The scattering of Madin-Darby canine kidney cells in vitro mimics key aspects of epithelial–mesenchymal transitions during development, carcinoma cell invasion, and metastasis. Scattering is induced by hepatocyte growth factor (HGF) and is thought to involve disruption of cadherin-dependent cell–cell junctions. Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell–cell junctions. We show that HGF does not trigger any detectable decrease in E-cadherin function, but increases integrin-mediated adhesion. Time-lapse imaging suggests that tension on cell–cell junctions may disrupt cell–cell adhesion. Varying the density and type of extracellular matrix proteins shows that scattering correlates with stronger integrin adhesion and increased phosphorylation of the myosin regulatory light chain. To directly test the role of integrin-dependent traction forces, substrate compliance was varied. Rigid substrates that produce high traction forces promoted scattering, in comparison to more compliant substrates. We conclude that integrin-dependent actomyosin traction force mediates the disruption of cell–cell adhesion during epithelial cell scattering.

The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools to automatically track and characterize this process in live cells without the need for fluorescent tagging, in three different physical aspects: increase in cell motility, loss of cell-cell adhesion, and spatial dispersion of cells. These tools were used to screen a library of drugs. We identified several efficient inhibitors of scattering and classified them as selective inhibitors of either motility or loss of cell-cell adhesion, or as non-selective inhibitors. We validated the inhibitors and putative targets from this screen in two unrelated model cell lines using pharmacological treatments and RNA interference (RNAi). We found that non-steroidal anti-inflammatory drugs inhibited cell-cell dissociation, that indirubins inhibited cell motility, and that cyclin-dependent kinase 1 and ribosomal S6 kinase were signaling intermediates in HGF-induced cell scattering. The assay will be suitable for larger-scale screenings of chemical compounds or RNAi libraries.

Sensor-data processing for the interpretation of a mobile robot's indoor environment, and the manipulation of this data for reliable localization, are still some of the most important issues in robotics. This article presents algorithms that determine the true position of a mobile robot, based on real 2-D and 3-D optical range and inten sity data. We start with the physics of the particular type of sensor used, so that the extraction of reliable and repeatable information (namely, edge coordinates) can be determined, taking into account the noise associated with each range sample and the possibility of optical multiple-path effects. Again, applying the physical model of the sensor, the estimated positions of the mobile robot and the uncertainty in these positions are determined. We demonstrate real experiments using 2-D and 3-D scan data taken in indoor environ ments. To update the robot's position reliably, we address the prob lem of matching the information recorded in a scan to, first, an a priori map, and second, to information recorded in previous scans, eliminating the need for an a priori map.

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Predicting the structure of a protein from its amino acid sequence is a complex process the understanding of which