The formulation of artificial reference standards for use within the ELISPOT assay

Whether to assess the functionality of equipment or as a determinate for the accuracy of assays, reference standards are essential for the purposes of standardisation and validation. The ELISPOT assay, developed over thirty years ago, has emerged as a leading immunological assay in the development of novel vaccines for the assessment of efficacy. However, with its widespread use, there is a growing demand for a greater level of standardisation across different laboratories. One of the major difficulties in achieving this goal has been the lack of definitive reference standards. This is partly due to the ex vivo nature of the assay, which relies on cells being placed directly into the wells. Thus, the aim of this thesis was to produce an artificial reference standard using liposomes, for use within the assay. Liposomes are spherical bilayer vesicles with an enclosed aqueous compartment and therefore are models for biological membranes. Initial work examined pre-design considerations in order to produce an optimal formulation that would closely mimic the action of the cells ordinarily placed on the assay. Recognition of the structural differences between liposomes and cells led to the formulation of liposomes with increased density. This was achieved by using a synthesised cholesterol analogue. By incorporating this cholesterol analogue in liposomes, increased sedimentation rates were observed within the first few hours. The optimal liposome formulation from these studies was composed of 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and brominated cholesterol (Brchol) at a 16:4:12 µMol ratio, based on a significantly higher (p<0.01) sedimentation (as determined by a percentage transmission of 59 ± 5.9 % compared to the control formulation at 29 ± 12 % after four hours). By considering a range of liposome formulations ‘proof of principle’ for using liposomes as ELISPOT reference standards was shown; recombinant IFN? cytokine was successfully entrapped within vesicles of different lipid compositions, which were able to promote spot formation within the ELISPOT assay. Using optimised liposome formulations composed of phosphatidylcholine with or without cholesterol (16 µMol total lipid) further development was undertaken to produce an optimised, scalable protocol for the production of liposomes as reference standards. A linear increase in spot number by the manipulation of cytokine concentration and/or lipid concentrations was not possible, potentially due to the saturation that occurred within the base of wells. Investigations into storage of the formulations demonstrated the feasibility of freezing and lyophilisation with disaccharide cryoprotectants, but also highlighted the need for further protocol optimisation to achieve a robust reference standard upon storage. Finally, the transfer of small-scale production to a medium lab-scale batch (40 mL) demonstrated this was feasible within the laboratory using the optimised protocol.

Structural optimization

The non-linear programming algorithms for the minimum weight design of structural frames are presented in this thesis. The first, which is applied to rigidly jointed and pin jointed plane frames subject to deflexion constraints, consists of a search in a feasible design space. Successive trial designs are developed so that the feasibility and the optimality of the designs are improved simultaneously. It is found that this method is restricted lo the design of structures with few unknown variables. The second non-linear programming algorithm is presented .in a general form. This consists of two types of search, one improving feasibility and the other optimality. The method speeds up the 'feasible direction' approach by obtaining a constant weight direction vector that is influenced by dominating constraints. For pin jointed plane and space frames this method is used to obtain a 'minimum weight' design which satisfies restrictions on stresses and deflexions. The matrix force method enables the design requirements to be expressed in a general form and the design problem is automatically formulated within the computer. Examples are given to explain the method and the design criteria are extended to include member buckling. Fundamental theorems are proposed and proved to confirm that structures are inter-related. These theorems are applicable to linear elastic structures and facilitate the prediction of the behaviour of one structure from the results of analysing another, more general, or related structure. It becomes possible to evaluate the significance of each member in the behaviour of a structure and the problem of minimum weight design is extended to include shape. A method is proposed to design structures of optimum shape with stress and deflexion limitations. Finally a detailed investigation is carried out into the design of structures to study the factors that influence their shape.

Extreme events, organizations and the politics of decision making

Purpose – Threats of extreme events, such as terrorist attacks or infrastructure breakdown, are potentially highly disruptive events for all types of organizations. This paper seeks to take a political perspective to power in strategic decision making and how this influences planning for extreme events. Design/methodology/approach – A sample of 160 informants drawn from 135 organizations, which are part of the critical national infrastructure in the UK, forms the empirical basis of the paper. Most of these organizations had publicly placed business continuity and preparedness as a strategic priority. The paper adopts a qualitative approach, coding data from focus groups. Findings – In nearly all cases there is a pre-existing dominant coalition which keeps business continuity decisions off the strategic agenda. The only exceptions to this are a handful of organizations which provide continuous production, such as some utilities, where disruption to business as usual can be readily quantified. The data reveal structural and decisional elements of the exercise of power. Structurally, the dominant coalition centralizes control by ensuring that only a few functional interests participate in decision making. Research limitations/implications – Decisional elements of power emphasize the dominance of calculative rationality where decisions are primarily made on information and arguments which can be quantified. Finally, the paper notes the recursive aspect of power relations whereby agency and structure are mutually constitutive over time. Organizational structures of control are maintained, despite the involvement of managers charged with organizational preparedness and resilience, who remain outside the dominant coalition. Originality/value – The paper constitutes a first attempt to show how planning for emergencies fits within the strategy-making process and how politically controlled this process is.

Exchange rate exposure:do size and foreign operations matter?

Purpose – The purpose of this paper is to examine the effect of firm size and foreign operations on the exchange rate exposure of UK non-financial companies from January 1981 to December 2001. Design/methodology/approach – The impact of the unexpected changes in exchange rates on firms’ stock returns is examined. In addition, the movements in bilateral, equally weighted (EQW) and trade-weighted and exchange rate indices are considered. The sample is classified according to firm size and the extent of firms’ foreign operations. In addition, structural changes on the relationship between exchange rate changes and individual firms’ stock returns are examined over three sub-periods: before joining the exchange rate mechanism (pre-ERM), during joining the ERM (in-ERM), and after departure from the ERM (post-ERM). Findings – The findings indicate that a higher percentage of UK firms are exposed to contemporaneous exchange rate changes than those reported in previous studies. UK firms’ stock returns are more affected by changes in the EQW, and US$ European currency unit exchange rate, and respond less significantly to the basket of 20 countries’ currencies relative to the UK pound exchange rate. It is found that exchange rate exposure has a more significant impact on stock returns of the large firms compared with the small and medium-sized companies. The evidence is consistent across all specifications using different exchange rate. The results provide evidence that the proportion of significant foreign exchange rate exposure is higher for firms which generate a higher percentage of revenues from abroad. The sensitivities of firms’ stock returns to exchange rate fluctuations are most evident in the pre-ERM and post-ERM periods. Practical implications – This study provides important implications for public policymakers, financial managers and investors on how common stock returns of various sectors react to exchange rate fluctuations. Originality/value – The empirical evidence supports the view that UK firms’ stock returns are affected by foreign exchange rate exposure.

Improving recombinant human adenosine A2A receptor production in yeast

Over 50% of clinically-marketed drugs target membrane proteins; in particular G protein-coupled receptors (GPCRs). GPCRs are vital to living cells, performing an active role in many processes, making them integral to drug development. In nature, GPCRs are not sufficiently abundant for research and their structural integrity is often lost during extraction from cell membranes. The objectives of this thesis were to increase recombinant yield of the GPCR, human adenosine A2A receptor (hA2AR) by investigating bioprocess conditions in large-scale Pichia pastoris and small-scale Saccharomyces cerevisiae cultivations. Extraction of hA2AR from membranes using novel polymers was also investigated. An increased yield of hA2AR from P. pastoris was achieved by investigating the methanol feeding regime. Slow, exponential feed during induction (μlow) was compared to a faster, exponential feed (μhigh) in 35 L pilot-scale bioreactors. Overall hA2AR yields were increased for the μlow cultivation (536.4pmol g-1) compared to the μhigh148.1 pmol g-1. hA2AR levels were maintained in cytotoxic methanol conditions and unexpectedly, pre-induction levels of hA2AR were detected. Small-scale bioreactor work showed that Design of Experiments (DoE) could be applied to screen for bioprocess conditions to give optimal hA2AR yields. Optimal conditions were retrieved for S. cerevisiae using a d-optimal screen and response surface methodology. The conditions were 22°C, pH 6.0, 30% DO without dimethyl sulphoxide. A polynomial equation was generated to predict hA2AR yields if conditions varied. Regarding the extraction, poly (maleic anhydride-styrene) or PMAS was successful in solubilising hA2AR from P. pastoris membranes compared with dodcecyl-β-D-maltoside (DDM) detergent. Variants of PMAS worked well as solubilising agents with either 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or cholesteryl hemisuccinate (CHS). Moreover, esterification of PMAS improved solubilisation, suggesting that increased hydrophobicity stabilises hA2AR during extraction. Overall, hA2AR yields were improved in both, P. pastoris and S. cerevisiae and the use of novel polymers for efficient extraction was achieved.

