Reachability determination in acyclic Petri nets by cell enumeration approach

Reachability is one of the most important behavioral properties of Petri nets. We propose in this paper a novel approach for solving the fundamental equation in the reachability analysis of acyclic Petri nets, which has been known to be NP-complete. More specifically, by adopting a revised version of the cell enumeration method for an arrangement of hyperplanes in discrete geometry, we develop an efficient solution scheme to identify firing count vector solution(s) to the fundamental equation on a bounded integer set, with a complexity bound of O((nu)^n−m), where n is the number of transitions, m is the number of places and u is the upper bound of the number of firings for all individual transitions.     

Surface reconstruction using Delaunay triangulation for applications in life sciences

The Delaunay triangulation is an established method to define neighborhood relations in multi-particle systems. In particular, this method was employed for interacting multi-cellular systems in Biology. The extension of this method to a sub-cellular level that considers the membrane and the inner structure of cells is not straight forward and subject of this article. It is the objective to use a three-dimensional Delaunay-triangulation as a basis for the definition of a triangulation of a subset of particles that form a surface.An essential problem of this objective is the conservation of the number of particles belonging to the surface. This excludes established surface reconstruction algorithms. The presented algorithm allows the definition of a triangulation within a subset of particles attributed to a surface without the deletion of particles. A particular challenge is the deletion of connection that infer three-dimensional structures in the surface. The presented method is suitable for many configurations. Its performance and its limitations are analyzed and discussed.The developed algorithm for the reconstruction of connections in a surface is suitable to be used for simulations of biological cells because of the inherent conservation of the number of particles attributed to the membrane.     

MoSuMo: A Semantic Web service to generate electrostatic potentials across solvent excluded protein surfaces and binding pockets

Investigations of molecular interactions can benefit from knowledge of the regions that correspond to binding sites and electrostatic potentials across molecular surfaces. In support of simulations aimed at a coarser level of granularity than molecular dynamics, we have developed MoSuMo, a SADI-based Semantic Web service for generating molecular surfaces from a set of 3D atomic coordinates. MoSuMo's service input requires a Protein Data Bank (PDB) identifier from which it obtains the PDB entry and for which it generates electrostatic potentials as vertex values across a geometric mesh that represents the molecular surface. Service inputs and outputs are specified as restrictions on classes from the Semanticscience Integrated Ontology (SIO), which is formalized using the Web Ontology Language (OWL). Binding sites containing their ligands are identified and described as sub-collections of surface vertices. Thus, MoSuMo provides a semantic web service for investigating molecular interactions including visualization.     

TimeLapseAnalyzer: multi-target analysis for live-cell imaging and time-lapse microscopy

The direct observation of cells over time using time-lapse microscopy can provide deep insights into many important biological processes. Reliable analyses of motility, proliferation, invasive potential or mortality of cells are essential to many studies involving live cell imaging and can aid in biomarker discovery and diagnostic decisions. Given the vast amount of image- and time-series data produced by modern microscopes, automated analysis is a key feature to capitalize the potential of time-lapse imaging devices. To provide fast and reproducible analyses of multiple aspects of cell behaviour, we developed TimeLapseAnalyzer. Apart from general purpose image enhancements and segmentation procedures, this extensible, self-contained, modular cross-platform package provides dedicated modalities for fast and reliable analysis of multi-target cell tracking, scratch wound healing analysis, cell counting and tube formation analysis in high throughput screening of live-cell experiments. TimeLapseAnalyzer is freely available (MATLAB, Open Source) at http://www.informatik.uni-ulm.de/ni/mitarbeiter/HKestler/tla.     

Experimental study of diffusion-based extraction from a cell suspension

A recently proposed application of microfluidics is the post-thaw processing of biological cells. Numerical simulations suggest that diffusion-based extraction of the cryoprotective agent dimethyl sulfoxide (DMSO) from blood cells is viable and more efficient than centrifugation, the conventional method of DMSO removal. In order to validate the theoretical model used in these simulations, a prototype was built and the flow of two parallel streams, a suspension of Jurkat cells containing DMSO and a wash stream that contained neither cells nor DMSO, was characterized experimentally. DMSO transport in a rectangular channel (depth 500 μm, width 25 mm and overall length 125 mm) was studied as a function of three dimensionless parameters: depth ratio of the streams, cell volume fraction in the cell solution, and the Peclet number (Pe) based on channel depth, average flow rate and the diffusion coefficient for DMSO in water. In our studies, values of Pe ranged from O(10³) to O(10⁴). Laminar flow was ensured by keeping the Reynolds number between O(1) and O(10). Experimental results based on visual and quantitative data demonstrate conclusively that a microfluidic device can effectively remove DMSO from liquid and cell laden streams without compromising cell recovery. Also, flow conditions in the microfluidic device appear to have no adverse effect on cell viability at the outlet. Further, the results demonstrate that we can predict the amount of DMSO removed from a given device with the theoretical model mentioned previously.     

A mass spectrometric strategy for profiling glycoproteinoses, Pompe disease, and sialic acid storage diseases

Glycoproteinoses, Pompe disease, and sialic acid storage diseases are characterized by a massive accumulation of unprocessed oligosaccharides and/or glycoconjugates in urine. The identification of these glycocompounds is essential for a proper diagnosis. In this study, we investigated the potential of MALDI‐TOF‐MS to identify glycocompounds present in urine from patients with different inborn errors of glycan metabolism. Urinary glycocompounds were permethylated, and analyzed using GC‐MS and MALDI‐TOF‐MS. In order to confirm tentative assignments, a second aliquot of urine was purified on a C18 Sep‐Pak cartridge and glycocompounds were desalted on a column of nonporous graphitized carbon. The glycocompounds were then sequentially on‐plate digested using an array of exoglycosidases. A range of disease‐specific oligosaccharides as well as glycopeptides was identified for all oligosacchariduria models. In addition, free sialic acid accumulated in urine from a patient suffering from French‐type sialuria, has been detected by a GC‐MS approach, which could be applied to other sialic acid storage diseases. This procedure is simple, and can be performed in few simple steps in less than 24 h. This current method can be applied for newborn screening for other inherited metabolic diseases as well as for assessing treatments in clinical trials.     

The cell probe complexity of succinct data structures

We consider time-space tradeoffs for static data structure problems in the cell probe model with word size 1 (the bit probe model). In this model, the goal is to represent n$n$-bit data with s=n+r$s=n+r$ bits such that queries (of a certain type) about the data can be answered by reading at most t$t$ bits of the representation. Ideally, we would like to keep both s$s$ and t$t$ small, but there are tradeoffs between the values of s$s$ and t$t$ that limit the possibilities of keeping both parameters small.     

Segmentation of microscope images of living cells

This paper describes a segmentation method combining a texture based technique with a contour based method. The technique is designed to enable the study of cell behaviour over time by segmenting brightfield microscope image sequences. The technique was tested on artificial images, based on images of living cells and on real sequences acquired from microscope observations of neutrophils and lymphocytes as well as on a sequence of MRI images. The results of the segmentation are compared with the results of the watershed and snake segmentation methods. The results show that the method is both effective and practical.

基于视觉的表格自动识别方法

表格是建筑工程图中表示信息的主要方式之一。计算机自动读图、读表技术对建筑业现代化有十分重要作用。借鉴人工读表的视觉原理和步骤, 针对表格形式的多变性等特点, 提出基于视觉、自顶向下的表格自动阅读方法, 有效地解决了表格格式分析, 识别并处理了耦合、嵌套、合并、复用等情况。