Showing papers by "University of Manchester published in 2003"

Geant4—a simulation toolkit

Abstract: G eant 4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from 250 eV and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics.

The biofilm matrix

Abstract: The extracellular matrix is a complex and extremely important component of all biofilms, providing architectural structure and mechanical stability to the attached population. The matrix is composed of cells, water and secreted/released extracellular macromolecules. In addition, a range of enzymic and regulatory activities can be found within the matrix. Together, these different components and activities are likely to interact and in so doing create a series of local environments within the matrix which co-exist as a functional consortium. The matrix architecture is also subject to a number of extrinsic factors, including fluctuations in nutrient and gaseous levels and fluid shear. Together, these intrinsic and extrinsic factors combine to produce a dynamic, heterogeneous microenvironment for the attached and enveloped cells.

Microfabricated adhesive mimicking gecko foot-hair.

Abstract: The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries1,2,3 However, only in the past few years2,3 has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos Each hair produces a miniscule force ≈10−7 N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of ≈10 N cm−2: sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling It is very tempting3 to create a new type of adhesive by mimicking the gecko mechanism Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved

Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores

Abstract: The Aurora/Ipl1 family of protein kinases plays multiple roles in mitosis and cytokinesis. Here, we describe ZM447439, a novel selective Aurora kinase inhibitor. Cells treated with ZM447439 progress through interphase, enter mitosis normally, and assemble bipolar spindles. However, chromosome alignment, segregation, and cytokinesis all fail. Despite the presence of maloriented chromosomes, ZM447439-treated cells exit mitosis with normal kinetics, indicating that the spindle checkpoint is compromised. Indeed, ZM447439 prevents mitotic arrest after exposure to paclitaxel. RNA interference experiments suggest that these phenotypes are due to inhibition of Aurora B, not Aurora A or some other kinase. In the absence of Aurora B function, kinetochore localization of the spindle checkpoint components BubR1, Mad2, and Cenp-E is diminished. Furthermore, inhibition of Aurora B kinase activity prevents the rebinding of BubR1 to metaphase kinetochores after a reduction in centromeric tension. Aurora B kinase activity is also required for phosphorylation of BubR1 on entry into mitosis. Finally, we show that BubR1 is not only required for spindle checkpoint function, but is also required for chromosome alignment. Together, these results suggest that by targeting checkpoint proteins to kinetochores, Aurora B couples chromosome alignment with anaphase onset.

Light Microscopy Techniques for Live Cell Imaging

Abstract: Since the earliest examination of cellular structures, biologists have been fascinated by observing cells using light microscopy. The advent of fluorescent labeling technologies plus the plethora of sophisticated light microscope techniques now available make studying dynamic processes in living cells almost commonplace. For anyone new to this area, however, it can be daunting to decide which techniques or equipment to try. Here, we aim to give a brief overview of the main approaches to live cell imaging, with some mention of their pros and cons.

An approach for measuring semantic similarity between words using multiple information sources

Abstract: Semantic similarity between words is becoming a generic problem for many applications of computational linguistics and artificial intelligence. This paper explores the determination of semantic similarity by a number of information sources, which consist of structural semantic information from a lexical taxonomy and information content from a corpus. To investigate how information sources could be used effectively, a variety of strategies for using various possible information sources are implemented. A new measure is then proposed which combines information sources nonlinearly. Experimental evaluation against a benchmark set of human similarity ratings demonstrates that the proposed measure significantly outperforms traditional similarity measures.

Image reconstruction algorithms for electrical capacitance tomography

Abstract: Electrical capacitance tomography (ECT) is used to image cross-sections of industrial processes containing dielectric material. This technique has been under development for more than a decade. The task of image reconstruction for ECT is to determine the permittivity distribution and hence material distribution over the cross-section from capacitance measurements. There are three principal difficulties with image reconstruction for ECT: (1) the relationship between the permittivity distribution and capacitance is non-linear and the electric field is distorted by the material present, the so-called 'soft-field' effect; (2) the number of independent measurements is limited, leading to an under-determined problem and (3) the inverse problem is ill posed and ill conditioned, making the solution sensitive to measurement errors and noise. Regularization methods are needed to treat this ill-posedness. This paper reviews existing image reconstruction algorithms for ECT, including linear back-projection, singular value decomposition, Tikhonov regularization, Newton–Raphson, iterative Tikhonov, the steepest descent method, Landweber iteration, the conjugate gradient method, algebraic reconstruction techniques, simultaneous iterative reconstruction techniques and model-based reconstruction. Some of these algorithms are examined by simulation and experiment for typical permittivity distributions. Future developments in image reconstruction for ECT are discussed.

Description logic programs: combining logic programs with description logic

Abstract: We show how to interoperate, semantically and inferentially, between the leading Semantic Web approaches to rules (RuleML Logic Programs) and ontologies (OWL/DAML+OIL Description Logic) via analyzing their expressive intersection. To do so, we define a new intermediate knowledge representation (KR) contained within this intersection: Description Logic Programs (DLP), and the closely related Description Horn Logic (DHL) which is an expressive fragment of first-order logic (FOL). DLP provides a significant degree of expressiveness, substantially greater than the RDF-Schema fragment of Description Logic. We show how to perform DLP-fusion: the bidirectional translation of premises and inferences (including typical kinds of queries) from the DLP fragment of DL to LP, and vice versa from the DLP fragment of LP to DL. In particular, this translation enables one to "build rules on top of ontologies": it enables the rule KR to have access to DL ontological definitions for vocabulary primitives (e.g., predicates and individual constants) used by the rules. Conversely, the DLP-fusion technique likewise enables one to "build ontologies on top of rules": it enables ontological definitions to be supplemented by rules, or imported into DL from rules. It also enables available efficient LP inferencing algorithms/implementations to be exploited for reasoning over large-scale DL ontologies.

Investigating semantic similarity measures across the Gene Ontology: the relationship between sequence and annotation.

Abstract: Motivation: Many bioinformatics data resources not only hold data in the form of sequences, but also as annotation. In the majority of cases, annotation is written as scientific natural language: this is suitable for humans, but not particularly useful for machine processing. Ontologies offer a mechanism by which knowledge can be represented in a form capable of such processing. In this paper we investigate the use of ontological annotation to measure the similarities in knowledge content or ‘semantic similarity’ between entries in a data resource. These allow a bioinformatician to perform a similarity measure over annotation in an analogous manner to those performed over sequences. Am easure of semantic similarity for the knowledge component of bioinformatics resources should afford a biologist a new tool in their repetoire of analyses. Results: We present the results from experiments that investigate the validity of using semantic similarity by comparison with sequence similarity. We show a simple extension that enables a semantic search of the knowledge held within sequence databases. Availability: Software available from http://www.russet.

An increased estimate of the merger rate of double neutron stars from observations of a highly relativistic system

Abstract: The merger of close binary systems containing two neutron stars should produce a burst of gravitational waves, as predicted by the theory of general relativity. A reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial in order to predict whether current gravity wave detectors will be successful in detecting such bursts. Present estimates of this rate are rather low, because we know of only a few double-neutron-star binaries with merger times less than the age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737-3039, which is a member of a highly relativistic double-neutron-star binary with an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time much shorter than for any other known neutron-star binary. Together with the relatively low radio luminosity of PSR J0737-3039, this timescale implies an order-of-magnitude increase in the predicted merger rate for double-neutron-star systems in our Galaxy (and in the rest of the Universe).

The politics of europeanization

Abstract: THEORISING EUROPEANIZATION 1. Introduction: In the name of Europe 2. The Europeanization of public policy 3. Conceptualising the domestic impact of Europe COMPARING INSTITUTIONAL CONTEXTS 4. Meeting the demands of EU membership: The Europeanization of national administrative systems 5. Variable geometry, multi-level governance: European integration and sub-national government in the new Millenium 6. Europeanization in comparative perspective: Institutional fit and national adaptation EUROPEANISATION AND POLICY ANALYSIS 7. Europeanization as interpretation, trnslation, and editing of public policies 8. Europeanization as Convergence: the regulation of media markets in the European Union 9. The impact of the European Union on environmental policies INTEREST GROUPS AND EUROPEANISATION 10. Europeanization and organisational change in national trade associations 11. Differential Europeanization: large and small firms in the EU policy process UNDERSTANDING 'EUROPE' AS A POLICY MODEL 12. The idea of the European social model: Limits and paradoxes of Europeanisation 13. Europeanisation goes east: power and uncertainty in the EU accession process CONCLUSIONS 14. Conclusions: A conversant research agenda

Description Logic Programs: Combining Logic Programs with Description Logic

Abstract: We show how to interoperate, semantically and inferentially, between the leading Semantic Web approaches to rules (RuleML Logic Programs) and ontologies (OWL/DAML+OIL Description Logic) via analyzing their expressive intersection. To do so, we define a new intermediate knowledge representation (KR) contained within this intersection: Description Logic Programs (DLP), and the closely related Description Horn Logic (DHL) which is an expressive fragment of first-order logic (FOL). DLP provides a significant degree of expressiveness, substantially greater than the RDF-Schema fragment of Description Logic. We show how to perform DLP-fusion: the bidirectional translation of premises and inferences (including typical kinds of queries) from the DLP fragment of DL to LP, and vice versa from the DLP fragment of LP to DL. In particular, this translation enables one to "build rules on top of ontologies": it enables the rule KR to have access to DL ontological definitions for vocabulary primitives (e.g., predicates and individual constants) used by the rules. Conversely, the DLP-fusion technique likewise enables one to "build ontologies on top of rules": it enables ontological definitions to be supplemented by rules, or imported into DL from rules. It also enables available efficient LP inferencing algorithms/implementations to be exploited for reasoning over large-scale DL ontologies.

A software framework for matchmaking based on semantic web technology

Abstract: An important objective of the Semantic Web is to make Electronic Commerce interactions more flexible and automated. To achieve this, standardization of ontologies, message content and message protocols will be necessary.In this paper we investigate how Semantic and Web Services technologies can be used to support service advertisement and discovery in e-commerce. In particular, we describe the design and implementation of a service matchmaking prototype which uses a DAML-S based ontology and a Description Logic reasoner to compare ontology based service descriptions. We also present the results of initial experiments testing the performance of this prototype implementation in a realistic agent based e-commerce scenario.

Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation.

Abstract: The content and structure of collagen is essential in governing the delivery of therapeutic molecules in tumors. Thus, simple histological staining of tumor tissue biopsies for collagen could be used to assess the accessibility of molecular therapeutics in tumors. Here we show that it is possible to optically image fibrillar collagen in tumors growing in mice using second-harmonic generation (SHG). Using this noninvasive technique, we estimated relative diffusive hindrance, quantified the dynamics of collagen modification after pharmacologic intervention and provided mechanistic insight into improved diffusive transport induced by the hormone relaxin. This technology could offer basic scientists and clinicians an enhanced ability to estimate the relative penetrabilities of molecular therapeutics.

Research methods used in developing and applying quality indicators in primary care

Abstract: Before we can take steps to improve the quality of health care, we need to define what quality care means. This article describes how to make best use of available evidence and reach a consensus on quality indicators

Demand-side view of electricity markets

Abstract: This tutorial paper discusses some aspects of electricity markets from the perspective of the demand-side. It argues that increasing the short-run price elasticity of the demand for electrical energy would improve the operation of these markets. It shows, however, that enhancing this elasticity is not an easy task. The tools that consumers and retailers of electrical energy need to participate more actively and effectively in electricity markets are discussed. The paper also describes how consumers of electricity can take part in the provision of power system security.

