bluuebunny/crossref_metadata_2025 huggingface dataset:
Total internal reflection fluorescence microscopy imaging-guided confocal single-molecule fluorescence spectroscopy
Authors: Zheng Desheng , Kaldaras Leonora , Lu H. Peter
Published: January 2012

We have developed an integrated spectroscopy system combining total internal reflection fluorescence microscopy imaging with confocal single-molecule fluorescence spectroscopy for two-dimensional interfaces. This spectroscopy approach is capable of both multiple molecules simultaneously sampling and in situ confocal fluorescence dynamics analyses of individual molecules of interest. We have demonstrated the calibration with fluorescent microspheres, and carried out single-molecule spectroscopy measurements. This integrated single-molecule spectroscopy is powerful in studies of single molecule dynamics at interfaces of biological and chemical systems.
Particle beam self-modulation instability in tapered and inhomogeneous plasma
Authors: Schroeder C. B. , Benedetti C. , Esarey E. , Grüner F. J. , Leemans W. P.
Published: January 2012

The particle beam self-modulation instability in tapered and inhomogeneous plasmas is analyzed via an evolution equation for the beam radius. For a sufficiently fast taper, the instability is suppressed, and the condition for growth suppression is derived. The form of the taper to phase lock a trailing witness bunch in the plasma wave driven by a self-modulated beam is determined, which can increase the energy gain by several orders of magnitude. Growth of the instability places stringent constraints on the initial background plasma density fluctuations.
Determination of the levitation limits of dust particles within the sheath in complex plasma experiments
Authors: Douglass Angela , Land Victor , Qiao Ke , Matthews Lorin , Hyde Truell
Published: January 2012

Experiments are performed in which dust particles are levitated at varying heights above the powered electrode in a radio frequency plasma discharge by changing the discharge power. The trajectories of particles dropped from the top of the discharge chamber are used to reconstruct the vertical electric force acting on the particles. The resulting data, together with the results from a self-consistent fluid model, are used to determine the lower levitation limit for dust particles in the discharge and the approximate height above the lower electrode where quasineutrality is attained, locating the sheath edge. These results are then compared with current sheath models. It is also shown that particles levitated within a few electron Debye lengths of the sheath edge are located outside the linearly increasing portion of the electric field.
Exploring quantum non-locality with de Broglie-Bohm trajectories
Authors: Christov Ivan P.
Published: January 2012

Here in this paper, it is shown how the quantum nonlocality reshapes probability distributions of quantum trajectories in configuration space. By variationally minimizing the ground state energy of helium atom, we show that there exists an optimal nonlocal quantum correlation length which also minimizes the mean integrated square error of the smooth trajectory ensemble with respect to the exact many-body wave function. The nonlocal quantum correlation length can be used for studies of both static and driven many-body quantum systems.
On the transition from microscopic to macroscopic electrodynamics
Authors: de Lange O. L. , Raab R. E. , Welter A.
Published: January 2012

Implicit in the change from microscopic electrodynamics to a macroscopic, multipole theory is a set of molecule-fixed coordinate systems – and hence an arbitrary set of molecular origins {On} – relative to which the positions of molecular constituents are specified. We examine the extent to which this theory satisfies a Van Vleck–Buckingham-type translational invariance with respect to the choice of {On} in a linear, homogeneous, anisotropic medium. For contributions above electric dipole order, the theory is only partially invariant, and therefore incomplete: the corresponding macroscopic Maxwell equations yield unphysical results for certain phenomena. We propose a fully invariant formulation, based on the use of invariant molecular polarizability tensors in the quantum-mechanical expressions for expectation values of molecular multipole moments induced by harmonic, plane electromagnetic waves. We show that expressions for the invariant polarizabilities can be discerned from the partially invariant theory, and we discuss the uniqueness of our procedure.
Kinetics of small single particle combustion of zirconium alloy
Authors: Wei Haoyan , Yoo Choong-Shik
Published: January 2012

We present quantitative kinetic information regarding small, 1-10 μm in diameter, single particle combustion of Zr-rich metal alloy foils subjected to either mechanical impacts or laser-ablation. The lights from combustion of metal fragments were recorded on a high-speed camera. The particle size was determined by the motion analysis of individual particle trajectory based on an aerodynamic drag law and further verified by the microstructure and chemical composition analysis of recovered post-burn particles. The measured particle sizes show a log-normal distribution centered at around 3.1 μm in diameter, and the composition of recovered particles is that of fully oxidized ZrO2. The temperature evolution of each particle along the space/time-trajectory is determined based on the thermal emission from combustion using a single-color photographic spectro-pyrometry. The result indicates that the particle has reached the maximum combustion temperature of 4000 K, well beyond the melting temperature of ZrO2, and undergone the solidification of molten ZrO2 during the cooling stage. It also shows that the maximum combustion temperature decreases linearly with increasing the particle diameter, following the correlation t = aD1.5–1.8 between the burn time (t) and the particle diameter (D). Combining the particle size, the burn time, and the particle temperature, both temperature and mass burn rates are obtained as a function of particle size. As the particle size increases, the temperature burn rate decreases, whereas the mass burn rate goes in the opposite direction.
Enhancement of the transverse non-reciprocal magneto-optical effect
Authors: Zayets V. , Saito H. , Yuasa S. , Ando K.
Published: January 2012

The methods to enhance the transverse non-reciprocal magneto-optical (nMO) effect have been studied. The transverse nMO effect occurs in the case when light propagates perpendicularly to the magnetic field. It was demonstrated that light can experience the transverse nMO effect only when it propagates in the vicinity of a boundary between two materials and the optical field at least in one material is evanescent. The magnitude of the transverse nMO effect is comparable to or greater than the magnitude of the longitudinal nMO effect. In the case of surface plasmons propagating at a boundary between the transition metal and the dielectric it is possible to magnify the transverse nMO effect and the magneto-optical figure-of-merit may increase from a few percents to above 100%.
Magnetoelectric coupling of laminated composites under combined thermal and magnetic loadings
Authors: Fang F. , Xu Y. T. , Yang W.
Published: January 2012

Laminated magnetoelectric (ME) composites are suitable for applications such as magnetic field sensors, transformers, and microwave resonators. Such applications frequently involve environments where the temperature alters. The present work investigates the temperature dependent ME coupling for three kinds of laminates, namely, Terfenol-D/PZT/Terfenol-D, Ni/PZT/Ni, and Metglas/PZT/Metglas. The Terfenol-D/PZT/Terfenol-D is shown to exhibit the best temperature stability. The peak value of the ME coefficient versus temperature curve is predicted for the laminates based on the equivalent circuit model, as well as the measurements of temperature dependent magnetostriction for Terfenol-D, Ni, and Metglas. The predictions agree well with the experimental data, implying that the piezomagnetic coefficient, d11,m, of the magnetic layer plays an important role in the temperature dependent ME coupling of the laminate.
Modeling of ferroelectric switching process in poly(vinylidene fluoride-trifluoroethylene) copolymer ultrathin films with electroactive interlayer
Authors: Hou Ying , Zhang Xiuli , Zhang Yuan , Xu Guoqiang , Xu Haisheng
Published: January 2012

A universal model and experiments on the polarization switching for ferroelectric poly(vinylidene fluoride-trifluoroethylene) copolymer ultra-thin films with an interface layer have been studied. It is found that polarization switching could complete if the capacitance of the interface layer is large enough compared with that of the ferroelectric film. Based on this model, a conducting polymer, poly(3,4-ethylene dioxythiophene)-poly(styrene sulfonic) acid, is introduced as an interface layer between metal electrodes and ferroelectric polymer film and the switching property measurements well agree with the simulation results of the model. These findings provide an effective route to enhance the polarization switching for the ferroelectric films, which is promising for potential applications.
Thermoelectric properties of Ni-doped CeFe4Sb12 skutterudites
Authors: Qiu P. F. , Liu R. H. , Yang J. , Shi X. , Huang X. Y. , Zhang W. , Chen L. D. , Yang Jihui , Singh D. J.
Published: January 2012

We have prepared Ni-doped p-type skutterudites CeyFe4−xNixSb12 and systematically studied their thermoelectric properties. The lattice parameters of these skutterudites are found to be sensitive to both the Ni content and Ce-filling fraction. With increasing Ni content, the electrical conductivity decreases and the Seebeck coefficient increases, consistent with the expected decrease in hole concentration due to the extra electrons introduced by Ni. All Ni-doped samples possess similar band gap values. We also find that the Ni-doped CeyFe4−xNixSb12 system has electrical transport properties similar to those of Co-doped CeyFe4−xCoxSb12 system at a similar nominal hole concentration based on a simple charge counting. We do, however, find a pronounced bi-polar phenomenon in thermal conductivity that rapidly increases for Ni-doped samples when temperature is above 600 K. Importantly, Ni-doped samples have higher dimensionless thermoelectric figures of merit values than CeFe4Sb12 over the entire temperature range measured. Therefore, Ni doping is useful for improving the energy conversion efficiency in applications.
Quantitative analysis of electroluminescence images from polymer solar cells
Authors: Seeland Marco , Rösch Roland , Hoppe Harald
Published: January 2012

We introduce the micro-diode-model (MDM) based on a discrete network of interconnected diodes, which allows for quantitative description of lateral electroluminescence emission images obtained from organic bulk heterojunction solar cells. Besides the distributed solar cell description, the equivalent circuit, respectively, network model considers interface and bulk resistances as well as the sheet resistance of the semitransparent electrode. The application of this model allows direct calculation of the lateral current and voltage distribution within the solar cell and thus accounts well for effects known as current crowding. In addition, network parameters such as internal resistances and the sheet-resistance of the higher resistive electrode can be determined. Furthermore, upon introduction of current sources the micro-diode-model also is able to describe and predict current-voltage characteristics for solar cell devices under illumination. The local nature of this description yields important conclusions concerning the geometry dependent performance and the validity of classical models and equivalent circuits describing thin film solar cells.
Fractional Brownian sheets run with nonlinear clocks
Authors: Wu Dongsheng
Published: January 2012

