Concurreny based transition refinement for the verification of distributed algorithms

We suggest a new notion of behaviour preserving transition refinement based on partial order semantics. This notion is called transition refinement. We introduced transition refinement for elementary (low-level) Petri Nets earlier. For modelling and verifying complex distributed algorithms, high-level (Algebraic) Petri nets are usually used. In this paper, we define transition refinement for Algebraic Petri Nets. This notion is more powerful than transition refinement for elementary Petri nets because it corresponds to the simultaneous refinement of several transitions in an elementary Petri net. Transition refinement is particularly suitable for refinement steps that increase the degree of distribution of an algorithm, e.g. when synchronous communication is replaced by asynchronous message passing. We study how to prove that a replacement of a transition is a transition refinement.

Multi-fluorescent silica colloids for encoding large combinatorial libraries

Large chemical libraries can be synthesized on solid-support beads by the combinatorial split-and-mix method. A major challenge associated with this type of library synthesis is distinguishing between the beads and their attached compounds. A new method of encoding these solid-support beads, 'colloidal bar-coding', involves attaching fluorescent silica colloids ('reporters') to the beads as they pass through the compound synthesis, thereby creating a fluorescent bar code on each bead. In order to obtain sufficient reporter varieties to bar code extremely large libraries, many of the reporters must contain multiple fluorescent dyes. We describe here the synthesis and spectroscopic analysis of various mono- and multi-fluorescent silica particles for this purpose. It was found that by increasing the amount of a single dye introduced into the particle reaction mixture, mono- fluorescent silica particles of increasing intensities could be prepared. This increase was highly reproducible and was observed for six different fluorescent dyes. Multi-fluorescent silica particles containing up to six fluorescent dyes were also prepared. The resultant emission intensity of each dye in the multi-fluorescent particles was found to be dependent upon a number of factors; the hydrolysis rate of each silane-dye conjugate, the magnitude of the inherent emission intensity of each dye within the silica matrix, and energy transfer effects between dyes. We show that by varying the relative concentration of each silane-dye conjugate in the synthesis of multi-fluorescent particles, it is possible to change and optimize the resultant emission intensity of each dye to enable viewing in a fluorescence detection instrument.

Materialized view selection under the maintenance time constraint

A data warehouse is a data repository which collects and maintains a large amount of data from multiple distributed, autonomous and possibly heterogeneous data sources. Often the data is stored in the form of materialized views in order to provide fast access to the integrated data. One of the most important decisions in designing a data warehouse is the selection of views for materialization. The objective is to select an appropriate set of views that minimizes the total query response time with the constraint that the total maintenance time for these materialized views is within a given bound. This view selection problem is totally different from the view selection problem under the disk space constraint. In this paper the view selection problem under the maintenance time constraint is investigated. Two efficient, heuristic algorithms for the problem are proposed. The key to devising the proposed algorithms is to define good heuristic functions and to reduce the problem to some well-solved optimization problems. As a result, an approximate solution of the known optimization problem will give a feasible solution of the original problem. (C) 2001 Elsevier Science B.V. All rights reserved.

Mathematical methods for spatially cohesive reserve design

The problem of designing spatially cohesive nature reserve systems that meet biodiversity objectives is formulated as a nonlinear integer programming problem. The multiobjective function minimises a combination of boundary length, area and failed representation of the biological attributes we are trying to conserve. The task is to reserve a subset of sites that best meet this objective. We use data on the distribution of habitats in the Northern Territory, Australia, to show how simulated annealing and a greedy heuristic algorithm can be used to generate good solutions to such large reserve design problems, and to compare the effectiveness of these methods.

Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII

The selection, synthesis and chromatographic evaluation of a synthetic affinity adsorbent for human recombinant factor VIIa is described. The requirement for a metal ion-dependent immunoadsorbent step in the purification of the recombinant human clotting factor, FVIIa, has been obviated by using the X-ray crystallographic structure of the complex of tissue factor (TF) and Factor VIIa and has directed our combinatorial approach to select, synthesise and evaluate a rationally-selected affinity adsorbent from a limited library of putative ligands. The selected and optimised ligand comprises a triazine scaffold bis-substituted with 3-aminobenzoic acid and has been shown to bind selectively to FVIIa in a Ca2+-dependent manner. The adsorbent purifies FVIIa to almost identical purity (>99%), yield (99%), activation/degradation profile and impurity content (∼1000 ppm) as the current immunoadsorption process, while displaying a 10-fold higher static capacity and substantially higher reusability and durability. © 2002 Elsevier Science B.V. All rights reserved.

Interval training program optimization in highly trained endurance cyclists

Purpose: The purpose of this study was to examine the influence of three different high-intensity interval training (HIT) regimens on endurance performance in highly trained endurance athletes. Methods: Before, and after 2 and 4 wk of training, 38 cyclists and triathletes (mean +/- SD; age = 25 +/- 6 yr; mass = 75 +/- 7 kg; (V)over dot O-2peak = 64.5 +/- 5.2 mL.kg(-1).min(-1)) performed: 1) a progressive cycle test to measure peak oxygen consumption ((V)over dotO(2peak)) and peak aerobic power output (PPO), 2) a time to exhaustion test (T-max) at their (V)over dotO(2peak) power output (P-max), as well as 3) a 40-kin time-trial (TT40). Subjects were matched and assigned to one of four training groups (G(1), N = 8, 8 X 60% T-max P-max, 1:2 work:recovery ratio; G(2), N = 9, 8 X 60% T-max at P-max, recovery at 65% HRmax; G(3), N = 10, 12 X 30 s at 175% PPO, 4.5-min recovery; G(CON), N = 11). In addition to G(1) G(2), and G(3) performing HIT twice per week, all athletes maintained their regular low-intensity training throughout the experimental period. Results: All HIT groups improved TT40 performance (+4.4 to +5.8%) and PPO (+3.0 to +6.2%) significantly more than G(CON) (-0.9 to + 1.1 %; P < 0.05). Furthermore, G(1) (+5.4%) and G(2) (+8.1%) improved their (V)over dot O-2peak significantly more than G(CON) (+ 1.0%; P < 0.05). Conclusion: The present study has shown that when HIT incorporates P-max as the interval intensity and 60% of T-max as the interval duration, already highly trained cyclists can significantly improve their 40-km time trial performance. Moreover, the present data confirm prior research, in that repeated supramaximal HIT can significantly improve 40-km time trial performance.

Exploring privileged structures: the combinatorial synthesis of cyclic peptides

Head-to-tail cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. They may therefore be considered to be privileged structures. This review outlines the strategies by which both macrocyclic cyclic peptides and cyclic dipeptides or diketopiperazines have been synthesised in combinatorial libraries. It also briefly outlines some of the biological applications of these molecules, thereby justifying their inclusion as privileged structures.