La nouvelle gouvernance financière de l’Etat en France

Reforma finansów publicznych we Francji, wprowadzona na mocy ustawy z 1 sierpnia 2001 r. (LOLF), która stała się swego rodzaju „konstytucją finansową”, dokonała głębokich przemian we francuskim prawie budżetowym. LOLF wpisuje się w historyczny proces reformy finansów publicznych, w proces polityczno-socjologiczny, a także proces międzynarodowych przemian publicznych systemów finansowych. Zawiera strategiczną koncepcję działań wykonywanych przez państwo i podejmowania decyzji dotyczących finansów publicznych. Dzięki niej możliwe jest unowocześnienie struktur politycznych i administracyjnych, a w konsekwencji przystosowanie państwa do nowych uwarunkowań gospodarczych i socjologicznych.Université Paris I Panthéon-Sorbonne (France

¿Tiene sentido todavía la autonomía financiera local?

En el presente artículo se examina la evolución del principio de la autonomía financiera local. A continuación, se analizan las últimas reformas que, como consecuencia de la normativa comunitaria, han afectado a las Haciendas locales. Finalmente, se propone una reconsideración del orden financiero y polític

Hepatitis C Virus (HCV) Genotype 1 Subtype Identification in New HCV Drug Development and Future Clinical Practice

International audienceBACKGROUND: With the development of new specific inhibitors of hepatitis C virus (HCV) enzymes and functions that may yield different antiviral responses and resistance profiles according to the HCV subtype, correct HCV genotype 1 subtype identification is mandatory in clinical trials for stratification and interpretation purposes and will likely become necessary in future clinical practice. The goal of this study was to identify the appropriate molecular tool(s) for accurate HCV genotype 1 subtype determination. METHODOLOGY/PRINCIPAL FINDINGS: A large cohort of 500 treatment-naïve patients eligible for HCV drug trials and infected with either subtype 1a or 1b was studied. Methods based on the sole analysis of the 5' non-coding region (5'NCR) by sequence analysis or reverse hybridization failed to correctly identify HCV subtype 1a in 22.8%-29.5% of cases, and HCV subtype 1b in 9.5%-8.7% of cases. Natural polymorphisms at positions 107, 204 and/or 243 were responsible for mis-subtyping with these methods. A real-time PCR method using genotype- and subtype-specific primers and probes located in both the 5'NCR and the NS5B-coding region failed to correctly identify HCV genotype 1 subtype in approximately 10% of cases. The second-generation line probe assay, a reverse hybridization assay that uses probes targeting both the 5'NCR and core-coding region, correctly identified HCV subtypes 1a and 1b in more than 99% of cases. CONCLUSIONS/SIGNIFICANCE: In the context of new HCV drug development, HCV genotyping methods based on the exclusive analysis of the 5'NCR should be avoided. The second-generation line probe assay is currently the best commercial assay for determination of HCV genotype 1 subtypes 1a and 1b in clinical trials and practice

Identification and Characterization of an Activating F229V Substitution in the V2 Vasopressin Receptor in an Infant with NSIAD

Gain-of-function mutations in the gene encoding the V2 vasopressin receptor (V2R) cause nephrogenic syndrome of inappropriate antidiuresis. To date, reported mutations lead to the substitution of arginine 137 by either a cysteine or leucine (R137C/L). Here, we describe a 3-month-old hyponatremic infant found to have a phenylalanine 229 to valine (F229V) substitution in V2R. Characterization of this substitution in vitro revealed that it leads to high constitutive activity of the receptor, compatible with spontaneous antidiuresis. In contrast to R137C/L mutant receptors, F229V receptors do not undergo spontaneous desensitization, which results in sustained, high basal activity. Notably, the V2R-selective inverse agonists tolvaptan and satavaptan completely silenced the constitutive signaling activity of the F229V mutant receptor, indicating that this substitution does not lock the receptor in an irreversible active state. Thus, inverse agonists might prove to be effective therapies for treating patients with this or other spontaneously activating mutations that do not lock the V2R in its active state. These results emphasize the importance of genetic testing and the functional characterization of mutant receptors for patients with nephrogenic syndrome of inappropriate antidiuresis because the results might inform treatment decisions