Let \documentclass[12pt]{minimal}\begin{document}$X=\lbrace X(t),\,t\in {\mathbb R}_+^N\rbrace$\end{document}X={X(t),t∈R+N} be an (N, d)-fractional Brownian sheet run with nonlinear clocks, that is, X(t) = BH(F1(t1), …, FN(tN)) for all \documentclass[12pt]{minimal}\begin{document}$t=(t_1,\ldots ,t_N)\in {\mathbb R}_+^N$\end{document}t=(t1,...,tN)∈R+N, where BH is an (N, d)-fractional Brownian sheet with Hurst indices H = (H1, …, HN) ∈ (0, 1)N, and where \documentclass[12pt]{minimal}\begin{document}$F_i:\, {\mathbb R}_+\rightarrow {\mathbb R}_+$\end{document}Fi:R+→R+ (i = 1, …, N) are N non-negative nondecreasing functions that satisfy bi-Lipschitz conditions. In this paper, we study sample path properties of fractional Brownian sheet run with nonlinear clocks X. We first derive a sharp modulus of continuity for X, and then determine the Hausdorff and packing dimensions of the range X([0, 1]N), the graph GrX([0, 1]N), and the level sets for the X. We also provide necessary and sufficient conditions for the existence of local times of X and investigate the joint continuity of the local times. Finally, we study the intersection behavior of two independent fractional Brownian sheets run with (possibly different) nonlinear clocks.
Polarization-independent negative refraction effect in SiO2-GaAs annular photonic crystals
Authors: Jiang Li-Yong , Wu Hong , Jia Wei , Li Xiang-Yin
Published: January 2012

We systematically investigated the negative refraction effect for both TM and TE polarization modes in SiO2-GaAs annular photonic crystals with triangular lattice. It was found that, in comparison with normal triangular-lattice air-holes photonic crystals, the annular photonic crystals have much lower and flatter band structures, which are quite beneficial to the formation of convex equifrequency surfaces for both polarizations. Further analyses on equifrequency surfaces and the electric field distribution of annular photonic crystals with different parameters have not only first demonstrated the possibility of polarization-independent negative refraction effect in annular photonic crystals, but also revealed some important laws to control the working frequency and performance of this remarkable effect.
Substrate independence of THz vibrational modes of polycrystalline thin films of molecular solids in waveguide THz-TDS
Authors: Harsha S. Sree , Melinger Joseph. S. , Qadri S. B. , Grischkowsky D.
Published: January 2012

The influence of the metal substrate on the measurement of high resolution THz vibrational modes of molecular solids with the waveguide THz-TDS technique is investigated. The sample film of salicylic acid is studied using waveguide THz-TDS on three different metal substrates and two-surface passivated substrates. The independence of the observed THz vibrational modes to the metal substrate is demonstrated. Independently, surface passivation is presented as a viable experimental addition to the waveguide THz-TDS technique to aid the characterization of samples with known reactivity to metal surfaces.
Prediction of reaction barriers and force-induced instabilities under mechanochemical conditions with an approximate model: A case study of the ring opening of 1,3-cyclohexadiene
Authors: Bailey Adrian , Mosey Nicholas J.
Published: January 2012

Mechanochemistry, the use of mechanical stresses to activate chemical reactions, has emerged as a topic of significant interest. The present study examines the use of an approximate model for the prediction of reaction barriers under mechanochemical conditions using the ring opening of 1,3-cyclohexadiene along conrotatory and disrotatory directions as a specific test case. To do this, reaction barriers are evaluated using quantum chemical methods with an external force applied between various pairs of atoms. The results show that the consequent effects on the barrier exhibit a significant dependence on the locations of the atoms used to apply the external force, and in some cases, force-induced instabilities occur that alter the fundamental nature of the reaction pathway. The ability of an approximate model based on a second-order expansion of the force-modified potential energy with respect to nuclear coordinates to reproduce this behavior is then assessed. Good agreement between the results obtained through the quantum chemical calculations and approximate model is attained when force-induced instabilities do not occur. In addition, a strategy for predicting when such instabilities occur is presented and found to yield results that are in qualitative agreement with the quantum chemical calculations. Finally, the response of the system to the external force is interpreted in terms of the parameters entering the model, which correspond to interatomic distances and stiffnesses, and possibly sheds lights on ways to design molecules that exhibit a desired chemical response to mechanochemical conditions.
Phase-only shaped laser pulses in optimal control theory: Application to indirect photofragmentation dynamics in the weak-field limit
Authors: Shu Chuan-Cun , Henriksen Niels E.
Published: January 2012

We implement phase-only shaped laser pulses within quantum optimal control theory for laser-molecule interaction. This approach is applied to the indirect photofragmentation dynamics of NaI in the weak-field limit. It is shown that optimized phase-modulated pulses with a fixed frequency distribution can substantially modify transient dissociation probabilities as well as the momentum distribution associated with the relative motion of Na and I.
Estimating the conditions for polariton condensation in organic thin-film microcavities
Authors: Bittner Eric R. , Silva Carlos
Published: January 2012

We examine the possibility of observing Bose condensation of a confined two-dimensional polariton gas in an organic quantum well. We deduce a suitable parameterization of a model polynomial Hamiltonian based upon the cavity geometry, the biexciton binding energy, and similar spectroscopic and structural data. By converting the sum-over-states to a semiclassical integration over D-dimensional phase space, we arrive at a principle of correspondence between ideal and non-ideal Bose gases that share a common critical exponent. Using our results, we can calculate the properties for a model cavity containing an anthracene thin film.
Room temperature, continuous wave lasing in microcylinder and microring quantum dot laser diodes
Authors: Munsch M. , Claudon J. , Malik N. S. , Gilbert K. , Grosse P. , Gérard J.-M. , Albert F. , Langer F. , Schlereth T. , Pieczarka M. M. , Höfling S. , Kamp M. , Forchel A. , Reitzenstein S.
Published: January 2012

We demonstrate room temperature, continuous wave lasing of laser diodes based on AlGaAs whispering gallery mode (WGM) resonators (microcylinder and microring) embedding a quantum dot (QD) active layer. Using InGaAlAs QDs, high-Q (>60 000) lasing modes are observed around 910 nm, up to 50 °C. Lasing with similar performance is obtained around 1230 nm, using InAs QDs. Furthermore, we show that the current injection in the active part of the device is improved in ring resonators, leading to threshold currents of approximately 4 mA for a device with 80 μm diameter. This geometry also suppresses WGMs with a high radial order, thus simplifying the lasing spectra. In these conditions, stable single-mode and two-color lasing can be obtained.
Modeling the quantum efficiency of controlled porosity dispenser photocathodes
Authors: Pan Z. , Jensen K. , O’Shea P.
Published: January 2012

A theoretical model of diffusion, evaporation, and rejuvenation of cesium on the surface of a controlled porosity dispenser photocathode is developed. The model applies a novel hexagonal meshgrid for increased numerical accuracy. For activation temperatures within the range of 400 K–1000 K, simulation found differences of less than 5% between the quantum efficiency (QE) maximum and minimum over ideal homogenous surfaces. Simulations suggest more variation for real cases to include real surface non uniformity. Changes in the QE map across the surface suggest that the emittance can change depending on temperature. Extensions to the model as well as connections to experiment are discussed.
A tunable, dual mode field-effect or single electron transistor
Authors: Roche B. , Voisin B. , Jehl X. , Wacquez R. , Sanquer M. , Vinet M. , Deshpande V. , Previtali B.
Published: January 2012

A dual mode device behaving either as a field-effect transistor or a single electron transistor (SET) has been fabricated using silicon-on-insulator metal oxide semiconductor technology. Depending on the back gate polarisation, an electron island is accumulated under the front gate of the device (SET regime), or a field-effect transistor is obtained by pinching off a bottom channel with a negative front gate voltage. The gradual transition between these two cases is observed. This dual function uses both vertical and horizontal tunable potential gradients in non-overlapped silicon-on-insulator channel.
Generalized essential energy space random walks to more effectively accelerate solute sampling in aqueous environment
Authors: Lv Chao , Zheng Lianqing , Yang Wei
Published: January 2012

Molecular dynamics sampling can be enhanced via the promoting of potential energy fluctuations, for instance, based on a Hamiltonian modified with the addition of a potential-energy-dependent biasing term. To overcome the diffusion sampling issue, which reveals the fact that enlargement of event-irrelevant energy fluctuations may abolish sampling efficiency, the essential energy space random walk (EESRW) approach was proposed earlier. To more effectively accelerate the sampling of solute conformations in aqueous environment, in the current work, we generalized the EESRW method to a two-dimension-EESRW (2D-EESRW) strategy. Specifically, the essential internal energy component of a focused region and the essential interaction energy component between the focused region and the environmental region are employed to define the two-dimensional essential energy space. This proposal is motivated by the general observation that in different conformational events, the two essential energy components have distinctive interplays. Model studies on the alanine dipeptide and the aspartate-arginine peptide demonstrate sampling improvement over the original one-dimension-EESRW strategy; with the same biasing level, the present generalization allows more effective acceleration of the sampling of conformational transitions in aqueous solution. The 2D-EESRW generalization is readily extended to higher dimension schemes and employed in more advanced enhanced-sampling schemes, such as the recent orthogonal space random walk method.
Long-range orientation correlation in liquids
Authors: Shelton David P.
Published: January 2012

Strong short-range intermolecular interactions result in position and orientation correlations between nearest neighbour molecules in isotropic liquids, and it is generally assumed that such correlations extend at most a few molecular diameters. This assumption is contradicted by results from second harmonic light scattering experiments presented here, which reveal long-range orientation correlations in several isotropic liquids including water. These experiments measure the polarization dependence of the scattered light, and the observations are interpreted in terms of transverse and longitudinal polar collective modes, as well as simple explicit models. The results revise our understanding of the structure of molecular liquids and provide a test of computational simulations.
Advantages of blue InGaN light-emitting diodes with InGaN-AlGaN-InGaN barriers
Authors: Kuo Yen-Kuang , Wang Tsun-Hsin , Chang Jih-Yuan
Published: January 2012

Efficiency enhancement of the blue InGaN light-emitting diodes (LEDs) with InGaN-AlGaN-InGaN barriers is studied numerically. The energy band diagrams, carrier concentrations in quantum wells, radiative recombination rate in active region, light-current performance curves, and internal quantum efficiency are investigated. The simulation results suggest that the blue InGaN/InGaN-AlGaN-InGaN LED has better performance over its conventional InGaN/GaN and InGaN/InGaN counterparts due to the appropriately modified energy band diagrams, which are caused mainly by the reduced polarization charges at the interface between the well and barrier.
Comment on “Structure and thermodynamics of hard-core Yukawa fluids: Thermodynamic perturbation approaches” [J. Chem. Phys, 135, 034505 (2011)]
Authors: Khanpour Mehrdad
Published: January 2012

We would like to show that what has been presented in the paper by Kim, Kim, and Seong [J. Chem. Phys, 135, 034505 (2011)]10.1063/1.3610400 is nothing but an unnecessarily complicated version of (optimized) random phase approximation.
Enhancement of light-extraction efficiency of SiNx light emitting devices through a rough Ag island film
Authors: Wang Feng , Li Dongsheng , Yang Deren , Que Duanlin
Published: January 2012

Based on an ITO/Ag/SiNx/p+-Si/Al structure, a significant enhancement of the external quantum efficiency was achieved compared with the device without Ag island film. Analysis showed that the increase of the light-extraction efficiency resulted from the surface roughening of ITO electrode has a main contribution to this enhancement. The increase of the internal quantum efficiency induced by the enhancement of spontaneous emission rate and the carrier injection level also has an instructive contribution. Our results demonstrate that localized surface plasmons enhanced SiNx-based light emitting devices show great promise for the development of efficiency Si-based optical device.
Hybrid inertial method for broadband scattering reduction
Authors: Martin Theodore P. , Orris Gregory J.
Published: January 2012

We combine a transformational acoustic (TA) conformal map with a scattering cancellation (SC) layer to produce a hybrid design that reduces the scattering cross-section of an object in an aqueous environment. Our method is an inertial design that does not rely on negative-valued media. Using multiple scattering theory for cylindrical shells, our calculations demonstrate that the hybrid design outperforms both a discretized transformational acoustic superlattice and a scattering cancellation layer over a broad frequency bandwidth. The hybrid method can be utilized to optimize performance over targeted frequency bands.
Wind - terrain effects on the propagation of wildfires in rugged terrain: fire channelling
Authors: Sharples Jason J. , McRae Richard H. D. , Wilkes Stephen R.
Published: January 2012

The interaction of wind, terrain and a fire burning in a landscape can produce a variety of unusual yet significant effects on fire propagation. One such example, in which a fire exhibits rapid spread in a direction transverse to the synoptic winds as well as in the usual downwind direction, is considered in this paper. This type of fire spread, which is referred to as ‘fire channelling’, is characterised by intense lateral and downwind spotting and production of extensive flaming zones. The dependence of fire channelling on wind and terrain is analysed using wind, terrain and multispectral fire data collected during the January 2003 Alpine fires over south-eastern Australia. As part of the analysis, a simple terrain-filter model is utilised to confirm a quantitative link between instances of fire channelling and parts of the terrain that are sufficiently steep and lee-facing. By appealing to the theory of wind–terrain interaction and the available evidence, several processes that could produce the atypical fire spread are considered and some discounted. Based on the processes that could not be discounted, and a previous analysis of wind regimes in rugged terrain, a likely explanation for the fire channelling phenomenon is hypothesised. Implications of fire channelling for bushfire risk management are also discussed.
FAK promotes recruitment of talin to nascent adhesions to control cell motility
Authors: Lawson Christine , Lim Ssang-Taek , Uryu Sean , Chen Xiao Lei , Calderwood David A. , Schlaepfer David D.
Published: January 2012

