Estimation du mode dans un espace vectoriel semi-normé

We investigate a nonparametric estimate of the mode of a density function of a random variable taking values in a semi-normed vectorial space of eventually infinite dimension. The strong consistency of the estimate is shown. Special attention will be paid to apply our result to the case where the probability distribution of our random variable satisfies a concentration condition. To cite this article: S. Dabo-Niang et al., C. R. Acad. Sci. Paris, Ser. I 339 (2004).     

Limits of rapid log P determination methods for highly lipophilic and flexible compounds

Lipophilicity is of crucial importance in many fields including pharmaceutical, environmental, cosmetic and food industries. Whereas different experimental strategies have been developed for rapid lipophilicity determination of new chemical entities, log P determination of highly lipophilic compounds is always challenging. In this study, three published chromatographic methods have been compared on a series of phenylalkanoic acids including the pro-perfume Haloscent^®D (HD-C12). Different log P values were obtained depending on the chromatographic method used for log P estimation. Molecular modelling suggested that log P variations may be due to the chromatographic conditions applied (isocratic or gradient mode, ratio methanol/water in the mobile phase), responsible of specific conformations of the molecule in solution. Thus, for flexible compounds, published methods have to be used with caution and considered as a good tool to estimate a log P range, depending on the molecular conformational state.     

Tilting and Tumbling in Transmembrane Anion Carriers: Activity Tuning through n‐Alkyl Substitution

Anion transport by synthetic carriers (anionophores) holds promise for medical applications, especially the treatment of cystic fibrosis. Among the factors which determine carrier activity, the size and disposition of alkyl groups is proving remarkably important. Herein we describe a series of dithioureidodecalin anionophores, in which alkyl substituents on one face are varied from C₀ to C₁₀ in two‐carbon steps. Activities increase then decrease as the chain length grows, peaking quite sharply at C₆. Molecular dynamics simulations showed the transporter chloride complexes releasing chloride as they approach the membrane‐aqueous interface. The free transporter then stays at the interface, adopting an orientation that depends on the alkyl substituent. If chloride release is prevented, the complex is positioned similarly. Longer chains tilt the binding site away from the interface, potentially freeing the transporter or complex to move through the membrane. However, chains which are too long can also slow transport by inhibiting movement, and especially reorientation, within the phospholipid bilayer.     

Partially Saturated Bicyclic Heteroaromatics as an sp3‐Enriched Fragment Collection

Fragment‐based lead generation has proven to be an effective means of identifying high‐quality lead compounds for drug discovery programs. However, the fragment screening sets often used are principally comprised of sp²‐rich aromatic compounds, which limits the structural (and hence biological) diversity of the library. Herein, we describe strategies for the synthesis of a series of partially saturated bicyclic heteroaromatic scaffolds with enhanced sp³ character. Subsequent derivatization led to a fragment collection featuring regio‐ and stereo‐controlled introduction of substituents on the saturated ring system, often with formation of new stereocenters.     

Nanowire Chemical/Biological Sensors: Status and a Roadmap for the Future

Chemiresistive sensors are becoming increasingly important as they offer an inexpensive option to conventional analytical instrumentation, they can be readily integrated into electronic devices, and they have low power requirements. Nanowires (NWs) are a major theme in chemosensor development. High surface area, interwire junctions, and restricted conduction pathways give intrinsically high sensitivity and new mechanisms to transduce the binding or action of analytes. This Review details the status of NW chemosensors with selected examples from the literature. We begin by proposing a principle for understanding electrical transport and transduction mechanisms in NW sensors. Next, we offer the reader a review of device performance parameters. Then, we consider the different NW types followed by a summary of NW assembly and different device platform architectures. Subsequently, we discuss NW functionalization strategies. Finally, we propose future developments in NW sensing to address selectivity, sensor drift, sensitivity, response analysis, and emerging applications.     

Relativistic electron transport and confinement within charge-insulated, mass-limited targets

We present experimental results on the interaction of short-pulse ultra-high-intensity laser beams with small size (“mass-limited”) targets. Several diagnostics (X-ray spectroscopy, K_α and optical imaging of target rear side) have been simultaneously used in order to characterize the laser-generated fast electron transport and energy deposition into the target material. Our results show that fast electrons are effectively confined inside the target by the induced space charge. This electrostatic confinement opens new opportunities to create “Warm Dense Matter” states characterized by solid-state density and temperatures of the order of a few tens of eV.     