Executive functions and their disorders.

Abstract: The term executive function defines complex cognitive processing requiring the co-ordination of several subprocesses to achieve a particular goal. Neuropsychological evidence suggests that executive processing is intimately connected with the intact function of the frontal cortices. Executive dysfunction has been associated with a range of disorders, and is generally attributed to structural or functional frontal pathology. Neuroimaging, with PET and fMRI, has confirmed the relationship; however, attempts to link specific aspects of executive functioning to discrete prefrontal foci have been inconclusive. Instead, the emerging view suggests that executive function is mediated by dynamic and flexible networks, that can be characterised using functional integration and effective connectivity analyses. This view is compatible with the clinical presentation of executive dysfunction associated with a range of pathologies, and also with evidence that recovery of executive function can occur after traumatic brain injury, perhaps due to functional reorganisation within executive networks.

Interactions among three distinct CesA proteins essential for cellulose synthesis

Abstract: In a screen to identify novel cellulose deficient mutants, three lines were shown to be allelic and define a novel complementation group, irregular xylem5 (irx5). IRX5 was cloned and encodes a member of the CesA family of cellulose synthase catalytic subunits (AtCesA4). irx5 plants have an identical phenotype to previously described mutations in two other members of this gene family (IRX1 and IRX3). IRX5, IRX3, and IRX1 are coexpressed in exactly the same cells, and all three proteins interact in detergent solubilized extracts, suggesting that three members of this gene family are required for cellulose synthesis in secondary cell walls. The association of IRX1 and IRX3 was reduced to undetectable levels in the absence of IRX5. Consequently, these data suggest that IRX5, IRX3, and IRX1 are all essential components of the cellulose synthesizing complex and the presence of all three subunits is required for the correct assembly of this complex.

Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis—State of the Art: Cystic Fibrosis Foundation Consensus Conference

Abstract: Because of the difficulties of recognizing allergic bronchopulmonary aspergillosis (ABPA) in the context of cystic fibrosis (because of overlapping clinical, radiographic, microbiologic, and immunologic features), advances in our understanding of the pathogenesis of allergic aspergillosis, new possibilities in therapy, and the need for agreed-upon definitions, an international consensus conference was convened. Areas addressed included fungal biology, immunopathogenesis, insights from animal models, diagnostic criteria, epidemiology, the use of new immunologic and genetic techniques in diagnosis, imaging modalities, pharmacology, and treatment approaches. Evidence from the existing literature was graded, and the consensus views were synthesized into this document and recirculated for affirmation. Virulence factors in Aspergillus that could aggravate these diseases, and particularly immunogenetic factors that could predispose persons to ABPA, were identified. New information has come from transgenic animals and recombinant fungal and host molecules. Diagnostic criteria that could provide a framework for monitoring were adopted, and helpful imaging features were identified. New possibilities in therapy produced plans for managing diverse clinical presentations.

Microbial reduction of metals and radionuclides.

Abstract: The microbial reduction of metals has attracted recent interest as these transformations can play crucial roles in the cycling of both inorganic and organic species in a range of environments and, if harnessed, may offer the basis for a wide range of innovative biotechnological processes. Under certain conditions, however, microbial metal reduction can also mobilise toxic metals with potentially calamitous effects on human health. This review focuses on recent research on the reduction of a wide range of metals including Fe(III), Mn(IV) and other more toxic metals such as Cr(VI), Hg(II), Co(III), Pd(II), Au(III), Ag(I), Mo(VI) and V(V). The reduction of metalloids including As(V) and Se(VI) and radionuclides including U(VI), Np(V) and Tc(VII) is also reviewed. Rapid advances over the last decade have resulted in a detailed understanding of some of these transformations at a molecular level. Where known, the mechanisms of metal reduction are discussed, alongside the environmental impact of such transformations and possible biotechnological applications that could utilise these activities.