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Showing papers by "University of Warwick published in 2002"


Journal ArticleDOI
09 May 2002-Nature
TL;DR: The 8,667,507 base pair linear chromosome of Streptomyces coelicolor is reported, containing the largest number of genes so far discovered in a bacterium.
Abstract: Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

3,077 citations


Book
01 Jan 2002
TL;DR: In the last few decades exchange rate economics has seen a number of developments, with substantial contributions to both the theory and empirics of exchange rate determination as mentioned in this paper. But, while our understanding of exchange rates has significantly improved, a few challenges and open questions remain in the exchange rate debate, enhanced by events including the launch of the Euro and the large number of recent currency crises.
Abstract: Description Contents Resources Courses About the Authors In the last few decades exchange rate economics has seen a number of developments, with substantial contributions to both the theory and empirics of exchange rate determination. Important developments in econometrics and the increasingly large availability of high-quality data have also been responsible for stimulating the large amount of empirical work on exchange rates in this period. Nonetheless, while our understanding of exchange rates has significantly improved, a number of challenges and open questions remain in the exchange rate debate, enhanced by events including the launch of the Euro and the large number of recent currency crises. This volume provides a selective coverage of the literature on exchange rates, focusing on developments from within the last fifteen years. Clear explanations of theories are offered, alongside an appraisal of the literature and suggestions for further research and analysis.

1,222 citations


Journal ArticleDOI
TL;DR: The infiltration of airway smooth muscle by mast cells is associated with the disordered airway function found in asthma.
Abstract: Background Asthma and eosinophilic bronchitis are characterized by similar inflammatory infiltrates in the submucosa of the lower airway However, eosinophilic bronchitis differs from asthma in that there is no variable airflow obstruction or airway hyperresponsiveness in the former condition We tested the hypothesis that there were differences between the two conditions in the microlocalization of mast cells within the airway smooth muscle Methods Immunohistochemical analysis of bronchial-biopsy specimens was completed in 17 subjects with asthma, 13 subjects with eosinophilic bronchitis, and 11 normal controls recruited from two centers Results Both groups with disease had a similar degree of submucosal eosinophilia and thickening of the basement membrane and lamina reticularis By contrast, the number of tryptase-positive mast cells in the bundles of airway smooth muscle from subjects with asthma (median, 51 mast cells per square millimeter of smooth muscle [range, 0 to 333]) was substantially high

1,218 citations


Journal ArticleDOI
TL;DR: Regulatable transgenic mouse models of oncogenesis have shed light on the role of c-MYC in tumour progression and provide hope for effective cancer therapies.
Abstract: Deregulated expression of c-MYC occurs in a broad range of human cancers and is often associated with poor prognosis, indicating a key role for this oncogene in tumour progression. However, as established human tumours often bear multiple genetic lesions, it is difficult to determine whether c-MYC is instrumental in the initiation/progression of the tumour, or indeed whether inactivating c-MYC would lead to tumour regression. Regulatable transgenic mouse models of oncogenesis have shed light on these issues and provide hope for effective cancer therapies.

1,142 citations


Journal ArticleDOI
TL;DR: The second generation of knowledge management, with its focus on tacit‐explicit knowledge conversion, replaced a first generation focus on timely information provision for decision support and in support of BPR initiatives, and is reaching the end.
Abstract: We are reaching the end of the second generation of knowledge management, with its focus on tacit‐explicit knowledge conversion Triggered by the SECI model of Nonaka, it replaced a first generation focus on timely information provision for decision support and in support of BPR initiatives Like BPR it has substantially failed to deliver on its promised benefits The third generation requires the clear separation of context, narrative and content management and challenges the orthodoxy of scientific management Complex adaptive systems theory is used to create a sense‐making model that utilises self‐organising capabilities of the informal communities and identifies a natural flow model of knowledge creation, disruption and utilisation However, the argument from nature of many complexity thinkers is rejected given the human capability to create order and predictability through collective and individual acts of freewill Knowledge is seen paradoxically, as both a thing and a flow requiring diverse management approaches

