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

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

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

Crystal Nucleation in a Supercooled Liquid with Glassy Dynamics

In simulations of supercooled, high-density liquid silica we study a range of temperature T in which we find both crystal nucleation, as well as the characteristic dynamics of a glass forming liquid, including a breakdown of the Stokes-Einstein relation. We find that the liquid cannot be observed below a homogeneous nucleation limit (HNL) at which the liquid crystallizes faster than it can equilibrate. We show that the HNL would occur at lower T, and perhaps not at all, if the Stokes-Einstein relation were obeyed, and hence that glassy dynamics plays a central role in setting a crystallization limit on the liquid state in this case. We also explore the relation of the HNL to the Kauzmann temperature, and test for spinodal-like effects near the HNL.Comment: 4 pages, 4 figure

Simulator test to study hot-flow problems related to a gas cooled reactor

An advance study of materials, fuel injection, and hot flow problems related to the gas core nuclear rocket is reported. The first task was to test a previously constructed induction heated plasma GCNR simulator above 300 kW. A number of tests are reported operating in the range of 300 kW at 10,000 cps. A second simulator was designed but not constructed for cold-hot visualization studies using louvered walls. A third task was a paper investigation of practical uranium feed systems, including a detailed discussion of related problems. The last assignment resulted in two designs for plasma nozzle test devices that could be operated at 200 atm on hydrogen

Reducing Polarization Mode Dispersion With Controlled Polarization Rotations

One of the fundamental limitations to high bit rate, long distance, telecommunication in optical fibers is Polarization Mode Dispersion (PMD). Here we introduce a conceptually new method to reduce PMD in optical fibers by carrying out controlled rotations of polarization at predetermined locations along the fiber. The distance between these controlled polarization rotations must be less than both the beat length and the mode coupling length of the fiber. This method can also be combined with the method in which the fiber is spun while it drawn. The incidence of imperfections on the efficiency of the method is analysed.Comment: 4 page