Quantitation of Cu+‐catalyzed Decomposition of S‐Nitrosoglutathione Using Saville and Electrochemical Detection: a Pronounced Effect of Glutathione and Copper Concentrations

S‐nitrosothiols (RSNOs) are composed of nitric oxide (NO) bound to the sulfhydryl group of amino acids of peptides or proteins. There is a great interest for their quantitation in biological fluids as they have a crucial impact on physiological and pathophysiological events. Most analytical methodologies for quantitation of RSNOs are based on their decomposition followed by the detection of the released NO. In order to obtain the optimal sensitivity for each detection method, the total decomposition of RSNOs is highly desired. The decomposition of RSNOs can be obtained by using catalytically active metal ions, such as Cu⁺, obtained from CuSO₄ in presence of a reducing agent such as glutathione (GSH) that is naturally present in biological environment. In this work, we have re‐investigated the decomposition of S‐nitrosoglutathione (GSNO) which is the most abundant in vivo low molecular weight RSNO, with a special emphasis on the effect of CuSO₄, GSH, and GSNO concentrations and of their ratio. To this aim, GSNO decomposition optimization was performed by both indirect (Griess assay) and direct (real time electrochemical detection of NO at NO‐microsensor) quantitation methods. Our results show that the ratio between CuSO₄, GSH and GSNO should be adjusted to tune the highest decomposition rate of GSNO and the most efficient electrochemical detection of released NO; also it shows the deleterious effect of very high GSH concentration on the detection of GSNO.     

Nanoscale Platelet Formation by Monounsaturated and Saturated Sophorolipids under Basic pH Conditions

The self‐assembly behavior of the yeast‐derived bolaamphiphile sophorolipid (SL) is generally studied under acidic/neutral pH conditions, at which micellar and fibrillar aggregates are commonly found, according to the (un)saturation of the aliphatic chain: the cis form, which corresponds to the oleic acid form of SL, spontaneously forms micelles, whereas the saturated form, which corresponds to the stearic acid form of SL, preferentially forms chiral fibers. By using small‐angle light and X‐ray scattering (SLS, SAXS) combined with high‐sensitivity transmission electron microscopy imaging under cryogenic conditions (cryo‐TEM), the nature of the self‐assembled structures formed by these two compounds above pH 10, which is the pH at which they are negatively charged due to the presence of a carboxylate group, has been explored. Under these conditions, these compounds self‐assemble into nanoscale platelets, despite the different molecular structures. This work shows that the electrostatic repulsion forces generated by COO^? mainly drive the self‐assembly process at basic pH, in contrast with that found at pH below neutrality, at which self‐assembly is driven by van der Waals forces and hydrogen bonding, and thus, is in agreement with previous findings on carbohydrate‐based gemini surfactants.     

La dynamique des tremblements de terre vue à travers le séisme de Landers du 28 juin 1992

We study the influence of initial conditions and of friction laws on the propagation of dynamic rupture during the earthquake of 28 June 1992 in Landers, California. We model this earthquake solving the elastodynamic wave equation by a finite difference method and we model observed accelerograms in order to get a better knowledge of the dynamic rupture process of this earthquake. In our model rupture propagates spontaneously under the simultaneous control of the initial stress field and friction. We model friction by a simple slip-weakening law. Finally, we inverted the initial stress field and the friction law from the radiation produced by 1992 Landers earthquake using a trial-and-error method. The dynamic model obtained by trial-and-error inversion provides a very satisfactory fit between synthetics and strong motion data. Rupture history and duration of the Landers earthquake are in good agreement with previous kinematic inversion results, without introducing major changes in final slip distribution on the fault. The solution of the dynamic inverse problem is non-unique because this problem is intrinsically ill-posed. Two complementary mechanical models were inverted in order to model the Landers earthquake, and to reproduce the seismic data. The first model corresponds to the asperity model in which only initial stress distribution is heterogeneous. The second model is a barrier model in which the initial stress was perfectly uniform while rupture resistance was heterogeneous. To cite this article: S. Peyrat et al., C. R. Mecanique 330 (2002) 235–248.