Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shiga toxin-encoding prophage

Humans play little role in the epidemiology of Escherichia coli O157:H7, a commensal bacterium of cattle. Why then does E. coli O157:H7 code for virulence determinants, like the Shiga toxins (Stxs), responsible for the morbidity and mortality of colonized humans? One possibility is that the virulence of these bacteria to humans is coincidental and these virulence factors evolved for and are maintained for other roles they play in the ecology of these bacteria. Here, we test the hypothesis that the carriage of the Stx-encoding prophage of E. coli O157:H7 increases the rate of survival of E. coli in the presence of grazing protozoa, Tetrahymena pyriformis. In the presence but not the absence of Tetrahymena, the carriage of the Stx-encoding prophage considerably augments the fitness of E. coli K-12 as well as clinical isolates of E. coli O157 by increasing the rate of survival of the bacteria in the food vacuoles of these ciliates. Grazing protozoa in the environment or natural host are likely to play a significant role in the ecology and maintenance of the Stx-encoding prophage of E. coli O157:H7 and may well contribute to the evolution of the virulence of these bacteria to colonize humans

Modelling mucociliary clearance

Mathematical modelling of the fluid mechanics of mucociliary clearance (MCC) is reviewed and future challenges for researchers are discussed. The morphology of the bronchial and tracheal airway surface liquid (ASL) and ciliated epithelium are briefly introduced. The cilia beat cycle, beat frequency and metachronal coordination are described, along with the rheology of the mucous layer. Theoretical modelling of MCC from the late 1960s onwards is reviewed, and distinctions between ‘phenomenological’, ‘slender body theory’ and recent ‘fluid–structure interaction’ models are explained.\ud \ud The ASL consists of two layers, an overlying mucous layer and underlying watery periciliary layer (PCL) which bathes the cilia. Previous models have predicted very little transport of fluid in the PCL compared with the mucous layer. Fluorescent tracer transport experiments on human airway cultures conducted by Matsui et al. [Matsui, H., Randell, S.H., Peretti, S.W., Davis, C.W., Boucher, R.C., 1998. Coordinated clearance of periciliary liquid and mucus from airway surfaces. J. Clin. Invest. 102 (6), 1125–1131] apparently showed equal transport in both the PCL and mucous layer. Recent attempts to resolve this discrepancy by the present authors are reviewed, along with associated modelling findings. These findings have suggested new insights into the interaction of cilia with mucus due to pressure gradients associated with the flat PCL/mucus interface. This phenomenon complements previously known mechanisms for ciliary propulsion. Modelling results are related to clinical findings, in particular the increased MCC observed in patients with pseudohypoaldosteronism. Recent important advances by several groups in modelling the fluid–structure interaction by which the cilia movement and fluid transport emerge from specification of internal mechanics, viscous and elastic forces are reviewed. Finally, we discuss the limitations of existing work, and the challenges for the next generation of models, which may provide further insight into this complex and vital system

Non-linear regression models for Approximate Bayesian Computation

Approximate Bayesian inference on the basis of summary statistics is well-suited to complex problems for which the likelihood is either mathematically or computationally intractable. However the methods that use rejection suffer from the curse of dimensionality when the number of summary statistics is increased. Here we propose a machine-learning approach to the estimation of the posterior density by introducing two innovations. The new method fits a nonlinear conditional heteroscedastic regression of the parameter on the summary statistics, and then adaptively improves estimation using importance sampling. The new algorithm is compared to the state-of-the-art approximate Bayesian methods, and achieves considerable reduction of the computational burden in two examples of inference in statistical genetics and in a queueing model.Comment: 4 figures; version 3 minor changes; to appear in Statistics and Computin

Indirect search for dark matter: prospects for GLAST

Possible indirect detection of neutralino, through its gamma-ray annihilation product, by the forthcoming GLAST satellite from our galactic halo, M31, M87 and the dwarf galaxies Draco and Sagittarius is studied. Gamma-ray fluxes are evaluated for the two representative energy thresholds, 0.1 GeV and 1.0 GeV, at which the spatial resolution of GLAST varies considerably. Apart from dwarfs which are described either by a modified Plummer profile or by a tidally-truncated King profiles, fluxes are compared for halos with central cusps and cores. It is demonstrated that substructures, irrespective of their profiles, enhance the gamma-ray emission only marginally. The expected gamma-ray intensity above 1 GeV at high galactic latitudes is consistent with the residual emission derived from EGRET data if the density profile has a central core and the neutralino mass is less than 50 GeV, whereas for a central cusp only a substantial enhancement would explain the observations. From M31, the flux can be detected above 0.1 GeV and 1.0 GeV by GLAST only if the neutralino mass is below 300 GeV and if the density profile has a central cusp, case in which a significant boost in the gamma-ray emission is produced by the central black hole. For Sagittarius, the flux above 0.1 GeV is detectable by GLAST provided the neutralino mass is below 50 GeV. From M87 and Draco the fluxes are always below the sensitivity limit of GLAST.Comment: 14 Pages, 7 Figures, 3 Tables, version to appear on Physical Review

