Cephem Potentiation by Inactivation of Nonessential Genes Involved in Cell Wall Biogenesis of ß-Lactamase-Producing Escherichia coli

Reversal of antimicrobial resistance is an appealing and largely unexplored strategy in drug discovery. The objective of this study was to identify potential targets for “helper” drugs reversing cephem resistance in Escherichia coli strains producing β-lactamases. A CMY-2-encoding plasmid was transferred by conjugation to seven isogenic deletion mutants exhibiting cephem hypersusceptibility. The effect of each mutation was evaluated by comparing the MICs in the wild type and the mutant harboring the same plasmid. Mutation of two genes encoding proteins involved in cell wall biosynthesis, dapF and mrcB, restored susceptibility to cefoxitin (FOX) and reduced the MICs of cefotaxime and ceftazidime, respectively, from the resistant to the intermediate category according to clinical breakpoints. The same mutants harboring a CTX-M-1-encoding plasmid fell into the intermediate or susceptible category for all three drugs. Individual deletion of dapF and mrcB in a clinical isolate of CTX-M-15-producing E. coli sequence type 131 (ST131) resulted in partial reversal of ceftazidime and cefepime resistance but did not reduce MICs below susceptibility breakpoints. Growth curve analysis indicated no fitness cost in a ΔmrcB mutant, whereas a ΔdapF mutant had a 3-fold longer lag phase than the wild type, suggesting that drugs targeting DapF may display antimicrobial activity, in addition to synergizing with selected cephems. DapF appeared to be a potential FOX helper drug target candidate, since dapF inactivation resulted in synergistic potentiation of FOX in the genetic backgrounds tested. The study showed that individual inactivation of two nonessential genes involved in cell wall biogenesis potentiates cephem activity according to drug- and strain-specific patterns

First Lattice Study of Ghost Propagators in SU(2) and SU(3) Gauge Theories

We present a numerical study of the ghost propagators in Landau gauge for SU(2) and SU(3) gauge theories at $\beta$=2.7 and $\beta$=6.0, respectively. Analyzing different lattice sizes up to $32^4$, we find small finite size effects. Down to the smallest available momenta, we observe no evidence for dipole behaviour of the ghost propagators.Comment: 7 pages, uuencoded compressed latex file, 2 figures include

A Guide to Precision Calculations in Dyson's Hierarchical Scalar Field Theory

The goal of this article is to provide a practical method to calculate, in a scalar theory, accurate numerical values of the renormalized quantities which could be used to test any kind of approximate calculation. We use finite truncations of the Fourier transform of the recursion formula for Dyson's hierarchical model in the symmetric phase to perform high-precision calculations of the unsubtracted Green's functions at zero momentum in dimension 3, 4, and 5. We use the well-known correspondence between statistical mechanics and field theory in which the large cut-off limit is obtained by letting beta reach a critical value beta_c (with up to 16 significant digits in our actual calculations). We show that the round-off errors on the magnetic susceptibility grow like (beta_c -beta)^{-1} near criticality. We show that the systematic errors (finite truncations and volume) can be controlled with an exponential precision and reduced to a level lower than the numerical errors. We justify the use of the truncation for calculations of the high-temperature expansion. We calculate the dimensionless renormalized coupling constant corresponding to the 4-point function and show that when beta -> beta_c, this quantity tends to a fixed value which can be determined accurately when D=3 (hyperscaling holds), and goes to zero like (Ln(beta_c -beta))^{-1} when D=4.Comment: Uses revtex with psfig, 31 pages including 15 figure

Lower thermosphere densities of N2, O and Ar under high latitude winter conditions

Measurements of the neutral thermosphere were conducted in northern Scandinavia during the Energy Budget Campaign. These measurements included determinations of N2, O, and Ar densities using rocket-borne experiments. The results obtained in the experiments are presented, taking into account also details regarding the employed experimental methods, and an evaluation of the significance of the data. It is found that there are striking differences in thermospheric distributions of the neutral constituents under different geomagnetic conditions. Under quiet geomagnetic conditions there was reasonable agreement with the United States Standard Atmosphere. The concentrations of N2 and Ar were about 70 percent of the predicted values, while the O concentration was about 2.5 times greater

High-Accuracy Calculations of the Critical Exponents of Dyson's Hierarchical Model

We calculate the critical exponent gamma of Dyson's hierarchical model by direct fits of the zero momentum two-point function, calculated with an Ising and a Landau-Ginzburg measure, and by linearization about the Koch-Wittwer fixed point. We find gamma= 1.299140730159 plus or minus 10^(-12). We extract three types of subleading corrections (in other words, a parametrization of the way the two-point function depends on the cutoff) from the fits and check the value of the first subleading exponent from the linearized procedure. We suggest that all the non-universal quantities entering the subleading corrections can be calculated systematically from the non-linear contributions about the fixed point and that this procedure would provide an alternative way to introduce the bare parameters in a field theory model.Comment: 15 pages, 9 figures, uses revte

Limitations for change detection in multiple Gabor targets

We investigate the limitations on the ability to detect when a target has changed, using Gabor targets as simple quantifiable stimuli. Using a partial report technique to equalise response variables, we show that the log of the Weber fraction for detecting a spatial frequency change is proportional to the log of the number of targets, with a set-size effect that is greater than that reported for visual search. This is not a simple perceptual limitation, because pre-cueing a single target out of four restores performance to the level found when only one target is present. It is argued that the primary limitation on performance is the division of attention across multiple targets, rather than decay within visual memory. However in a simplified change detection experiment without cueing, where only one target of the set changed, not only was the set size effect still larger, but it was greater at 2000 msec ISI than at 250 msec ISI, indicating a possible memory component. The steepness of the set size effects obtained suggests that even moderate complexity of a stimulus in terms of number of component objects can overload attentional processes, suggesting a possible low-level mechanism for change blindness

Survey Research in Finance: Views from Journal Editors

We survey editors from 15 core and 35 non-core finance journals to learn their views about specific issues involving survey research. Based on responses from 25 editors, none of their journals has an established policy involving the publication of survey research. The evidence shows that survey-based manuscripts typically go through the same review process as other manuscripts. However, editors of core versus non-core journals have mixed views about the role that survey research should play in the finance literature. The editors provide their views about the strengths and weaknesses of survey research as well as topic areas that would benefit from using this approach. A review of a finance journals shows that the publication of survey-based papers is an infrequent event for most journals