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

Molecular models of N-Benzyladriamycin-14-valerate (AD 198) in complex with the phorbol ester-binding C1b domain of protein kinase C-δ

N-Benzyladriamycin-14-valerate (AD 198) is a semisynthetic anthracycline with experimental antitumor activity superior to that of doxorubicin (DOX). AD 198, unlike DOX, only weakly binds DNA, is a poor inhibitor of topoisomerase II, and circumvents anthracycline-resistance mechanisms, suggesting a unique mechanism of action for this novel analogue. The phorbol ester receptors, protein kinase C (PKC) and β2-chimaerin, were recently identified as selective targets for AD 198 in vitro. In vitro, AD 198 competes with [3H]PDBu for binding to a peptide containing the isolated C1b domain of PKC-δ (δC1b domain). In the present study molecular modeling is used to investigate the interaction of AD 198 with the δC1b domain. Three models are identified wherein AD 198 binds into the groove formed between amino acid residues 6-13 and 21-27 of the δC1b domain in a manner similar to that reported for phorbol-13-acetate and other ligands of the C1 domain. Two of the identified models are consistent with previous experimental data demonstrating the importance of the 14-valerate side chain of AD 198 in binding to the C1 domain as well as current data demonstrating that translocation of PKC-α to the membrane requires the 14-valerate substituent. In this regard, the carbonyl of the 14-valerate participates in hydrogen bonding to the δC1b while the acyl chain is positioned for stabilization of the membrane-bound protein-ligand complex in a manner analogous to the acyl chains of the phorbol esters. These studies provide a structural basis for the interaction of AD 198 with the δC1b domain and a starting point for the rational design of potential new drugs targeting PKC and other proteins with C1 domains

Molecular recognition in the sphingosine 1-phosphate receptor family

Computational modeling and its application in ligand screening and ligand receptor interaction studies play important roles in structure-based drug design. A series of sphingosine 1-phosphate (S1P) receptor ligands with varying potencies and receptor selectivities were docked into homology models of the S1P1-5 receptors. These studies provided molecular insights into pharmacological trends both across the receptor family as well as at single receptors. This study identifies ligand recognition features that generalize across the S1P receptor family, features unique to the S1P4 and S1P5 receptors, and suggests significant structural differences of the S1P2 receptor. Docking results reveal a previously unknown sulfur-aromatic interaction between the S1P4 C5.44 sulfur atom and the phenyl ring of benzimidazole as well as π-π interaction between F3.33 of S1P1,4,5 and aromatic ligands. The findings not only confirm the importance of a cation-π interaction between W4.64 and the ammonium of S1P at S1P4 but also predict the same interaction at S1P5. S1P receptor models are validated for pharmacophore development including database mining and new ligand discovery and serve as tools for ligand optimization to improve potency and selectivity. © 2007 Elsevier Inc. All rights reserved

An Examination of Whether People Prefer Agents Whose Gestures Mimic Their Own

Abstract. Do people prefer gestures that are similar to their own? There is evidence that in conversation, people will tend to adopt the postures, gestures and mannerisms of their interaction partners [1]. This mirroring, sometimes called the “chameleon effect”, is associated with affiliation, rapport and liking. It may be that a useful way to build rapport in human-agent/robot interaction is to have the agent/robot perform gestures similar to the human. As a step towards that, this study explores if people prefer gestures similar to their own over gestures similar to those of other people. Participants were asked to evaluate a series of agent motions, some of which mimic their own gestures, and rate their preference. A second study first showed participants videos of their own gesturing to see if self-awareness would impact their preference. Different scenarios for soliciting gesture behavior were also explored. Evidence suggests people do have some preference for motions similar to their own, but self-awareness has no effect