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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 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 .
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
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