Reconstruction and thermal stability of the cubic SiC(001) surfaces

The (001) surfaces of cubic SiC were investigated with ab-initio molecular dynamics simulations. We show that C-terminated surfaces can have different c(2x2) and p(2x1) reconstructions, depending on preparation conditions and thermal treatment, and we suggest experimental probes to identify the various reconstructed geometries. Furthermore we show that Si-terminated surfaces exhibit a p(2x1) reconstruction at T=0, whereas above room temperature they oscillate between a dimer row and an ideal geometry below 500 K, and sample several patterns including a c(4x2) above 500 K.Comment: 12 pages, RevTeX, figures 1 and 2 available in gif form at http://irrmawww.epfl.ch/fg/sic/fig1.gif and http://irrmawww.epfl.ch/fg/sic/fig2.gi

Electron scattering from molecules and molecular aggregates of biological relevance

In this Topical Review we survey the current state of the art in the study of low energy electron collisions with biologically relevant molecules and molecular clusters. We briefly describe the methods and techniques used in the investigation of these processes and summarise the results obtained so far for DNA constituents and their model compounds, amino acids, peptides and other biomolecules. The applications of the data obtained is briefly described as well as future required developments

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

How What We See and What We Know Influence Iconic Gesture Production

In face-to-face communication, speakers typically integrate information acquired through different sources, including what they see and what they know, into their communicative messages. In this study, we asked how these different input sources influence the frequency and type of iconic gestures produced by speakers during a communication task, under two degrees of task complexity. Specifically, we investigated whether speakers gestured differently when they had to describe an object presented to them as an image or as a written word (input modality) and, additionally, when they were allowed to explicitly name the object or not (task complexity). Our results show that speakers produced more gestures when they attended to a picture. Further, speakers more often gesturally depicted shape information when attended to an image, and they demonstrated the function of an object more often when they attended to a word. However, when we increased the complexity of the task by forbidding speakers to name the target objects, these patterns disappeared, suggesting that speakers may have strategically adapted their use of iconic strategies to better meet the task’s goals. Our study also revealed (independent) effects of object manipulability on the type of gestures produced by speakers and, in general, it highlighted a predominance of molding and handling gestures. These gestures may reflect stronger motoric and haptic simulations, lending support to activation-based gesture production accounts

Recent advances in computer-aided drugs design methods

A number of computational advances have had significant impact on the field of computer-aided drug design over the last several years. These advances can be grouped into three basic areas: conformational modelling (of small molecules, macromolecules and their complexes), property modelling (of physical, biological and chemical properties) and molecular design (to optimise physical, biological or chemical properties). The current state of the art in each of these areas is introduced. Recent patents related to these three topics are critically reviewed and their impact on the field of computer-aided drug design is assessed

HIV-1 integrase inhibition: Binding sites, structure activity relationships and future perspectives

The integrase enzyme encoded by the human immunodeficiency virus plays an integral role in the viral life cycle, but is as yet unexploited as a clinical drug target. Integrase processes the viral DNA in the cytoplasm, translocates to the nucleus, and catalyzes viral DNA insertion into the host genome. A wide variety of chemical structures inhibit integrase in vitro, yet few of these apparently promising compounds have demonstrated similar efficacy in vivo. Multiple binding targets have been identified for different integrase inhibitors. These targets include the integrase enzyme prior to substrate binding, the viral DNA substrate, and the preintegration complex consisting of oligomeric integrase and the viral DNA. Some known inhibitors are effective only in the presence of divalent manganese as the active site metal ion cofactor, whereas others do not discriminate between manganese and magnesium ions. Integrase inhibition in response to ligand binding at one of multiple sites renders derivation of a simple set of structure activity relationships challenging. Progress toward this goal is reviewed in the context of experimental and theoretical structural information about integrase

Structural characteristics of lysophosphatidic acid biological targets

Lysophosphatidic acid (LPA; 1-acyl-3-phosphoglycerol) exerts its biological activity through both extracellular and intracellular targets. Receptor targets include the cell-surface G-protein-coupled receptors LPA1-4 and the nuclear PPAR-γ (peroxisome-proliferator-activated receptor γ). Enzyme targets include the secreted cancer cell motility factor, autotaxin, and the transmembrane phosphatases, LPP1-3 (where LPP stands for lipid phosphate phosphatase). Ion channel targets include the two pore domain ion channels in the TREK family, TREK-1, TREK-2 and TRAAK. Structural features of these targets and their interactions with LPA are reviewed. ©2005 Biochemical Society