Damping of a nanomechanical oscillator strongly coupled to a quantum dot

We present theoretical and experimental results on the mechanical damping of an atomic force microscope cantilever strongly coupled to a self-assembled InAs quantum dot. When the cantilever oscillation amplitude is large, its motion dominates the charge dynamics of the dot which in turn leads to nonlinear, amplitude-dependent damping of the cantilever. We observe highly asymmetric lineshapes of Coulomb blockade peaks in the damping that reflect the degeneracy of energy levels on the dot, in excellent agreement with our strong coupling theory. Furthermore, we predict that excited state spectroscopy is possible by studying the damping versus oscillation amplitude, in analogy to varying the amplitude of an ac gate voltage.Comment: 4+ pages, 4 figure

Structure of the recombinant antibody Fab fragment f3p4

The structure of the antibody Fab fragment f3p4, which was selected from a subset of the synthetic HuCAL antibody library to bind the sodium citrate symporter CitS, is described at 1.92 A resolution. Comparison with computational models revealed deviations in a few framework positions and in the binding loops. The crystals belong to space group P2(1)2(1)2 and contain four molecules in the asymmetric unit, with unit-cell parameters a=102.77, b=185.92, c=102.97 A. These particular unit-cell parameters allowed pseudo-merohedral twinning; interestingly, the twinning law relates a twofold screw axis to a twofold axis

Sorption, Desorption and Exchange of Cesium on Glaciofluvial Deposits

Distribution ratios and isotherms for Sorption, desorption and isotope-exchange of cesium (labelled with Cs-137) were measured on grain size fractions (<2mm) of quatemary glaciofluvial deposits. Sediment materials from two locations within Switzerland and synthetic groundwaters of different compositions were used. The investigated concentration range for cesium was 10"" — 10"' M. Cesium introduced into the system with the solid phase may influence the measurements at the lowest concentrations. Depending on the experimental conditions, the distribution ratios vary between 3 and 30'000 ml/g. The isotherms are non-linear. Normalization of the cesium concentration in the solid with the cation-exchange capacity leads to nearly identical isotherms for all size fractions of the two geographic locations. Desorption and exchange are retarded at the higher cesium concentrations. This can be explained by structural changes in clay minerals which dominate the Sorption of cesium on this material. Variations in the composition of the groundwater influence the Sorption of cesium only sHghtly; potassium and hydrogen ions are the main competitors

Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin

Cysteine cathepsins often contribute to cancer progression due to their overexpression in the tumour microenvironment and therefore present attractive targets for non-invasive diagnostic imaging. However, the development of highly selective and versatile small molecule probes for cathepsins has been challenging. Here, we targeted tumour-associated cathepsin B using designed ankyrin repeat proteins (DARPins). The selective DARPin 8h6 inhibited cathepsin B with picomolar affinity (Ki = 35 pM) by binding to a site with low structural conservation in cathepsins, as revealed by the X-ray structure of the complex. DARPin 8h6 blocked cathepsin B activity in tumours ex vivo and was successfully applied in in vivo optical imaging in two mouse breast cancer models, in which cathepsin B was bound to the cell membrane or secreted to the extracellular milieu by tumour and stromal cells. Our approach validates cathepsin B as a promising diagnostic and theranostic target in cancer and other inflammation-associated diseases

Tuning the drug efflux activity of an ABC transporter in vivo by in vitro selected DARPin binders.

ABC transporters use the energy from binding and hydrolysis of ATP to import or extrude substrates across the membrane. Using ribosome display, we raised designed ankyrin repeat proteins (DARPins) against detergent solubilized LmrCD, a heterodimeric multidrug ABC exporter from Lactococcus lactis. Several target-specific DARPin binders were identified that bind to at least three distinct, partially overlapping epitopes on LmrD in detergent solution as well as in native membranes. Remarkably, functional screening of the LmrCD-specific DARPin pools in L. lactis revealed three homologous DARPins which, when generated in LmrCD-expressing cells, strongly activated LmrCD-mediated drug transport. As LmrCD expression in the cell membrane was unaltered upon the co-expression of activator DARPins, the activation is suggested to occur at the level of LmrCD activity. Consistent with this, purified activator DARPins were found to stimulate the ATPase activity of LmrCD in vitro when reconstituted in proteoliposomes. This study suggests that membrane transporters are tunable in vivo by in vitro selected binding proteins. Our approach could be of biopharmaceutical importance and might facilitate studies on molecular mechanisms of ABC transporters

Extending Qualitative Spatial Theories with Emergent Spatial Concepts: An Automated Reasoning Approach

Qualitative Spatial Reasoning is an exciting research field of the Knowledge Representation and Reasoning paradigm whose application often requires the extension, refinement or combination of existent theories (as well as the associated calculus). This paper addresses the issue of the sound spatial interpretation of formal extensions of such theories; particularly the interpretation of the extension and the desired representational features. The paper shows how to interpret certain kinds of extensions of Region Connection Calculus (RCC) theory. We also show how to rebuild the qualitative calculus of these extensions.Junta de Andalucía TIC-606