RESPONSABILITE ET CONTROLABILITE : UNE APPROCHE EMPIRIQUE

Dans la doctrine classique du contrôle de gestion, la notion de responsabilité est fondée sur le principe de contrôlabilité. Dans un contexte incertain et marqué par de fortes interdépendances, ce principe est problématique. Cet article propose une exploration empirique des pratiques et discours des entreprises à ce sujet.responsabilité ; contrôlabilité ; évaluation de performance

La position des managers face au principe de controlabilité

A partir d'une enquête auprès de 265 managers, cette recherche étudie leur position au regard du principe de contrôlabilité. Elle examine, d'une part si les managers considèrent que les facteurs incontrôlables sont neutralisés lors de l'évaluation de leur performance, d'autre part s'ils estiment souhaitable que cette neutralisation soit faite.contrôlabilité; évaluation de performance; manager; enquête

Norepinephrine-induced loss of phosphatidylinositol from isolated rat liver plasma membrane Effects of divalent cations

AbstractNorepinephrine at 5 μM induces a rapid (60 s) and specific loss of phosphatidylinositol (PtdIns) when added to isolated rat liver plasma membranes. The hormone action is inhibited by the α-adrenergic antagonist phentolamine (20 μM). Depletion of Mg2+ and Ca2+ singly or in combination from the incubation buffer mimicks the hormone effect on PtdIns breakdown. No further effect on PtdIns degradation could be measured when norepinephrine was added to the cation-depleted buffers. Addition of the Ca2+ ionophore A23187 to the isolated membranes has no effect. It is concluded that PtdIns degradation can be provoked in isolated rat liver plasma membrane through α-adrenergic receptor activation and that this effect is dependent on divalent cations in the sense that loss of cations from the membrane allows degradation to commence

Estimation de la perméabilité d'une argilite partiellement saturée par méthode inverse

Une méthode inverse est développée pour identifier la perméabilité d'une argilite en conditions partiellement saturées par interprétation d'essais de séchage. L'essai de séchage consiste à mesurer la variation de masse, dont la cinétique est liée à la perméabilité, d'un échantillon de roche sous humidité relative variable. Les couplages hydromécaniques et la présence de gaz résultent en un problème direct de diffusion non linéaire, résolu par éléments finis. Le modèle de comportement choisi est le modèle thermoporoélastique non linéaire de Coussy, et différents effets de couplage ont été pris en compte. L'interprétation de l'essai de séchage est alors un problème d'identification de paramètres, ramené à un problème inverse, consistant à minimiser une fonctionnelle quantifiant l'écart entre les variations de masse mesurées au cours de l'essai et calculées par éléments finis, lesquelles dépendent des paramètres à identifier, c'est-à-dire des paramètres caractérisant la perméabilité

Pétrofabrique et propriétés mécaniques des argilites

The petrofabric of mudstones influences their thermal, hydraulic and mechanical properties. Measurements of thermal diffusivity, permeability and velocity of ultrasonic waves show that the anisotropy of these properties in this rock is rather low. The diminution of Biot coefficient with axial stress cannot be explained only by the diminution of porosity even by considering an incompressible matrix to 1% for an axial stress varying from 8 to 24 MPa corresponds. The origin of the diminution could be explained by the loss of connection of part of the porous system, hitherto connected, under the effect of an increasing axial stress. An isotropic elastoplastic model is a reasonable approach for the description of the mechanical behaviour of mudstone. However, it is useful to take into account the damage by microfissuring, which could not be neglected and must be considered coupled with plasticity

NMR studies of telomeric nucleoprotein complexes involving the Myb-like domain of the human telomeric protein TRF2

In order to study the binding of the Myb-like domain of the human telomeric protein TRF2 (Myb-TRF2) with different structural components of the t-loop model, we report NMR studies of the binding of Myb-TRF2 protein with two repeats human telomeric DNA under three conformations. Our results showed that Myb-TRF2 binds to the duplex and even to the quadruplex and the random coil G-rich strand. The solution structure of Myb-TRF2 reported here looks like Myb-TRF1 suggesting similar DNA binding mode. As a matter of fact, we have shown that its binding to the human telomeric duplex presents great similarities with this of Myb-TRF1

The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA

TRF1 and TRF2 are key proteins in human telomeres, which, despite their similarities, have different behaviors upon DNA binding. Previous work has shown that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative torsion on the adjacent DNA, a property that is thought to lead to the stimulation of single-strand invasion and was proposed to favor telomeric DNA looping. In this report, we show that these activities, originating from the central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but are repressed in the full-length protein by the presence of an acidic domain at the N-terminus. Strikingly, a similar repression is observed on TRF2 through the binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and biochemical studies suggest that the N-terminal domains of TRF proteins originate from a gradual extension of the coding sequences of a duplicated ancestral gene with a consequential progressive alteration of the biochemical properties of these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2 have evolved to finely regulate their ability to condense DNA

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria