Classification and analysis of integrating frameworks in multiscale modelling

Chemical engineers are turning to multiscale modelling to extend traditional modelling approaches into new application areas and to achieve higher levels of detail and accuracy. There is, however, little advice available on the best strategy to use in constructing a multiscale model. This paper presents a starting point for the systematic analysis of multiscale models by defining several integrating frameworks for linking models at different scales. It briefly explores how the nature of the information flow between the models at the different scales is influenced by the choice of framework, and presents some restrictions on model-framework compatibility. The concepts are illustrated with reference to the modelling of a catalytic packed bed reactor. (C) 2004 Elsevier Ltd. All rights reserved.

The measurement of nicotine in human plasma by high-performance liquid chromatography-electrospray-tandem mass spectrometry

The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 muL) with added deuterium-labeled d(3)-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 mL) followed by back-extraction into 0.1% formic acid (50 muL). Chromatography was performed on a phenyl Novapak column with a mobile phase consisting of 50% 10 mM ammonium fortriate (pH 3.3) and acetonitrile (50:50, vol/vol). A flow rate of 0.2 mL/min resulted in a total analysis time of 5 minutes per sample. Mass spectrometric detection was by selected reactant monitoring (nicotine m/z 163.2 --> 130.2; IS m/z 166.2 --> 87.2). The assay was linear from 0.5 to 100 mug/L (r > 0.993, n = 9). The accuracy and imprecision of the method for quality control sampleswere 87.5% to 113% and < 10.2%, respectively. Interday accuracy and imprecision at the limit of quantification (0.5 mug/L) was 113% and 7.2% (n = 4). The process efficiency for nicotine in plasma was > 75%. The method described has good process efficiency, stabilized nicotine, avoided concentration steps, and most importantly minimized potential contamination. Further, we have established that water-based standards and controls are interchangeable with plasma-based samples. This method was used successfully to measure the pharmacokinetic profiles of subjects involved in the development of an aerosol inhalation drug delivery system.

Transcriptional response of sugarcane roots to methyl jasmonate

The effect of methyl jasmonate treatment on gene expression in sugarcane roots signalling between roots and shoots was studied. A collection of 829 ESTs were obtained from sugarcane roots treated with the defence-regulator methyl jasmonate (MJ) treatment. A subset of 747 of these were combined with 4793 sugarcane ESTs obtained from stem tissues in a cDNA microarray and experiments undertaken to identify genes that were induced in roots 24-120 h following treatment with MJ. Two data analysis systems (t-statistic and tRMA) were used to analyse the microarray results and these methods identified a common set of 21 ESTs corresponding to transcripts significantly induced by MJ in roots and 23 that were reduced in expression following MJ treatment. The induction of six transcripts identified in the microarray analysis was tested and confirmed using northern blotting. Homologues of genes encoding lipoxygenase and PR-10 proteins were induced 824 It after MJ treatment while the other four selected transcripts were induced at later time points. Following treatment of roots with MJ, the lipoxygenase homologue, but not the PR-10 homologue, was induced in untreated stem and leaf tissues. The PR-10 homologue and a PR-1 homologue, but not the lipoxygenase homologue, were induced in untreated tissues after the application of SA to roots. Repeated foliar application of MJ had no apparent effects on plant growth and was demonstrated to increase lipoxygenase transcripts in roots, but did not increase transcript levels-of other genes tested. These results lay a foundation for further studies of induced pest and disease resistance in sugarcane roots. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Continuous variable tripartite entanglement from twin nonlinearities

In this work, we analyse and compare the continuous variable tripartite entanglement available from the use of two concurrent or cascaded X (2) nonlinearities. We examine both idealized travelling-wave models and more experimentally realistic intracavity models, showing that tripartite entangled outputs are readily producible. These may be a useful resource for applications such as quantum cryptography and teleportation.

Spatial indexing for scalability in FCA

The paper provides evidence that spatial indexing structures offer faster resolution of Formal Concept Analysis queries than B-Tree/Hash methods. We show that many Formal Concept Analysis operations, computing the contingent and extent sizes as well as listing the matching objects, enjoy improved performance with the use of spatial indexing structures such as the RD-Tree. Speed improvements can vary up to eighty times faster depending on the data and query. The motivation for our study is the application of Formal Concept Analysis to Semantic File Systems. In such applications millions of formal objects must be dealt with. It has been found that spatial indexing also provides an effective indexing technique for more general purpose applications requiring scalability in Formal Concept Analysis systems. The coverage and benchmarking are presented with general applications in mind.

Proteome analysis of extracellular proteins regulated by the las and rhl quorum sensing systems in Pseudomonas aeruginosa PAO1

The las and rhl quorum sensing (QS) systems regulate the expression of several genes in response to cell density changes in Pseudomonas aeruginosa. Many of these genes encode surface-associated or secreted virulence factors. Proteins from stationary phase culture supernatants were collected from wild-type and P. aeruginosa PAO1 mutants deficient in one or more of the lasRI, rhIRI and vfr genes and analysed using two-dimensional gel electrophoresis. All mutants released significantly lower amounts of protein than the wild-type. Protein spot patterns from each strain were compared using image analysis and visible spot differences were identified using mass spectrometry. Several previously unknown OS-regulated proteins were characterized, including an aminopeptidase (PA2939), an endoproteinase (PrpL) and a unique 'hypothetical' protein (PA0572), which could not be detected in the culture supernatants of Delta/as mutants, although they were unaffected in Deltarhl mutants. Chitin-binding protein (CbpD) and a hypothetical protein (PA4944) with similarity to host factor I (HF-1) could not be detected when any of the lasRI or rhIRI genes were disrupted. Fourteen proteins were present at significantly greater levels in the culture supernatants of OS mutants, suggesting that QS may also negatively control the expression of some genes. Increased levels of two-partner secretion exoproteins (PA0041 and PA4625) were observed and may be linked to increased stability of their cognate transporters in a CS-defective background. Known QS-regulated extracellular proteins, including elastase (lasB), LasA protease (lasA) and alkaline metalloproteinase (aprA) were also detected.

Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK

Objective: To evaluate the cost of atrial fibrillation (AF) to health and social services in the UK in 1995 and, based on epidemiological trends, to project this estimate to 2000. Design, setting, and main outcome measures: Contemporary estimates of health care activity related to AF were applied to the whole population of the UK on an age and sex specific basis for the year 1995. The activities considered ( and costs calculated) were hospital admissions, outpatient consultations, general practice consultations, and drug treatment ( including the cost of monitoring anticoagulant treatment). By adjusting for the progressive aging of the British population and related increases in hospital admissions, the cost of AF was also projected to the year 2000. Results: There were 534 000 people with AF in the UK during 1995. The direct'' cost of health care for these patients was pound 244 million (similar toE350 million) or 0.62% of total National Health Service ( NHS) expenditure. Hospitalisations and drug prescriptions accounted for 50% and 20% of this expenditure, respectively. Long term nursing home care after hospital admission cost an additional pound46.4 million (similar toE66 million). The direct cost of AF rose to pound459 million (similar toE655 million) in 2000, equivalent to 0.97% of total NHS expenditure based on 1995 figures. Nursing home costs rose to pound111 million (similar toE160 million). Conclusions: AF is an extremely costly public health problem.

Does pharmacogenomics provide an ethical challenge to the utilisation of cost-effectiveness analysis by public health systems?

Pharmacogenomics promotes an understanding of the genetic basis for differences in efficacy or toxicity of drugs in different individuals. Implementation of the outcomes of pharmacogenomic research into clinical practice presents a number of difficulties for healthcare. This paper aims to highlight one of the Unique ethical challenges which pharmacogenomics presents for the utilisation of cost-effectiveness analysis by public health systems. This paper contends that pharmacogenomics provides a challenge to fundamental principles which underlie most systems for deciding which drugs should be publicly subsidised. Pharmacogenomics brings into focus the conflict between equality and utility in the context of using cost-effectiveness analysis to aid distribution of a limited national drug budget.

A simulation model of cereal-legume intercropping systems for semi-arid regions II. Model application

Smallholder farmers in Africa practice traditional cropping techniques such as intercropping. Intercropping is thought to offer higher productivity and resource milisation than sole cropping. In this study, risk associated with maize-bean intercropping was evaluated by quantifying long-term yield in both intercropping and sole cropping in a semi-arid region of South Africa (Bloemfontein, Free State) with reference to rainfall variability. The crop simulation model was run with different cultural practices (planting date and plant density) for 52 summer crop growing seasons (1950/1951-2001/2002). Eighty-one scenarios, consisted of three levels of initial soil water, planting date, maize population, and bean population, were simulated. From the simulation outputs, the total land equivalent ratio (LER) was greater than one. The intercrop (equivalent to sole maize) had greater energy value (EV) than sole beans, and the intercrop (equivalent to sole beans) had greater monetary value (MV) than sole maize. From these results, it can be concluded that maize-bean intercropping is advantageous for this semi-arid region. Soil water at planting was the most important factor of all scenario factors, followed by planting date. Irrigation application at planting, November/December planting and high plant density of maize for EV and beans for MV can be one of the most effective cultural practices in the study region. With regard to rainfall variability, seasonal (October-April) rainfall positively affected EV and MV, but not LER. There was more intercrop production in La Nina years than in El Nino years. Thus, better cultural practices may be selected to maximize maize-bean intercrop yields for specific seasons in the semi-arid region based on the global seasonal outlook. (c) 2004 Elsevier B.V. All rights reserved.