Cell migration is a dynamic process that involves the continuous formation, maturation, and turnover of matrix–cell adhesion sites. New (nascent) adhesions form at the protruding cell edge in a tension-independent manner and are comprised of integrin receptors, signaling, and cytoskeletal-associated proteins. Integrins recruit focal adhesion kinase (FAK) and the cytoskeletal protein talin to nascent adhesions. Canonical models support a role for talin in mediating FAK localization and activation at adhesions. Here, alternatively, we show that FAK promotes talin recruitment to nascent adhesions occurring independently of talin binding to β1 integrins. The direct binding site for talin on FAK was identified, and a point mutation in FAK (E1015A) prevented talin association and talin localization to nascent adhesions but did not alter integrin-mediated FAK recruitment and activation at adhesions. Moreover, FAK E1015A inhibited cell motility and proteolytic talin cleavage needed for efficient adhesion dynamics. These results support an alternative linkage for FAK–talin interactions within nascent adhesions essential for the control of cell migration.
Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration
Authors: Rainero Elena , Caswell Patrick T. , Muller Patricia A.J. , Grindlay Joan , McCaffrey Mary W. , Zhang Qifeng , Wakelam Michael J.O. , Vousden Karen H. , Graziani Andrea , Norman Jim C.
Published: January 2012

Inhibition of αvβ3 integrin or expression of oncogenic mutants of p53 promote invasive cell migration by enhancing endosomal recycling of α5β1 integrin under control of the Rab11 effector Rab-coupling protein (RCP). In this paper, we show that diacylglycerol kinase α (DGK-α), which phosphorylates diacylglycerol to phosphatidic acid (PA), was required for RCP to be mobilized to and tethered at the tips of invasive pseudopods and to allow RCP-dependent α5β1 recycling and the resulting invasiveness of tumor cells. Expression of a constitutive-active mutant of DGK-α drove RCP-dependent invasion in the absence of mutant p53 expression or αvβ3 inhibition, and conversely, an RCP mutant lacking the PA-binding C2 domain was not capable of being tethered at pseudopod tips. These data demonstrate that generation of PA downstream of DGK-α is essential to connect expression of mutant p53s or inhibition of αvβ3 to RCP and for this Rab11 effector to drive the trafficking of α5β1 that is required for tumor cell invasion through three-dimensional matrices.
FAK and talin: Who is taking whom to the integrin engagement party?
Authors: Serrels Bryan , Frame Margaret C.
Published: January 2012

In this issue, Lawson et al. provide new insight into the relationship between FAK and talin during assembly of integrin adhesions on fibronectin. They show that FAK is upstream of talin, and that talin is not required for FAK recruitment or for integrin activation at nascent adhesions. However, FAK-talin binding is required for adhesion turnover and cell motility. The findings question the view that talin is always upstream of focal adhesion protein recruitment to clustered integrin sites.
The development of the BSAC standardized method of disc diffusion testing
Authors: Andrews Jennifer M.
Published: January 2012

The BSAC Working Party on Susceptibility Testing has developed a standardized method of disc susceptibility testing that has been ‘field tested’ in 19 diagnostic laboratories in the UK and Ireland. The method employs semi-defined media, a semi-confluent inoculum and relates zones of inhibition with BSAC-specified MIC breakpoints to interpret susceptibility. The bacteria selected for the trial included clinical isolates and control strains from the ATCC and NCTC national collections. Organisms were chosen because they had known attributes, such as being fully susceptible or having a demonstrated mechanism of resistance. The results from this survey are very encouraging. With the commonly isolated Enterobacteriaceae, specifically Escherichia coli, Proteus mirabilis and Klebsiella spp., no major problems were observed except with gentamicin and cefuroxime. In the case of gentamicin, problems were associated with resistant strains of P. mirabilis, with MICs of 2 mg/L, being falsely reported as susceptible. For cefuroxime, it is not unexpected that results were unreliable, as the MIC distribution straddles the in vitro breakpoint concentration (following the results of this study the MIC and zone diameter breakpoints have been amended to improve reporting). No major problems were encountered for Pseudomonas aeruginosa with the agents studied. The ‘field survey’ has shown that disc testing is unreliable for determining the susceptibility of coagulase-negative staphylococci to teicoplanin, and that the detection of glycopeptide resistance in enterococci is improved by incubation for a full 24 h. Inconsistencies observed with fastidious organisms were associated with incorrect inocula. Zone diameter data for the control strains studied provide information that can be utilized by diagnostic laboratories to monitor the daily performance of testing.
BSAC standardized disc susceptibility testing method
Authors:   for the BSAC Working Party on Susceptibility Testing, Andrews Jennifer M.
Published: January 2012

For nearly a decade microbiologists have used the MIC breakpoints published in the BSAC Guide to Susceptibility Testing to interpret susceptibility. Historically, and unlike the rest of Europe, the UK and Ireland have used a comparative method of disc testing to interpret susceptibility rather than one based on a correlation between MIC and zone of inhibition. Although innovative when introduced in the 1970s, Stokes' comparative method has evolved ad hoc and it has become increasingly apparent that there is a need for a standardized method of disc testing that is correlated with BSAC MIC breakpoints. The method described here, like all other standardized methods of disc testing, cannot be adapted by the user, and interpretative criteria are only applicable if the method is adhered to fully. A major advantage of this approach to susceptibility testing is that data from several sources can be combined for surveillance of resistance, a task that has been made much easier by the introduction of this method and coincides with the availability of automated zone measuring devices. It is hoped that the method described here will provide the core document for standard operating procedures; however, changes will necessarily occur over time as the method is developed and refined.
Determination of minimum inhibitory concentrations
Authors: Andrews Jennifer M.
Published: January 2012