A further 'degree of freedom' in the rotational evolution of stars

Observational and theoretical investigations provide evidence for non-uniform spot and magnetic flux distributions on rapidly rotating stars, which have a significant impact on their angular momentum loss rate through magnetised winds. Supplementing the formalism of MacGregor & Brenner (1991) with a latitude-dependent magnetised wind model, we analyse the effect of analytically prescribed surface distributions of open magnetic flux with different shapes and degrees of non-uniformity on the rotational evolution of a solar-like star. The angular momentum redistribution inside the star is treated in a qualitative way, assuming an angular momentum transfer between the rigidly-rotating radiative and convective zones on a constant coupling timescale of 15 Myr; for the sake of simplicity we disregard interactions with circumstellar disks. We find that non-uniform flux distributions entail rotational histories which differ significantly from those of classical approaches, with differences cumulating up to 200% during the main sequence phase. Their impact is able to mimic deviations of the dynamo efficiency from linearity of up to 40% and nominal dynamo saturation limits at about 35 times the solar rotation rate. Concentrations of open magnetic flux at high latitudes thus assist in the formation of very rapidly rotating stars in young open clusters, and ease the necessity for a dynamo saturation at small rotation rates. However, since our results show that even minor amounts of open flux at intermediate latitudes, as observed with Zeeman-Doppler imaging techniques, are sufficient to moderate this reduction of the AM loss rate, we suggest that non-uniform flux distributions are a complementary rather than an alternative explanation for very rapid stellar rotation.Comment: 12 pages, 13 figures, accepted for publication by A&

Planet Migration and Disk Destruction due to Magneto-Centrifugal Stellar Winds

This paper investigates the influence of magneto-centrifugally driven or simply magnetic winds of rapidly-rotating, strongly-magnetized T Tauri stars in causing the inward or outward migration of close-in giant planets. The azimuthal ram pressure of the magnetized wind acting on the planet tends to increase the planet's angular momentum and cause outward migration if the star's rotation period $P_*$ is less than the planet's orbital period $P_p$. In the opposite case, $P_* > P_p$, the planet migrates inward. Thus, planets orbiting at distances larger (smaller) than $0.06 {\rm AU}(P_*/5{\rm d})^{2/3}$ tend to be pushed outward (inward), where $P_*$ is the rotation period of the star assumed to have the mass of the sun. The magnetic winds are likely to occur in T Tauri stars where the thermal speed of the gas close to the star is small, where the star's magnetic field is strong, and where the star rotates rapidly. The time-scale for appreciable radial motion of the planet is estimated as $\sim 2 - 20$ Myr. A sufficiently massive close-in planet may cause tidal locking and once this happens the radial migration due to the magnetic wind ceases. The magnetic winds are expected to be important for planet migration for the case of a multipolar magnetic field rather than a dipole field where the wind is directed away from the equatorial plane and where a magnetospheric cavity forms. The influence of the magnetic wind in eroding and eventually destroying the accretion disk is analyzed. A momentum integral is derived for the turbulent wind/disk boundary layer and this is used to estimate the disk erosion time-scale as $\sim 1-10^2$ Myr, with the lower value favored.Comment: 8 pages, 6 figure

Surface proteins of Shiga toxin-producing Escherichia coli mediate association with milk fat globules in raw milk

IntroductionBy adhering to host cells and colonizing tissues, bacterial pathogens can successfully establish infection. Adhesion is considered the first step of the infection process and bacterial adhesion to anti-adhesive compounds is now seen as a promising strategy to prevent infectious diseases. Among the natural sources of anti-adhesive molecules, the membrane of milk fat globules (MFGs) is of interest because of its compositional diversity of proteins and glycoconjugates. However, few studies have focused on the bacterial molecules involved in MFG- mediated inhibition of bacterial adhesion to enterocytes.MethodsWe used three pathogenic Shiga toxin-producing Escherichia coli (STEC) strains (O26:H11 str. 21765, O157:H7 str. EDL933, and O103:H3 str. PMK5) as models to evaluate whether STEC surface proteins are involved in the affinity of STEC for MFG membrane proteins (MFGMPs). The affinity of STEC for MFGMPs was assessed both indirectly by a natural raw milk creaming test and directly by an adhesion test. Mass spectrometry was used to identify enriched STEC proteins within the protein fraction of MFGMs. Bacterial mutants were constructed and their affinity to MFGs were measured to confirm the role of the identified proteins.ResultsWe found that free STEC surface proteins inhibit the concentration of the pathogen in the MFG-enriched cream in a strain-dependent manner. Moreover, the OmpA and FliC proteins were identified within the protein fraction of MFGMs. Our results suggest that FliC protein participates in STEC adhesion to MFGMPs but other STEC molecules may also participate.DiscussionFor the first time, this study highlighted, the involvement of STEC surface proteins in the affinity for MFGs. The mechanism of STEC-MFG association is still not fully understood but our results confirm the existence of receptor/ligand type interactions between the bacteria and MFGs. Further studies are needed to identify and specify the molecules involved in this interaction. These studies should consider the likely involvement of several factors, including adhesion molecules, and the diversity of each STEC strain