Functional-structural plant modelling using a combination of architectural analysis, L-systems and a canonical model of function

This paper presents a new method for producing a functional-structural plant model that simulates response to different growth conditions, yet does not require detailed knowledge of underlying physiology. The example used to present this method is the modelling of the mountain birch tree. This new functional-structural modelling approach is based on linking an L-system representation of the dynamic structure of the plant with a canonical mathematical model of plant function. Growth indicated by the canonical model is allocated to the structural model according to probabilistic growth rules, such as rules for the placement and length of new shoots, which were derived from an analysis of architectural data. The main advantage of the approach is that it is relatively simple compared to the prevalent process-based functional-structural plant models and does not require a detailed understanding of underlying physiological processes, yet it is able to capture important aspects of plant function and adaptability, unlike simple empirical models. This approach, combining canonical modelling, architectural analysis and L-systems, thus fills the important role of providing an intermediate level of abstraction between the two extremes of deeply mechanistic process-based modelling and purely empirical modelling. We also investigated the relative importance of various aspects of this integrated modelling approach by analysing the sensitivity of the standard birch model to a number of variations in its parameters, functions and algorithms. The results show that using light as the sole factor determining the structural location of new growth gives satisfactory results. Including the influence of additional regulating factors made little difference to global characteristics of the emergent architecture. Changing the form of the probability functions and using alternative methods for choosing the sites of new growth also had little effect. (c) 2004 Elsevier B.V. All rights reserved.

Theory of strongly correlated electron systems. I. Intersite coulomb interaction and the approximation of renormalized fermions in total energy calculations

The diagrammatic strong-coupling perturbation theory (SCPT) for correlated electron systems is developed for intersite Coulomb interaction and for a nonorthogonal basis set. The construction is based on iterations of exact closed equations for many - electron Green functions (GFs) for Hubbard operators in terms of functional derivatives with respect to external sources. The graphs, which do not contain the contributions from the fluctuations of the local population numbers of the ion states, play a special role: a one-to-one correspondence is found between the subset of such graphs for the many - electron GFs and the complete set of Feynman graphs of weak-coupling perturbation theory (WCPT) for single-electron GFs. This fact is used for formulation of the approximation of renormalized Fermions (ARF) in which the many-electron quasi-particles behave analogously to normal Fermions. Then, by analyzing: (a) Sham's equation, which connects the self-energy and the exchange- correlation potential in density functional theory (DFT); and (b) the Galitskii and Migdal expressions for the total energy, written within WCPT and within ARF SCPT, a way we suggest a method to improve the description of the systems with correlated electrons within the local density approximation (LDA) to DFT. The formulation, in terms of renormalized Fermions LIDA (RF LDA), is obtained by introducing the spectral weights of the many electron GFs into the definitions of the charge density, the overlap matrices, effective mixing and hopping matrix elements, into existing electronic structure codes, whereas the weights themselves have to be found from an additional set of equations. Compared with LDA+U and self-interaction correction (SIC) methods, RF LDA has the advantage of taking into account the transfer of spectral weights, and, when formulated in terms of GFs, also allows for consideration of excitations and nonzero temperature. Going beyond the ARF SCPT, as well as RF LIDA, and taking into account the fluctuations of ion population numbers would require writing completely new codes for ab initio calculations. The application of RF LDA for ab initio band structure calculations for rare earth metals is presented in part 11 of this study (this issue). (c) 2005 Wiley Periodicals, Inc.

Improvement of the Derjaguin-Broekhoff-de Boer theory for capillary condensation/evaporation of nitrogen in mesoporous systems and its implications for pore size analysis of MCM-41 silicas and related materials

In this work, we propose an improvement of the classical Derjaguin-Broekhoff-de Boer (DBdB) theory for capillary condensation/evaporation in mesoporous systems. The primary idea of this improvement is to employ the Gibbs-Tolman-Koenig-Buff equation to predict the surface tension changes in mesopores. In addition, the statistical film thickness (so-called t-curve) evaluated accurately on the basis of the adsorption isotherms measured for the MCM-41 materials is used instead of the originally proposed t-curve (to take into account the excess of the chemical potential due to the surface forces). It is shown that the aforementioned modifications of the original DBdB theory have significant implications for the pore size analysis of mesoporous solids. To verify our improvement of the DBdB pore size analysis method (IDBdB), a series of the calcined MCM-41 samples, which are well-defined materials with hexagonally ordered cylindrical mesopores, were used for the evaluation of the pore size distributions. The correlation of the IDBdB method with the empirically calibrated Kruk-Jaroniec-Sayari (KJS) relationship is very good in the range of small mesopores. So, a major advantage of the IDBdB method is its applicability for small mesopores as well as for the mesopore range beyond that established by the KJS calibration, i.e., for mesopore radii greater than similar to4.5 nm. The comparison of the IDBdB results with experimental data reported by Kruk and Jaroniec for capillary condensation/evaporation as well as with the results from nonlocal density functional theory developed by Neimark et al. clearly justifies our approach. Note that the proposed improvement of the classical DBdB method preserves its original simplicity and simultaneously ensures a significant improvement of the pore size analysis, which is confirmed by the independent estimation of the mean pore size by the powder X-ray diffraction method.