Experimental evidence for 56Ni-core breaking from the low-spin structure of the N=Z nucleus 58Cu

Low-spin states in the odd-odd N=Z nucleus 58Cu were investigated with the 58Ni(p,n gamma)58Cu fusion evaporation reaction at the FN-tandem accelerator in Cologne. Seventeen low spin states below 3.6 MeV and 17 new transitions were observed. Ten multipole mixing ratios and 17 gamma-branching ratios were determined for the first time. New detailed spectroscopic information on the 2+,2 state, the Isobaric Analogue State (IAS) of the 2+,1,T=1 state of 58Ni, makes 58Cu the heaviest odd-odd N=Z nucleus with known B(E2;2+,T=1 --> 0+,T=1) value. The 4^+ state at 2.751 MeV, observed here for the first time, is identified as the IAS of the 4+,1,T=1 state in 58Ni. The new data are compared to full pf-shell model calculations with the novel GXPF1 residual interaction and to calculations within a pf5/2 configurational space with a residual surface delta interaction. The role of the 56Ni core excitations for the low-spin structure in 58Cu is discussed.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Coherent QCD phenomena in the Coherent Pion-Nucleon and Pion-Nucleus Production of Two Jets at High Relative Momenta

We use QCD to compute the cross section for coherent production of a di-jet (treated as a $q\bar q$ moving at high relative transverse momentum,$\kappa_t$). In the target rest frame,the space-time evolution of this reaction is dominated by the process in which the high $\kappa_t$ $q\bar q$ component of the pion wave function is formed before reaching the target. It then interacts through two gluon exchange. In the approximation of keeping the leading order in powers of $\alpha_s$ and all orders in $\alpha_{s}\ln(\kappa_{t}^2/k_{0}^2),$ the amplitudes for other processes are shown to be smaller at least by a power of $\alpha_{s}$. The resulting dominant amplitude is proportional to $z(1-z) \kappa_t^{-4}$ ($z$ is the fraction light-cone(+)momentum carried by the quark in the final state) times the skewed gluon distribution of the target. For the pion scattering by a nuclear target, this means that at fixed $x_{N}= 2\kappa_{t}^2/s$ (but $\kappa_{t}^2\to \infty$) the nuclear process in which there is only a single interaction is the most important one to contribute to the reaction. Thus in this limit color transparency phenomena should occur.These findings are in accord with E971 experiment at FNAL. We also re-examine a potentially important nuclear multiple scattering correction which is positive and $\propto A^{1/3}/\kappa_t^4$. The meaning of the signal obtained from the experimental measurement of pion diffraction into two jets is also critically examined and significant corrections are identified.We show also that for values of $\kappa_t$ achieved at fixed target energies, di-jet production by the e.m. field of the nucleus leads to an insignificant correction which gets more important as $\kappa_t$ increases.Comment: 23 pages, 9 figure

Complementarity of the CERN Large Hadron Collider and the e+e−e^+e^- International Linear Collider

The next-generation high-energy facilities, the CERN Large Hadron Collider (LHC) and the prospective $e^+e^-$ International Linear Collider (ILC), are expected to unravel new structures of matter and forces from the electroweak scale to the TeV scale. In this report we review the complementary role of LHC and ILC in drawing a comprehensive and high-precision picture of the mechanism breaking the electroweak symmetries and generating mass, and the unification of forces in the frame of supersymmetry.Comment: 14 pages, 17 figures, to be published in "Supersymmetry on the Eve of the LHC", a special volume of European Physical Journal C, Particles and Fields (EPJC) in memory of Julius Wes

Effect of Periodontal Treatment on Glycemic Control of Diabetic Patients: A systematic review and meta-analysis

OBJECTIVE There is growing evidence that periodontitis may affect general health. This study was assigned to explore the robustness of observations that periodontal therapy leads to the improvement of glycemic control in diabetic patients. RESEARCH DESIGN AND METHODS A literature search (until March 2009) was carried out using two databases (MEDLINE and the Cochrane Library) with language restriction to English. Selection of publications was based on 1) original investigations, 2) controlled periodontal intervention studies where the diabetic control group received no periodontal treatment, and 3) study duration of ≥3 months. RESULTS Screening of the initial 639 identified studies and reference checking resulted in five suitable articles. A total of 371 patients were included in this analysis with periodontitis as predictor and the actual absolute change in A1C (ΔA1C) as the outcome. The duration of follow-up was 3-9 months. All studies described a research population of type 2 diabetic patients in whom glycemic control improved after periodontal therapy compared with the control group (range ΔA1C: Δ−1.17 up to Δ−0.05%). The studies in a meta-analysis demonstrated a weighted mean difference of ΔA1C before and after therapy of −0.40% (95% CI −0.77 to −0.04%, P = 0.03) favoring periodontal intervention in type 2 diabetic patients. Nevertheless, this improvement in %A1C must be interpreted with care due to limited robustness as evidenced by heterogeneity among studies (59.5%, P = 0.04). CONCLUSIONS The present meta-analysis suggests that periodontal treatment leads to an improvement of glycemic control in type 2 diabetic patients for at least 3 months