Communications Biophysics

Contains reports on three research projects.National Institutes of Health (Grant 5 P01 GM14940-04

The Index-Based Subgraph Matching Algorithm (ISMA): Fast Subgraph Enumeration in Large Networks Using Optimized Search Trees

Subgraph matching algorithms are designed to find all instances of predefined subgraphs in a large graph or network and play an important role in the discovery and analysis of so-called network motifs, subgraph patterns which occur more often than expected by chance. We present the index-based subgraph matching algorithm (ISMA), a novel tree-based algorithm. ISMA realizes a speedup compared to existing algorithms by carefully selecting the order in which the nodes of a query subgraph are investigated. In order to achieve this, we developed a number of data structures and maximally exploited symmetry characteristics of the subgraph. We compared ISMA to a naive recursive tree-based algorithm and to a number of well-known subgraph matching algorithms. Our algorithm outperforms the other algorithms, especially on large networks and with large query subgraphs. An implementation of ISMA in Java is freely available at http://sourceforge.net/projects/isma

Motion Pattern Encapsulation for Data-Driven Constraint-Based Motion Editing

The growth of motion capture systems have contributed to the proliferation of human motion database, mainly because human motion is important in many applications, ranging from games entertainment and films to sports and medicine. However, the captured motions normally attend specific needs. As an effort for adapting and reusing captured human motions in new tasks and environments and improving the animator’s work, we present and discuss a new data-driven constraint-based animation system for interactive human motion editing. This method offers the compelling advantage that it provides faster deformations and more natural-looking motion results compared to goal-directed constraint-based methods found in the literature

Reversal of MDR1-associated resistance to topotecan by PAK-200S, a new dihydropyridine analogue, in human cancer cell lines

Recent data suggest that expression of the membrane P170-glycoprotein (P-gp) may confer resistance to the topoisomerase- I-interactive agent topotecan. The present study describes the cellular effects of a new dihydropyridine analogue, PAK-200S, on P-gp-mediated resistance to topotecan in human breast and ovarian tumour cells. PAK-200S at a non-cytotoxic concentration of 2.0 μM completely reversed resistance to topotecan in P-gp-expressing MCF-7/adr (breast) and A2780/Dx5 (ovarian) tumour cells, respectively, with no effects on parental cells. Cellular pharmacokinetic studies by reversed-phase high-performance liquid chromatography analysis showed significantly lower cellular drug concentrations of the pharmacologically active closed-ring lactone of topotecan in multidrug-resistant cells than in parental cells. PAK-200S was effective in restoring the cellular lactone concentrations of topotecan in resistant MCF-7/adr cells to levels comparable to those obtained in parental cells. Furthermore, exposure of MCF-7/adr cells to topotecan in the presence of PAK-200S significantly increased the induction of protein-linked DNA breaks. PAK-200S did not alter nuclear topoisomerase I-mediated ex vivo pBR322 DNA plasmid unwinding activity and topoisomerase-I protein expression. These results suggest that reversal of P-gp-mediated resistance to topotecan by PAK-200S was related to the restoration of cellular drug concentrations of the active lactone form of topotecan rather than a direct effect on topoisomerase-I function. © 1999 Cancer Research Campaig