Activities of fluconazole, caspofungin, anidulafungin, and amphotericin B on planktonic and biofilm Candida species determined by microcalorimetry.

We investigated the activities of fluconazole, caspofungin, anidulafungin, and amphotericin B against Candida species in planktonic form and biofilms using a highly sensitive assay measuring growth-related heat production (microcalorimetry). C. albicans, C. glabrata, C. krusei, and C. parapsilosis were tested, and MICs were determined by the broth microdilution method. The antifungal activities were determined by isothermal microcalorimetry at 37°C in RPMI 1640. For planktonic Candida, heat flow was measured in the presence of antifungal dilutions for 24 h. Candida biofilm was formed on porous glass beads for 24 h and exposed to serial dilutions of antifungals for 24 h, and heat flow was measured for 48 h. The minimum heat inhibitory concentration (MHIC) was defined as the lowest antifungal concentration reducing the heat flow peak by ≥50% (≥90% for amphotericin B) at 24 h for planktonic Candida and at 48 h for Candida biofilms (measured also at 24 h). Fluconazole (planktonic MHICs, 0.25 to >512 μg/ml) and amphotericin B (planktonic MHICs, 0.25 to 1 μg/ml) showed higher MHICs than anidulafungin (planktonic MHICs, 0.015 to 0.5 μg/ml) and caspofungin (planktonic MHICs, 0.125 to 0.5 μg/ml). Against Candida species in biofilms, fluconazole's activity was reduced by >1,000-fold compared to its activity against the planktonic counterparts, whereas echinocandins and amphotericin B mainly preserved their activities. Fluconazole induced growth of planktonic C. krusei at sub-MICs. At high concentrations of caspofungin (>4 μg/ml), paradoxical growth of planktonic C. albicans and C. glabrata was observed. Microcalorimetry enabled real-time evaluation of antifungal activities against planktonic and biofilm Candida organisms. It can be used in the future to evaluate new antifungals and antifungal combinations and to study resistant strains.

The heat shock response in moss plants is regulated by specific calcium-permeable channels in the plasma membrane.

Land plants are prone to strong thermal variations and must therefore sense early moderate temperature increments to induce appropriate cellular defenses, such as molecular chaperones, in anticipation of upcoming noxious temperatures. To investigate how plants perceive mild changes in ambient temperature, we monitored in recombinant lines of the moss Physcomitrella patens the activation of a heat-inducible promoter, the integrity of a thermolabile enzyme, and the fluctuations of cytoplasmic calcium. Mild temperature increments, or isothermal treatments with membrane fluidizers or Hsp90 inhibitors, induced a heat shock response (HSR) that critically depended on a preceding Ca(2+) transient through the plasma membrane. Electrophysiological experiments revealed the presence of a Ca(2+)-permeable channel in the plasma membrane that is transiently activated by mild temperature increments or chemical perturbations of membrane fluidity. The amplitude of the Ca(2+) influx during the first minutes of a temperature stress modulated the intensity of the HSR, and Ca(2+) channel blockers prevented HSR and the onset of thermotolerance. Our data suggest that early sensing of mild temperature increments occurs at the plasma membrane of plant cells independently from cytosolic protein unfolding. The heat signal is translated into an effective HSR by way of a specific membrane-regulated Ca(2+) influx, leading to thermotolerance.

Shocks and institutions in a job matching model

This paper explains the divergent behavior of European an US unemploymentrates using a job market matching model of the labor market with aninteraction between shocks an institutions. It shows that a reduction inTF growth rates, an increase in real interest rates, and an increase intax rates leads to a permanent increase in unemployment rates when thereplacement rates or initial tax rates are high, while no increase inunemployment occurs when institutions are "employment friendly". The paperalso shows that an increase in turbulence, modelle as an increase probabilityof skill loss, is not a robust explanation for the European unemploymentpuzzle in the context of a matching model with both endogenous job creationand job estruction.

RNA pentaloop structures as effective targets of regulators belonging to the RsmA/CsrA protein family.

