable motional resistance Rx of one-dimensional, cyclic and cross-coupled architectures of electrostatically transduced MEMS resonators operating in the 250 kHz range. Monte Carlo numerical simulations which accounted for up to 0.75% variation in critical resonator feature sizes were initiated on 1, 2, 3, 4, 5 and 9 coupled MEMS resonators for three distinct coupling architectures. Improvements of 100X in the spread of Rx and 2.7X in mean achievable Rx are reported for the case of 9 resonators when implemented in the cross-coupled topology, as opposed to the traditional one-dimensional chain. © 2013 IEEE.

Mechanics of biological networks: from the cell cytoskeleton to connective tissue.

From the cell cytoskeleton to connective tissues, fibrous networks are ubiquitous in metazoan life as the key promoters of mechanical strength, support and integrity. In recent decades, the application of physics to biological systems has made substantial strides in elucidating the striking mechanical phenomena observed in such networks, explaining strain stiffening, power law rheology and cytoskeletal fluidisation - all key to the biological function of individual cells and tissues. In this review we focus on the current progress in the field, with a primer into the basic physics of individual filaments and the networks they form. This is followed by a discussion of biological networks in the context of a broad spread of recent in vitro and in vivo experiments.

Integrated avalanche diode for 600 v Trench IGBT over-voltage protection

Avalanche multiplication has been one of the major destructive failure mechanisms in IGBTs; in order to avoid operating an IGBT under abnormal conditions, it is desirable to develop peripheral protecting circuits monolithically integrated without compromising the operation and performance of the IGBT. In this paper, a monolithically integrated avalanche diode (D av) for 600V Trench IGBT over-voltage protection is proposed. The mix-mode transient simulation proves the clamping capability of the D av when the IGBT is experiencing over-voltage stress in unclamped inductive switching (UIS) test. The spread of avalanche energy, which prevents hot-spot formation, through the help of the avalanche diode feeding back a large fraction of the avalanche current to a gate resistance (R G) is also explained. © 2011 IEEE.

Electric times in olfaction.

Recent work established the spread of interglomerular excitation in the Drosophila antennal lobe. Two papers in this issue of Neuron, by Huang et al. and Yaksi and Wilson, show that cholinergic krasavietz local interneurons are a major substrate for this spread of excitation, predominantly via electrical coupling.