Searching oligo sets of human chromosome 12 using evolutionary strategies

DNA Microarray is a powerful tool to measure the level of a mixed population of nucleic acids at one time, which has great impact in many aspects of life sciences research. In order to distinguish nucleic acids with very similar composition by hybridization, it is necessary to design microarray probes with high specificities and sensitivities. Highly specific probes correspond to probes having unique DNA sequences; whereas highly sensitive probes correspond to those with melting temperature within a desired range and having no secondary structure. The selection of these probes from a set of functional DNA sequences (exons) constitutes a computationally expensive discrete non-linear search problem. We delegate the search task to a simple yet effective Evolution Strategy algorithm. The computational efficiency is also greatly improved by making use of an available bioinformatics tool.

Potent cyclic antagonists of the complement C5a receptor on human polymorphonulcear leukocytes. Relationships between structures and activity

Human C5a is a plasma protein with potent chemoattractant and pro-inflammatory properties, and its overexpression correlates with severity of inflammatory diseases. C5a binds to its G protein-coupled receptor (C5aR) on polymorphonuclear leukocytes (PMNLs) through a high-affinity helical bundle and a low-affinity C terminus, the latter being solely responsible for receptor activation. Potent and selective C5a antagonists are predicted to be effective anti-inflammatory drugs, but no pharmacophore for small molecule antagonists has yet been developed, and it would significantly aid drug design. We have hypothesized that a turn conformation is important for activity of the C terminus of C5a and herein report small cyclic peptides that are stable turn mimics with potent antagonism at C5aR on human PMNLs. A comparison of solution structures for the C terminus of C5a, small acyclic peptide ligands, and cyclic antagonists supports the importance of a turn for receptor binding. Competition between a cyclic antagonist and either C5a or an acyclic agonist for C5aR on PMNLs supports a common or overlapping binding site on the C5aR. Structure-activity relationships for 60 cyclic analogs were evaluated by competitive radioligand binding with C5a (affinity) and myeloperoxidase release (antagonist potency) from human PMNLs, with 20 compounds having high antagonist potencies (IC50, 20 nM(-1) muM). Computer modeling comparisons reveal that potent antagonists share a common cyclic backbone shape, with affinity-determining side chains of defined volume projecting from the cyclic scaffold. These results define a new pharmacophore for C5a antagonist development and advance our understanding of ligand recognition and receptor activation of this G protein-coupled receptor.

A multiresolution terrain model for efficient visualization query processing

Multiresolution Triangular Mesh (MTM) models are widely used to improve the performance of large terrain visualization by replacing the original model with a simplified one. MTM models, which consist of both original and simplified data, are commonly stored in spatial database systems due to their size. The relatively slow access speed of disks makes data retrieval the bottleneck of such terrain visualization systems. Existing spatial access methods proposed to address this problem rely on main-memory MTM models, which leads to significant overhead during query processing. In this paper, we approach the problem from a new perspective and propose a novel MTM called direct mesh that is designed specifically for secondary storage. It supports available indexing methods natively and requires no modification to MTM structure. Experiment results, which are based on two real-world data sets, show an average performance improvement of 5-10 times over the existing methods.

Direct mesh: A multiresolution approach to terrain visualization

Terrain can be approximated by a triangular mesh consisting millions of 3D points. Multiresolution triangular mesh (MTM) structures are designed to support applications that use terrain data at variable levels of detail (LOD). Typically, an MTM adopts a tree structure where a parent node represents a lower-resolution approximation of its descendants. Given a region of interest (ROI) and a LOD, the process of retrieving the required terrain data from the database is to traverse the MTM tree from the root to reach all the nodes satisfying the ROI and LOD conditions. This process, while being commonly used for multiresolution terrain visualization, is inefficient as either a large number of sequential I/O operations or fetching a large amount of extraneous data is incurred. Various spatial indexes have been proposed in the past to address this problem, however level-by-level tree traversal remains a common practice in order to obtain topological information among the retrieved terrain data. A new MTM data structure called direct mesh is proposed. We demonstrate that with direct mesh the amount of data retrieval can be substantially reduced. Comparing with existing MTM indexing methods, a significant performance improvement has been observed for real-life terrain data.

Reflective web interface agent

Web interface agent is used with web browsers to assist users in searching and interactions with the WWW. It is used for a variety of purposes, such as web-enabled remote control, web interactive visualization, and e-commerce activities. User may be aware or unaware of its existence. The intelligence of interface agent consists in its capability of learning and decision-making in performing interactive functions on behalf of a user. However, since web is an open system environment, the reasoning mechanism in an agent should be able to adapt changes and make decisions on exceptional situations, and therefore use meta knowledge. This paper proposes a framework of Reflective Web Interface Agent (RWIA) that is to provide causal connections between the application interfaces and the knowledge model of the interface agent. A prototype is also implemented for the purpose of demonstration.

Maintaining human agency in the design on context-aware systems: Design games in a dental surgery

This paper describes a series of design games, specifically aimed at exploring shifts in human agency in order to inform the design of context-aware applications. The games focused on understanding information handling issues in dental practice with participants from a university dental school playing an active role in the activities. Participatory design activities help participants to reveal potential implicit technical resources that can be presented explicitly in technologies in order to assist humans in managing their interactions with and amidst technical systems gracefully.