In the Gac/Rsm signal transduction pathway of Pseudomonas fluorescens CHA0, the dimeric RNA-binding proteins RsmA and RsmE, which belong to the vast bacterial RsmA/CsrA family, effectively repress translation of target mRNAs containing a typical recognition sequence near the translation start site. Three small RNAs (RsmX, RsmY, RsmZ) with clustered recognition sequences can sequester RsmA and RsmE and thereby relieve translational repression. According to a previously established structural model, the RsmE protein makes optimal contacts with an RNA sequence 5'- (A)/(U)CANGGANG(U)/(A)-3', in which the central ribonucleotides form a hexaloop. Here, we questioned the relevance of the hexaloop structure in target RNAs. We found that two predicted pentaloop structures, AGGGA (in pltA mRNA encoding a pyoluteorin biosynthetic enzyme) and AAGGA (in mutated pltA mRNA), allowed effective interaction with the RsmE protein in vivo. By contrast, ACGGA and AUGGA were poor targets. Isothermal titration calorimetry measurements confirmed the strong binding of RsmE to the AGGGA pentaloop structure in an RNA oligomer. Modeling studies highlighted the crucial role of the second ribonucleotide in the loop structure. In conclusion, a refined structural model of RsmE-RNA interaction accommodates certain pentaloop RNAs among the preferred hexaloop RNAs.

The second law of thermodynamics and the global climate system : A review of the maximum entropy production principle

The long-term mean properties of the global climate system and those of turbulent fluid systems are reviewed from a thermodynamic viewpoint. Two general expressions are derived for a rate of entropy production due to thermal and viscous dissipation (turbulent dissipation) in a fluid system. It is shown with these expressions that maximum entropy production in the Earth s climate system suggested by Paltridge, as well as maximum transport properties of heat or momentum in a turbulent system suggested by Malkus and Busse, correspond to a state in which the rate of entropy production due to the turbulent dissipation is at a maximum. Entropy production due to absorption of solar radiation in the climate system is found to be irrelevant to the maximized properties associated with turbulence. The hypothesis of maximum entropy production also seems to be applicable to the planetary atmospheres of Mars and Titan and perhaps to mantle convection. Lorenz s conjecture on maximum generation of available potential energy is shown to be akin to this hypothesis with a few minor approximations. A possible mechanism by which turbulent fluid systems adjust themselves to the states of maximum entropy production is presented as a selffeedback mechanism for the generation of available potential energy. These results tend to support the hypothesis of maximum entropy production that underlies a wide variety of nonlinear fluid systems, including our planet as well as other planets and stars

Second differential of the entropy as a criterion for the stability in low-dimensional climate models

The second differential of the entropy is used for analysing the stability of a thermodynamic climatic model. A delay time for the heat flux is introduced whereby it becomes an independent variable. Two different expressions for the second differential of the entropy are used: one follows classical irreversible thermodynamics theory; the second is related to the introduction of response time and is due to the extended irreversible thermodynamics theory. the second differential of the classical entropy leads to unstable solutions for high values of delay times. the extended expression always implies stable states for an ice-free earth. When the ice-albedo feedback is included, a discontinuous distribution of stable states is found for high response times. Following the thermodynamic analysis of the model, the maximum rates of entropy production at the steady state are obtained. A latitudinally isothermal earth produces the extremum in global entropy production. the material contribution to entropy production (by which we mean the production of entropy by material transport of heat) is a maximum when the latitudinal distribution of temperatures becomes less homogeneous than present values

Thrusting, extension, and doming during the polyphase tectonometamorphic evolution of the High Himalayan Crystalline Zone in NW India

In the NW Himalaya of India, high-grade metamorphic rocks of the High Himalayan Crystalline Zone (HHCZ) are exposed as a 50 km large dome along the Miyar and Gianbul valleys. This Gianbul dome is cored by migmatitic paragneiss formed at peak conditions around 750 degreesC and 8 kbar, and symmetrically surrounded by sillimanite, kyanite +/- staurolite, garnet, biotite, and chlorite Barrovian mineral zones. Thermobarometric and structural investigations reveal that the Gianbul dome results from a polyphase tectono-metamorphic evolution. The first phase corresponds to the NE-directed thrusting of the Shikar Beh nappe, that is responsible for the Barrovian prograde metamorphic field gradient in the southern limb of the dome. In the northern limb of the dome, the Barrovian prograde metamorphism is the consequence of a second tectonic phase, associated with the SW-directed thrusting of the Nyimaling-Tsarap nappe. Following these crustal thickening events, exhumation and doming of the HHCZ high-grade rocks were controlled by extension along the north-dipping Zanskar Shear Zone, in the frontal part of the Nyimaling-Tsarap nappe, as well as by coeval to late extension along the south-dipping Khanjar Shear Zone, in the southern limb of the Gianbul dome. Rapid syn-convergence extension along both of these detachments induced a nearly isothermal decompression, resulting in a high-temperature/low-pressure metamorphic overprint, as well as enhanced partial melting. Such a rapid exhumation within a compressional orogenic context appears unlikely to be controlled solely by granitic diapirism. Alternatively, large-scale doming in the Himalaya could reflect a sub-vertical ductile extrusion of partially melted rocks.