Minimum inhibitory concentrations (MICs) are defined as the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation, and minimum bactericidal concentrations (MBCs) as the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic-free media. MICs are used by diagnostic laboratories mainly to confirm resistance, but most often as a research tool to determine the in vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints. MBC determinations are undertaken less frequently and their major use has been reserved for isolates from the blood of patients with endocarditis. Standardized methods for determining MICs and MBCs are described in this paper. Like all standardized procedures, the method must be adhered to and may not be adapted by the user. The method gives information on the storage of standard antibiotic powder, preparation of stock antibiotic solutions, media, preparation of inocula, incubation conditions, and reading and interpretation of results. Tables giving expected MIC ranges for control NCTC and ATCC strains are also supplied.
Quality assurance of antimicrobial susceptibility testing by disc diffusion
Authors: King Anna , Brown Derek F. J.
Published: January 2012

Quality assurance is essential to ensure the quality of antimicrobial susceptibility tests by diffusion methods. Routine internal quality control testing with a range of control strains is a major part of the quality assurance process, as it facilitates monitoring of the performance of the test. Most standardized methods include tables of acceptable zone size ranges for control strains and, in addition to checking that control zone diameters are within the published ranges, rules or statistical approaches may be applied to indicate deviations from acceptable performance. If control tests indicate unacceptable performance, the source(s) of the error should be investigated and may include problems with media, antimicrobial discs, inoculum and plate reading. Participation in external quality assessment schemes provides an independent assessment of performance although the number of strains distributed in such schemes is limited. Internal quality assessment in which routine tests are repeated with the identity of the organisms blinded is a useful complementary approach to external quality assessment and may detect problem areas not highlighted by other control methods. Education is an important part of the quality assurance process. Knowledge of atypical results for different organism–agent combinations may provide warning of possibly erroneous results, and an understanding of the limitations and sources of error in disc diffusion methods contributes significantly to the recognition, resolution and avoidance of errors.
Instrumentation in antimicrobial susceptibility testing
Authors: Felmingham David , Brown Derek F. J.
Published: January 2012

Studies in the 1960s demonstrated the problems of variability in susceptibility testing methods, especially those affecting the performance of disc diffusion procedures. These studies made apparent the need for standardization and resulted in more clearly defined performance limits for growth medium, incubation conditions, inoculum concentration, disc content for diffusion methods, the setting of interpretative MIC breakpoints and the establishment of quality control parameters. More recently, there has been a growing interest in the use of instrumentation for reading disc diffusion tests and the endpoints of agar or broth dilution MIC determinations. Instrumentation ranges in complexity from the simple optical reading of zones of inhibition or growth endpoints, requiring operator interpretation, to more sophisticated devices for reading, recording and ‘expert system’ analysis of results with interfacing of instruments to laboratory information management systems. Some of the more developed systems are fully automated and can also identify the organisms tested. The pressure to reduce labour costs and provide results earlier favours the use of more automated systems whilst the requirement for resistance surveillance provides impetus for the use of systems that provide quantitative results and electronic data handling.
Interpretative reading: recognizing the unusual and inferring resistance mechanisms from resistance phenotypes
Authors: Livermore David M. , Winstanley Trevor G. , Shannon Kevin P.
Published: January 2012

If isolates are speciated and if a sufficient range of antibiotics is tested, underlying resistance mechanisms can often be inferred from the antibiogram data. This allows: (i) anomalous combinations of phenotype and organism to be reconsidered; (ii) prediction of further antibiotics that deserve testing; and (iii) the suppression of susceptibilities that are anomalous in the light of the inferred mechanism. This ‘interpretative reading’ is widely undertaken in France but is largely precluded in the UK by limited speciation and the testing of narrow ranges of antibiotics. Nevertheless, UK laboratories should be aware of: (i) grossly anomalous combinations of species and phenotype, demanding reference laboratory confirmation; (ii) useful indicator drugs, where resistance implies a mechanism conferring other resistances that may be less obvious in direct tests; and (iii) antibiotics that are prone to select resistant mutants of particular species during therapy. Details of these combinations of organism and resistance are presented. Relationships between antibiogram and mechanism are also presented to allow full interpretative reading for those testing wide panels of drugs versus speciated isolates.
Preface
Authors: Barnes Rosemary A. , Johnson Elizabeth M. , Odds Frank C.
Published: January 2012

The clinical problems caused by life-threatening, deeptissue fungal infections affect many different medical and surgical specialities where immunosuppression through disease or therapeutic advance has created a substantial sub-category of patients at risk of mycosis. Amphotericin B remains one of the first-line agents for treatment of almost all systemic mycoses, but the agent in its conventional deoxycholate formulation carries a serious penalty in terms of nephrotoxicity. Novel, lipid-associated formulations of amphotericin B have been introduced to combat the toxicity problem without loss of therapeutic efficacy.

