Near-optimal design of Global Positioning System (GPS) networks using the Tabu Search technique

This paper describes an optimization technique based on an heuristic procedure which is applied to analyse and improve the efficiency of the design of Global Positioning System (GPS) surveying networks. GPS is a valuable survey tool because of its ability to increase the accuracy, speed and flexibility of a survey. A GPS network can be defined as a number of stations, which are co-ordinated by a series of sessions, formed by placing receivers on stations. The goal is to select the best order in which these sessions can be organised to give the best possible schedule. Generally, solving large networks to optimality requires impractical computational time. This paper proposes a Tabu Search technique which provides optimal or near-optimal solutions for large networks with an acceptable amount of computational effort. Computational results for several case studies with known and unknown optimal schedules have been presented to assess the performance of the proposed technique.     

The de novo design of median molecules within a property range of interest

Summary In this paper an application is presented of the median molecule workflow to the de novo design of novel molecular entities with a property profile of interest. Median molecules are structures that are optimised to be similar to a set of existing molecules of interest as an approach for lead exploration and hopping. An overview of this workflow is provided together with an example of an instance using the similarity to camphor and menthol as objectives. The methodology of the experiments is defined and the workflow is applied to designing novel molecules for two physical property datasets: mean molecular polarisability and aqueous solubility. This paper concludes with a discussion of the characteristics of this method.     

Optimisation of the connection between TA-MS systems together with improved data interpretation for TA-MS applications

TA-MS provides chemical and thermal response information. In order for this information to be meaningful sampling must be performed with minimum dead volume and without cold spots. Dead volume leads to response lag and peak broadening. Cold spots result in sample condensation, leading to inaccurate data and potentially inlet blockage. This paper describes a hot zone inlet system and 'in-situ' probe both of which provide fast response, zero dead volume sampling directly to the MS. The paper also discusses data interpretation methodologies and introduces 'soft ionisation' as a means of providing simplified analysis of complex mixtures. This revised version was published online in July 2006 with corrections to the Cover Date.     

Separation of chlamydosporol epimers by reversed-phase HPLC using commercial solvent optimisation software

Summary Two epimers of the mycotoxin chlamydosporol were separated by HPLC on an RP-18 column using a quaternary mobile phase consisting of water (79.1%), methanol (10.0%), acetonitrile (10.4%) and tetrahydrofuran (0.5%), with a flow rate of 1 ml min^–1. This optimal composition of mobile phase, with which the resolution value for the two epimers (1 and2) was 2.73 with retention times of 5.88 and 7.12 min, respectively, was achieved by the application of Philips Solvent Optimisation Software PU 6100. The presence of free silanols on the stationary phase was shown to be an essential requirement for the separation of the chlamydosporol epimers.     

Multivariate optimisation of the experimental conditions for determination of three methylxanthines by reversed-phase high-performance liquid chromatography

Caffeine (1,3,7-trimethylxanthine), theobromine (3,7-dimethylxanthine) and theophylline (1,3-dimethylxanthine) are the most important naturally occurring methylxanthines. Caffeine is a constituent of coffee and other beverage and included in many medicines. Theobromine and theophylline are formed as metabolites of caffeine in humans, and are also present in tea, cocoa and chocolate products.

In order to improve the chromatographic resolution (R_s) with a good analysis time, experimental designs were applied for multivariate optimisation of the experimental conditions of an isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method used for the simultaneous determination of caffeine, theobromine and theophylline. The optimisation process was carried out in two steps using full three-level factorial designs. The factors optimised were: flow rate and mobile phase composition. Optimal conditions for the separation of the three methylxanthines were obtained using a mixture of water/ethanol/acetic acid (75:24:1%, v/v/v) as mobile phase and a flow rate of 1.0 mL min⁻¹. The RP-HPLC/UV method was validated in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, recovery and the precision, calculated as relative standard deviation (R.S.D.). In these conditions, the LOD was 0.10 μg L⁻¹ for caffeine, 0.07 μg L⁻¹ for theobromine and 0.06 μg L⁻¹ for theophylline. The proposed method is fast, requires no extraction step or derivatization and was suitable for quantification of these methylxanthines in coffee, tea and human urine samples.     

Parallel iterative solution-phase synthesis of 5-amino-1-aryl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid amide derivatives

The parallel iterative solution-phase synthesis of 5-amino-1-aryl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid amide derivatives is described. The key intermediate 2,6-bis-aminopyridine-4-carboxylic acid methyl ester was synthesised in a two step procedure in 64% overall yield and elaborated to a variety of triazolopyridine-5-carboxylic acid methyl ester by selective pyridine-N-amination, condensation of the adduct with a wide selection of aldehydes and subsequent cyclisation and oxidation. The desired esters were obtained in yields up to 70%. The final transformation to the amide derivatives was accomplished by application of carefully optimised reaction conditions thus giving access to a library of total 500 triazolopyridine amide derivatives. Iterative synthetic cycles (12-48 library members each) allowing for maximal flexibility in chemistry and maximal efficiency in in vitro biological activity optimisation guided by molecular modelling efforts constitute a synergistic procedure for rapid lead optimisation.     

