New Insights into Glycopeptide Antibiotic Binding to Cell Wall Precursors using SPR and NMR Spectroscopy

Glycopeptide antibiotics, such as vancomycin and teicoplanin, are used to treat life‐threatening infections caused by multidrug‐resistant Gram‐positive pathogens. They inhibit bacterial cell wall biosynthesis by binding to the D ‐Ala‐D ‐Ala C‐terminus of peptidoglycan precursors. Vancomycin‐resistant bacteria replace the dipeptide with the D ‐Ala‐D ‐Lac depsipeptide, thus reducing the binding affinity of the antibiotics with their molecular targets. Herein, studies of the interaction of teicoplanin, teicoplanin‐like A40926, and of their semisynthetic derivatives (mideplanin, MDL63,246, dalbavancin) with peptide analogues of cell‐wall precursors by NMR spectroscopy and surface plasmon resonance (SPR) are reported. NMR spectroscopy revealed the existence of two different complexes in solution, when the different glycopeptides interact with Ac2Kd AlaD AlaOH. Despite the NMR experimental conditions, which are different from those employed for the SPR measurements, the NMR spectroscopy results parallel those deduced in the chip with respect to the drastic binding difference existing between the D ‐Ala and the D ‐Lac terminating analogues, confirming that all these antibiotics share the same primary molecular mechanism of action and resistance. Kinetic analysis of the interaction between the glycopeptide antibiotics and immobilized AcKd AlaD AlaOH by SPR suggest a dimerization process that was not observed by NMR spectroscopy in DMSO solution. Moreover, in SPR, all glycopeptides with a hydrophobic acyl chain present stronger binding with a hydrophobic surface than vancomycin, indicating that additional interactions through the employed surface are involved. In conclusion, SPR provides a tool to differentiate between vancomycin and other glycopeptides, and the calculated binding affinities at the surface seem to be more relevant to in vitro antimicrobial activity than the estimations from NMR spectroscopy analysis.     

Synthesis of Optically Active β-Halogeno-Phosphinates via Asymmetric Selection

Growing interest has been devoted in the last few years to the synthesis of optically active β-halogenoethyl sulphoxides¹ and sulphilimines² via chiral discrimination. In this context we have developed a synthesis of optically active isopropyl vinylphenylphosphinates 1 via kinetic resolution of isopropyl β-halogenoethylphenylphosphinates 2(a-c) by chiral bases (3–6) and we have studied the influence of the resolving agent and of the leaving group on the kinetic resolution.     

Slowing down and range of a beam of particles

To analyze the many effects taking place when a beam of particles passes through a medium, two types of problems must be solved: first of all, one needs to know the cross-sections for the interactions between the test particles (t.p.) and the field particles (f.p.); then, one must solve the transport equations, in terms of energy, position and time. Much effort has been put into calculating cross-sections, even through very sophisticated quantum-mechanical models. However, often these cross sections have been used within otherwise very scanty transport models, mostly the well known “continuous slowing down approximation”. The errors embedded in such transport models make such detailed cross-section calculations unjustified. Besides, for slow particles, the effects of the thermal agitation and chemical bonding of the atoms in the target need to be taken into account to compute properly the range and the stopping power.

In the present work a simple but more realistic transport model is described, that brings out the importance of phenomena that are completely disregarded by the continuous slowing down approximation, like energy straggling for slow particles. A BGK kernel and realistic collision frequencies can be used in this model, particularly for meaningful comparison with experimental results.     

Space distribution and energy straggling of charged particles via Fokker-Planck equation

Summary The Fokker-Planck equation describing a beam of charged particles entering a homogeneous medium is solved here for a stationary case. Interactions are taken into account through Coulomb cross-section. Starting from the charged-particle distribution as a function of velocity and penetration depth, some important kinetic quantities are calculated, like mean velocity, range and the loss of energy per unit space. In such quantities the energy straggling is taken into account. This phenomenon is not considered in the continuous slowing-down approximation that is commonly used to obtain the range and the stopping power. Finally the well-known Bohr or Bethe formula is found as a first-order approximation of the Fokker-Planck equation. The authors of this paper have agreed to not receive the proofs for correction.     

Kinetic approach to the propagation of electromagnetic waves in a weakly ionized plasma

Summary High-frequency wave phenomena in a partially ionized plasma are analysed in the frame of the kinetic theory without resorting to perturbation techniques. In particular, we obtain the electron distribution function in an external electric field alternating in both time and position, and then the electrical conductivity and the dispersion relation. Corrections to the results of the macroscopic theory are evaluated up to any desired order.

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Riassunto Il fenomeno della propagazione di un'onda elettromagnetica in un plasma parzialmente ionizzato è analizzato nell'ambito della teoria cinetica. Il metodo proposto consente di ricavare la funzione di distribuzione degli elettroni senza dover ricorrere a tecniche perturbative. Si riportano le espressioni esatte della conducibilità elettrica e della legge di dispersione e, quindi, le correzioni da apportare ai risultati ottenuti con la teoria macroscopica.

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Резюме В рамках кинетической теории анализизируется явление распространения электромагнитных волн в частично ионизованной плазме. Предложенный метод позволяет получить электронную функцию распределения во внешнем электрическом поле без использования теории возмущений. Затем определяются электрическая проводимость и дисперсионное соотношение. Поправки к резулятатам макроскопической теории оцениваются в любом желаемом порядке.

