Proceedings of the Eindhoven FASTAR Days 2004 : Eindhoven, The Netherlands, September 3-4, 2004

The Eindhoven FASTAR Days (EFD) 2004 were organized by the Software Construction group of the Department of Mathematics and Computer Science at the Technische Universiteit Eindhoven. On September 3rd and 4th 2004, over thirty participants|hailing from the Czech Republic, Finland, France, The Netherlands, Poland and South Africa|gathered at the Department to attend the EFD. The EFD were organized in connection with the research on finite automata by the FASTAR Research Group, which is centered in Eindhoven and at the University of Pretoria, South Africa. FASTAR (Finite Automata Systems|Theoretical and Applied Research) is an in- ternational research group that aims to lead in all areas related to finite state systems. The work in FASTAR includes both core and applied parts of this field. The EFD therefore focused on the field of finite automata, with an emphasis on practical aspects and applications. Eighteen presentations, mostly on subjects within this field, were given, by researchers as well as students from participating universities and industrial research facilities. This report contains the proceedings of the conference, in the form of papers for twelve of the presentations at the EFD. Most of them were initially reviewed and distributed as handouts during the EFD. After the EFD took place, the papers were revised for publication in these proceedings. We would like to thank the participants for their attendance and presentations, making the EFD 2004 as successful as they were. Based on this success, it is our intention to make the EFD into a recurring event. Eindhoven, December 2004 Loek Cleophas Bruce W. Watso

Proceedings of the Eindhoven FASTAR Days 2004 : Eindhoven, The Netherlands, September 3-4, 2004

The Eindhoven FASTAR Days (EFD) 2004 were organized by the Software Construction group of the Department of Mathematics and Computer Science at the Technische Universiteit Eindhoven. On September 3rd and 4th 2004, over thirty participants|hailing from the Czech Republic, Finland, France, The Netherlands, Poland and South Africa|gathered at the Department to attend the EFD. The EFD were organized in connection with the research on finite automata by the FASTAR Research Group, which is centered in Eindhoven and at the University of Pretoria, South Africa. FASTAR (Finite Automata Systems|Theoretical and Applied Research) is an in- ternational research group that aims to lead in all areas related to finite state systems. The work in FASTAR includes both core and applied parts of this field. The EFD therefore focused on the field of finite automata, with an emphasis on practical aspects and applications. Eighteen presentations, mostly on subjects within this field, were given, by researchers as well as students from participating universities and industrial research facilities. This report contains the proceedings of the conference, in the form of papers for twelve of the presentations at the EFD. Most of them were initially reviewed and distributed as handouts during the EFD. After the EFD took place, the papers were revised for publication in these proceedings. We would like to thank the participants for their attendance and presentations, making the EFD 2004 as successful as they were. Based on this success, it is our intention to make the EFD into a recurring event. Eindhoven, December 2004 Loek Cleophas Bruce W. Watso

Behaviour of NBD-head group labelled phosphatidylethanolamines in POPC bilayers: a molecular dynamics study

A complete homologous series of fluorescent phosphatidylethanolamines (diCnPE), labelled at the head group with a 7-nitrobenz-2-oxa-1,3-diazo-4-yl(NBD) fluorophore and inserted in 1-palmitoyl, 2-oleoyl-snglycero- 3-phosphocholine (POPC) bilayers, was studied using atomistic molecular dynamics simulations. The longer-chained derivatives of NBD-diCnPE, with n = 14, 16, and 18, are commercially available, and widely used as fluorescent membrane probes. Properties such as location of atomic groups and acyl chain order parameters of both POPC and NBD-diCnPE, fluorophore orientation and hydrogen bonding, membrane electrostatic potential and lateral diffusion were calculated for all derivatives in the series. Most of these probes induce local disordering of POPC acyl chains, which is on the whole counterbalanced by ordering resulting from binding of sodium ions to lipid carbonyl/glycerol oxygen atoms. An exception is found for NBD-diC16PE, which displays optimal matching with POPC acyl chain length and induces a slight local ordering of phospholipid acyl chains. Compared to previously studied fatty amines, acyl chain-labelled phosphatidylcholines, and sterols bearing the same fluorescent tag, the chromophore in NBD-diCnPE locates in a similar region of the membrane (near the glycerol backbone/carbonyl region) but adopts a different orientation (with the NO2 group facing the interior of the bilayer). This modification leads to an inverted orientation of the P–N axis in the labelled lipid, which affects the interface properties, such as the membrane electrostatic potential and hydrogen bonding to lipid head group atoms. The implications of this study for the interpretation of the photophysical properties of NBD-diCnPE (complex fluorescence emission kinetics, differences with other NBD lipid probes) are discussed

