Efficient and accurate experimental design for enzyme kinetics: Bayesian studies reveal a systematic approach

In areas such as drug development, clinical diagnosis and biotechnology research, acquiring details about the kinetic parameters of enzymes is crucial. 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. We demonstrate that a Bayesian approach (the use of prior knowledge) can produce major gains quantifiable in terms of information, productivity and accuracy of each experiment. Developing the use of Bayesian Utility functions, we have used a systematic method to identify the optimum experimental designs for a number of kinetic model data sets. This has enabled the identification of trends between kinetic model types, sets of design rules and the key conclusion that such designs should be based on some prior knowledge of K-M and/or the kinetic model. We suggest an optimal and iterative method for selecting features of the design such as the substrate range, number of measurements and choice of intermediate points. The final design collects data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. (C) 2003 Elsevier Science B.V. All rights reserved.

Design of a turn-linker-turn foldamer by incorporating meta-amino benzoic acid in the middle of a helix forming hexapeptide sequence: A helix breaking approach

Single crystal X-ray diffraction studies reveal that the incorporation of meta-amino benzoic acid in the middle of a helix forming hexapeptide sequence such as in peptide I Boc-Ile(1)-Aib(2)-Val(3)-m-ABA(4)-Ile(5)-Aib(6)-Leu(7)-OMe (Aib: alpha-amino isobutyric acid: m-ABA: meta-amino benzoic acid) breaks the helix propagation to produce a turn-linker-turn (T-L-T) foldamer in the solid state. In the crystalline state two conformational isomers of peptide I self-assemble in antiparallel fashion through intermolecular hydrogen bonds and aromatic pi-pi interactions to form a molecular duplex. The duplexes are further interconnected through intermolecular hydrogen bonds to form a layer of peptides. The layers are stacked one on top of the other through van der Waals interactions to form hydrophilic channels filled with solvent methanol. (C) 2009 Elsevier B.V. All rights reserved.

A comparison between classical techniques and eigenstructure assignment in the design of a longitudinal instrument landing system

Although modern control techniques such as eigenstructure assignment have been given extensive coverage in control literature there is a reluctance to use them in practice as they are often not believed to be as `visible' or as simple as classical methods. A simple aircraft example is used, and it is shown that eigenstructure assignment can be used easily to produce a more viable controller than with simple classical techniques.

Design and management of sustainable built environments

The United Nation Intergovernmental Panel on Climate Change (IPCC) makes it clear that climate change is due to human activities and it recognises buildings as a distinct sector among the seven analysed in its 2007 Fourth Assessment Report. Global concerns have escalated regarding carbon emissions and sustainability in the built environment. The built environment is a human-made setting to accommodate human activities, including building and transport, which covers an interdisciplinary field addressing design, construction, operation and management. Specifically, Sustainable Buildings are expected to achieve high performance throughout the life-cycle of siting, design, construction, operation, maintenance and demolition, in the following areas: • energy and resource efficiency; • cost effectiveness; • minimisation of emissions that negatively impact global warming, indoor air quality and acid rain; • minimisation of waste discharges; and • maximisation of fulfilling the requirements of occupants’ health and wellbeing. Professionals in the built environment sector, for example, urban planners, architects, building scientists, engineers, facilities managers, performance assessors and policy makers, will play a significant role in delivering a sustainable built environment. Delivering a sustainable built environment needs an integrated approach and so it is essential for built environment professionals to have interdisciplinary knowledge in building design and management . Building and urban designers need to have a good understanding of the planning, design and management of the buildings in terms of low carbon and energy efficiency. There are a limited number of traditional engineers who know how to design environmental systems (services engineer) in great detail. Yet there is a very large market for technologists with multi-disciplinary skills who are able to identify the need for, envision and manage the deployment of a wide range of sustainable technologies, both passive (architectural) and active (engineering system),, and select the appropriate approach. Employers seek applicants with skills in analysis, decision-making/assessment, computer simulation and project implementation. An integrated approach is expected in practice, which encourages built environment professionals to think ‘out of the box’ and learn to analyse real problems using the most relevant approach, irrespective of discipline. The Design and Management of Sustainable Built Environment book aims to produce readers able to apply fundamental scientific research to solve real-world problems in the general area of sustainability in the built environment. The book contains twenty chapters covering climate change and sustainability, urban design and assessment (planning, travel systems, urban environment), urban management (drainage and waste), buildings (indoor environment, architectural design and renewable energy), simulation techniques (energy and airflow), management (end-user behaviour, facilities and information), assessment (materials and tools), procurement, and cases studies ( BRE Science Park). Chapters one and two present general global issues of climate change and sustainability in the built environment. Chapter one illustrates that applying the concepts of sustainability to the urban environment (buildings, infrastructure, transport) raises some key issues for tackling climate change, resource depletion and energy supply. Buildings, and the way we operate them, play a vital role in tackling global greenhouse gas emissions. Holistic thinking and an integrated approach in delivering a sustainable built environment is highlighted. Chapter two demonstrates the important role that buildings (their services and appliances) and building energy policies play in this area. Substantial investment is required to implement such policies, much of which will earn a good return. Chapters three and four discuss urban planning and transport. Chapter three stresses the importance of using modelling techniques at the early stage for strategic master-planning of a new development and a retrofit programme. A general framework for sustainable urban-scale master planning is introduced. This chapter also addressed the needs for the development of a more holistic and pragmatic view of how the built environment performs, , in order to produce tools to help design for a higher level of sustainability and, in particular, how people plan, design and use it. Chapter four discusses microcirculation, which is an emerging and challenging area which relates to changing travel behaviour in the quest for urban sustainability. The chapter outlines the main drivers for travel behaviour and choices, the workings of the transport system and its interaction with urban land use. It also covers the new approach to managing urban traffic to maximise economic, social and environmental benefits. Chapters five and six present topics related to urban microclimates including thermal and acoustic issues. Chapter five discusses urban microclimates and urban heat island, as well as the interrelationship of urban design (urban forms and textures) with energy consumption and urban thermal comfort. It introduces models that can be used to analyse microclimates for a careful and considered approach for planning sustainable cities. Chapter six discusses urban acoustics, focusing on urban noise evaluation and mitigation. Various prediction and simulation methods for sound propagation in micro-scale urban areas, as well as techniques for large scale urban noise-mapping, are presented. Chapters seven and eight discuss urban drainage and waste management. The growing demand for housing and commercial developments in the 21st century, as well as the environmental pressure caused by climate change, has increased the focus on sustainable urban drainage systems (SUDS). Chapter seven discusses the SUDS concept which is an integrated approach to surface water management. It takes into consideration quality, quantity and amenity aspects to provide a more pleasant habitat for people as well as increasing the biodiversity value of the local environment. Chapter eight discusses the main issues in urban waste management. It points out that population increases, land use pressures, technical and socio-economic influences have become inextricably interwoven and how ensuring a safe means of dealing with humanity’s waste becomes more challenging. Sustainable building design needs to consider healthy indoor environments, minimising energy for heating, cooling and lighting, and maximising the utilisation of renewable energy. Chapter nine considers how people respond to the physical environment and how that is used in the design of indoor environments. It considers environmental components such as thermal, acoustic, visual, air quality and vibration and their interaction and integration. Chapter ten introduces the concept of passive building design and its relevant strategies, including passive solar heating, shading, natural ventilation, daylighting and thermal mass, in order to minimise heating and cooling load as well as energy consumption for artificial lighting. Chapter eleven discusses the growing importance of integrating Renewable Energy Technologies (RETs) into buildings, the range of technologies currently available and what to consider during technology selection processes in order to minimise carbon emissions from burning fossil fuels. The chapter draws to a close by highlighting the issues concerning system design and the need for careful integration and management of RETs once installed; and for home owners and operators to understand the characteristics of the technology in their building. Computer simulation tools play a significant role in sustainable building design because, as the modern built environment design (building and systems) becomes more complex, it requires tools to assist in the design process. Chapter twelve gives an overview of the primary benefits and users of simulation programs, the role of simulation in the construction process and examines the validity and interpretation of simulation results. Chapter thirteen particularly focuses on the Computational Fluid Dynamics (CFD) simulation method used for optimisation and performance assessment of technologies and solutions for sustainable building design and its application through a series of cases studies. People and building performance are intimately linked. A better understanding of occupants’ interaction with the indoor environment is essential to building energy and facilities management. Chapter fourteen focuses on the issue of occupant behaviour; principally, its impact, and the influence of building performance on them. Chapter fifteen explores the discipline of facilities management and the contribution that this emerging profession makes to securing sustainable building performance. The chapter highlights a much greater diversity of opportunities in sustainable building design that extends well into the operational life. Chapter sixteen reviews the concepts of modelling information flows and the use of Building Information Modelling (BIM), describing these techniques and how these aspects of information management can help drive sustainability. An explanation is offered concerning why information management is the key to ‘life-cycle’ thinking in sustainable building and construction. Measurement of building performance and sustainability is a key issue in delivering a sustainable built environment. Chapter seventeen identifies the means by which construction materials can be evaluated with respect to their sustainability. It identifies the key issues that impact the sustainability of construction materials and the methodologies commonly used to assess them. Chapter eighteen focuses on the topics of green building assessment, green building materials, sustainable construction and operation. Commonly-used assessment tools such as BRE Environmental Assessment Method (BREEAM), Leadership in Energy and Environmental Design ( LEED) and others are introduced. Chapter nineteen discusses sustainable procurement which is one of the areas to have naturally emerged from the overall sustainable development agenda. It aims to ensure that current use of resources does not compromise the ability of future generations to meet their own needs. Chapter twenty is a best-practice exemplar - the BRE Innovation Park which features a number of demonstration buildings that have been built to the UK Government’s Code for Sustainable Homes. It showcases the very latest innovative methods of construction, and cutting edge technology for sustainable buildings. In summary, Design and Management of Sustainable Built Environment book is the result of co-operation and dedication of individual chapter authors. We hope readers benefit from gaining a broad interdisciplinary knowledge of design and management in the built environment in the context of sustainability. We believe that the knowledge and insights of our academics and professional colleagues from different institutions and disciplines illuminate a way of delivering sustainable built environment through holistic integrated design and management approaches. Last, but not least, I would like to take this opportunity to thank all the chapter authors for their contribution. I would like to thank David Lim for his assistance in the editorial work and proofreading.

