Intracellular demography and the dynamics of Salmonella enterica infections.

An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium (S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary (though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance.

Intracellular demography and the dynamics of Salmonella enterica infections.

An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium (S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary (though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance.

Time-frequency spectral estimation of speech

In recent years there has been a growing interest amongst the speech research community into the use of spectral estimators which circumvent the traditional quasi-stationary assumption and provide greater time-frequency (t-f) resolution than conventional spectral estimators, such as the short time Fourier power spectrum (STFPS). One distribution in particular, the Wigner distribution (WD), has attracted considerable interest. However, experimental studies have indicated that, despite its improved t-f resolution, employing the WD as the front end of speech recognition system actually reduces recognition performance; only by explicitly re-introducing t-f smoothing into the WD are recognition rates improved. In this paper we provide an explanation for these findings. By treating the spectral estimation problem as one of optimization of a bias variance trade off, we show why additional t-f smoothing improves recognition rates, despite reducing the t-f resolution of the spectral estimator. A practical adaptive smoothing algorithm is presented, whicy attempts to match the degree of smoothing introduced into the WD with the time varying quasi-stationary regions within the speech waveform. The recognition performance of the resulting adaptively smoothed estimator is found to be comparable to that of conventional filterbank estimators, yet the average temporal sampling rate of the resulting spectral vectors is reduced by around a factor of 10. © 1992.

Geometrical properties and turbulent flame speed measurements in stationary premixed V-flames using direct numerical simulation

Three dimensional, fully compressible direct numerical simulations (DNS) of premixed turbulent flames are carried out in a V-flame configuration. The governing equations and the numerical implementation are described in detail, including modifications made to the Navier-Stokes Characteristic Boundary Conditions (NSCBC) to accommodate the steep transverse velocity and composition gradients generated when the flame crosses the boundary. Three cases, at turbulence intensities, u′/sL, of 1, 2, and 6 are considered. The influence of the flame holder on downstream flame properties is assessed through the distributions of the surface-conditioned displacement speed, curvature and tangential strain rates, and compared to data from similarly processed planar flames. The distributions are found to be indistinguishable from planar flames for distances greater than about 17δth downstream of the flame holder, where δth is the laminar flame thermal thickness. Favre mean fields are constructed, and the growth of the mean flame brush is found to be well described by simple Taylor type diffusion. The turbulent flame speed, sT is evaluated from an expression describing the propagation speed of an isosurface of the mean reaction progress variable c̃ in terms of the imbalance between the mean reactive, diffusive, and turbulent fluxes within the flame brush. The results are compared to the consumption speed, sC, calculated from the integral of the mean reaction rate, and to the predictions of a recently developed flame speed model (Kolla et al., Combust Sci Technol 181(3):518-535, 2009). The model predictions are improved in all cases by including the effects of mean molecular diffusion, and the overall agreement is good for the higher turbulence intensity cases once the tangential convective flux of c̃ is taken into account. © 2010 Springer Science+Business Media B.V.

Metabolite and transcriptome analysis of Campylobacter jejuni in vitro growth reveals a stationary-phase physiological switch.

Campylobacter jejuni is a prevalent cause of food-borne diarrhoeal illness in humans. Understanding of the physiological and metabolic capabilities of the organism is limited. We report a detailed analysis of the C. jejuni growth cycle in batch culture. Combined transcriptomic, phenotypic and metabolic analysis demonstrates a highly dynamic 'stationary phase', characterized by a peak in motility, numerous gene expression changes and substrate switching, despite transcript changes that indicate a metabolic downshift upon the onset of stationary phase. Video tracking of bacterial motility identifies peak activity during stationary phase. Amino acid analysis of culture supernatants shows a preferential order of amino acid utilization. Proton NMR (1H-NMR) highlights an acetate switch mechanism whereby bacteria change from acetate excretion to acetate uptake, most probably in response to depletion of other substrates. Acetate production requires pta (Cj0688) and ackA (Cj0689), although the acs homologue (Cj1537c) is not required. Insertion mutants in Cj0688 and Cj0689 maintain viability less well during the stationary and decline phases of the growth cycle than wild-type C. jejuni, suggesting that these genes, and the acetate pathway, are important for survival.

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.

Quasi-static three-point bending of carbon fiber sandwich beams with square honeycomb cores

Sandwich beams comprising identical face sheets and a square honeycomb core were manufactured from carbon fiber composite sheets. Analytical expressions were derived for four competing collapse mechanisms of simply supported and clamped sandwich beams in three-point bending: core shear, face microbuckling, face wrinkling, and indentation. Selected geometries of sandwich beams were tested to illustrate these collapse modes, with good agreement between analytic predictions and measurements of the failure load. Finite element (FE) simulations of the three-point bending responses of these beams were also conducted by constructing a FE model by laying up unidirectional plies in appropriate orientations. The initiation and growth of damage in the laminates were included in the FE calculations. With this embellishment, the FE model was able to predict the measured load versus displacement response and the failure sequence in each of the composite beams. © 2011 American Society of Mechanical Engineers.

Damage development in an armor ceramic under quasi-static indentation

The objective of the present study is to assess the capabilities of a recently developed mechanism-based model for inelastic deformation and damage in structural ceramics. In addition to conventional lattice plasticity, the model accounts for microcrack growth and coalescence as well as granular flow following comminution. The assessment is made through a coupled experimental/computational study of the indentation response of a commercial armor ceramic. The experiments include examinations of subsurface damage zones along with measurements of residual surface profiles and residual near-surface stresses. Extensive finite element computations are conducted in parallel. Comparisons between experiment and simulation indicate that the most discriminating metric in the assessment is the spatial extent of subsurface damage following indentation. Residual stresses provide additional validation. In contrast, surface profiles of indents are dictated largely by lattice plasticity and thus provide minimal additional insight into the inelastic deformation resulting from microcracking or granular flow. A satisfactory level of correlation is obtained using property values that are either measured directly or estimated from physically based arguments, without undue reliance on adjustable (nonphysical) parameters. © 2011 The American Ceramic Society.