Structural aspects of molecular recognition

This thesis describes the design, implementation and application of a novel docking algorithm. Chapter 1 reviews some important facts about proteins and protein structure. Several molecular recognition systems are examined in detail. This Chapter also reviews a representative set of recent protein/protein docking methods and discusses their relative merits. Chapter 2 sets out the aims of the new docking algorithm, called DAPMatch, and gives full details of its implementation on a parallel architecture computer. The testing of the algorithm is also discussed. Subsequent chapters describe the application of the DAPMatch algorithm to a number of docking problems. DAPMatch is used to reconstruct the known structures of three antibody/lysozyme complexes, using the unbound structure of lysozyme. For the first time a model of the D1.3 antibody is used as a target molecule for a docking algorithm. These results are presented in Chapter 3 and analysed in detail to demonstrate their significance; non-native solutions are also examined. Chapter 4 describes the practical use of the DAPMatch algorithm in a modelling situation, to construct a hypothetical structure for the high molecular weight epidermal growth factor complex. Chapter 5 describes the adaptation of the DAPMatch algorithm to investigate α-helix/α-helix docking, and presents the results obtained. Chapter 6 explains the conclusions that were derived from this work, and suggests possible future enhancements to the algorithm

Alternative Splicing and Protein Structure Evolution

In den letzten Jahren gab es in verschiedensten Bereichen der Biologie einen dramatischen Anstieg verfügbarer, experimenteller Daten. Diese erlauben zum ersten Mal eine detailierte Analyse der Funktionsweisen von zellulären Komponenten wie Genen und Proteinen, die Analyse ihrer Verknüpfung in zellulären Netzwerken sowie der Geschichte ihrer Evolution. Insbesondere der Bioinformatik kommt hier eine wichtige Rolle in der Datenaufbereitung und ihrer biologischen Interpretation zu. In der vorliegenden Doktorarbeit werden zwei wichtige Bereiche der aktuellen bioinformatischen Forschung untersucht, nämlich die Analyse von Proteinstrukturevolution und Ähnlichkeiten zwischen Proteinstrukturen, sowie die Analyse von alternativem Splicing, einem integralen Prozess in eukaryotischen Zellen, der zur funktionellen Diversität beiträgt. Insbesondere führen wir mit dieser Arbeit die Idee einer kombinierten Analyse der beiden Mechanismen (Strukturevolution und Splicing) ein. Wir zeigen, dass sich durch eine kombinierte Betrachtung neue Einsichten gewinnen lassen, wie Strukturevolution und alternatives Splicing sowie eine Kopplung beider Mechanismen zu funktioneller und struktureller Komplexität in höheren Organismen beitragen. Die in der Arbeit vorgestellten Methoden, Hypothesen und Ergebnisse können dabei einen Beitrag zu unserem Verständnis der Funktionsweise von Strukturevolution und alternativem Splicing bei der Entstehung komplexer Organismen leisten wodurch beide, traditionell getrennte Bereiche der Bioinformatik in Zukunft voneinander profitieren können

