Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90 years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75 years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7 years the number of families with all participating siblings aged 95 years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.

The Structure of Design Processes: ideal and reality in Bruce Archer’s 1968 doctoral thesis

The paper centres on a single document, the 1968 doctoral thesis of L Bruce Archer. It traces the author’s earlier publications and the sources that informed and inspired his thinking, as a way of understanding the trajectory of his ideas and the motivations for his work at the Royal College of Art from 1962. Analysis of the thesis suggests that Archer’s ambition for a rigorous ‘science of design’ inspired by algorithmic approaches was increasingly threatened with disruption by his experience of large, complex design projects. His attempts to deal with this problem are shown to involve a particular interpretation of cybernetics. The paper ends with Archer’s own retrospective view and a brief account of his dramatically changed opinions. Archer is located as both a theorist and someone intensely interested in the commercial world of industrial design.

B-spline and neuro-fuzzy models design with function and derivative equalities

The design of neuro-fuzzy models is still a complex problem, as it involves not only the determination of the model parameters, but also its structure. Of special importance is the incorporation of a priori information in the design process. In this paper two known design algorithms for B-spline models will be updated to account for function and derivatives equality restrictions, which are important when the neural model is used for performing single or multi-objective optimization on-line.

Urban design, central London and the ‘crisis’ 2007-2013: business as usual?

London is changing, to a breath-taking extent. Beneath this fast paced activity, new patterns are forming and divisions that had been relatively unremarked before are now becoming increasingly visible. The ‘square mile’ of the City of London, which is now identified by some dramatically tall buildings, forms a contrast to the traditional urbanism of the City of Westminster, the majority of which is covered by conservation area legislation. This paper will consider this contrast from the perspective of urban design, examining both the wider development context for these changes and the separate design policies of these two historic organisations of local government. One of the key questions to be investigated is how these changes have impacted on the character of central London as a place. Moving on from the well-rehearsed debates about London’s skyline, the paper considers the significance of urban design in the context of a global urban spatial economy. It suggests that central London faces severe dilemmas about its future if the growth scenario continues.

From design-for-test to design-for-debug-and-test: analysis of requirements and limitations for 1149.1

The increasing complexity of VLSI circuits and the reduced accessibility of modern packaging and mounting technologies restrict the usefulness of conventional in-circuit debugging tools, such as in-circuit emulators for microprocessors and microcontrollers. However, this same trend enables the development of more complex products, which in turn require more powerful debugging tools. These conflicting demands could be met if the standard scan test infrastructures now common in most complex components were able to match the debugging requirements of design verification and prototype validation. This paper analyses the main debug requirements in the design of microprocessor-based applications and the feasibility of their implementation using the mandatory, optional and additional operating modes of the standard IEEE 1149.1 test infrastructure.

Differences in ERP use and value across Iberian Manufacturing and Services SMEs

Enterprise Resource Planning (ERP) system literature reports very little research on post-adoption stages, that is, actual usage and value. Even fewer studies focus on the specificities of an industry analysis. Based on the Technology-Organizational-Environment (TOE) framework and the Resource-Based View (RBV) theory, we develop a research model to measure and examine determinants of ERP use and value and their impact in the Iberian region (Portugal and Spain) across Manufacturing and Services industries in Small and Medium Enterprises (SMEs). The empirical test was conducted through structural equation modelling, using data from 261 firms in the peninsula in the Manufacturing and Service industries. Results show that amongst ERP use determinants, Training is the most important determinant for Service firms and Compatibility for Manufacturing firms. Firm size, Analytics, and Collaboration contribute to ERP Value in both industries, with Analytics being more important for the Service industry. The paper provides insight into which determinants contribute to ERP use and ERP value in Iberian Manufacturing and Services SMEs, offering managerial and academic implications.

System Design: UML Activity and Sequence Diagrams

In this session we look at how to model flow of control and interactions between components using UML Activity and Sequence Diagrams. This is an introductory session and so for Activity Diagrams we only cover branching, forks and joins and swim lanes, and for Sequence we cover lifelines, messages and returns, and alt, par and opt frames.

Yecla : a gaze upon your town : (a sample of activities design to work and communicate in english on your town).

Subtítulo tomado de la cub

Teaching art and design : addressing issues and identifying directions.

Promueve el desarrollo profesional de los profesores especialistas en arte y diseño, tanto de los que se preparan para enseñar, como de los recién titulados o los más experimentados. Así, este recurso surge como respuesta a los debates sobre dos iniciativas de gran alcance promovidas por el gobierno: la introducción del National Currículo y la reforma de la educación y formación del profesorado. Estas medidas llevaron a los profesores de arte y diseño a aplicar, de forma rápida, el plan de estudios para Arte y a prepararse para su nuevo papel en la escuela, a través de cursos iniciales de formación. También, aborda el libro los problemas actuales en la enseñanza del arte y el diseño, e identifica las direcciones que han de seguir el desarrollo de sus futuros programas de estudios, con especial referencia a la fase de secundaria.

Research by Design is up and running

This paper explores the context of and developments in Research by Design (RbD) as currently developing in Schools of Architecture. It starts from noticing that the design studio is the core of the bachelor and master curriculum. Extending this position to PhD research implies the search for research where the design process is the main method of researching and creating knowledge and understanding. These developments connect to similar developments in the arts. Mode 1 and mode 2 knowledge, reflection and other knowledge processes are the base for developing knowledge for the field of architecture when practice and designing are the main method of research. The paper concludes with observing many PhD and research projects building on design activities and practice are currently under way and are supported by academia. They produce a specific type of knowledge and understanding, usually opening up problems and exploring boundaries.

A novel Bayesian approach to drug design with simple and complex enzymes: Use with lens aldehyde dehydrogenase and the glyoxalase pathway

Purpose: Acquiring details of kinetic parameters of enzymes is crucial to biochemical understanding, drug development, and clinical diagnosis in ocular diseases. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. Methods: We have developed Bayesian utility functions to minimise kinetic parameter variance involving differentiation of model expressions and matrix inversion. These have been applied to the simple kinetics of the enzymes in the glyoxalase pathway (of importance in posttranslational modification of proteins in cataract), and the complex kinetics of lens aldehyde dehydrogenase (also of relevance to cataract). Results: Our successful application of Bayesian statistics has allowed us to identify a set of rules for designing optimum kinetic experiments iteratively. Most importantly, the distribution of points in the range is critical; it is not simply a matter of even or multiple increases. At least 60 % must be below the KM (or plural if more than one dissociation constant) and 40% above. This choice halves the variance found using a simple even spread across the range.With both the glyoxalase system and lens aldehyde dehydrogenase we have significantly improved the variance of kinetic parameter estimation while reducing the number and costs of experiments. Conclusions: We have developed an optimal and iterative method for selecting features of design such as substrate range, number of measurements and choice of intermediate points. Our novel approach minimises parameter error and costs, and maximises experimental efficiency. It is applicable to many areas of ocular drug design, including receptor-ligand binding and immunoglobulin binding, and should be an important tool in ocular drug discovery.

Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine

Resistant strains of Plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in vivo (oral ID50 of 25 mu mol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17 mu M). Metaquine shows strong affinity for the putative antimalarial receptor, heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum mechanical calculations (HF/6-31+G*) reveal important regions of protonation and bonding thought to persist at parasitic vacuolar pH concordant with our receptor model. Formation of drug-heme adduct in solution was confirmed using high-resolution positive ion electrospray mass spectrometry. Metaquine showed strong binding with the receptor in a 1: 1 ratio (log K = 5.7 +/- 0.1) that was predicted by molecular mechanics calculations. This study illustrates a rational multidisciplinary approach for the development of new 4-aminoquinoline antimalarials, with efficacy superior to chloroquine, based on the use of a pharmacophore model.