Senior management leadership, social support, job design and stressor-to-strain relationships in hospital practice

Purpose: The purpose of this paper is to examine the effect of the quality of senior management leadership on social support and job design, whose main effects on strains, and moderating effects on work stressors-to-strains relationships were assessed. Design/methodology/approach: A survey involving distribution of questionnaires was carried out on a random sample of health care employees in acute hospital practice in the UK. The sample comprised 65,142 respondents. The work stressors tested were quantitative overload and hostile environment, whereas strains were measured through job satisfaction and turnover intentions. Structural equation modelling and moderated regression analyses were used in the analysis. Findings: Quality of senior management leadership explained 75 per cent and 94 per cent of the variance of social support and job design respectively, whereas work stressors explained 51 per cent of the variance of strains. Social support and job design predicted job satisfaction and turnover intentions, as well as moderated significantly the relationships between quantitative workload/hostility and job satisfaction/turnover intentions. Research limitations/implications: The findings are useful to management and to health employees working in acute/specialist hospitals. Further research could be done in other counties to take into account cultural differences and variations in health systems. The limitations included self-reported data and percept-percept bias due to same source data collection. Practical implications: The quality of senior management leaders in hospitals has an impact on the social environment, the support given to health employees, their job design, as well as work stressors and strains perceived. Originality/value: The study argues in favour of effective senior management leadership of hospitals, as well as ensuring adequate support structures and job design. The findings may be useful to health policy makers and human resources managers. © Emerald Group Publishing Limited.

Functional recombinant protein is present in the pre-induction phases of Pichia pastoris cultures when grown in bioreactors, but not shake-flasks

Background - Pichia pastoris is a widely-used host for recombinant protein production; expression is typically driven by methanol-inducible alcohol oxidase (AOX) promoters. Recently this system has become an important source of recombinant G protein-coupled receptors (GPCRs) for structural biology and drug discovery. The influence of diverse culture parameters (such as pH, dissolved oxygen concentration, medium composition, antifoam concentration and culture temperature) on productivity has been investigated for a wide range of recombinant proteins in P. pastoris. In contrast, the impact of the pre-induction phases on yield has not been as closely studied. In this study, we examined the pre-induction phases of P. pastoris bioreactor cultivations producing three different recombinant proteins: the GPCR, human A2a adenosine receptor (hA2aR), green fluorescent protein (GFP) and human calcitonin gene-related peptide receptor component protein (as a GFP fusion protein; hCGRP-RCP-GFP). Results - Functional hA2aR was detected in the pre-induction phases of a 1 L bioreactor cultivation of glycerol-grown P. pastoris. In a separate experiment, a glycerol-grown P. pastoris strain secreted soluble GFP prior to methanol addition. When glucose, which has been shown to repress AOX expression, was the pre-induction carbon source, hA2aR and GFP were still produced in the pre-induction phases. Both hA2aR and GFP were also produced in methanol-free cultivations; functional protein yields were maintained or increased after depletion of the carbon source. Analysis of the pre-induction phases of 10 L pilot scale cultivations also demonstrated that pre-induction yields were at least maintained after methanol induction, even in the presence of cytotoxic concentrations of methanol. Additional bioreactor data for hCGRP-RCP-GFP and shake-flask data for GFP, horseradish peroxidase (HRP), the human tetraspanins hCD81 and CD82, and the tight-junction protein human claudin-1, demonstrated that bioreactor but not shake flask cultivations exhibit recombinant protein production in the pre-induction phases of P. pastoris cultures. Conclusions - The production of recombinant hA2aR, GFP and hCGRP-RCP-GFP can be detected in bioreactor cultivations prior to methanol induction, while this is not the case for shake-flask cultivations of GFP, HRP, hCD81, hCD82 and human claudin-1. This confirms earlier suggestions of leaky expression from AOX promoters, which we report here for both glycerol- and glucose-grown cells in bioreactor cultivations. These findings suggest that the productivity of AOX-dependent bioprocesses is not solely dependent on induction by methanol. We conclude that in order to maximize total yields, pre-induction phase cultivation conditions should be optimized, and that increased specific productivity may result in decreased biomass yields.

Using genetic programming and decision trees for generating structural descriptions of four bar mechanisms

Four bar mechanisms are basic components of many important mechanical devices. The kinematic synthesis of four bar mechanisms is a difficult design problem. A novel method that combines the genetic programming and decision tree learning methods is presented. We give a structural description for the class of mechanisms that produce desired coupler curves. Constructive induction is used to find and characterize feasible regions of the design space. Decision trees constitute the learning engine, and the new features are created by genetic programming.

Managing enterprise resource planning and multi-organisational enterprise governance:a new contingency framework for the enterprisation of operations

This research has been undertaken to determine how successful multi-organisational enterprise strategy is reliant on the correct type of Enterprise Resource Planning (ERP) information systems being used. However there appears to be a dearth of research as regards strategic alignment between ERP systems development and multi-organisational enterprise governance as guidelines and frameworks to assist practitioners in making decision for multi-organisational collaboration supported by different types of ERP systems are still missing from theoretical and empirical perspectives. This calls for this research which investigates ERP systems development and emerging practices in the management of multi-organisational enterprises (i.e. parts of companies working with parts of other companies to deliver complex product-service systems) and identify how different ERP systems fit into different multi-organisational enterprise structures, in order to achieve sustainable competitive success. An empirical inductive study was conducted using the Grounded Theory-based methodological approach based on successful manufacturing and service companies in the UK and China. This involved an initial pre-study literature review, data collection via 48 semi-structured interviews with 8 companies delivering complex products and services across organisational boundaries whilst adopting ERP systems to support their collaborative business strategies – 4 cases cover printing, semiconductor manufacturing, and parcel distribution industries in the UK and 4 cases cover crane manufacturing, concrete production, and banking industries in China in order to form a set of 29 tentative propositions that have been validated via a questionnaire receiving 116 responses from 16 companies. The research has resulted in the consolidation of the validated propositions into a novel concept referred to as the ‘Dynamic Enterprise Reference Grid for ERP’ (DERG-ERP) which draws from multiple theoretical perspectives. The core of the DERG-ERP concept is a contingency management framework which indicates that different multi-organisational enterprise paradigms and the supporting ERP information systems are not the result of different strategies, but are best considered part of a strategic continuum with the same overall business purpose of multi-organisational cooperation. At different times and circumstances in a partnership lifecycle firms may prefer particular multi-organisational enterprise structures and the use of different types of ERP systems to satisfy business requirements. Thus the DERG-ERP concept helps decision makers in selecting, managing and co-developing the most appropriate multi-organistional enterprise strategy and its corresponding ERP systems by drawing on core competence, expected competitiveness, and information systems strategic capabilities as the main contingency factors. Specifically, this research suggests that traditional ERP(I) systems are associated with Vertically Integrated Enterprise (VIE); whilst ERPIIsystems can be correlated to Extended Enterprise (EE) requirements and ERPIII systems can best support the operations of Virtual Enterprise (VE). The contribution of this thesis is threefold. Firstly, this work contributes to a gap in the extant literature about the best fit between ERP system types and multi-organisational enterprise structure types; and proposes a new contingency framework – the DERG-ERP, which can be used to explain how and why enterprise managers need to change and adapt their ERP information systems in response to changing business and operational requirements. Secondly, with respect to a priori theoretical models, the new DERG-ERP has furthered multi-organisational enterprise management thinking by incorporating information system strategy, rather than purely focusing on strategy, structural, and operational aspects of enterprise design and management. Simultaneously, the DERG-ERP makes theoretical contributions to the current IS Strategy Formulation Model which does not explicitly address multi-organisational enterprise governance. Thirdly, this research clarifies and emphasises the new concept and ideas of future ERP systems (referred to as ERPIII) that are inadequately covered in the extant literature. The novel DERG-ERP concept and its elements have also been applied to 8 empirical cases to serve as a practical guide for ERP vendors, information systems management, and operations managers hoping to grow and sustain their competitive advantage with respect to effective enterprise strategy, enterprise structures, and ERP systems use; referred to in this thesis as the “enterprisation of operations”.

