Stochastic dynamics of adhesion clusters under shared constant force and with rebinding

Single receptor-ligand bonds have finite lifetimes, so that biological systems can dynamically react to changes in their environment. In cell adhesion, adhesion bonds usually act cooperatively in adhesion clusters. Outside the cellular context, adhesion clusters can be probed quantitatively by attaching receptors and ligands to opposing surfaces. Here we present a detailed theoretical analysis of the stochastic dynamics of a cluster of parallel bonds under shared constant loading and with rebinding. Analytical solutions for the appropriate one-step master equation are presented for special cases, while the general case is treated with exact stochastic simulations. If the completely dissociated state is modeled as an absorbing boundary, mean cluster lifetime is finite and can be calculated exactly. We also present a detailed analysis of fluctuation effects and discuss various approximations to the full stochastic description.Comment: Revtex, 29 pages, 23 postscript figures included (some with reduced image quality

A Development Environment for Visual Physics Analysis

The Visual Physics Analysis (VISPA) project integrates different aspects of physics analyses into a graphical development environment. It addresses the typical development cycle of (re-)designing, executing and verifying an analysis. The project provides an extendable plug-in mechanism and includes plug-ins for designing the analysis flow, for running the analysis on batch systems, and for browsing the data content. The corresponding plug-ins are based on an object-oriented toolkit for modular data analysis. We introduce the main concepts of the project, describe the technical realization and demonstrate the functionality in example applications

Performance of the CMS Pixel Detector at an upgraded LHC

The CMS experiment will include a pixel detector for pattern recognition and vertexing. It will consist of three barrel layers and two endcaps on each side, providing three space-points up to a pseudoraditity of 2.1. Taking into account the expected limitations of its performance in the LHC environment an 8-9 layer pixel detector for an upgraded LHC is discussed.Comment: Contribution to the 10th European Symposium on Semiconductor Detectors, June 12 - 16, 2005 in Wildbad Kreuth, Germany. 6 pages, 4 figures, 1 table. Referee's comments implemente

A generative framework for the study of delusions

Despite the ubiquity of delusional information processing in psychopathology and everyday life, formal characterizations of such inferences are lacking. In this article, we propose a generative framework that entails a computational mechanism which, when implemented in a virtual agent and given new information, generates belief updates (i.e., inferences about the hidden causes of the information) that resemble those seen in individuals with delusions. We introduce a particular form of Dirichlet process mixture model with a sampling-based Bayesian inference algorithm. This procedure, depending on the setting of a single parameter, preferentially generates highly precise (i.e. over-fitting) explanations, which are compartmentalized and thus can co-exist despite being inconsistent with each other. Especially in ambiguous situations, this can provide the seed for delusional ideation. Further, we show by simulation how the excessive generation of such over-precise explanations leads to new information being integrated in a way that does not lead to a revision of established beliefs. In all configurations, whether delusional or not, the inference generated by our algorithm corresponds to Bayesian inference. Furthermore, the algorithm is fully compatible with hierarchical predictive coding. By virtue of these properties, the proposed model provides a basis for the empirical study and a step toward the characterization of the aberrant inferential processes underlying delusions

Building CMS Pixel Barrel Detectur Modules

For the barrel part of the CMS pixel tracker about 800 silicon pixel detector modules are required. The modules are bump bonded, assembled and tested at the Paul Scherrer Institute. This article describes the experience acquired during the assembly of the first ~200 modules.Comment: 5 pages, 7 figures, Vertex200

When it Pays to Rush: Interpreting Morphogen Gradients Prior to Steady-State

During development, morphogen gradients precisely determine the position of gene expression boundaries despite the inevitable presence of fluctuations. Recent experiments suggest that some morphogen gradients may be interpreted prior to reaching steady-state. Theoretical work has predicted that such systems will be more robust to embryo-to-embryo fluctuations. By analysing two experimentally motivated models of morphogen gradient formation, we investigate the positional precision of gene expression boundaries determined by pre-steady-state morphogen gradients in the presence of embryo-to-embryo fluctuations, internal biochemical noise and variations in the timing of morphogen measurement. Morphogens that are direct transcription factors are found to be particularly sensitive to internal noise when interpreted prior to steady-state, disadvantaging early measurement, even in the presence of large embryo-to-embryo fluctuations. Morphogens interpreted by cell-surface receptors can be measured prior to steady-state without significant decrease in positional precision provided fluctuations in the timing of measurement are small. Applying our results to experiment, we predict that Bicoid, a transcription factor morphogen in Drosophila, is unlikely to be interpreted prior to reaching steady-state. We also predict that Activin in Xenopus and Nodal in zebrafish, morphogens interpreted by cell-surface receptors, can be decoded in pre-steady-state.Comment: 18 pages, 3 figure

Qualification Procedures of the CMS Pixel Barrel Modules

The CMS pixel barrel system will consist of three layers built of about 800 modules. One module contains 66560 readout channels and the full pixel barrel system about 48 million channels. It is mandatory to test each channel for functionality, noise level, trimming mechanism, and bump bonding quality. Different methods to determine the bump bonding yield with electrical measurements have been developed. Measurements of several operational parameters are also included in the qualification procedure. Among them are pixel noise, gains and pedestals. Test and qualification procedures of the pixel barrel modules are described and some results are presented.Comment: 7 Pages, 7 Figures. Contribution to Pixel 2005, September 5-8, 2005, Bonn, Germna

Radiation hardness of CMS pixel barrel modules

Pixel detectors are used in the innermost part of the multi purpose experiments at LHC and are therefore exposed to the highest fluences of ionising radiation, which in this part of the detectors consists mainly of charged pions. The radiation hardness of all detector components has thoroughly been tested up to the fluences expected at the LHC. In case of an LHC upgrade, the fluence will be much higher and it is not yet clear how long the present pixel modules will stay operative in such a harsh environment. The aim of this study was to establish such a limit as a benchmark for other possible detector concepts considered for the upgrade. As the sensors and the readout chip are the parts most sensitive to radiation damage, samples consisting of a small pixel sensor bump-bonded to a CMS-readout chip (PSI46V2.1) have been irradiated with positive 200 MeV pions at PSI up to 6E14 Neq and with 21 GeV protons at CERN up to 5E15 Neq. After irradiation the response of the system to beta particles from a Sr-90 source was measured to characterise the charge collection efficiency of the sensor. Radiation induced changes in the readout chip were also measured. The results show that the present pixel modules can be expected to be still operational after a fluence of 2.8E15 Neq. Samples irradiated up to 5E15 Neq still see the beta particles. However, further tests are needed to confirm whether a stable operation with high particle detection efficiency is possible after such a high fluence.Comment: Contribution to the 11th European Symposium on Semiconductor Detectors June 7-11, 2009 Wildbad Kreuth, German

Dynamic force spectroscopy on multiple bonds: experiments and model

We probe the dynamic strength of multiple biotin-streptavidin adhesion bonds under linear loading using the biomembrane force probe setup for dynamic force spectroscopy. Measured rupture force histograms are compared to results from a master equation model for the stochastic dynamics of bond rupture under load. This allows us to extract the distribution of the number of initially closed bonds. We also extract the molecular parameters of the adhesion bonds, in good agreement with earlier results from single bond experiments. Our analysis shows that the peaks in the measured histograms are not simple multiples of the single bond values, but follow from a superposition procedure which generates different peak positions.Comment: to appear in Europhysics Letter