Two component Emden sphere

The theory of a self-gravitating gas sphere is given. The gravitational field is generated by two components, each of which is an independent isothermal gas. Various quantities of interest, such as density profiles, core radii of both components, masses, free-free luminosity, surface brightness, central surface density, and overestimate of central mass density, are given for different values of both parameters which arise naturally (ratio of central densities, ratio of rms velocities). Fundamental changes appear when comparison is made with a theory in which the second component is a 'test component'. Procedures are given for the complete analysis of real astrophysical configurations such as clusters of galaxies or globular clusters.

Activity of bone cement loaded with daptomycin alone or in combination with gentamicin or PEG600 against Staphylococcus epidermidis biofilms.

Daptomycin is a promising candidate for local treatment of bone infection due to its activity against multi-resistant staphylococci. We investigated the activity of antibiotic-loaded PMMA against Staphylococcus epidermidis biofilms using an ultra-sensitive method bacterial heat detection method (microcalorimetry). PMMA cylinders loaded with daptomycin alone or in combination with gentamicin or PEG600, vancomycin and gentamicin were incubated with S. epidermidis-RP62A in tryptic soy broth (TSB) for 72h. Cylinders were thereafter washed and transferred in microcalorimetry ampoules pre-filled with TSB. Bacterial heat production, proportional to the quantity of biofilm on the PMMA, was measured by isothermal microcalorimetry at 37°C. Heat detection time was considered time to reach 20μW. Experiments were performed in duplicate. The heat detection time was 5.7-7.0h for PMMA without antibiotics. When loaded with 5% of daptomycin, vancomycin or gentamicin, detection times were 5.6-16.4h, 16.8-35.7h and 4.7-6.2h, respectively. No heat was detected when 5% gentamicin or 0.5% PEG600 was added to the daptomycin-loaded PMMA. The study showed that vancomycin was superior to daptomycin and gentamicin in inhbiting staphylococcal adherence in vitro. However, PMMA loaded with daptomycin combined with gentamicin or PEG600 completely inhibited S. epidermidis-biofilm formation. PMMA loaded with these combinations may represent effective strategies for local treatment in the presence of multi-resistant staphylococci.

The Mont-Mort metapelites: Variscan metamorphism and geodynamic context (Brianconnais basement, Western Alps, Switzerland)

The Mont-Mort metapelites are one of the best preserved relies of the Variscan unit in the Brianconnais basement. These micaschists crystallized during a poly-phase metamorphic cycle, under amphibolite facies conditions. Mineral parageneses and geothermobarometric calculations indicate a two-stage evolution. Stage (1) (550-600 degrees C and 5-8 kbar) is documented by assemblages of zoned garnet, staurolite, kyanite(?), biotite, muscovite, quartz and pla gioclase. Stage (2) (550-600 degrees C and 2 kbar) is illustrated by assemblages of andalusite, sillimanite, muscovite, biotite. This metamorphic evolution is characterized by a nearly isothermal decompression path, terminating with the formation of andalusite-bearing veins. U-Pb monazite dates at 330 Ma and Ar-40/Ar-39 muscovite dates at 290-310 Ma (without substantial evidence of argon resetting) point to Variscan metamorphism and yield an estimate of the time interval between the thermal peak and the retrogression stage within this part of the Brianconnais basement. Restoring the Brianconnais and other Alpine basement units within an existing geodynamic model of Cordillera construction and destruction, it is possible to understand better the transition from a medium pressure/high temperature regime (collision with a peak metamorphism around 330 Ma) to low-P/high-T conditions (decompression in an extensional regime) with high geothermal gradient, as recorded by the successive Variscan parageneses within the Mont-Mort metapelites.

Analysis of the near-intrinsic and extrinsic photocapacitance due to the EL2 level in boron implanted GaAs

A detailed analysis of the photocapacitance signal at the near‐band and extrinsic energetic ranges in Schottky barriers obtained on horizontal Bridgman GaAs wafers, which were implanted with boron at different doses and annealed at several temperatures, has been carried out by using the optical isothermal transient spectroscopy, OITS. The optical cross sections have been determined as well as the quenching efficiency of the EL2 level which has been found to be independent of the annealing temperature. Moreover, the quenching relaxation presents two significant features: (i) a strong increase of the quenching efficiency from 1.35 eV on and (ii) a diminution of the quenching transient amplitude in relation with that shown by the fundamental EL2 level. In order to explain this behavior, different cases are discussed assuming the presence of several energy levels, the existence of an optical recuperation, or the association of the EL2 trap with two levels located, respectively, at Ev+0.45 eV and Ec−0.75 eV. The theoretical simulation, taking into account these two last cases, is in agreement with the experimental photocapacitance data at low temperature, as well as at room temperature where the EL2 filling phototransient shows an anomalous behavior. Moreover, unlike the previous data reported for the EL2 electron optical cross section, the values found using our experimental technique are in agreement with the behavior deduced from the theoretical calculation. The utilization of the OITS method has also allowed the determination of another level, whose faster optical contribution is often added to that of the EL2 level when the DLOS or standard photocapacitance is used.