Automated Problem Domain Cognition Process in Information Systems Design

An automated cognitive approach for the design of Information Systems is presented. It is supposed to be used at the very beginning of the design process, between the stages of requirements determination and analysis, including the stage of analysis. In the context of the approach used either UML or ERD notations may be used for model representation. The approach provides the opportunity of using natural language text documents as a source of knowledge for automated problem domain model generation. It also simplifies the process of modelling by assisting the human user during the whole period of working upon the model (using UML or ERD notations).

Editorial overview:new protein production tools for structural biology

Full text: The idea of producing proteins from recombinant DNA hatched almost half a century ago. In his PhD thesis, Peter Lobban foresaw the prospect of inserting foreign DNA (from any source, including mammalian cells) into the genome of a λ phage in order to detect and recover protein products from Escherichia coli [ 1 and 2]. Only a few years later, in 1977, Herbert Boyer and his colleagues succeeded in the first ever expression of a peptide-coding gene in E. coli — they produced recombinant somatostatin [ 3] followed shortly after by human insulin. The field has advanced enormously since those early days and today recombinant proteins have become indispensable in advancing research and development in all fields of the life sciences. Structural biology, in particular, has benefitted tremendously from recombinant protein biotechnology, and an overwhelming proportion of the entries in the Protein Data Bank (PDB) are based on heterologously expressed proteins. Nonetheless, synthesizing, purifying and stabilizing recombinant proteins can still be thoroughly challenging. For example, the soluble proteome is organized to a large part into multicomponent complexes (in humans often comprising ten or more subunits), posing critical challenges for recombinant production. A third of all proteins in cells are located in the membrane, and pose special challenges that require a more bespoke approach. Recent advances may now mean that even these most recalcitrant of proteins could become tenable structural biology targets on a more routine basis. In this special issue, we examine progress in key areas that suggests this is indeed the case. Our first contribution examines the importance of understanding quality control in the host cell during recombinant protein production, and pays particular attention to the synthesis of recombinant membrane proteins. A major challenge faced by any host cell factory is the balance it must strike between its own requirements for growth and the fact that its cellular machinery has essentially been hijacked by an expression construct. In this context, Bill and von der Haar examine emerging insights into the role of the dependent pathways of translation and protein folding in defining high-yielding recombinant membrane protein production experiments for the common prokaryotic and eukaryotic expression hosts. Rather than acting as isolated entities, many membrane proteins form complexes to carry out their functions. To understand their biological mechanisms, it is essential to study the molecular structure of the intact membrane protein assemblies. Recombinant production of membrane protein complexes is still a formidable, at times insurmountable, challenge. In these cases, extraction from natural sources is the only option to prepare samples for structural and functional studies. Zorman and co-workers, in our second contribution, provide an overview of recent advances in the production of multi-subunit membrane protein complexes and highlight recent achievements in membrane protein structural research brought about by state-of-the-art near-atomic resolution cryo-electron microscopy techniques. E. coli has been the dominant host cell for recombinant protein production. Nonetheless, eukaryotic expression systems, including yeasts, insect cells and mammalian cells, are increasingly gaining prominence in the field. The yeast species Pichia pastoris, is a well-established recombinant expression system for a number of applications, including the production of a range of different membrane proteins. Byrne reviews high-resolution structures that have been determined using this methylotroph as an expression host. Although it is not yet clear why P. pastoris is suited to producing such a wide range of membrane proteins, its ease of use and the availability of diverse tools that can be readily implemented in standard bioscience laboratories mean that it is likely to become an increasingly popular option in structural biology pipelines. The contribution by Columbus concludes the membrane protein section of this volume. In her overview of post-expression strategies, Columbus surveys the four most common biochemical approaches for the structural investigation of membrane proteins. Limited proteolysis has successfully aided structure determination of membrane proteins in many cases. Deglycosylation of membrane proteins following production and purification analysis has also facilitated membrane protein structure analysis. Moreover, chemical modifications, such as lysine methylation and cysteine alkylation, have proven their worth to facilitate crystallization of membrane proteins, as well as NMR investigations of membrane protein conformational sampling. Together these approaches have greatly facilitated the structure determination of more than 40 membrane proteins to date. It may be an advantage to produce a target protein in mammalian cells, especially if authentic post-translational modifications such as glycosylation are required for proper activity. Chinese Hamster Ovary (CHO) cells and Human Embryonic Kidney (HEK) 293 cell lines have emerged as excellent hosts for heterologous production. The generation of stable cell-lines is often an aspiration for synthesizing proteins expressed in mammalian cells, in particular if high volumetric yields are to be achieved. In his report, Buessow surveys recent structures of proteins produced using stable mammalian cells and summarizes both well-established and novel approaches to facilitate stable cell-line generation for structural biology applications. The ambition of many biologists is to observe a protein's structure in the native environment of the cell itself. Until recently, this seemed to be more of a dream than a reality. Advances in nuclear magnetic resonance (NMR) spectroscopy techniques, however, have now made possible the observation of mechanistic events at the molecular level of protein structure. Smith and colleagues, in an exciting contribution, review emerging ‘in-cell NMR’ techniques that demonstrate the potential to monitor biological activities by NMR in real time in native physiological environments. A current drawback of NMR as a structure determination tool derives from size limitations of the molecule under investigation and the structures of large proteins and their complexes are therefore typically intractable by NMR. A solution to this challenge is the use of selective isotope labeling of the target protein, which results in a marked reduction of the complexity of NMR spectra and allows dynamic processes even in very large proteins and even ribosomes to be investigated. Kerfah and co-workers introduce methyl-specific isotopic labeling as a molecular tool-box, and review its applications to the solution NMR analysis of large proteins. Tyagi and Lemke next examine single-molecule FRET and crosslinking following the co-translational incorporation of non-canonical amino acids (ncAAs); the goal here is to move beyond static snap-shots of proteins and their complexes and to observe them as dynamic entities. The encoding of ncAAs through codon-suppression technology allows biomolecules to be investigated with diverse structural biology methods. In their article, Tyagi and Lemke discuss these approaches and speculate on the design of improved host organisms for ‘integrative structural biology research’. Our volume concludes with two contributions that resolve particular bottlenecks in the protein structure determination pipeline. The contribution by Crepin and co-workers introduces the concept of polyproteins in contemporary structural biology. Polyproteins are widespread in nature. They represent long polypeptide chains in which individual smaller proteins with different biological function are covalently linked together. Highly specific proteases then tailor the polyprotein into its constituent proteins. Many viruses use polyproteins as a means of organizing their proteome. The concept of polyproteins has now been exploited successfully to produce hitherto inaccessible recombinant protein complexes. For instance, by means of a self-processing synthetic polyprotein, the influenza polymerase, a high-value drug target that had remained elusive for decades, has been produced, and its high-resolution structure determined. In the contribution by Desmyter and co-workers, a further, often imposing, bottleneck in high-resolution protein structure determination is addressed: The requirement to form stable three-dimensional crystal lattices that diffract incident X-ray radiation to high resolution. Nanobodies have proven to be uniquely useful as crystallization chaperones, to coax challenging targets into suitable crystal lattices. Desmyter and co-workers review the generation of nanobodies by immunization, and highlight the application of this powerful technology to the crystallography of important protein specimens including G protein-coupled receptors (GPCRs). Recombinant protein production has come a long way since Peter Lobban's hypothesis in the late 1960s, with recombinant proteins now a dominant force in structural biology. The contributions in this volume showcase an impressive array of inventive approaches that are being developed and implemented, ever increasing the scope of recombinant technology to facilitate the determination of elusive protein structures. Powerful new methods from synthetic biology are further accelerating progress. Structure determination is now reaching into the living cell with the ultimate goal of observing functional molecular architectures in action in their native physiological environment. We anticipate that even the most challenging protein assemblies will be tackled by recombinant technology in the near future.

