Antimicrobial Peptide Dendrimer Chimera

We recently reported the discovery of antimicrobial peptide dendrimers (AMPDs) acting by a membrane‐disruptive mechanism against multidrug resistant pathogenic bacteria. Here, we combined amino acid sequence elements from different AMPDs with different activity profiles to form AMPD chimeras. By joining the outer branches of TNS18 , an AMPD active against Pseudomonas aeruginosa, Acinetobacter baumannii and methicillin resistant Staphylococcus aureus, with the core of T7 , another AMPD active against P. aeruginosa, A. baumannii and Klebsiella pneumoniae, we obtained AMPD chimera DC5 displaying all previously observed activities while retaining a similar mechanism of action. These experiments show that chimera design represents a useful strategy to improve the properties of AMPDs.     

Genomics‐Driven Discovery of NO‐Donating Diazeniumdiolate Siderophores in Diverse Plant‐Associated Bacteria

Siderophores are key players in bacteria–host interactions, with the main function to provide soluble iron for their producers. Gramibactin from rhizosphere bacteria expands siderophore function and diversity as it delivers iron to the host plant and features an unusual diazeniumdiolate moiety for iron chelation. By mutational analysis of the grb gene cluster, we identified genes (grbD and grbE) necessary for diazeniumdiolate formation. Genome mining using a GrbD‐based network revealed a broad range of orthologous gene clusters in mainly plant‐associated Burkholderia/Paraburkholderia species. Two new types of diazeniumdiolate siderophores, megapolibactins and plantaribactin were fully characterized. In vitro assays and in vivo monitoring experiments revealed that the iron chelators also liberate nitric oxide (NO) in plant roots. This finding is important since NO donors are considered as biofertilizers that maintain iron homeostasis and increase overall plant fitness.     

Biosynthesis and Ether‐Bridge Formation in Nargenicin Macrolides

The nargenicin family of antibiotics are macrolides containing a rare ether‐bridged cis‐decalin motif. Several of these compounds are highly active against multi‐drug resistant organisms. Despite the identification of the first members of this family almost 40 years ago, the genetic basis for the production of these molecules and the enzyme responsible for formation of the oxa bridge, remain unknown. Here, the 85 kb nargenicin biosynthetic gene cluster was identified from a human pathogenic Nocardia arthritidis isolate and this locus is solely responsible for nargenicin production. Further investigation of this locus revealed a putative iron‐α‐ketoglutarate‐dependent dioxygenase, which was found to be responsible for the formation of the ether bridge from the newly identified deoxygenated precursor, 8,13‐deoxynargenicin. Uncovering the nargenicin biosynthetic locus provides a molecular basis for the rational bioengineering of these interesting antibiotic macrolides.     

Fictitious domain approach for numerical modelling of Navier–Stokes equations

This study investigates a fictitious domain model for the numerical solution of various incompressible viscous flows. It is based on the so‐called Navier–Stokes/Brinkman and energy equations with discontinuous coefficients all over an auxiliary embedding domain. The solid obstacles or walls are taken into account by a penalty technique. Some volumic control terms are directly introduced in the governing equations in order to prescribe immersed boundary conditions. The implicit numerical scheme, which uses an upwind finite volume method on staggered Cartesian grids, is of second‐order accuracy in time and space. A multigrid local mesh refinement is also implemented, using the multi‐level Zoom Flux Interface Correction (FIC) method, in order to increase the precision where it is needed in the domain. At each time step, some iterations of the augmented Lagrangian method combined with a preconditioned Krylov algorithm allow the divergence‐free velocity and pressure fields be solved for. The tested cases concern external steady or unsteady flows around a circular cylinder, heated or not, and the channel flow behind a backward‐facing step. The numerical results are shown in good agreement with other published numerical or experimental data. Copyright © 2000 John Wiley & Sons, Ltd.     

Bileptons: present limits and future prospects

We define bileptons to be bosons coupling to a pair of leptons and construct the most general dimension four lagrangian involving scalar and vector bileptons. We concentrate on fields with lepton number 2, and derive model independent bounds on their masses and couplings from low-energy data. In addition, we study their signals in high-energy experiments and forecast the discovery potential of future colliders. Received: 24 April 1997 / Published online: 20 February 1998     

On the Singularity of the Free Energy at a First Order Phase Transition

At first order phase transition the free energy does not have an analytic continuation in the thermodynamical variable, which is conjugate to an order parameter for the transition. This result is proved at low temperature for lattice models with finite range interaction and two periodic ground-states, under the only condition that they satisfy the Peierls condition.Supported by Fonds National Suisse de la Recherche Scientifique.     

Detection of single-electron charging in an individual InAs quantum dot by noncontact atomic-force microscopy

Single-electron charging in an individual InAs quantum dot was observed by electrostatic force measurements with an atomic-force microscope (AFM). The resonant frequency shift and the dissipated energy of an oscillating AFM cantilever were measured as a function of the tip-back electrode voltage, and the resulting spectra show distinct jumps when the tip was positioned above the dot. The observed jumps in the frequency shift, with corresponding peaks in dissipation, are attributed to a single-electron tunneling between the dot and the back electrode governed by the Coulomb blockade effect, and are consistent with a model based on the free energy of the system. The observed phenomenon may be regarded as the "force version" of the Coulomb blockade effect.