On the artificial creation of the EL2 center by means of boron implantation in gallium arsenide

In the present work, an analysis of the dark and optical capacitance transients obtained from Schottky Au:GaAs barriers implanted with boron has been carried out by means of the isothermal transient spectroscopy (ITS) and differential and optical ITS techniques. Unlike deep level transient spectroscopy, the use of these techniques allows one to easily distinguish contributions to the transients different from those of the usual deep trap emission kinetics. The results obtained show the artificial creation of the EL2, EL6, and EL5 defects by the boron implantation process. Moreover, the interaction mechanism between the EL2 and other defects, which gives rise to the U band, has been analyzed. The existence of a reorganization process of the defects involved has been observed, which prevents the interaction as the temperature increases. The activation energy of this process has been found to be dependent on the temperature of the annealing treatment after implantation, with values of 0.51 and 0.26 eV for the as‐implanted and 400 °C annealed samples, respectively. The analysis of the optical data has corroborated the existence of such interactions involving all the observed defects that affect their optical parameters

Entropy change and magnetocaloric effect in Gd5(SixGe1-x)4

Isothermal magnetization curves up to 23 T have been measured in Gd5Si1.8Ge2.2. We show that the values of the entropy change at the first-order magnetostructural transition, obtained from the Clausius-Clapeyron equation and the Maxwell relation, are coincident, provided the Maxwell relation is evaluated only within the transition region and the maximum applied field is high enough to complete the transition. These values are also in agreement with the entropy change obtained from differential scanning calorimetry. We also show that a simple phenomenological model based on the temperature and field dependence of the magnetization accounts for these results.

Temperature and magnetic-field dependence of the elastic constants of Ni-Mn-Al magnetic Heusler alloy

We report on measurements of the adiabatic second-order elastic constants of the off-stoichiometric Ni54Mn23Al23 single-crystalline Heusler alloy. The variation in the temperature dependence of the elastic constants has been investigated across the magnetic transition and over a broad temperature range. Anomalies in the temperature behavior of the elastic constants have been found in the vicinity of the magnetic phase transition. Measurements under applied magnetic field, both isothermal and variable temperature, show that the value of the elastic constants depends on magnetic order, thus giving evidence for magnetoelastic coupling in this alloy system.

Biofilm formation on bone grafts and bone graft substitutes: comparison of different materials by a standard in vitro test and microcalorimetry.

We analyzed the initial adhesion and biofilm formation of Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984) on various bone grafts and bone graft substitutes under standardized in vitro conditions. In parallel, microcalorimetry was evaluated as a real-time microbiological assay in the investigation of biofilm formation and material science research. The materials beta-tricalcium phosphate (beta-TCP), processed human spongiosa (Tutoplast) and poly(methyl methacrylate) (PMMA) were investigated and compared with polyethylene (PE). Bacterial counts (log(10) cfu per sample) were highest on beta-TCP (S. aureus 7.67 +/- 0.17; S. epidermidis 8.14 +/- 0.05) while bacterial density (log(10) cfu per surface) was highest on PMMA (S. aureus 6.12 +/- 0.2, S. epidermidis 7.65 +/- 0.13). Detection time for S. aureus biofilms was shorter for the porous materials (beta-TCP and processed human spongiosa, p < 0.001) compared to the smooth materials (PMMA and PE), with no differences between beta-TCP and processed human spongiosa (p > 0.05) or PMMA and PE (p > 0.05). In contrast, for S. epidermidis biofilms the detection time was different (p < 0.001) between all materials except between processed human spongiosa and PE (p > 0.05). The quantitative analysis by quantitative culture after washing and sonication of the material demonstrated the importance of monitoring factors like specific surface or porosity of the test materials. Isothermal microcalorimetry proved to be a suitable tool for an accurate, non-invasive and real-time microbiological assay, allowing the detection of bacterial biomass without removing the biofilm from the surface.