This supplement is based upon papers presented at an international symposium held in Australia on 8–9 July 2000. It focuses on AmBisome, a liposome-encapsulated formulation of amphotericin B, and draws together information on many general aspects of the diagnosis and treatment of deep tissue mycoses as well as providing a comprehensive set of reviews of all aspects of AmBisome —its pharmacology, toxicology, pharmacokinetics and clinical efficacy in a variety of mycoses and patient types. There is now considerably more clinical experience with lipid forms of amphotericin B than when the previous supplement on AmBisome was published by the Journal of Antimicrobial Chemotherapy in October 1999.1

Because the topic of the supplement is a formulation of an antifungal agent, not the agent itself, and because lipid-based formulations can vary in composition even when they are nominally prepared in the same way, we have taken the unusual step of referring to the various amphotericin B lipid formulations, and to ‘conventional’ amphotericin B-deoxycholate for injection, by their trade names.

The editors would like to thank Christine Burley of the JAC Editorial Office, and Regine Buffels of Gilead Sciences for their untiring support and assistance in the preparation of this supplement.

Reference

1. Speller, D. C. E. & Warnock, D. W. (Eds). (1991). Liposomal amphotericin B (AmBisome) in the treatment of systemic fungal infection. Journal of Antimicrobial Chemotherapy28, Suppl. B, 1–118.
Diagnosis of fungal infections: current status
Authors: Stevens David A.
Published: January 2012

Diagnosing infections remains a problem in the management of fungal diseases, particularly in the immunocompromised host. Signs and symptoms are non-specific, colonization is difficult to distinguish from invasive disease, blood cultures are commonly negative and patients are often unable to undergo invasive diagnostic procedures. This situation has led to the strategy of initiating empirical therapy in the high-risk patient. A variety of tests has been applied to several body fluids. At the simplest level, the clinician must be familiar with the appearance of various fungi in tissue. Non-culture methods include antibody- and antigen-based assays, metabolite detection and molecular identification. The latter includes PCR identification of fungal DNA from body fluid samples using conserved or specific genome sequences. Detection of glucan in blood has been achieved using crab amoebocyte lysate. With aspergillosis, predictive clinical correlates have been defined, respiratory tract cultures are highly predictive of invasive disease in the appropriate setting and certain CT scan findings enable early diagnosis. Bronchoalveolar lavage is also very useful. Galactomannan antigen testing of blood is routine in some European centres, with EIA methodology supplanting agglutination because of apparently greater sensitivity. PCR has been made specific by genus-specific probes, with 100% sensitivity and reasonable specificity. In candidosis, the number of sites of colonization correlates with invasion. Tests for mannan antibodies and antigenaemia are currently of interest. Metabolite assays appeared promising but have not been pursued commercially. In cryptococcosis, pronase treatment of serum has reduced false positives and false negatives, and improved reproducibility of titres. Birdseed agar improves culture specificity. In coccidioidomycosis, serology is the exemplar for all mycology. Gene probes have accelerated diagnosis by culture. In histoplasmosis, the antigenuria test's high sensitivity and specificity has dispelled the chronic confusion in interpreting antibody test results.
AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience
Authors: Adler-Moore Jill , Proffitt Richard T.
Published: January 2012

Amphotericin B is the treatment of choice for life-threatening systemic fungal infections such as candidosis and aspergillosis. To improve this drug's efficacy and reduce its acute and chronic toxicities, several lipid formulations of the drug have been developed, including AmBisome, a liposomal formulation of amphotericin B. The liposome is composed of high transition temperature phospholipids and cholesterol, designed to incorporate amphotericin B securely into the liposomal bilayer. AmBisome can bind to fungal cell walls, where the liposome is disrupted. The amphotericin B, after being released from the liposomes, is thought to transfer through the cell wall and bind to ergosterol in the fungal cell membrane. This mechanism of action of AmBisome results in its potent in vitro fungicidal activity while the integrity of the liposome is maintained in the presence of mammalian cells, for which it has minimal toxicity. In animal models, AmBisome is effective in treating both intracellular (leishmaniasis and histoplasmosis) and extracellular (candidosis and aspergillosis) systemic infections. Because of its low toxicity at the organ level, intravenous AmBisome can be safely delivered at markedly high doses of amphotericin B (1–30 mg/kg) for the treatment of systemic fungal infections. AmBisome has a circulating half-life of 5–24 h in animals, and in animal models appears to localize at sites of infection in the brain (cryptococcosis, aspergillosis, coccidioidomycosis), lungs (blastomycosis, paracoccidioidomycosis, aspergillosis) and kidneys (candidosis), delivering amphotericin B that remains bioavailable in tissues for several weeks following treatment.