A subset-oriented algorithm for minimizing the number of steps required for synthesis of cyclic-peptide libraries

Libraries of cyclic peptides are being synthesized using combinatorial chemistry for high throughput screening in the drug discovery process. This paper describes the min_syn_steps.cpp program (available at http://www.imb.uq.edu.au/groups/smythe/tran), which after inputting a list of cyclic peptides to be synthesized, removes cyclic redundant sequences and calculates synthetic strategies which minimize the synthetic steps as well as the reagent requirements. The synthetic steps and reagent requirements could be minimized by finding common subsets within the sequences for block synthesis. Since a brute-force approach to search for optimum synthetic strategies is impractically large, a subset-orientated approach is utilized here to limit the size of the search. (C) 2002 Elsevier Science Ltd. All rights reserved.

FPGA field oriented control of an axial flux motor-in-wheel

This paper presents the design and the prototype implementation of a three-phase power inverter developed to drive a motor-in-wheel. The control system is implemented in a FPGA (Field Programmable Gate Array) device. The paper describes the Field Oriented Control (FOC) algorithm and the Space Vector Modulation (SVM) technique that were implemented. The control platform uses a Spartan-3E FPGA board, programmed with Verilog language. Simulation and experimental results are presented to validate the developed system operation under different load conditions. Finally are presented conclusions based on the experimental results.

Towards the design and implementation of aspect-oriented programming for spreadsheets

A spreadsheet usually starts as a simple and singleuser software artifact, but, as frequent as in other software systems, quickly evolves into a complex system developed by many actors. Often, different users work on different aspects of the same spreadsheet: while a secretary may be only involved in adding plain data to the spreadsheet, an accountant may define new business rules, while an engineer may need to adapt the spreadsheet content so it can be used by other software systems.Unfortunately,spreadsheetsystemsdonotoffermodular mechanisms, and as a consequence, some of the previous tasks may be defined by adding intrusive “code” to the spreadsheet. In this paper we go through the design and implementation of an aspect-oriented language for spreadsheets so that users can work on different aspects of a spreadsheet in a modular way. For example, aspects can be defined in order to introduce new business rules to an existing spreadsheet, or to manipulate the spreadsheet data to be ported to another system. Aspects are defined as aspect-oriented program specifications that are dynamically woven into the underlying spreadsheet by an aspect weaver. In this aspect-oriented style of spreadsheet development, differentusers develop,orreuse,aspects withoutaddingintrusive code to the original spreadsheet. Such code is added/executed by the spreadsheet weaving mechanism proposed in this paper.

Majorization arrow in quantum-algorithm design

We apply majorization theory to study the quantum algorithms known so far and find that there is a majorization principle underlying the way they operate. Grover's algorithm is a neat instance of this principle where majorization works step by step until the optimal target state is found. Extensions of this situation are also found in algorithms based in quantum adiabatic evolution and the family of quantum phase-estimation algorithms, including Shor's algorithm. We state that in quantum algorithms the time arrow is a majorization arrow.

EADock : design of a new molecular docking algorithm and some of its applications

3 Summary 3. 1 English The pharmaceutical industry has been facing several challenges during the last years, and the optimization of their drug discovery pipeline is believed to be the only viable solution. High-throughput techniques do participate actively to this optimization, especially when complemented by computational approaches aiming at rationalizing the enormous amount of information that they can produce. In siiico techniques, such as virtual screening or rational drug design, are now routinely used to guide drug discovery. Both heavily rely on the prediction of the molecular interaction (docking) occurring between drug-like molecules and a therapeutically relevant target. Several softwares are available to this end, but despite the very promising picture drawn in most benchmarks, they still hold several hidden weaknesses. As pointed out in several recent reviews, the docking problem is far from being solved, and there is now a need for methods able to identify binding modes with a high accuracy, which is essential to reliably compute the binding free energy of the ligand. This quantity is directly linked to its affinity and can be related to its biological activity. Accurate docking algorithms are thus critical for both the discovery and the rational optimization of new drugs. In this thesis, a new docking software aiming at this goal is presented, EADock. It uses a hybrid evolutionary algorithm with two fitness functions, in combination with a sophisticated management of the diversity. EADock is interfaced with .the CHARMM package for energy calculations and coordinate handling. A validation was carried out on 37 crystallized protein-ligand complexes featuring 11 different proteins. The search space was defined as a sphere of 15 R around the center of mass of the ligand position in the crystal structure, and conversely to other benchmarks, our algorithms was fed with optimized ligand positions up to 10 A root mean square deviation 2MSD) from the crystal structure. This validation illustrates the efficiency of our sampling heuristic, as correct binding modes, defined by a RMSD to the crystal structure lower than 2 A, were identified and ranked first for 68% of the complexes. The success rate increases to 78% when considering the five best-ranked clusters, and 92% when all clusters present in the last generation are taken into account. Most failures in this benchmark could be explained by the presence of crystal contacts in the experimental structure. EADock has been used to understand molecular interactions involved in the regulation of the Na,K ATPase, and in the activation of the nuclear hormone peroxisome proliferatoractivated receptors a (PPARa). It also helped to understand the action of common pollutants (phthalates) on PPARy, and the impact of biotransformations of the anticancer drug Imatinib (Gleevec®) on its binding mode to the Bcr-Abl tyrosine kinase. Finally, a fragment-based rational drug design approach using EADock was developed, and led to the successful design of new peptidic ligands for the a5ß1 integrin, and for the human PPARa. In both cases, the designed peptides presented activities comparable to that of well-established ligands such as the anticancer drug Cilengitide and Wy14,643, respectively. 3.2 French Les récentes difficultés de l'industrie pharmaceutique ne semblent pouvoir se résoudre que par l'optimisation de leur processus de développement de médicaments. Cette dernière implique de plus en plus. de techniques dites "haut-débit", particulièrement efficaces lorsqu'elles sont couplées aux outils informatiques permettant de gérer la masse de données produite. Désormais, les approches in silico telles que le criblage virtuel ou la conception rationnelle de nouvelles molécules sont utilisées couramment. Toutes deux reposent sur la capacité à prédire les détails de l'interaction moléculaire entre une molécule ressemblant à un principe actif (PA) et une protéine cible ayant un intérêt thérapeutique. Les comparatifs de logiciels s'attaquant à cette prédiction sont flatteurs, mais plusieurs problèmes subsistent. La littérature récente tend à remettre en cause leur fiabilité, affirmant l'émergence .d'un besoin pour des approches plus précises du mode d'interaction. Cette précision est essentielle au calcul de l'énergie libre de liaison, qui est directement liée à l'affinité du PA potentiel pour la protéine cible, et indirectement liée à son activité biologique. Une prédiction précise est d'une importance toute particulière pour la découverte et l'optimisation de nouvelles molécules actives. Cette thèse présente un nouveau logiciel, EADock, mettant en avant une telle précision. Cet algorithme évolutionnaire hybride utilise deux pressions de sélections, combinées à une gestion de la diversité sophistiquée. EADock repose sur CHARMM pour les calculs d'énergie et la gestion des coordonnées atomiques. Sa validation a été effectuée sur 37 complexes protéine-ligand cristallisés, incluant 11 protéines différentes. L'espace de recherche a été étendu à une sphère de 151 de rayon autour du centre de masse du ligand cristallisé, et contrairement aux comparatifs habituels, l'algorithme est parti de solutions optimisées présentant un RMSD jusqu'à 10 R par rapport à la structure cristalline. Cette validation a permis de mettre en évidence l'efficacité de notre heuristique de recherche car des modes d'interactions présentant un RMSD inférieur à 2 R par rapport à la structure cristalline ont été classés premier pour 68% des complexes. Lorsque les cinq meilleures solutions sont prises en compte, le taux de succès grimpe à 78%, et 92% lorsque la totalité de la dernière génération est prise en compte. La plupart des erreurs de prédiction sont imputables à la présence de contacts cristallins. Depuis, EADock a été utilisé pour comprendre les mécanismes moléculaires impliqués dans la régulation de la Na,K ATPase et dans l'activation du peroxisome proliferatoractivated receptor a (PPARa). Il a également permis de décrire l'interaction de polluants couramment rencontrés sur PPARy, ainsi que l'influence de la métabolisation de l'Imatinib (PA anticancéreux) sur la fixation à la kinase Bcr-Abl. Une approche basée sur la prédiction des interactions de fragments moléculaires avec protéine cible est également proposée. Elle a permis la découverte de nouveaux ligands peptidiques de PPARa et de l'intégrine a5ß1. Dans les deux cas, l'activité de ces nouveaux peptides est comparable à celles de ligands bien établis, comme le Wy14,643 pour le premier, et le Cilengitide (PA anticancéreux) pour la seconde.

Product information management system design framework for production oriented company

Diplomityössä luodaan viitekehys tuotetiedonhallintajärjestelmän esisuunnittelua varten. Siinä on kolme ulottuvuutta: lisäarvontuotto-, toiminnallisuus- ja ohjelmistoulottuvuus. Viitekehys auttaa- tunnistamaan lisäarvontuottokomponentit, joihin voidaan vaikuttaa tiettyjen ohjelmistoluokkien tarjoamilla tuotetiedonhallintatoiminnallisuuksilla. Viitekehyksen järjestelmäsuunnittelullista näkökulmaa hyödynnetään tutkittavissa yritystapauksissa perustuen laskentamatriisin muotoon mallinnettuihin ulottuvuuksien välisiin suhteisiin. Matriisiin syötetään lisäarvontuotto- ja toiminnallisuuskomponenttien saamat tärkeydet kohdeyrityksessä suoritetussa haastattelututkimuksessa. Matriisin tuotos on tietyn ohjelmiston soveltuvuus kyseisen yrityksen tapauksessa. Soveltuvuus on joukko tunnuslukuja, jotka analysoidaan tulostenkäsittelyvaiheessa. Soveltuvuustulokset avustavat kohdeyritystä sen valitessa lähestymistapaansa tuotetiedonhallintaan - ja kuvaavat esisuunnitellun tuotetiedonhallintajärjestelmän. Viitekehyksen rakentaminen vaatii perinpohjaisen lähestymistavan merkityksellisten lisäarvontuotto- ja toiminnallisuuskomponenttien sekä ohjelmistoluokkien määrittämiseen. Määritystyö perustuu työssä yksityiskohtaisesti laadittujen menetelmien ja komponenttiryhmitysten hyödyntämiselle. Kunkin alueen analysointi mahdollistaa viitekehyksen ja laskentamatriisin rakentamisen yhdenmukaisten määritysten perusteella. Viitekehykselle on ominaista sen muunneltavuus. Nykymuodossaan se soveltuu elektroniikka- ja high-tech yrityksille. Viitekehystä voidaan hyödyntää myös muilla toimialoilla muokkaamalla lisäarvontuottokomponentteja kunkin toimialan intressien mukaisesti. Vastaavasti analysoitava ohjelmisto voidaan valita tapauskohtaisesti. Laskentamatriisi on kuitenkin ensin päivitettävä valitun ohjelmiston kyvykkyyksillä, minkä jälkeen viitekehys voi tuottaa soveltuvuustuloksia kyseiseen yritystapaukseen perustuen

Design and Control of Permanent Magnet Synchronous Machine for Hybrid Electric Vehicle

This master’s thesis mainly focuses on the design requirements of an Electric drive for Hybrid car application and its control strategy to achieve a wide speed range. It also emphasises how the control and performance requirements are transformed into its design variables. A parallel hybrid topology is considered where an IC engine and an electric drive share a common crank shaft. A permanent magnet synchronous machine (PMSM) is used as an electric drive machine. Performance requirements are converted into Machine design variables using the vector model of PMSM. Main dimensions of the machine are arrived using analytical approach and Finite Element Analysis (FEA) is used to verify the design and performance. Vector control algorithm was used to control the machine. The control algorithm was tested in a low power PMSM using an embedded controller. A prototype of 10 kW PMSM was built according to the design values. The prototype was tested in the laboratory using a high power converter. Tests were carried out to verify different operating modes. The results were in agreement with the calculations.

A feature-based object-oriented expert system to model and support product design

In this paper a computer program to model and support product design is presented. The product is represented through a hierarchical structure that allows the user to navigate across the product’s components, and it aims at facilitating each step of the detail design process. A graphical interface was also developed, which shows visually to the user the contents of the product structure. Features are used as building blocks for the parts that compose the product, and object-oriented methodology was used as a means to implement the product structure. Finally, an expert system was also implemented, whose knowledge base rules help the user design a product that meets design and manufacturing requirements.

An Error-Localization, Validation and Optimization Tool for Embedded Code Augmentation: an Architecture Oriented Approach

Embedded systems are usually designed for a single or a specified set of tasks. This specificity means the system design as well as its hardware/software development can be highly optimized. Embedded software must meet the requirements such as high reliability operation on resource-constrained platforms, real time constraints and rapid development. This necessitates the adoption of static machine codes analysis tools running on a host machine for the validation and optimization of embedded system codes, which can help meet all of these goals. This could significantly augment the software quality and is still a challenging field.Embedded systems are usually designed for a single or a specified set of tasks. This specificity means the system design as well as its hardware/software development can be highly optimized. Embedded software must meet the requirements such as high reliability operation on resource-constrained platforms, real time constraints and rapid development. This necessitates the adoption of static machine codes analysis tools running on a host machine for the validation and optimization of embedded system codes, which can help meet all of these goals. This could significantly augment the software quality and is still a challenging field.Embedded systems are usually designed for a single or a specified set of tasks. This specificity means the system design as well as its hardware/software development can be highly optimized. Embedded software must meet the requirements such as high reliability operation on resource-constrained platforms, real time constraints and rapid development. This necessitates the adoption of static machine codes analysis tools running on a host machine for the validation and optimization of embedded system codes, which can help meet all of these goals. This could significantly augment the software quality and is still a challenging field.Embedded systems are usually designed for a single or a specified set of tasks. This specificity means the system design as well as its hardware/software development can be highly optimized. Embedded software must meet the requirements such as high reliability operation on resource-constrained platforms, real time constraints and rapid development. This necessitates the adoption of static machine codes analysis tools running on a host machine for the validation and optimization of embedded system codes, which can help meet all of these goals. This could significantly augment the software quality and is still a challenging field.This dissertation contributes to an architecture oriented code validation, error localization and optimization technique assisting the embedded system designer in software debugging, to make it more effective at early detection of software bugs that are otherwise hard to detect, using the static analysis of machine codes. The focus of this work is to develop methods that automatically localize faults as well as optimize the code and thus improve the debugging process as well as quality of the code.Validation is done with the help of rules of inferences formulated for the target processor. The rules govern the occurrence of illegitimate/out of place instructions and code sequences for executing the computational and integrated peripheral functions. The stipulated rules are encoded in propositional logic formulae and their compliance is tested individually in all possible execution paths of the application programs. An incorrect sequence of machine code pattern is identified using slicing techniques on the control flow graph generated from the machine code.An algorithm to assist the compiler to eliminate the redundant bank switching codes and decide on optimum data allocation to banked memory resulting in minimum number of bank switching codes in embedded system software is proposed. A relation matrix and a state transition diagram formed for the active memory bank state transition corresponding to each bank selection instruction is used for the detection of redundant codes. Instances of code redundancy based on the stipulated rules for the target processor are identified.This validation and optimization tool can be integrated to the system development environment. It is a novel approach independent of compiler/assembler, applicable to a wide range of processors once appropriate rules are formulated. Program states are identified mainly with machine code pattern, which drastically reduces the state space creation contributing to an improved state-of-the-art model checking. Though the technique described is general, the implementation is architecture oriented, and hence the feasibility study is conducted on PIC16F87X microcontrollers. The proposed tool will be very useful in steering novices towards correct use of difficult microcontroller features in developing embedded systems.

A Faster 2D Technique for the design of Combinational Digital Circuits Using Genetic Algorithm

Combinational digital circuits can be evolved automatically using Genetic Algorithms (GA). Until recently this technique used linear chromosomes and and one dimensional crossover and mutation operators. In this paper, a new method for representing combinational digital circuits as 2 Dimensional (2D) chromosomes and suitable 2D crossover and mutation techniques has been proposed. By using this method, the convergence speed of GA can be increased significantly compared to the conventional methods. Moreover, the 2D representation and crossover operation provides the designer with better visualization of the evolved circuits. In addition to this, a technique to display automatically the evolved circuits has been developed with the help of MATLAB

An Improved Design of Combinational Digital Circuits with Multiplexers using Genetic Algorithm

This paper presents a new approach to the design of combinational digital circuits with multiplexers using Evolutionary techniques. Genetic Algorithm (GA) is used as the optimization tool. Several circuits are synthesized with this method and compared with two design techniques such as standard implementation of logic functions using multiplexers and implementation using Shannon’s decomposition technique using GA. With the proposed method complexity of the circuit and the associated delay can be reduced significantly

Design, implementation and application of a generic framework for integrated regional land-use modeling

Land use is a crucial link between human activities and the natural environment and one of the main driving forces of global environmental change. Large parts of the terrestrial land surface are used for agriculture, forestry, settlements and infrastructure. Given the importance of land use, it is essential to understand the multitude of influential factors and resulting land use patterns. An essential methodology to study and quantify such interactions is provided by the adoption of land-use models. By the application of land-use models, it is possible to analyze the complex structure of linkages and feedbacks and to also determine the relevance of driving forces. Modeling land use and land use changes has a long-term tradition. In particular on the regional scale, a variety of models for different regions and research questions has been created. Modeling capabilities grow with steady advances in computer technology, which on the one hand are driven by increasing computing power on the other hand by new methods in software development, e.g. object- and component-oriented architectures. In this thesis, SITE (Simulation of Terrestrial Environments), a novel framework for integrated regional sland-use modeling, will be introduced and discussed. Particular features of SITE are the notably extended capability to integrate models and the strict separation of application and implementation. These features enable efficient development, test and usage of integrated land-use models. On its system side, SITE provides generic data structures (grid, grid cells, attributes etc.) and takes over the responsibility for their administration. By means of a scripting language (Python) that has been extended by language features specific for land-use modeling, these data structures can be utilized and manipulated by modeling applications. The scripting language interpreter is embedded in SITE. The integration of sub models can be achieved via the scripting language or by usage of a generic interface provided by SITE. Furthermore, functionalities important for land-use modeling like model calibration, model tests and analysis support of simulation results have been integrated into the generic framework. During the implementation of SITE, specific emphasis was laid on expandability, maintainability and usability. Along with the modeling framework a land use model for the analysis of the stability of tropical rainforest margins was developed in the context of the collaborative research project STORMA (SFB 552). In a research area in Central Sulawesi, Indonesia, socio-environmental impacts of land-use changes were examined. SITE was used to simulate land-use dynamics in the historical period of 1981 to 2002. Analogous to that, a scenario that did not consider migration in the population dynamics, was analyzed. For the calculation of crop yields and trace gas emissions, the DAYCENT agro-ecosystem model was integrated. In this case study, it could be shown that land-use changes in the Indonesian research area could mainly be characterized by the expansion of agricultural areas at the expense of natural forest. For this reason, the situation had to be interpreted as unsustainable even though increased agricultural use implied economic improvements and higher farmers' incomes. Due to the importance of model calibration, it was explicitly addressed in the SITE architecture through the introduction of a specific component. The calibration functionality can be used by all SITE applications and enables largely automated model calibration. Calibration in SITE is understood as a process that finds an optimal or at least adequate solution for a set of arbitrarily selectable model parameters with respect to an objective function. In SITE, an objective function typically is a map comparison algorithm capable of comparing a simulation result to a reference map. Several map optimization and map comparison methodologies are available and can be combined. The STORMA land-use model was calibrated using a genetic algorithm for optimization and the figure of merit map comparison measure as objective function. The time period for the calibration ranged from 1981 to 2002. For this period, respective reference land-use maps were compiled. It could be shown, that an efficient automated model calibration with SITE is possible. Nevertheless, the selection of the calibration parameters required detailed knowledge about the underlying land-use model and cannot be automated. In another case study decreases in crop yields and resulting losses in income from coffee cultivation were analyzed and quantified under the assumption of four different deforestation scenarios. For this task, an empirical model, describing the dependence of bee pollination and resulting coffee fruit set from the distance to the closest natural forest, was integrated. Land-use simulations showed, that depending on the magnitude and location of ongoing forest conversion, pollination services are expected to decline continuously. This results in a reduction of coffee yields of up to 18% and a loss of net revenues per hectare of up to 14%. However, the study also showed that ecological and economic values can be preserved if patches of natural vegetation are conservated in the agricultural landscape. -----------------------------------------------------------------------

Performance-Driven Microfabrication-Oriented Methodology for MEMS Conceptual Design with Application in Microfluidic Device Design

Performance and manufacturability are two important issues that must be taken into account during MEMS design. Existing MEMS design models or systems follow a process-driven design paradigm, that is, design starts from the specification of process sequence or the customization of foundry-ready process template. There has been essentially no methodology or model that supports generic, high-level design synthesis for MEMS conceptual design. As a result, there lacks a basis for specifying the initial process sequences. To address this problem, this paper proposes a performance-driven, microfabrication-oriented methodology for MEMS conceptual design. A unified behaviour representation method is proposed which incorporates information of both physical interactions and chemical/biological/other reactions. Based on this method, a behavioural process based design synthesis model is proposed, which exploits multidisciplinary phenomena for design solutions, including both the structural components and their configuration for the MEMS device, as well as the necessary substances for the chemical/biological/other reactions. The model supports both forward and backward synthetic search for suitable phenomena. To ensure manufacturability, a strategy of using microfabrication-oriented phenomena as design knowledge is proposed, where the phenomena are developed from existing MEMS devices that have associated MEMS-specific microfabrication processes or foundry-ready process templates. To test the applicability of the proposed methodology, the paper also studies microfluidic device design and uses a micro-pump design for the case study.

A genetic algorithm for the design of a fuzzy controller for active queue management

Active queue management (AQM) policies are those policies of router queue management that allow for the detection of network congestion, the notification of such occurrences to the hosts on the network borders, and the adoption of a suitable control policy. This paper proposes the adoption of a fuzzy proportional integral (FPI) controller as an active queue manager for Internet routers. The analytical design of the proposed FPI controller is carried out in analogy with a proportional integral (PI) controller, which recently has been proposed for AQM. A genetic algorithm is proposed for tuning of the FPI controller parameters with respect to optimal disturbance rejection. In the paper the FPI controller design metodology is described and the results of the comparison with random early detection (RED), tail drop, and PI controller are presented.

The systolic array genetic algorithm, an example of systolic arrays as a reconfigurable design methodology

We advocate the use of systolic design techniques to create custom hardware for Custom Computing Machines. We have developed a hardware genetic algorithm based on systolic arrays to illustrate the feasibility of the approach. The architecture is independent of the lengths of chromosomes used and can be scaled in size to accommodate different population sizes. An FPGA prototype design can process 16 million genes per second.