Methodologies for the generation of design summer years for building energy simulation using UKCP09 probabilitic climate projections

Design summer years representing near-extreme hot summers have been used in the United Kingdom for the evaluation of thermal comfort and overheating risk. The years have been selected from measured weather data basically representative of an assumed stationary climate. Recent developments have made available ‘morphed’ equivalents of these years by shifting and stretching the measured variables using change factors produced by the UKCIP02 climate projections. The release of the latest, probabilistic, climate projections of UKCP09 together with the availability of a weather generator that can produce plausible daily or hourly sequences of weather variables has opened up the opportunity for generating new design summer years which can be used in risk-based decision-making. There are many possible methods for the production of design summer years from UKCP09 output: in this article, the original concept of the design summer year is largely retained, but a number of alternative methodologies for generating the years are explored. An alternative, more robust measure of warmth (weighted cooling degree hours) is also employed. It is demonstrated that the UKCP09 weather generator is capable of producing years for the baseline period, which are comparable with those in current use. Four methodologies for the generation of future years are described, and their output related to the future (deterministic) years that are currently available. It is concluded that, in general, years produced from the UKCP09 projections are warmer than those generated previously. Practical applications: The methodologies described in this article will facilitate designers who have access to the output of the UKCP09 weather generator (WG) to generate Design Summer Year hourly files tailored to their needs. The files produced will differ according to the methodology selected, in addition to location, emissions scenario and timeslice.

A slugfest of intuitions: contextualism and experimental design

This paper considers ways that experimental design can affect judgments about informally presented context shifting experiments. Reasons are given to think that judgments about informal context shifting experiments are affected by an exclusive reliance on binary truth value judgments and by experimenter bias. Exclusive reliance on binary truth value judgments may produce experimental artifacts by obscuring important differences of degree between the phenomena being investigated. Experimenter bias is an effect generated when, for example, experimenters disclose (even unconsciously) their own beliefs about the outcome of an experiment. Eliminating experimenter bias from context shifting experiments makes it far less obvious what the “intuitive” responses to those experiments are. After it is shown how those different kinds of bias can affect judgments about informal context shifting experiments, those experiments are revised to control for those forms of bias. The upshot of these investigations is that participants in the contextualist debate who employ informal experiments should pay just as much attention to the design of their experiments as those who employ more formal experimental techniques if they want to avoid obscuring the phenomena they aim to uncover

Isotype: design and contexts 1925–1971

The work in graphic communication carried out by Otto Neurath and his associates – now commonly known simply as Isotype – has been the subject of much interest in recent years. Conceived and developed in the 1920s as ‘the Vienna method of pictorial statistics’, this approach to designing information had from its inception the power to grow and spread internationally. Political developments in Europe played their part in its development, and production moved to the Netherlands (1934) and to England (1940), where the Isotype Institute continued to produce work until 1971. Bringing together the latest research, this book is the first comprehensive, detailed account of its subject. The Austrian, Dutch, and English years of Isotype are described here freshly and extensively. There are chapters on the notable extensions of Isotype to Soviet Russia, the USA, and Africa. Isotype work in film and in designing for children is fully documented and discussed. Between these main chapters the book presents interludes documenting Isotype production visually. Three appendices reprint key documents. In its international coverage and its extensions into the wider terrain of history, this book opens a new vista in graphic design.

Knowledge-based design cost estimation through extending industry foundation classes

In order to overcome divergence of estimation with the same data, the proposed digital costing process adopts an integrated design of information system to design the process knowledge and costing system together. By employing and extending a widely used international standard, industry foundation classes, the system can provide an integrated process which can harvest information and knowledge of current quantity surveying practice of costing method and data. Knowledge of quantification is encoded from literatures, motivation case and standards. It can reduce the time consumption of current manual practice. The further development will represent the pricing process in a Bayesian Network based knowledge representation approach. The hybrid types of knowledge representation can produce a reliable estimation for construction project. In a practical term, the knowledge management of quantity surveying can improve the system of construction estimation. The theoretical significance of this study lies in the fact that its content and conclusion make it possible to develop an automatic estimation system based on hybrid knowledge representation approach.

Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design

Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids.

Production of milk foams by steam injection: the effects of steam pressure and nozzle design

Foam properties depend on the physico-chemical characteristics of the continuous phase, the method of production and process conditions employed; however the preparation of barista-style milk foams in coffee shops by injection of steam uses milk as its main ingredient which limits the control of foam properties by changing the biochemical characteristics of the continuous phase. Therefore, the control of process conditions and nozzle design are the only ways available to produce foams with diverse properties. Milk foams were produced employing different steam pressures (100-280 kPa gauge) and nozzle designs (ejector, plunging-jet and confined-jet nozzles). The foamability of milk, and the stability, bubble size and texture of the foams were investigated. Variations in steam pressure and nozzle design changed the hydrodynamic conditions during foam production, resulting in foams having a range of properties. Steam pressure influenced foam characteristics, although the net effect depended on the nozzle design used. These results suggest that, in addition to the physicochemical determinants of milk, the foam properties can also be controlled by changing the steam pressure and nozzle design.