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Christian Reich

Publications and source records attributed to Christian Reich.

4 recordsLinked to original sources

Structure and mobility of lipid membranes on a thermoplastic substrate.

Supported lipid membranes constitute one of the most important model systems for cell membranes. The properties of lipid membranes supported by the hydrophobic solid polymer cyclic olefin copolymer (COC) were investigated. Lipid layers consisting of varying amounts of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP, cationic) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC, neutral) prepared by vesicle fusion and solvent exchange were compared. All lipid mixtures coated the COC surface homogeneously forming a fluid membrane as verified by fluorescence microscopy and fluorescence recovery after photobleaching (FRAP). The exact structure of the supported membranes was determined by synchrotron reflectivity experiments using a microfluidic chamber. The X-ray data are in agreement with a compressed (head-to-head distance = 29 angstroms) and less densely packed bilayer.

Cations↗

Detection of activity centers in cellular pathways using transcript profiling.

We present a new computational method for identifying regulated pathway components in transcript profiling (TP) experiments by evaluating transcriptional activity in the context of known biological pathways. We construct a graph representing thousands of protein functional relationships by integrating knowledge from public databases and review articles. We use the notion of distance in a graph to define pathway neighborhoods. The pathways perturbed in an experiment are then identified as the subgraph induced by the genes, referred to as activity centers, having significant density of transcriptional activity in their functional neighborhoods. We illustrate the predictive power of this approach by performing and analyzing an experiment of TP53 overexpression in NCI-H125 cells. The detected activity centers are in agreement with the known TP53 activation effects and our independent experimental results. We also apply the method to a serum starvation experiment using HEY cells and investigate the predicted activity of the transcription factor MYC. Finally, we discuss interesting properties of the activity center approach and its possible applications beyond the comparison of two experiments.

Algorithms↗

Computational knowledge integration in biopharmaceutical research.

An initiative to increase biopharmaceutical research productivity by capturing, sharing and computationally integrating proprietary scientific discoveries with public knowledge is described. This initiative involves both organisational process change and multiple interoperating software systems. The software components rely on mutually supporting integration techniques. These include a richly structured ontology, statistical analysis of experimental data against stored conclusions, natural language processing of public literature, secure document repositories with lightweight metadata, web services integration, enterprise web portals and relational databases. This approach has already begun to increase scientific productivity in our enterprise by creating an organisational memory (OM) of internal research findings, accessible on the web. Through bringing together these components it has also been possible to construct a very large and expanding repository of biological pathway information linked to this repository of findings which is extremely useful in analysis of DNA microarray data. This repository, in turn, enables our research paradigm to be shifted towards more comprehensive systems-based understandings of drug action.

Algorithms↗

Torque patterns of the limbs of small therian mammals during locomotion on flat ground.

In three species of small therian mammals (Scandentia: Tupaia glis, Rodentia: Galea musteloides and Lagomorpha: Ochotona rufescens) the net joint forces and torques acting during stance phase in the four kinematically relevant joints of the forelimbs (scapular pivot, shoulder joint, elbow joint, wrist joint) and the hindlimbs (hip joint, knee joint, ankle joint, intratarsal joint) were determined by inverse dynamic analysis. Kinematics were measured by cineradiography (150 frames s(-1)). Synchronously ground reaction forces were acquired by forceplates. Morphometry of the extremities was performed by a scanning method using structured illumination. The vector sum of ground reaction forces and weight accounts for most of the joint force vector. Inertial effects can be neglected since errors of net joint forces amount at most to 10 %. The general time course of joint torques is comparable for all species in all joints of the forelimb and in the ankle joint. Torques in the intratarsal joints differ between tailed and tail-less species. The torque patterns in the knee and hip joint are unique to each species. For the first time torque patterns are described completely for the forelimb including the scapula as the dominant propulsive segment. The results are compared with the few torque data available for various joints of cats (Felis catus), dogs (Canis lupus f. familiaris), goats (Capra sp.) and horses (Equus przewalskii f. caballus).

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