Characterisation of the effects of salicylidene acylhydrazide compounds on type three secretion in Escherichia coli O157:H7

Recent work has highlighted a number of compounds that target bacterial virulence by affecting gene regulation. In this work, we show that small-molecule inhibitors affect the expression of the type III secretion system (T3SS) of <i>Escherichia coli</i> O157:H7 in liquid culture and when the bacteria are attached to bovine epithelial cells. The inhibition of T3SS expression resulted in a reduction in the capacity of the bacteria to form attaching and effacing lesions. Our results show a marked variation in the ability of four structurally-related compounds to inhibit the T3SS of a panel of isolates. Using transcriptomics, we provide a comprehensive analysis of the conserved- and inhibitor-specific transcriptional responses to the four compounds. These analyses of gene expression show that numerous virulence genes, located on horizontally-acquired DNA elements, are affected by the compounds but the number of genes significantly affected varied markedly between the compounds. Overall, we highlight the importance of assessing the effect of such "anti-virulence" agents on a range of isolates and discuss the possible mechanisms which may lead to the co-ordinate down-regulation of horizontally acquired virulence genes

Quantum Cosmology Aspects Of D3 Branes and Tachyon Dynamics

We investigate aspects of quantum cosmology in relation to string cosmology systems that are described in terms of the Dirac-Born-Infeld action. Using the Silverstein-Tong model, we analyze the Wheeler-DeWitt equation for the rolling scalar and gravity as well for $R\times{S^3}$ universe, by obtaining the wave functions for all dynamical degrees of freedom of the system. We show, that in some cases one can construct a time dependent version of the Wheeler-DeWitt (WDW) equation for the moduli field $\phi$. We also explore in detail the minisuperspace description of the rolling tachyon when non-minimal gravity tachyon couplings are inserted into the tachyon action.Comment: 29 pages, 3 figures, REVTeX 4; v2 clarifications, comments and references added; v3 more typos corrected, additional comments on the minisuperspace description of unstable universes, version published in JHE

Significance Tests for Periodogram Peaks

We discuss methods currently in use for determining the significance of peaks in the periodograms of time series. We discuss some general methods for constructing significance tests, false alarm probability functions, and the role played in these by independent random variables and by empirical and theoretical cumulative distribution functions. We also discuss the concept of "independent frequencies" in periodogram analysis. We propose a practical method for estimating the significance of periodogram peaks, applicable to all time series irrespective of the spacing of the data. This method, based on Monte Carlo simulations, produces significance tests that are tailor-made for any given astronomical time series.Comment: 22 pages, 11 Encapsulated Postscript figures, AAS LaTeX v5.2 Submitted to Ap

Superconductivity in the SU(N) Anderson Lattice at U=\infty

We present a mean-field study of superconductivity in a generalized N-channel cubic Anderson lattice at U=\infty taking into account the effect of a nearest-neighbor attraction J. The condition U=\infty is implemented within the slave-boson formalism considering the slave bosons to be condensed. We consider the $f$-level occupancy ranging from the mixed valence regime to the Kondo limit and study the dependence of the critical temperature on the various model parameters for each of three possible Cooper pairing symmetries (extended s, d-wave and p-wave pairing) and find interesting crossovers. It is found that the d- and p- wave order parameters have, in general, very similar critical temperatures. The extended s-wave pairing seems to be relatively more stable for electronic densities per channel close to one and for large values of the superconducting interaction J.Comment: Seven Figures; one appendix. Accepted for publication in Phys. Rev.

Transport properties of strongly correlated metals:a dynamical mean-field approach

The temperature dependence of the transport properties of the metallic phase of a frustrated Hubbard model on the hypercubic lattice at half-filling are calculated. Dynamical mean-field theory, which maps the Hubbard model onto a single impurity Anderson model that is solved self-consistently, and becomes exact in the limit of large dimensionality, is used. As the temperature increases there is a smooth crossover from coherent Fermi liquid excitations at low temperatures to incoherent excitations at high temperatures. This crossover leads to a non-monotonic temperature dependence for the resistance, thermopower, and Hall coefficient, unlike in conventional metals. The resistance smoothly increases from a quadratic temperature dependence at low temperatures to large values which can exceed the Mott-Ioffe-Regel value, hbar a/e^2 (where "a" is a lattice constant) associated with mean-free paths less than a lattice constant. Further signatures of the thermal destruction of quasiparticle excitations are a peak in the thermopower and the absence of a Drude peak in the optical conductivity. The results presented here are relevant to a wide range of strongly correlated metals, including transition metal oxides, strontium ruthenates, and organic metals.Comment: 19 pages, 9 eps figure

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's) : an ARChiVe Cohort Study

OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n\u2009=\u200948) or GPA (n\u2009=\u2009183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding