The European Declarative System, Database, and Languages

The EP2025 EDS project develops a highly parallel information server that supports established high-value interfaces. We describe the motivation for the project, the architecture of the system, and the design and application of its database and language subsystems. The Elipsys logic programming language, its advanced applications, EDS Lisp, and the Metal machine translation system are examined.

Global hydrology modelling and uncertainty: running multiple ensembles with a campus grid.

Uncertainties associated with the representation of various physical processes in global climate models (GCMs) mean that, when projections from GCMs are used in climate change impact studies, the uncertainty propagates through to the impact estimates. A complete treatment of this ‘climate model structural uncertainty’ is necessary so that decision-makers are presented with an uncertainty range around the impact estimates. This uncertainty is often underexplored owing to the human and computer processing time required to perform the numerous simulations. Here, we present a 189-member ensemble of global river runoff and water resource stress simulations that adequately address this uncertainty. Following several adaptations and modifications, the ensemble creation time has been reduced from 750 h on a typical single-processor personal computer to 9 h of high-throughput computing on the University of Reading Campus Grid. Here, we outline the changes that had to be made to the hydrological impacts model and to the Campus Grid, and present the main results. We show that, although there is considerable uncertainty in both the magnitude and the sign of regional runoff changes across different GCMs with climate change, there is much less uncertainty in runoff changes for regions that experience large runoff increases (e.g. the high northern latitudes and Central Asia) and large runoff decreases (e.g. the Mediterranean). Furthermore, there is consensus that the percentage of the global population at risk to water resource stress will increase with climate change.