New Interfaces and Approaches to Machine Learning When Classifying Gestures within Music

Interactive music uses wearable sensors (i.e., gestural interfaces—GIs) and biometric datasets to reinvent traditional human–computer interaction and enhance music composition. In recent years, machine learning (ML) has been important for the artform. This is because ML helps process complex biometric datasets from GIs when predicting musical actions (termed performance gestures). ML allows musicians to create novel interactions with digital media. Wekinator is a popular ML software amongst artists, allowing users to train models through demonstration. It is built on the Waikato Environment for Knowledge Analysis (WEKA) framework, which is used to build supervised predictive models. Previous research has used biometric data from GIs to train specific ML models. However, previous research does not inform optimum ML model choice, within music, or compare model performance. Wekinator offers several ML models. Thus, we used Wekinator and the Myo armband GI and study three performance gestures for piano practice to solve this problem. Using these, we trained all models in Wekinator and investigated their accuracy, how gesture representation affects model accuracy and if optimisation can arise. Results show that neural networks are the strongest continuous classifiers, mapping behaviour differs amongst continuous models, optimisation can occur and gesture representation disparately affects model mapping behaviour; impacting music practice.     

The coordination of the catalytic zinc ion in alcohol dehydrogenase studied by combined quantum-chemical and molecular mechanics calculations

Summary The coordination number of the catalytic zinc ion in alcohol dehydrogenase has been studied by integrated ab initio quantum-chemical and molecular mechanics geometry optimisations involving the whole enzyme. A four-coordinate active-site zinc ion is 100–200 kJ/mol more stable than a five-coordinate one, depending on the ligands. The only stable binding site for a fifth ligand at the zinc ion is opposite to the normal substrate site, in a small cavity buried behind the zinc ion. The zinc coordination sphere has to be strongly distorted to accommodate a ligand in this site, and the ligand makes awkward contacts with surrounding atoms. Thus, the results do not support proposals attributing an important role to five-coordinate zinc complexes in the catalytic mechanism of alcohol dehydrogenase. The present approach makes it possible also to quantify the strain induced by the enzyme onto the zinc ion and its ligands; it amounts to 42–87 kJ/mol for four-coordinate active-site zinc ion complexes and 131–172 kJ/mol for five-coordinate ones. The four-coordinate structure with a water molecule bound to the zinc ion is about 20 kJ/mol less strained than the corresponding structure with a hydroxide ion, indicating that the enzyme does not speed up the reaction by forcing the zinc coordination sphere into a structure similar to the reaction intermediates.     

Evolutionary structural optimisation using an additive algorithm

The evolutionary structural optimisation (ESO) method has been under continuous development since 1992. Traditionally, the method was conceived from the engineering perspective that the topology and shape of structures were naturally conservative for safety reasons and therefore contained an excess of material. To move from the conservative design to a more optimum design would therefore involve the removal of material. Thus the ESO method started from a design space much bigger than the optimum and the final topology or shape emerged by a process of removal of unwanted/inefficient/lowly stresses material. The original algorithms allowed for two forms of evolution. One was there the understressed material could be removed from anywhere in the allowable design space, and with compensation for checker-boarding this produces an optimum topology under the prescribed environments. The second form only allows removal from the surface or parts of the surface (called nibbling in the ESO lexicon); this produces a Min–Max situation where the maximum surface stress is reduced to a minimum. It has been demonstrated that the ESO process produces a surface that is an iso-stress contour thus satisfying the Min–Max optimality criterion. The present paper addresses the opposite evolutionary process whereby the structure evolves from a base which is the minimum structural form required to carry the load regardless of the magnitude of the stress levels. Material is added in the proximity of high stress to ameliorate its effect and hence the final structural form emerges. Only singly connected regions are formed in the present analysis and thus the additive ESO process is the opposite of the nibbling SO, mentioned above, that produces optimum surface shapes. The paper presents a brief background to the current state of structural optimisation research. This is followed by a discussion of the strategies for the additive ESO (AESO) algorithm and two examples are presented.     

Sequential stopping rules for the multistart algorithm in global optimisation

In this paper a sequential stopping rule is developed for the Multistart algorithm. A statistical model for the values of the observed local maxima of an objective function is introduced in the framework of Bayesian non-parametric statistics. A suitablea-priori distribution is proposed which is general enough and which leads to computationally manageable expressions for thea-posteriori distribution. Sequential stopping rules of thek-step look-ahead kind are then explicitly derived, and their numerical effectiveness compared.