In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa

Time-kill curves of Pseudomonas aeruginosa exposed to gentamicin or ticarcilhn in vitro were correlated with time-kill curves obtained with various dosage schedules of the same study drugs in granulocytopenic mice. An instantaneous, fast and drug-dependent killing pattern was found in vitro with gentamicin. This pattern corresponded to bacterial killing in vivo which was clearly dependent on peak drug levels. In contrast, slow bacterial killing with little relationship to concentration was found in vitro with ticarcilhn and proved to correlate with an antibacterial effect in vivo seen at trough levels. We conclude that in-vitro time-kill curves of antimicrobial agents may be predictive for optimizing dosage regimens in viv

Dissipation scales and anomalous sinks in steady two-dimensional turbulence

In previous papers I have argued that the \emph{fusion rules hypothesis}, which was originally introduced by L'vov and Procaccia in the context of the problem of three-dimensional turbulence, can be used to gain a deeper insight in understanding the enstrophy cascade and inverse energy cascade of two-dimensional turbulence. In the present paper we show that the fusion rules hypothesis, combined with \emph{non-perturbative locality}, itself a consequence of the fusion rules hypothesis, dictates the location of the boundary separating the inertial range from the dissipation range. In so doing, the hypothesis that there may be an anomalous enstrophy sink at small scales and an anomalous energy sink at large scales emerges as a consequence of the fusion rules hypothesis. More broadly, we illustrate the significance of viewing inertial ranges as multi-dimensional regions where the fully unfused generalized structure functions of the velocity field are self-similar, by considering, in this paper, the simplified projection of such regions in a two-dimensional space, involving a small scale $r$ and a large scale $R$, which we call, in this paper, the $(r, R)$-plane. We see, for example, that the logarithmic correction in the enstrophy cascade, under standard molecular dissipation, plays an essential role in inflating the inertial range in the $(r, R)$ plane to ensure the possibility of local interactions. We have also seen that increasingly higher orders of hyperdiffusion at large scales or hypodiffusion at small scales make the predicted sink anomalies more resilient to possible violations of the fusion rules hypothesis.Comment: 22 pages, resubmitted to Phys. Rev.

Vortex Tubes in Turbulence Velocity Fields at Reynolds Numbers 300-1300

The most elementary structures of turbulence, i.e., vortex tubes, are studied using velocity data obtained in a laboratory experiment for boundary layers with microscale Reynolds numbers 295-1258. We conduct conditional averaging for enhancements of a small-scale velocity increment and obtain the typical velocity profile for vortex tubes. Their radii are of the order of the Kolmogorov length. Their circulation velocities are of the order of the root-mean-square velocity fluctuation. We also obtain the distribution of the interval between successive enhancements of the velocity increment as the measure of the spatial distribution of vortex tubes. They tend to cluster together below about the integral length and more significantly below about the Taylor microscale. These properties are independent of the Reynolds number and are hence expected to be universal.Comment: 8 pages, to appear in Physical Review

Area limit laws for symmetry classes of staircase polygons

We derive area limit laws for the various symmetry classes of staircase polygons on the square lattice, in a uniform ensemble where, for fixed perimeter, each polygon occurs with the same probability. This complements a previous study by Leroux and Rassart, where explicit expressions for the area and perimeter generating functions of these classes have been derived.Comment: 18 pages, 3 figure

Ureide Metabolism in Non-nodulated Phaseolus vulgaris L

The distribution of ureide-N was studied throughout vegetative and reproductive growth of non-nodulated Phaseolus vulgaris L. (bushbean) grown in nitrate nutrient solution. Largest increases in ureide-N per plant were correlated with flowering and early pod formation and with seed filling. Highest amounts of ureides per organ were measured in stems and axillary trifoliates. Highest concentrations (μmol ureide-N g−1 fr. wt.) were measured in young developing organs and stems. Seeds did not accumulate ureides until the ureide content of pods had reached a maximum. Results obtained using the inhibitor of xanthine oxidase, allopurinol, are consistent with the origin of ureides via purine degradation but alternative pathways cannot be discounted. Leaves and stems were shown to have the ability to degrade allantoate via an enzymic proces

The Statistics of Crumpled Paper

A statistical study of crumpled paper is allowed by a minimal 1D model: a self-avoiding line bent at sharp angles -- in which resides the elastic energy -- put in a confining potential. Many independent equilibrium configurations are generated numerically and their properties are investigated. At small confinement, the distribution of segment lengths is log-normal in agreement with previous predictions and experiments. At high confinement, the system approaches a jammed state with a critical behavior, whereas the length distribution follows a Gamma law which parameter is predicted as a function of the number of layers in the system

Range-separated density-functional theory with random phase approximation: detailed formalism and illustrative applications

Using Green-function many-body theory, we present the details of a formally exact adiabatic-connection fluctuation-dissipation density-functional theory based on range separation, which was sketched in Toulouse, Gerber, Jansen, Savin and Angyan, Phys. Rev. Lett. 102, 096404 (2009). Range-separated density-functional theory approaches combining short-range density functional approximations with long-range random phase approximations (RPA) are then obtained as well-identified approximations on the long-range Green-function self-energy. Range-separated RPA-type schemes with or without long-range Hartree-Fock exchange response kernel are assessed on rare-gas and alkaline-earth dimers, and compared to range-separated second-order perturbation theory and range-separated coupled-cluster theory.Comment: 15 pages, 3 figures, 2 table

Antibiotic Therapy of Infections Due to Pseudomonas aeruginosa in Normal and Granulocytopenic Mice: Comparison of Murine and Human Pharmacokinetics

An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With β-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a single-bolus injection that tended to be more active. Thus, when tested in conventional small-animal models, aminoglycoside activity may be overestimated, whereas β-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and β-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitr