Transport and magnetic properties of LT annealed Ga1-xMnxAs

We present the results of low temperature (LT) annealing studies of Ga1-xMnxAs epilayers grown by low temperature molecular beam epitaxy in a wide range of Mn concentrations (0.01<x<0.084). Transport measurements in low and high magnetic fields as well as SQUID measurements were performed on a wide range of samples, serving to establish optimal conditions of annealing. Optimal annealing procedure succeeded in the Curie temperatures higher than 110K. The highest value of Curie temperature estimated from the maximum in the temperature dependence of zero-field resistivity (Tr) was 127K. It is generally observed that annealing leads to large changes in the magnetic and transport properties of GaMnAs in the very narrow range of annealing temperature close to the growth temperature.Comment: XXXI International School on the Physics of Semiconducting Compounds Jaszowiec 2002, will be published in Acta Physica Polonica

Optical Evidence of Multiphase Coexistence in Single Crystalline (La,Pr,Ca)MnO3

We investigated temperature (T)- and magnetic field-dependent optical conductivity spectra (\s\w) of a La_5/8-yPr_yCa_3/8MnO_3 (y~0.35) single crystal, showing intriguing phase coexistence at low T. At T_C < T < T_CO, a dominant charge-ordered phase produces a large optical gap energy of ~0.4 eV. At T < T_C, at least two absorption bands newly emerge below 0.4 eV. Analyses of (\s\w) indicate that the new bands should be attributed to a ferromagnetic metallic and a charge-disordered phase that coexist with the charge-ordered phase. This optical study clearly shows that La_5/8-yPrCa_3/8MnO_3 (y~0.35) is composed of multiphases that might have different lattice strains.Comment: A single file with 9 figures embedded, to appear in Phys. Rev.

Quantum Size Effect transition in percolating nanocomposite films

We report on unique electronic properties in Fe-SiO2 nanocomposite thin films in the vicinity of the percolation threshold. The electronic transport is dominated by quantum corrections to the metallic conduction of the Infinite Cluster (IC). At low temperature, mesoscopic effects revealed on the conductivity, Hall effect experiments and low frequency electrical noise (random telegraph noise and 1/f noise) strongly support the existence of a temperature-induced Quantum Size Effect (QSE) transition in the metallic conduction path. Below a critical temperature related to the geometrical constriction sizes of the IC, the electronic conductivity is mainly governed by active tunnel conductance across barriers in the metallic network. The high 1/f noise level and the random telegraph noise are consistently explained by random potential modulation of the barriers transmittance due to local Coulomb charges. Our results provide evidence that a lowering of the temperature is somehow equivalent to a decrease of the metal fraction in the vicinity of the percolation limit.Comment: 21 pages, 8 figure

Network Models of TEM β-Lactamase Mutations Coevolving under Antibiotic Selection Show Modular Structure and Anticipate Evolutionary Trajectories

Understanding how novel functions evolve (genetic adaptation) is a critical goal of evolutionary biology. Among asexual organisms, genetic adaptation involves multiple mutations that frequently interact in a non-linear fashion (epistasis). Non-linear interactions pose a formidable challenge for the computational prediction of mutation effects. Here we use the recent evolution of β-lactamase under antibiotic selection as a model for genetic adaptation. We build a network of coevolving residues (possible functional interactions), in which nodes are mutant residue positions and links represent two positions found mutated together in the same sequence. Most often these pairs occur in the setting of more complex mutants. Focusing on extended-spectrum resistant sequences, we use network-theoretical tools to identify triple mutant trajectories of likely special significance for adaptation. We extrapolate evolutionary paths (n = 3) that increase resistance and that are longer than the units used to build the network (n = 2). These paths consist of a limited number of residue positions and are enriched for known triple mutant combinations that increase cefotaxime resistance. We find that the pairs of residues used to build the network frequently decrease resistance compared to their corresponding singlets. This is a surprising result, given that their coevolution suggests a selective advantage. Thus, β-lactamase adaptation is highly epistatic. Our method can identify triplets that increase resistance despite the underlying rugged fitness landscape and has the unique ability to make predictions by placing each mutant residue position in its functional context. Our approach requires only sequence information, sufficient genetic diversity, and discrete selective pressures. Thus, it can be used to analyze recent evolutionary events, where coevolution analysis methods that use phylogeny or statistical coupling are not possible. Improving our ability to assess evolutionary trajectories will help predict the evolution of clinically relevant genes and aid in protein design

Enumerating Pathways of Proton Abstraction Based on a Spatial and Electrostatic Analysis of Residues in the Catalytic Site

The pathways of proton abstraction (PA), a key aspect of most catalytic reactions, is often controversial and highly debated. Ultrahigh-resolution diffraction studies, molecular dynamics, quantum mechanics and molecular mechanic simulations are often adopted to gain insights in the PA mechanisms in enzymes. These methods require expertise and effort to setup and can be computationally intensive. We present a push button methodology – Proton abstraction Simulation (PRISM) – to enumerate the possible pathways of PA in a protein with known 3D structure based on the spatial and electrostatic properties of residues in the proximity of a given nucleophilic residue. Proton movements are evaluated in the vicinity of this nucleophilic residue based on distances, potential differences, spatial channels and characteristics of the individual residues (polarity, acidic, basic, etc). Modulating these parameters eliminates their empirical nature and also might reveal pathways that originate from conformational changes. We have validated our method using serine proteases and concurred with the dichotomy in PA in Class A β-lactamases, both of which are hydrolases. The PA mechanism in a transferase has also been corroborated. The source code is made available at www.sanchak.com/prism

Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments

A comparative study of class-D beta-lactamases.

Three class-D beta-lactamases (OXA2, OXA1 and PSE2) were produced and purified to protein homogeneity. 6 beta-Iodopenicillanate inactivated the OXA2 enzyme without detectable turnover. Labelling of the same beta-lactamase with 6 beta-iodo[3H]penicillanate allowed the identification of Ser-70 as the active-site serine residue. In agreement with previous reports, the apparent M(r) of the OXA2 enzyme as determined by molecular-sieve filtration, was significantly higher than that deduced from the gene sequence, but this was not due to an equilibrium between a monomer and a dimer. The heterogeneity of the OXA2 beta-lactamase on ion-exchange chromatography contrasted with the similarity of the catalytic properties of the various forms. A first overview of the enzymic properties of the three 'oxacillinases' is presented. With the OXA2 enzyme, 'burst' kinetics, implying branched pathways, seemed to prevail with many substrates