Evaluation of an awareness distribution mechanism: a simulation approach

In distributed software engineering, the role of informal communication is frequently overlooked. Participants simply employ their own ad-hoc methods of informal communication. Consequently such communication is haphazard, irregular, and rarely recorded as part of the project documentation. Thus, a need for tool support to facilitate more systematic informal communication via awareness has been identified. The tool proposed is based on the provision of awareness support that recognises the complete context of the evolution of software artefacts rather than single events. Peer-to-Peer (P2P) networking has been successfully employed to develop various distributed software engineering support tools. However, there are scalability problems inherent in naive P2P networks. To this end a semantic overlay network organisation algorithm has been developed and tested in simulation prior to deployment as part of a forthcoming awareness extension to the Eclipse environment. The simulation verified that the self-organisation algorithm was suitable for arranging a P2P network, but several unexpected behaviours were observed. These included wandering nodes, starved nodes, and local maxima. Each of these problems required modification of the original algorithm design to solve or ameliorate them

A survey of parallel execution strategies for transitive closure and logic programs

An important feature of database technology of the nineties is the use of parallelism for speeding up the execution of complex queries. This technology is being tested in several experimental database architectures and a few commercial systems for conventional select-project-join queries. In particular, hash-based fragmentation is used to distribute data to disks under the control of different processors in order to perform selections and joins in parallel. With the development of new query languages, and in particular with the definition of transitive closure queries and of more general logic programming queries, the new dimension of recursion has been added to query processing. Recursive queries are complex; at the same time, their regular structure is particularly suited for parallel execution, and parallelism may give a high efficiency gain. We survey the approaches to parallel execution of recursive queries that have been presented in the recent literature. We observe that research on parallel execution of recursive queries is separated into two distinct subareas, one focused on the transitive closure of Relational Algebra expressions, the other one focused on optimization of more general Datalog queries. Though the subareas seem radically different because of the approach and formalism used, they have many common features. This is not surprising, because most typical Datalog queries can be solved by means of the transitive closure of simple algebraic expressions. We first analyze the relationship between the transitive closure of expressions in Relational Algebra and Datalog programs. We then review sequential methods for evaluating transitive closure, distinguishing iterative and direct methods. We address the parallelization of these methods, by discussing various forms of parallelization. Data fragmentation plays an important role in obtaining parallel execution; we describe hash-based and semantic fragmentation. Finally, we consider Datalog queries, and present general methods for parallel rule execution; we recognize the similarities between these methods and the methods reviewed previously, when the former are applied to linear Datalog queries. We also provide a quantitative analysis that shows the impact of the initial data distribution on the performance of methods

AONT-LT: a Data Protection Scheme for Cloud and Cooperative Storage Systems

We propose a variant of the well-known AONT-RS scheme for dispersed storage systems. The novelty consists in replacing the Reed-Solomon code with rateless Luby transform codes. The resulting system, named AONT-LT, is able to improve the performance by dispersing the data over an arbitrarily large number of storage nodes while ensuring limited complexity. The proposed solution is particularly suitable in the case of cooperative storage systems. It is shown that while the AONT-RS scheme requires the adoption of fragmentation for achieving widespread distribution, thus penalizing the performance, the new AONT-LT scheme can exploit variable length codes which allow to achieve very good performance and scalability.Comment: 6 pages, 8 figures, to be presented at the 2014 High Performance Computing & Simulation Conference (HPCS 2014) - Workshop on Security, Privacy and Performance in Cloud Computin

Visualising the structure of document search results: A comparison of graph theoretic approaches

This is the post-print of the article - Copyright @ 2010 Sage PublicationsPrevious work has shown that distance-similarity visualisation or ‘spatialisation’ can provide a potentially useful context in which to browse the results of a query search, enabling the user to adopt a simple local foraging or ‘cluster growing’ strategy to navigate through the retrieved document set. However, faithfully mapping feature-space models to visual space can be problematic owing to their inherent high dimensionality and non-linearity. Conventional linear approaches to dimension reduction tend to fail at this kind of task, sacrificing local structural in order to preserve a globally optimal mapping. In this paper the clustering performance of a recently proposed algorithm called isometric feature mapping (Isomap), which deals with non-linearity by transforming dissimilarities into geodesic distances, is compared to that of non-metric multidimensional scaling (MDS). Various graph pruning methods, for geodesic distance estimation, are also compared. Results show that Isomap is significantly better at preserving local structural detail than MDS, suggesting it is better suited to cluster growing and other semantic navigation tasks. Moreover, it is shown that applying a minimum-cost graph pruning criterion can provide a parameter-free alternative to the traditional K-neighbour method, resulting in spatial clustering that is equivalent to or better than that achieved using an optimal-K criterion

Development and prospective application of chemoinformatic tools to explore new ligand chemistry and protein biology

Drug discovery and design is a tedious and expensive process whose small chances of success necessitates the development of novel chemoinformatic approaches and concepts. Their common goal is the efficient and robust identification of promising chemical matter and the reliable prediction of its properties. Computer-aided drug discovery and design (CADDD) and its multifarious installments throughout the different phases of the drug discovery pipeline contribute significantly to the expansion of the hits, the understanding of their structure-activity relationship and their rational diversification. They alleviate the development’s costs and its time-demand thus support the search for the needle in the haystack – a potent hit. The HTS-driven brute-force nature of current and of the decades’ past discovery and design strategies compelled researchers to develop ideas and algorithms in order to interfere with the pipeline and prevent its frequent failures. In the introduction, I describe the drug discovery and design pipeline and point out interfaces where CADDD contributes to its success. In Part 1 of this thesis, I present a novel methodology that supports the early-stage hit discovery processes through a fragment-based reduced graph similarity approach (RedFrag). It is a chimeric algorithm that combines fingerprint-based similarity calculation with scaffold-hopping-enabling graph isomorphism. We thoroughly investigated its performance retro- and prospectively. It uses a new type of reduced graph that does not suffer from information loss during its construction and bypasses the necessity of feature definitions. Built upon chemical epitopes resulting from molecule fragmentation, the reduced graph embodies physico-chemical and 2D-structural properties of a molecule. Reduced graphs are compared with a continuous-similarity-distance-driven maximal common subgraph algorithm, which calculates similarity at the fragmental and topological levels. The second chapter, Part 2, is dedicated to PrenDB: A digital compendium of the reaction space of prenyltransferases of the dimethylallyltryptophan synthase (DMATS) superfamily. Their catalytical transformations represent a major skeletal diversification step in the biosynthesis of secondary metabolites including the indole alkaloids. DMATS enzymes thus contribute significantly to the biological and pharmacological diversity of small molecule metabolites. The attachment of the prenyl donor to lead- or drug-like molecules renders the prenyltransferases useful in the access of chemical space that is difficult to reach by conventional synthesis. In PrenDB, we collected the substrates, enzymes and products. We then used a newly developed algorithm based on molecular fragmentation to automatically extract reactive chemical epitopes. The analysis of the collected data sheds light on the thus far explored substrate space of DMATS enzymes. We supplemented the browsable database with algorithmic prediction routines in order to assess the prenylability of novel compounds and did so for a set of 38 molecules. In a case study, Part 3, we investigated the regioselectivity of five prenyltransferases in the presence of unnatural prenyl donors. Detailed biochemical investigations revealed the acceptance of these dimethylallyl pyrophosphate (DMAPP) analogs by all tested enzymes with different relative activities and regioselectivities. In order to understand the activity profiles and their differences on a molecular level we investigated the interaction within the enzyme-prenyl donor-substrate system with molecular dynamics. Our experiments show that the reactivity of a prenyl donor strongly correlates with the distance of its electrophilic, reactive atom and the nucleophilic center of the substrate molecule. It renders the first step towards a better mechanistic understanding of the reactivity of prenyltransferases and expands significantly the potential usage and rational design of tryptophan prenylating enzymes as biocatalysts for Friedel–Crafts alkylation. Lastly, in Part 4, we present the synergistic potential of combined ligand- and structure-based drug discovery methodologies applied to the β2-adrenergic receptor (β2AR). The β2AR is a G protein-coupled receptor (GPCR) and a well-explored target. By the joint application of fingerprint-based similarity, substructure-based searches and docking we discovered 13 ligands – ten of which were novel – of this particular GPCR. Of note, two of the molecules used as starting points for the similarity and substructure searches distinguish themselves from other β2AR antagonists by their unique scaffold. Thus, the usage of a multistep hierarchical or parallel screening approach enabled us to use these unique structural features and discover novel chemical matter beyond the bounds of the ligand space known so far and emphasize the intrinsic complementarity of ligand- and structure-based approaches. The molecules described in this work allow us to explore the ligand space around the previously reported molecules in greater detail, leading to insights into their structure-activity relationship. In addition, we also characterized our hits with experimental binding and selectivity data and discussed it based on their putative binding modes derived by docking