Iron Uptake and Homeostasis in Microorganisms

Preface. Iron is considered to be a minor element employed, in a variety of forms, by nearly all living organisms. In some cases, it is utilised in large quantities, for instance for the formation of magnetosomes within magnetotactic bacteria or during use of iron as a respiratory donor or acceptor by iron oxidising or reducing bacteria. However, in most cases the role of iron is restricted to its use as a cofactor or prosthetic group assisting the biological activity of many different types of protein. The key metabolic processes that are dependent on iron as a cofactor are numerous; they include respiration, light harvesting, nitrogen fixation, the Krebs cycle, redox stress resistance, amino acid synthesis and oxygen transport. Indeed, it is clear that Life in its current form would be impossible in the absence of iron. One of the main reasons for the reliance of Life upon this metal is the ability of iron to exist in multiple redox states, in particular the relatively stable ferrous (Fe2+) and ferric (Fe3+) forms. The availability of these stable oxidation states allows iron to engage in redox reactions over a wide range of midpoint potentials, depending on the coordination environment, making it an extremely adaptable mediator of electron exchange processes. Iron is also one of the most common elements within the Earth’s crust (5% abundance) and thus is considered to have been readily available when Life evolved on our early, anaerobic planet. However, as oxygen accumulated (the ‘Great oxidation event’) within the atmosphere some 2.4 billion years ago, and as the oceans became less acidic, the iron within primordial oceans was converted from its soluble reduced form to its weakly-soluble oxidised ferric form, which precipitated (~1.8 billion years ago) to form the ‘banded iron formations’ (BIFs) observed today in Precambrian sedimentary rocks around the world. These BIFs provide a geological record marking a transition point away from the ancient anaerobic world towards modern aerobic Earth. They also indicate a period over which the bio-availability of iron shifted from abundance to limitation, a condition that extends to the modern day. Thus, it is considered likely that the vast majority of extant organisms face the common problem of securing sufficient iron from their environment – a problem that Life on Earth has had to cope with for some 2 billion years. This struggle for iron is exemplified by the competition for this metal amongst co-habiting microorganisms who resort to stealing (pirating) each others iron supplies! The reliance of micro-organisms upon iron can be disadvantageous to them, and to our innate immune system it represents a chink in the microbial armour, offering an opportunity that can be exploited to ward off pathogenic invaders. In order to infect body tissues and cause disease, pathogens must secure all their iron from the host. To fight such infections, the host specifically withdraws available iron through the action of various iron depleting processes (e.g. the release of lactoferrin and lipocalin-2) – this represents an important strategy in our defence against disease. However, pathogens are frequently able to deploy iron acquisition systems that target host iron sources such as transferrin, lactoferrin and hemoproteins, and thus counteract the iron-withdrawal approaches of the host. Inactivation of such host-targeting iron-uptake systems often attenuates the pathogenicity of the invading microbe, illustrating the importance of ‘the battle for iron’ in the infection process. The role of iron sequestration systems in facilitating microbial infections has been a major driving force in research aimed at unravelling the complexities of microbial iron transport processes. But also, the intricacy of such systems offers a challenge that stimulates the curiosity. One such challenge is to understand how balanced levels of free iron within the cytosol are achieved in a way that avoids toxicity whilst providing sufficient levels for metabolic purposes – this is a requirement that all organisms have to meet. Although the systems involved in achieving this balance can be highly variable amongst different microorganisms, the overall strategy is common. On a coarse level, the homeostatic control of cellular iron is maintained through strict control of the uptake, storage and utilisation of available iron, and is co-ordinated by integrated iron-regulatory networks. However, much yet remains to be discovered concerning the fine details of these different iron regulatory processes. As already indicated, perhaps the most difficult task in maintaining iron homeostasis is simply the procurement of sufficient iron from external sources. The importance of this problem is demonstrated by the plethora of distinct iron transporters often found within a single bacterium, each targeting different forms (complex or redox state) of iron or a different environmental condition. Thus, microbes devote considerable cellular resource to securing iron from their surroundings, reflecting how successful acquisition of iron can be crucial in the competition for survival. The aim of this book is provide the reader with an overview of iron transport processes within a range of microorganisms and to provide an indication of how microbial iron levels are controlled. This aim is promoted through the inclusion of expert reviews on several well studied examples that illustrate the current state of play concerning our comprehension of how iron is translocated into the bacterial (or fungal) cell and how iron homeostasis is controlled within microbes. The first two chapters (1-2) consider the general properties of microbial iron-chelating compounds (known as ‘siderophores’), and the mechanisms used by bacteria to acquire haem and utilise it as an iron source. The following twelve chapters (3-14) focus on specific types of microorganism that are of key interest, covering both an array of pathogens for humans, animals and plants (e.g. species of Bordetella, Shigella, , Erwinia, Vibrio, Aeromonas, Francisella, Campylobacter and Staphylococci, and EHEC) as well as a number of prominent non-pathogens (e.g. the rhizobia, E. coli K-12, Bacteroides spp., cyanobacteria, Bacillus spp. and yeasts). The chapters relay the common themes in microbial iron uptake approaches (e.g. the use of siderophores, TonB-dependent transporters, and ABC transport systems), but also highlight many distinctions (such as use of different types iron regulator and the impact of the presence/absence of a cell wall) in the strategies employed. We hope that those both within and outside the field will find this book useful, stimulating and interesting. We intend that it will provide a source for reference that will assist relevant researchers and provide an entry point for those initiating their studies within this subject. Finally, it is important that we acknowledge and thank wholeheartedly the many contributors who have provided the 14 excellent chapters from which this book is composed. Without their considerable efforts, this book, and the understanding that it relays, would not have been possible. Simon C Andrews and Pierre Cornelis

High-throughput proteomics using matrix-assisted laser desorption/ ionization mass spectrometry

