The small quinolone derived compound HT61 enhances the effect of tobramycin against Pseudomonas aeruginosa in vitro and in vivo.

HT61 is a small quinolone-derived compound previously demonstrated to exhibit bactericidal activity against gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). When combined with the classical antibiotics and antiseptics neomycin, gentamicin, mupirocin and chlorhexidine, HT61 demonstrated synergistic bactericidal activity against both MSSA and MRSA infections in vitro. In this study, we investigated the individual antimicrobial activity of HT61 alongside its capability to increase the efficacy of tobramycin against both a tobramycin sensitive laboratory reference strain (PAO1) and tobramycin resistant clinical isolates (RP73, NN2) of the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa). Using broth microdilution methods, the MICs of HT61 against all strains were assessed, as well as the effect of HT61 in combination with tobramycin using both the chequerboard method and bacterial time-kill assays. A murine model of pulmonary infection was also used to evaluate the combination therapy of tobramycin and HT61 in vivo. In these studies, we demonstrated significant synergism between HT61 and Tobramycin against the tobramycin resistant P. aeruginosa strains RP73 and NN2, whilst an additive/intermediate effect was observed for P. aeruginosa strain PA01 which was further confirmed using bacterial time kill analysis. In addition, the enhancement of tobramycin by HT61 was also evident in in vitro assays of biofilm eradication. Finally, in vivo studies revealed analogous effects to those observed in vitro with HT61 when administered in combination with tobramycin against each of the three P. aeruginosa strains at the highest tested dose (10 mg/kg)

Topological properties of quantum periodic Hamiltonians

We consider periodic quantum Hamiltonians on the torus phase space (Harper-like Hamiltonians). We calculate the topological Chern index which characterizes each spectral band in the generic case. This calculation is made by a semi-classical approach with use of quasi-modes. As a result, the Chern index is equal to the homotopy of the path of these quasi-modes on phase space as the Floquet parameter (\theta) of the band is varied. It is quite interesting that the Chern indices, defined as topological quantum numbers, can be expressed from simple properties of the classical trajectories.Comment: 27 pages, 14 figure

Giant Anisotropy of Spin-Orbit Splitting at the Bismuth Surface

We investigate the bismuth (111) surface by means of time and angle resolved photoelectron spectroscopy. The parallel detection of the surface states below and above the Fermi level reveals a giant anisotropy of the Spin-Orbit (SO) spitting. These strong deviations from the Rashba-like coupling cannot be treated in $\textbf{k}\cdot \textbf{p}$ perturbation theory. Instead, first principle calculations could accurately reproduce the experimental dispersion of the electronic states. Our analysis shows that the giant anisotropy of the SO splitting is due to a large out-of plane buckling of the spin and orbital texture.Comment: 5 pages, 4 figure

Semi-classical study of the Quantum Hall conductivity

The semi-classical study of the integer Quantum Hall conductivity is investigated for electrons in a bi-periodic potential $V(x,y)$. The Hall conductivity is due to the tunnelling effect and we concentrate our study to potentials having three wells in a periodic cell. A non-zero topological conductivity requires special conditions for the positions, and shapes of the wells. The results are derived analytically and well confirmed by numerical calculations.Comment: 23 pages, 13 figure

Effects of nanoparticles on murine macrophages

Metallic nanoparticles are more and more widely used in an increasing number of applications. Consequently, they are more and more present in the environment, and the risk that they may represent for human health must be evaluated. This requires to increase our knowledge of the cellular responses to nanoparticles. In this context, macrophages appear as an attractive system. They play a major role in eliminating foreign matter, e.g. pathogens or infectious agents, by phagocytosis and inflammatory responses, and are thus highly likely to react to nanoparticles. We have decided to study their responses to nanoparticles by a combination of classical and wide-scope approaches such as proteomics. The long term goal of this study is the better understanding of the responses of macrophages to nanoparticles, and thus to help to assess their possible impact on human health. We chose as a model system bone marrow-derived macrophages and studied the effect of commonly used nanoparticles such as TiO2 and Cu. Classical responses of macrophage were characterized and proteomic approaches based on 2D gels of whole cell extracts were used. Preliminary proteomic data resulting from whole cell extracts showed different effects for TiO2-NPs and Cu-NPs. Modifications of the expression of several proteins involved in different pathways such as, for example, signal transduction, endosome-lysosome pathway, Krebs cycle, oxidative stress response have been underscored. These first results validate our proteomics approach and open a new wide field of investigation for NPs impact on macrophagesComment: Nanosafe2010: International Conference on Safe Production and Use of Nanomaterials 16-18 November 2010, Grenoble, France, Grenoble : France (2010

NH_3(1_0-0_0) in the pre-stellar core L1544

Pre-stellar cores represent the initial conditions in the process of star and planet formation, therefore it is important to study their physical and chemical structure. Because of their volatility, nitrogen-bearing molecules are key to study the dense and cold gas present in pre-stellar cores. The NH_3 rotational transition detected with Herschel-HIFI provides a unique combination of sensitivity and spectral resolution to further investigate physical and chemical processes in pre-stellar cores. Here we present the velocity-resolved Herschel-HIFI observations of the ortho-NH_3(1_0-0_0) line at 572 GHz and study the abundance profile of ammonia across the pre-stellar core L1544 to test current theories of its physical and chemical structure. Recently calculated collisional coefficients have been included in our non-LTE radiative transfer code to reproduce Herschel observations. A gas-grain chemical model, including spin-state chemistry and applied to the (static) physical structure of L1544 is also used to infer the abundance profile of ortho-NH_3 . The hyperfine structure of ortho-NH_3(1_0-0_0) is resolved for the first time in space. All the hyperfine components are strongly self-absorbed. The profile can be reproduced if the core is contracting in quasi-equilibrium, consistent with previous work, and if the NH_3 abundance is slightly rising toward the core centre, as deduced from previous interferometric observations of para-NH_3(1,1). The chemical model overestimates the NH_3 abundance at radii between ~ 4000 and 15000 AU by about two orders of magnitude and underestimates the abundance toward the core centre by more than one order of magnitude. Our observations show that chemical models applied to static clouds have problems in reproducing NH_3 observations.Comment: accepted for publication in A&A Letter

Radial velocity eclipse mapping of exoplanets

Planetary rotation rates and obliquities provide information regarding the history of planet formation, but have not yet been measured for evolved extrasolar planets. Here we investigate the theoretical and observational perspective of the Rossiter-McLauglin effect during secondary eclipse (RMse) ingress and egress for transiting exoplanets. Near secondary eclipse, when the planet passes behind the parent star, the star sequentially obscures light from the approaching and receding parts of the rotating planetary surface. The temporal block of light emerging from the approaching (blue-shifted) or receding (red-shifted) parts of the planet causes a temporal distortion in the planet's spectral line profiles resulting in an anomaly in the planet's radial velocity curve. We demonstrate that the shape and the ratio of the ingress-to-egress radial velocity amplitudes depends on the planetary rotational rate, axial tilt and impact factor (i.e. sky-projected planet spin-orbital alignment). In addition, line asymmetries originating from different layers in the atmosphere of the planet could provide information regarding zonal atmospheric winds and constraints on the hot spot shape for giant irradiated exoplanets. The effect is expected to be most-pronounced at near-infrared wavelengths, where the planet-to-star contrasts are large. We create synthetic near-infrared, high-dispersion spectroscopic data and demonstrate how the sky-projected spin axis orientation and equatorial velocity of the planet can be estimated. We conclude that the RMse effect could be a powerful method to measure exoplanet spins.Comment: 7 pages, 3 figures, 1 table, accepted for publication in ApJ on 2015 June 1

The failed liberalisation of Algeria and the international context: a legacy of stable authoritarianism

The paper attempts to challenge the somewhat marginal role of international factors in the study of transitions to democracy. Theoretical and practical difficulties in proving causal mechanisms between international variables and domestic outcomes can be overcome by defining the international dimension in terms of Western dominance of world politics and by identifying Western actions towards democratising countries. The paper focuses on the case of Algeria, where international factors are key in explaining the initial process of democratisation and its following demise. In particular, the paper argues that direct Western policies, the pressures of the international system and external shocks influence the internal distribution of power and resources, which underpins the different strategies of all domestic actors. The paper concludes that analysis based purely on domestic factors cannot explain the process of democratisation and that international variables must be taken into more serious account and much more detailed