Efflux-mediated multiresistance in Gram-negative bacteria

ABSTRACTMultiresistance in Gram-negative pathogens, particularly Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Acinetobacter spp. and the Enterobacteriaceae, is a significant problem in medicine today. While multiple mechanisms often contribute to multiresistance, a broadly distributed family of three-component multidrug efflux systems is an increasingly recognised determinant of both intrinsic and acquired multiresistance in these organisms. Homologues of these efflux systems are also readily identifiable in the genome sequences of a wide range of Gram-negative organisms, pathogens and non-pathogens alike, where they probably promote efflux-mediated resistance to multiple antimicrobials. Significantly, these systems often accommodate biocides, raising the spectre of biocide-mediated selection of multiresistance in Gram-negative pathogens. While there is some debate as to the natural function of these efflux systems, only some of which are inducible by their antimicrobial substrates, their contribution to resistance in a variety of pathogens nonetheless makes them reasonable targets for therapeutic intervention. Indeed, given the incredible chemical diversity of substrates accommodated by these efflux systems, it is likely that many novel or yet to be discovered antimicrobials will themselves be efflux substrates and, as such, efflux inhibitors may become an important component of Gram-negative antimicrobial therapy

Evaluation of massless-spring modeling of suspension-line elasticity during the parachute unfurling process

A general theory on mathematical modeling of elastic parachute suspension lines during the unfurling process was developed. Massless-spring modeling of suspension-line elasticity was evaluated in detail. For this simple model, equations which govern the motion were developed and numerically integrated. The results were compared with flight test data. In most regions, agreement was satisfactory. However, poor agreement was obtained during periods of rapid fluctuations in line tension

Free energy surface of ST2 water near the liquid-liquid phase transition

We carry out umbrella sampling Monte Carlo simulations to evaluate the free energy surface of the ST2 model of water as a function two order parameters, the density and a bond-orientational order parameter. We approximate the long-range electrostatic interactions of the ST2 model using the reaction-field method. We focus on state points in the vicinity of the liquid-liquid critical point proposed for this model in earlier work. At temperatures below the predicted critical temperature we find two basins in the free energy surface, both of which have liquid-like bond orientational order, but differing in density. The pressure and temperature dependence of the shape of the free energy surface is consistent with the assignment of these two basins to the distinct low density and high density liquid phases previously predicted to occur in ST2 water.Comment: 8 pages, 9 figure

Reckoning Roanoke: A Historiographical Examination of the Lost Colony

The disappearance of the Lost Colony of Roanoke is an American mystery which has baffled historians for centuries. This paper takes a historiographical view of the works of academics Lee Miller and James Horn, comparing their research and conclusions on the topic. Miller’s belief that the colony was sabotaged by English secretary of state Sir. Francis Walsingham and Horn’s theory that an English desire for mineral wealth and poor preparation for survival in the New World brought about their demise are each analyzed for their legitimacy, research gaps, and possible biases. Through this analysis, it is concluded that the field of study on the attempted colonization of Roanoke and the settlers who disappeared there could benefit from a broader consideration for factors, outside of English politics and Native American relations, which may have contributed to the Lost Colonists\u27 disappearance

Letter to the Editor - Conservation of Freshwater Mussels in Iowa

Freshwater mussels occur in a variety of aquatic ecosystems worldwide but nowhere is mussel species richness as high as is reported in North America. With nearly 300 recorded species in the U.S., mussels are key components of freshwater biodiversity playing a vital role in benthic communities. Ecologically important in biological processing and nutrient cycling, mussels are also an important food item for a variety of mammals including mink, otter, and raccoon. In addition to ecological importance, freshwater mussels have been economically important in the production of cultured pearls

Nonlinear c-axis transport in Bi_2Sr_2CaCu_2O_(8+d) from two-barrier tunneling

Motivated by the peculiar features observed through intrinsic tunneling spectroscopy of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ mesas in the normal state, we have extended the normal state two-barrier model for the c-axis transport [M. Giura et al., Phys. Rev. B {\bf 68}, 134505 (2003)] to the analysis of $dI/dV$ curves. We have found that the purely normal-state model reproduces all the following experimental features: (a) the parabolic $V$-dependence of $dI/dV$ in the high-$T$ region (above the conventional pseudogap temperature), (b) the emergence and the nearly voltage-independent position of the "humps" from this parabolic behavior lowering the temperature, and (c) the crossing of the absolute $dI/dV$ curves at a characteristic voltage $V^\times$. Our findings indicate that conventional tunneling can be at the origin of most of the uncommon features of the c axis transport in Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$. We have compared our calculations to experimental data taken in severely underdoped and slightly underdoped Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ small mesas. We have found good agreement between the data and the calculations, without any shift of the calculated dI/dV on the vertical scale. In particular, in the normal state (above $T^\ast$) simple tunneling reproduces the experimental dI/dV quantitatively. Below $T^\ast$ quantitative discrepancies are limited to a simple rescaling of the voltage in the theoretical curves by a factor $\sim$2. The need for such modifications remains an open question, that might be connected to a change of the charge of a fraction of the carriers across the pseudogap opening.Comment: 7 pages, 5 figure

"Swarm relaxation": Equilibrating a large ensemble of computer simulations

It is common practice in molecular dynamics and Monte Carlo computer simulations to run multiple, separately-initialized simulations in order to improve the sampling of independent microstates. Here we examine the utility of an extreme case of this strategy, in which we run a large ensemble of $M$ independent simulations (a "swarm"), each of which is relaxed to equilibrium. We show that if $M$ is of order $10^3$, we can monitor the swarm's relaxation to equilibrium, and confirm its attainment, within $\sim 10\bar\tau$, where $\bar\tau$ is the equilibrium relaxation time. As soon as a swarm of this size attains equilibrium, the ensemble of $M$ final microstates from each run is sufficient for the evaluation of most equilibrium properties without further sampling. This approach dramatically reduces the wall-clock time required, compared to a single long simulation, by a factor of several hundred, at the cost of an increase in the total computational effort by a small factor. It is also well-suited to modern computing systems having thousands of processors, and is a viable strategy for simulation studies that need to produce high-precision results in a minimum of wall-clock time. We present results obtained by applying this approach to several test cases.Comment: 12 pages. To appear in Eur. Phy. J. E, 201