It has become evident that the mystery of life will not be deciphered just by decoding its blueprint, the genetic code. In the life and biomedical sciences, research efforts are now shifting from pure gene analysis to the analysis of all biomolecules involved in the machinery of life. One area of these postgenomic research fields is proteomics. Although proteomics, which basically encompasses the analysis of proteins, is not a new concept, it is far from being a research field that can rely on routine and large-scale analyses. At the time the term proteomics was coined, a gold-rush mentality was created, promising vast and quick riches (i.e., solutions to the immensely complex questions of life and disease). Predictably, the reality has been quite different. The complexity of proteomes and the wide variations in the abundances and chemical properties of their constituents has rendered the use of systematic analytical approaches only partially successful, and biologically meaningful results have been slow to arrive. However, to learn more about how cells and, hence, life works, it is essential to understand the proteins and their complex interactions in their native environment. This is why proteomics will be an important part of the biomedical sciences for the foreseeable future. Therefore, any advances in providing the tools that make protein analysis a more routine and large-scale business, ideally using automated and rapid analytical procedures, are highly sought after. This review will provide some basics, thoughts and ideas on the exploitation of matrix-assisted laser desorption/ ionization in biological mass spectrometry - one of the most commonly used analytical tools in proteomics - for high-throughput analyses.

A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone (PZ-S), benign prostatic hyperplasia (BPH-S), and cancer (CA-S) to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone, or BPH-1 epithelial cells alone produced no visible grafts. Recombining PZ-S with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining CA-S with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye stained specimens is an efficient method to generate high quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo which mimics the natural history of these diseases.

Rapid parallel expression in E-coli and insect cells: Analysis of five lef gene products of the Autographa californica multiple nuclear polyhedrosis virus (AcMNPV)

A number of strategies are emerging for the high throughput (HTP) expression of recombinant proteins to enable structural and functional study. Here we describe a workable HTP strategy based on parallel protein expression in E. coli and insect cells. Using this system we provide comparative expression data for five proteins derived from the Autographa californica polyhedrosis virus genome that vary in amino acid composition and in molecular weight. Although the proteins are part of a set of factors known to be required for viral late gene expression, the precise function of three of the five, late expression factors (lefs) 6, 7 and 10, is unknown. Rapid expression and characterisation has allowed the determination of their ability to bind DNA and shown a cellular location consistent with their properties. Our data point to the utility of a parallel expression strategy to rapidly obtain workable protein expression levels from many open reading frames (ORFs).

High-throughput proteomics using matrix-assisted laser desorption/ionization mass spectrometry

It has become evident that the mystery of life will not be deciphered just by decoding its blueprint, the genetic code. In the life and biomedical sciences, research efforts are now shifting from pure gene analysis to the analysis of all biomolecules involved in the machinery of life. One area of these postgenomic research fields is proteomics. Although proteomics, which basically encompasses the analysis of proteins, is not a new concept, it is far from being a research field that can rely on routine and large-scale analyses. At the time the term proteomics was coined, a gold-rush mentality was created, promising vast and quick riches (i.e., solutions to the immensely complex questions of life and disease). Predictably, the reality has been quite different. The complexity of proteomes and the wide variations in the abundances and chemical properties of their constituents has rendered the use of systematic analytical approaches only partially successful, and biologically meaningful results have been slow to arrive. However, to learn more about how cells and, hence, life works, it is essential to understand the proteins and their complex interactions in their native environment. This is why proteomics will be an important part of the biomedical sciences for the foreseeable future. Therefore, any advances in providing the tools that make protein analysis a more routine and large-scale business, ideally using automated and rapid analytical procedures, are highly sought after. This review will provide some basics, thoughts and ideas on the exploitation of matrix-assisted laser desorption/ionization in biological mass spectrometry - one of the most commonly used analytical tools in proteomics - for high-throughput analyses.

Failure of a control strategy for a hybrid air-conditioning and wind catchers/towers system at Bluewater shopping malls in Kent

Purpose – To evaluate the control strategy for a hybrid natural ventilation wind catchers and air-conditioning system and to assess the contribution of wind catchers to indoor air environments and energy savings if any. Design/methodology/approach – Most of the modeling techniques for assessing wind catchers performance are theoretical. Post-occupancy evaluation studies of buildings will provide an insight into the operation of these building components and help to inform facilities managers. A case study for POE was presented in this paper. Findings – The monitoring of the summer and winter month operations showed that the indoor air quality parameters were kept within the design target range. The design control strategy failed to record data regarding the operation, opening time and position of wind catchers system. Though the implemented control strategy was working effectively in monitoring the operation of mechanical ventilation systems, i.e. AHU, did not integrate the wind catchers with the mechanical ventilation system. Research limitations/implications – Owing to short-falls in the control strategy implemented in this project, it was found difficult to quantify and verify the contribution of the wind catchers to the internal conditions and, hence, energy savings. Practical implications – Controlling the operation of the wind catchers via the AHU will lead to isolation of the wind catchers in the event of malfunctioning of the AHU. Wind catchers will contribute to the ventilation of space, particularly in the summer months. Originality/value – This paper demonstrates the value of POE as indispensable tool for FM professionals. It further provides insight into the application of natural ventilation systems in building for healthier indoor environments at lower energy cost. The design of the control strategy for natural ventilation and air-conditioning should be considered at the design stage involving the FM personnel.

A system's model for maintenance support and decision making in building services systems

Modern buildings are designed to enhance the match between environment, spaces and the people carrying out work, so that the well-being and the performance of the occupants are all in harmony. Building services are systems that facilitate a healthy working environment within which workers productivity can be optimised in the buildings. However, the maintenance of these services is fraught with problems that may contribute to up to 50% of the total life cycle cost of the building. Maintenance support is one area which is not usually designed into the system as this is not common practice in the services industry. The other areas of shortfall for future designs are; client requirements, commissioning, facilities management data and post occupancy evaluation feedback which needs to be adequately planned to capture and document this information for use in future designs. At the University of Reading an integrated approach has been developed to assemble the multitude of aspects inherent in this field. The means records required and measured achievements for the benefit of both building owners and practitioners. This integrated approach can be represented in a Through Life Business Model (TLBM) format using the concept of Integrated Logistic Support (ILS). The prototype TLBM developed utilises the tailored tools and techniques of ILS for building services. This TLBM approach will facilitate the successful development of a databank that would be invaluable in capturing essential data (e.g. reliability of components) for enhancing future building services designs, life cycle costing and decision making by practitioners, in particular facilities managers.

PASSCLAIM - gut health and immunity

Background The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. Aim To define normal function of the gut and immune system and describe available methods of measuring it. Results We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be "improved". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo, measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens, determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.

Semantic-driven context-aware visual information indexing and retrieval: applied in the film post-production domain

A large volume of visual content is inaccessible until effective and efficient indexing and retrieval of such data is achieved. In this paper, we introduce the DREAM system, which is a knowledge-assisted semantic-driven context-aware visual information retrieval system applied in the film post production domain. We mainly focus on the automatic labelling and topic map related aspects of the framework. The use of the context- related collateral knowledge, represented by a novel probabilistic based visual keyword co-occurrence matrix, had been proven effective via the experiments conducted during system evaluation. The automatically generated semantic labels were fed into the Topic Map Engine which can automatically construct ontological networks using Topic Maps technology, which dramatically enhances the indexing and retrieval performance of the system towards an even higher semantic level.

Information system evolvability, feedback and pattern languages

Information systems for business are frequently heavily reliant on software. Two important feedback-related effects of embedding software in a business process are identified. First, the system dynamics of the software maintenance process can become complex, particularly in the number and scope of the feedback loops. Secondly, responsiveness to feedback can have a big effect on the evolvability of the information system. Ways have been explored to provide an effective mechanism for improving the quality of feedback between stakeholders during software maintenance. Understanding can be improved by using representations of information systems that are both service-based and architectural in scope. The conflicting forces that encourage change or stability can be resolved using patterns and pattern languages. A morphology of information systems pattern languages has been described to facilitate the identification and reuse of patterns and pattern languages. The kind of planning process needed to achieve consensus on a system's evolution is also considered.