Linear dispersive pre-defined peak amplitude modulation of spectrally modulated airy-based pulses

Spectrally modulated Airy-based pulses peak amplitude modulation (PAM) in linear dispersive media is investigated, designed, and numerically simulated. As it is shown here, it is possible to design the spectral modulation of the initial Airy-based pulses to obtain a pre-defined PAM profile as the pulse propagates. Although optical pulses self-amplitude modulation is a well-known effect under non-linear propagation, the designed Airy-based pulses exhibit PAM under linear dispersive propagation. This extraordinary linear propagation property can be applied in many kinds of dispersive media, enabling its use in a broad range of experiments and applications. © 2013 Optical Society of America.

Two-B or not two-B? Design patterns for hybrid metaheuristics

Real world search problems, characterised by nonlinearity, noise and multidimensionality, are often best solved by hybrid algorithms. Techniques embodying different necessary features are triggered at specific iterations, in response to the current state of the problem space. In the existing literature, this alternation is managed either statically (through pre-programmed policies) or dynamically, at the cost of high coupling with algorithm inner representation. We extract two design patterns for hybrid metaheuristic search algorithms, the All-Seeing Eye and the Commentator patterns, which we argue should be replaced by the more flexible and loosely coupled Simple Black Box (Two-B) and Utility-based Black Box (Three-B) patterns that we propose here. We recommend the Two-B pattern for purely fitness based hybridisations and the Three-B pattern for more generic search quality evaluation based hybridisations.

Practical design considerations of cascaded hybrid battery storage systems

The high cost of batteries has led to investigations in using second-life ex-transportation batteries for grid support applications. Vehicle manufacturers currently all have different specifications for battery chemistry, arrangement of cells, capacity and voltage. With anticipated new developments in battery chemistry which could also affect these parameters, there are, as yet, no standards defining parameters in second life applications. To overcome issues relating to sizing and to prevent future obsolescence for the rest of the energy storage system, a cascaded topology with an operating envelope design approach has been used to connect together modules. This topology offers advantages in terms of system reliability. The design methodology is validated through a set of experimental results resulting in the creation of surface maps looking at the operation of the converter (efficiency and inductor ripple current). The use of a pre-defined module operating envelope also offers advantages for developing new operational strategies for systems with both hybrid battery energy systems and also hybrid systems including other energy sources such as solar power.

Pre-existent expectancy effects in the relationship between caffeine and performance

The present study investigated the impact of pre-existent expectancy regarding the effects of the caffeine load of a drink and the perception of the caffeine content on subjective mood and vigilance performance. Caffeine deprived participants (N=25) were tested in four conditions (within subjects design), using a 2 × 2 design, with caffeine load and information regarding the caffeine content of the drink. In two sessions, they were given caffeinated coffee and in two were given decaffeinated coffee. Within these two conditions, on one occasion they were given accurate information about the drink and on the other they were given inaccurate information about the drink. Mood and vigilance performance were assessed post ingestion. Caffeine was found to enhance performance, but only when participants were accurately told they were receiving it. When decaffeinated coffee was given, performance was poorer, irrespective of expectancy. However, when caffeine was given, but participants were told it was decaffeinated coffee, performance was as poor as when no caffeine had been administered. There were no easily interpretable effects on mood. The pharmacological effects of caffeine appear to act synergistically with expectancy. © 2010.