Micromechanical study of two-phase flow during air sparging

Air sparging (AS) is an in-situ soil/groundwater remediation technology, which involves the injection of pressurized air/oxygen through an air sparging well below the region of contamination. The efficiency of the in-situ sparging system is mainly controlled by the extent of contact between injected air and contaminated soil and pore fluid. Hence, characterizing the mechanisms governing movement of air through saturated porous media is therefore critical to the design of an effective cleanup treatment. However, in spite of the success of air sparging as a remediation technique for the clean-up of contaminated soils, to date, the fundamental mechanisms or the physics of air flow through porous media are not well understood. In this research, the micro-mechanics of air sparging are studied in order to understand the physical processes of air migration and air spatial occurring on the pore scale during air sparging. First, the void space in the porous medium is characterized by pore network consisting of connected pore bodies by bonds. Two approaches of generating 3D stochastic pore networks were proposed. The first methodology is to directly extract pore structure from a computer simulated packing of spheres. The second methodology is to generate an equivalent 3D pore network of porous media, in which the centers of voids are located in a regular lattice with constant pore center distance. Both algorithms were validated by comparing the predicted permeability of randomly packed spherical particles with published experimental data. The results showed that the predicted permeability values were in good agreement with those measured, confirming that the proposed algorithms can capture the main geometrical information and the topological information of random packing of spheres. Secondly, based on the developed network model, a rule-based dynamic two-phase flow model was developed in order to study the dynamic flow properties of air water two-phase flow during air sparging. The rules for phase movement and redistribution are devised to honor the imbibition and drainage physics at pore scale. The system is forward integrated in time using the Euler scheme. For each time step, the distribution of the phases leads to a recalculation of the effective viscosities in the network, capillary pressures across the menisci, and thus the coefficients in the equations for the pressure field. When the pressure field is known, the flow field follows automatically and the integration step can be performed. Finally, the developed dynamic model was used to study the rate-dependent drainage process during air sparging. Two types of numerical tests were performed: one is with one-step air injection pressure while the other one is with multistep air injection pressures. During the two types of numerical tests, the effect of the capillary number and geometrical properties of the network on the dynamic flow properties of air water two-phase flow including residual saturation, changing rate of water/air saturation, air and water spatial distribution, dynamic phase transitions, nonwetting fractional flow, air and water relative permeability and capillary pressure curve were systematically investigated. The results show that all this information for describing the air water two-phase flow properties is not an intrinsic property of the porous medium, but on the contrary, it is affected by the air water flow rate and historical distribution of air water phase. It is also shown that the developed model can capture the dynamic effects on all these data. At the end of this research, two different ways of performing micro to macro level analysis to obtain the macro behaviors of air water two-phase flow by using micro-mechanics were also briefly discussed. In all, this research has laid substantial basis on understanding the mechanisms of the air water two-phase flow process during air sparging

Analysis of coding principles in the olfactory system and their application in cheminformatics

Unser Geruchssinn vermittelt uns die Wahrnehmung der chemischen Welt. Im Laufe der Evolution haben sich in unserem olfaktorischen System Mechanismen entwickelt, die wahrscheinlich optimal auf die Erfüllung dieser Aufgabe angepasst sind. Die Analyse dieser Verarbeitungsstrategien verspricht Einblicke in effiziente Algorithmen für die Kodierung und Verarbeitung chemischer Information, deren Entwicklung und Anwendung dem Kern der Chemieinformatik entspricht. In dieser Arbeit nähern wir uns der Entschlüsselung dieser Mechanismen durch die rechnerische Modellierung von funktionellen Einheiten des olfaktorischen Systems. Hierbei verfolgten wir einen interdisziplinären Ansatz, der die Gebiete der Chemie, der Neurobiologie und des maschinellen Lernens mit einbezieht

Structural decomposition and structural relaxation of solvation shells of hydrated molecular ionic liquids and protein solutions

Die vorliegende Arbeit liefert neue methodische Beitraege zur Untersuchung der Struktur und Dynamik von Biomolekuelen in Loesung mittels Voronoi-Analyse von Computersimulationen. Dabei werden sowohl kollektive wie auch Einteilchen-Eigenschaften der Solvathuellen und des Bulk-Mediums betrachtet. Als Modellproteine dienen Ubiquitin (PDB-code: 1UBQ), Calbindin (1CLB) und eine Phospholipase (2PLD) deren Solvatation in Wasser einen wesentlichen Bestandteil dieser Arbeit darstellt. Darueber hinaus werden Vorstudien zu Molekularen Ionischen Fluessigkeiten (MIL) angestellt die in den letzten Jahren unter anderem als umweltvertraegliche polare Loesungsmittel in den Vordergrund getreten sind. Trifluoroazetat-, Tetrafluoroborat- und Trifluoromethylsulfonat- Salze von alkyliertem Imidazolium werden einerseits in Reinform, andererseits in Mischung mit Wasser untersucht. Neu an dieser Arbeit ist zunaechst die Atom-aufgeloeste Tesselierung, die fuer Systeme mit 30000 Atomen mit periodischen Randbedingungen ueber hundertausende Zeitschritte sehr rechenintensiv, und daher nur durch die effiziente Implementierung geeigneter Algorithmen zu bewerkstelligen ist. Auf dieser Grundlage werden weitestgehend parameterfreie Ansaetze zur lokalen und globalen Strukturanalyse entwickelt die einerseits mit konventionellen Methoden wie etwa Radialen Verteilungsfunktionen und Orientierungskorrelationsfunktionen verglichen werden, andererseits zusaetzliche Moeglichkeiten der Interpretation bieten. Position und Orientierung von benachbarten Molekuelen kann direkt anhand von graphentheoretischen Interaktionen beschrieben und interpretiert werden. Ein Markov-Modell fuer die Dynamik innerhalb und zwischen einzelnen Solvathuellen wird entwickelt und auf MIL Systeme angewendet.The present work provides new methodical contributions to investigation of structural and dynamic behaviour of solvated biomolecules using Voronoi analysis of computer simulations. Thereby, collective as well as single particle properties of solvation shells and the bulk medium are considered. The three proteins ubiquitin (PDB-code: 1UBQ), calbindin (1CLB) and phospholipase (2PLD) serve as model systems. The study of their solvation in water is an integral part of this work. Moreover, preliminary studies of Molecular Ionic Liquids (MIL) are being made, that have come to the fore in recent years as environmentally compliant polar solvents. Alkylated imidazolium salts of Trifluoroacetate, Tetrafluoroborate and Trifluoromethylsulfonate are analysed in the pure form as well as mixed with water. For one thing, new in this work is the atom-resolved tesselation, that is computationally demanding for systems with about 30000 atoms and periodic boundary conditions over 100-thousands of time steps and hence is to be managed only by the efficient implementation of suitable algorithms. Widely parameter free approaches to local and global structure analysis are developed on this basis and compared to conventional methods like radial distribution functions and orientation correlation functions. Furthermore, they provide additional possibilities for interpretation. Position and orientation of neighbouring molecules can be described and interpreted directly by graph theoretical interactions. A Markov model for dynamics within and between solvation shells is being developed and applied to MIL systems

Computational methods for molecular docking

This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Recently, it has been demonstrated that the knowledge of the three-dimensional structure of the protein can be used to derive new protein ligands with improved binding properties. This tutorial focuses on the following questions: What is its binding affinity toward a particular receptor? What are putative conformations of a ligand at the binding site? What are the similarities of different ligands in terms of their recognition capabilities? Where and in which orientation will a ligand bind to the active site? How is a new putative protein ligand selected? An overview is presented of the algorithms which are presently used to handle and predict protein-ligand interactions and to dock small molecule ligands into proteins

Methods for Structural Pattern Recognition: Complexity and Applications

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