Dependence of Indian monsoon rainfall on moisture fluxes across the Arabian Sea and the impact of coupled model sea surface temperature biases

The Arabian Sea is an important moisture source for Indian monsoon rainfall. The skill of climate models in simulating the monsoon and its variability varies widely, while Arabian Sea cold sea surface temperature (SST) biases are common in coupled models and may therefore influence the monsoon and its sensitivity to climate change. We examine the relationship between monsoon rainfall, moisture fluxes and Arabian Sea SST in observations and climate model simulations. Observational analysis shows strong monsoons depend on moisture fluxes across the Arabian Sea, however detecting consistent signals with contemporaneous summer SST anomalies is complicated in the observed system by air/sea coupling and large-scale induced variability such as the El Niño-Southern Oscillation feeding back onto the monsoon through development of the Somali Jet. Comparison of HadGEM3 coupled and atmosphere-only configurations suggests coupled model cold SST biases significantly reduce monsoon rainfall. Idealised atmosphere-only experiments show that the weakened monsoon can be mainly attributed to systematic Arabian Sea cold SST biases during summer and their impact on the monsoon-moisture relationship. The impact of large cold SST biases on atmospheric moisture content over the Arabian Sea, and also the subsequent reduced latent heat release over India, dominates over any enhancement in the land-sea temperature gradient and results in changes to the mean state. We hypothesize that a cold base state will result in underestimation of the impact of larger projected Arabian Sea SST changes in future climate, suggesting that Arabian Sea biases should be a clear target for model development.

A review on Northern Hemisphere sea-ice, storminess and the North Atlantic Oscillation: observations and projected changes

The Arctic has undergone substantial changes over the last few decades in various cryospheric and derivative systems and processes. Of these, the Arctic sea ice regime has seen some of the most rapid change and is one of the most visible markers of Arctic change outside the scientific community. This has drawn considerable attention not only from the natural sciences, but increasingly, from the political and commercial sectors as they begin to grapple with the problems and opportunities that are being presented. The possible impacts of past and projected changes in Arctic sea ice, especially as it relates to climatic response, are of particular interest and have been the subject of increasing research activity. A review of the current knowledge of the role of sea ice in the climate system is therefore timely. We present a review that examines both the current state of understanding, as regards the impacts of sea-ice loss observed to date, and climate model projections, to highlight hypothesised future changes and impacts on storm tracks and the North Atlantic Oscillation. Within the broad climate-system perspective, the topics of storminess and large-scale variability will be specifically considered. We then consider larger-scale impacts on the climatic system by reviewing studies that have focused on the interaction between sea-ice extent and the North Atlantic Oscillation. Finally, an overview of the representation of these topics in the literature in the context of IPCC climate projections is presented. While most agree on the direction of Arctic sea-ice change, the rates amongst the various projections vary greatly. Similarly, the response of storm tracks and climate variability are uncertain, exacerbated possibly by the influence of other factors. A variety of scientific papers on the relationship between sea-ice changes and atmospheric variability have brought to light important aspects of this complex topic. Examples are an overall reduction in the number of Arctic winter storms, a northward shift of mid-latitude winter storms in the Pacific and a delayed negative NAO-like response in autumn/winter to a reduced Arctic sea-ice cover (at least in some months). This review paper discusses this research and the disagreements, bringing about a fresh perspective on this issue.

The system identification and control of Hammerstein system using non-uniform rational B-spline neural network and particle swarm optimization

In this paper a new system identification algorithm is introduced for Hammerstein systems based on observational input/output data. The nonlinear static function in the Hammerstein system is modelled using a non-uniform rational B-spline (NURB) neural network. The proposed system identification algorithm for this NURB network based Hammerstein system consists of two successive stages. First the shaping parameters in NURB network are estimated using a particle swarm optimization (PSO) procedure. Then the remaining parameters are estimated by the method of the singular value decomposition (SVD). Numerical examples including a model based controller are utilized to demonstrate the efficacy of the proposed approach. The controller consists of computing the inverse of the nonlinear static function approximated by NURB network, followed by a linear pole assignment controller.