     

New Trends in Magnetic Exchange Bias

The study of layered magnetic structures is one of the hottest topics in magnetism due to the growing attraction of applications in magnetic sensors and magnetic storage media, such as random access memory. For almost half a century, new discoveries have driven researchers to re-investigate magnetism in thin film structures. Phenomena such as giant magnetoresistance, tunneling magnetoresistance, exchange bias and interlayer exchange coupling led to new ideas to construct devices, based not only on semiconductors but on a variety of magnetic materials Upon cooling fine cobalt particles in a magnetic field through the Néel temperature of their outer antiferromagnetic oxide layer, Meiklejohn and Bean discovered exchange bias in 1956. The exchange bias effect through which an antiferromagnetic AF layer can cause an adjacent ferromagnetic F layer to develop a preferred direction of magnetization, is widely used in magnetoelectronics technology to pin the magnetization of a device reference layer in a desired direction. However, the origin and effects due to exchange interaction across the interface between antiferromagneic and ferromagnetic layers are still debated after about fifty years of research, due to the extreme difficulty associated with the determination of the magnetic interfacial structure in F/AF bilayers. Indeed, in an AF/F bilayer system, the AF layer acts as “the invisible man” during conventional magnetic measurements and the presence of the exchange coupling is evidenced indirectly through the unusual behavior of the adjacent F layer. Basically, the coercive field of the F layer increases in contact with the AF and, in some cases, its hysteresis loop is shifted by an amount called exchange bias field. Thus, AF/F exchange coupling generates a new source of anisotropy in the F layer. This induced anisotropy strongly depends on basic features such as the magnetocrystalline anisotropy, crystallographic and spin structures, defects, domain patterns etc of the constituant layers. The spirit of this topical issue is, for the first time, to gather and survey recent and original developments, both experimental and theoretical, which bring new insights into the physics of exchange bias. It has been planned in relation with an international workshop exclusively devoted to exchange bias, namely IWEBMN’04 (International Workshop on Exchange Bias in Magnetic Nanostructures) that took place in Anglet, in the south west of France, from 16th to 18th September 2004. The conference gathered worldwide researchers in the area, both experimentalists and theoreticians. Several research paths are particularly active in the field of magnetic exchange coupling. The conference, as well as this topical issue, which was also open to contributions from scientists not participating in the conference, has been organized according to the following principles: 1. Epitaxial systems: Since the essential behavior of exchange bias critically depends on the atomic-level chemical and spin structure at the interface between the ferromagnetic and antiferromagnetic components, epitaxial AF/F systems in which the quality of the interface and the crystalline coherence are optimized and well known are ideal candidates for a better understanding of the underlying physics of exchange bias. The dependence of exchange bias on the spin configurations at the interfaces can be accomplished by selecting different crystallographic orientations. The role of interface roughness can also be understood from thin-film systems by changing the growth parameters, and correlations between the interface structure and exchange bias can be made, as reported in this issue. 2. Out-of-plane magnetized systems: While much important work has been devoted to the study of structures with in-plane magnetization, little has been done on the study of exchange bias and exchange coupling in samples with out-of-plane magnetization. Some systems can exhibit either in-plane or out-of-plane exchange bias, depending on the field cooling direction. This is of particular interest since it allows probing of the three-dimensional spin structure of the AF layer. The interface magnetic configuration is extremely important in the perpendicular geometry, as the short-range exchange coupling competes with a long-range dipolar interaction; the induced uniaxial anisotropy must overcome the demagnetization energy to establish perpendicular anisotropy films. Those new studies are of primary importance for the magnetic media industry as perpendicular recording exhibits potential for strongly increased storage densities. 3. Parameters tuning exchange bias in polycrystalline samples and magnetic configurations: Different parameters can be used to tune the exchange bias coupling in polycrystalline samples similar to those used in devices. Particularly fascinating aspects are the questions of the appearance of exchange bias or coercivity in ferromagnet/antiferromagnet heterostructures, and its relation to magnetic configurations formed on either side of the interface. Several papers report on either growth choices or post preparation treatments that enable tuning of the exchange bias in bilayers. The additional complexity and novel features of the exchange coupled interface make the problem particularly rich. 4. Dynamics and magnetization reversal: Linear response experiments, such as ferromagnetic resonance, have been used with great success to identify interface, surface anisotropies and interlayer exchange in multilayer systems. The exchange bias structure is particularly well suited to study because interface driven changes in the spin wave frequencies in the ferromagnet can be readily related to interlayer exchange and anisotropy parameters associated with the antiferromagnet. Because the exchange bias is intimately connected with details of the magnetization process during reversal and the subsequent formation of hysteresis, considerations of time dependence and irreversible processes are also relevant. Thermal processes like the training effect manifesting itself in changes in the hysteretic characteristics depending on magnetic history can lead to changes in the magnetic configurations. This section contains an increasing number of investigations of dynamics in exchange bias coupled bilayers, and in particular those of the intriguing asymmetric magnetization reversal in both branches of a hysteresis loop. The Editors of the topical issue: Alexandra Mougin Laboratoire de Physique des Solides, UMR CNRS 8502, Université Paris Sud, F-91405 Orsay, France Stéphane Mangin Laboratoire de Physique des Matériaux, UMR CNRS 7556, Université Henri Poincaré, F-54506 Nancy, France Jean-Francois Bobo Laboratoire de Physique de la Matière Condensée - NMH, FRE 2686 CNRS ONERA, 2 avenue Edouard Belin, F-31400 Toulouse, France Alois Loidl Experimentalphysik V, EKM, Institut für Physik, Universität Augsburg, Universitätsstrasse 1, D-86135, Augsburg, Germany     

A U-statistic test in competing risk models

We consider a situation in which systems are subject to failure from competing risks or could be censored from an independent censoring process. A procedure, based on a U-statistic, is proposed for testing the equality of two failure rates in the competing risks set. Under independence assumptions, the asymptotic distribution of the statistic is given and used to construct the test. To cite this article: N. Molinari, C. R. Acad. Sci. Paris, Ser. I 341 (2005).