The analysis of the three-dimensional (3-D) structure of tumoral invasion fronts of carcinoma of the uterine cervix is the prerequisite for understanding their architectural-functional relationship. The variation range of the invasion patterns known so far reaches from a smooth tumor-host boundary surface to more diffusely spreading patterns, which all are supposed to have a different prognostic relevance. As a very decisive limitation of previous studies, all morphological assessments just could be done verbally referring to single histological sections. Therefore, the intention of this paper is to get an objective quantification of tumor invasion based on 3-D reconstructed tumoral tissue data. The image processing chain introduced here is capable to reconstruct selected parts of tumor invasion fronts from histological serial sections of remarkable extent (90-500 slices). While potentially gaining good accuracy and reasonably high resolution, microtome cutting of large serial sections especially may induce severe artifacts like distortions, folds, fissures or gaps. Starting from stacks of digitized transmitted light color images, an overall of three registration steps are the main parts of the presented algorithm. By this, we achieved the most detailed 3-D reconstruction of the invasion of solid tumors so far. Once reconstructed, the invasion front of the segmented tumor is quantified using discrete compactness.

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Abstract. Observations have shown that, prior to substorm explosions, thin current sheets are formed in the plasma sheet of the Earth's magnetotail. This provokes the question, to what extent current-sheet thinning and substorm onsets are physically, maybe even causally, related. To answer this question, one has to understand the plasma stability of thin current sheets. Kinetic eects must be taken into account since particle scales are reached in the course of tail current-sheet thinning. We present the results of theoretical investigations of the stability of thin current sheets and about the most unstable mode of their decay. Our conclusions are based upon a non-local linear dispersion analysis of a crossmagnetic ®eld instability of Harris-type current sheets. We found that a sausage-mode bulk current instability starts after a sheet has thinned down to the ion inertial length. We also present the results of three-dimensional electromagnetic PIC-code simulations carried out for mass ratios up to w i am e 64. They verify the linearly predicted properties of the sausage mode decay of thin current sheets in the parameter range of interest.

Observations have shown that, prior to substorm explosions, thin current sheets are formed in the plasma sheet of the Earth's magnetotail. This provokes the question, to what extent current-sheet thinning and substorm onsets are physically, maybe even causally, related. To answer this question, one has to understand the plasma stability of thin current sheets. Kinetic eects must be taken into account since particle scales are reached in the course of tail current-sheet thinning. We present the results of theoretical investigations of the stability of thin current sheets and about the most unstable mode of their decay. Our conclusions are based upon a non-local linear dispersion analysis of a crossmagnetic ®eld instability of Harris-type current sheets. We found that a sausage-mode bulk current instability starts after a sheet has thinned down to the ion inertial length. We also present the results of three-dimensional electromagnetic PIC-code simulations carried out for mass ratios up to w i am e 64. They verify the linearly predicted properties of the sausage mode decay of thin current sheets in the parameter range of interest.

Therapeutic application of mesenchymal stem cells (MSC) requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM) that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The ‘tool box’ of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.