1,025 citations


Journal ArticleDOI
TL;DR: The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion.
Abstract: The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH. The acid medium may be important in some pathological conditions. In addition, the ability of flavonoids to reduce iron and copper ions and their activity-structure relationships were also investigated. To fulfill these objectives, flavones (apigenin, luteolin, kaempferol, quercetin, myricetin and rutin), isoflavones (daidzein and genistein), flavanones (taxifolin, naringenin and naringin) and a flavanol (catechin) were investigated. All flavonoids studied show higher reducing capacity for copper ions than for iron ions. The flavonoids with better Fe3+ reducing activity are those with a 2,3-double bond and possessing both the catechol group in the B-ring and the 3-hydroxyl group. The copper reducing activity seems to depend largely on the number of hydroxyl groups. The chelation studies were carried out by means of ultraviolet spectroscopy and electrospray ionisation mass spectrometry. Only flavones and the flavanol catechin interact with metal ions. At pH 7.4 and pH 5.5 all flavones studied appear to chelate Cu2+ at the same site, probably between the 5-hydroxyl and the 4-oxo groups. Myricetin and quercetin, however, at pH 7.4, appear to chelate Cu2+ additionally at the ortho-catechol group, the chelating site for catechin with Cu2+ at pH 7.4. Chelation studies of Fe3+ to flavonoids were investigated only at pH 5.5. Only myricetin and quercetin interact strongly with Fe3+, complexation probably occurring again between the 5-hydroxyl and the 4-oxo groups. Their behaviour can be explained by their ability to reduce Fe3+ at pH 5.5, suggesting that flavonoids reduce Fe3+ to Fe2+ before association.

875 citations


Journal ArticleDOI
TL;DR: In this paper, the phase transition from the high-temperature prototypic cubic structure to one of tetragonal (673-773) and then rhombohedral structures (5-528) has been established.
Abstract: Rietveld neutron powder profile analysis of the compound Na0.5Bi0.5TiO3 (NBT) is reported over the temperature range 5–873 K. The sequence of phase transitions from the high-temperature prototypic cubic structure (above 813 K), to one of tetragonal (673–773 K) and then rhombohedral structures (5–528 K) has been established. Coexisting tetragonal/cubic (773–813 K) and rhombohedral/tetragonal (with an upper temperature limit of 145 K between 528 and 673 K) phases have also been observed. Refinements have revealed that the rhombohedral phase, space group R3c, with aH = 5.4887 (2), cH = 13.5048 (8) A, V = 352.33 (3) A3, Z = 6 and Dx = 5.99 Mg m−3, exhibits an antiphase, a−a−a− oxygen tilt system, ω = 8.24 (4)°, with parallel cation displacements at room temperature. The tetragonal phase, space group P4bm, with aT = 5.5179 (2), cT = 3.9073 (2) A, V = 118.96 (1) A3, Z = 2 and Dx = 5.91 Mg m−3, possesses an unusual combination of in-phase, a0a0c+ oxygen octahedra tilts, ω = 3.06 (2)°, and antiparallel cation displacements along the polar axis. General trends of cation displacements and the various deviations of the octahedral network from the prototypic cubic perovskite structure have been established and their systematic behaviour with temperature is reported. An investigation of phase transition behaviour using second harmonic generation (SHG) to establish the centrosymmetric or non-centrosymmetric nature of the various phases is also reported.

799 citations


Journal ArticleDOI
TL;DR: The service concept is defined and how it can be used to enhance a variety of service design processes is described, including service design planning and service recovery design processes.

779 citations


Journal ArticleDOI
TL;DR: The energy functional of nonlinear plate theory is a curvature functional for surfaces rst proposed on physical grounds by G. Kirchhoff in 1850 as mentioned in this paper, and it arises as a 0-limit of three-dimensional nonlinear elasticity theory as the thickness of a plate goes to zero.
Abstract: The energy functional of nonlinear plate theory is a curvature functional for surfaces rst proposed on physical grounds by G. Kirchhoff in 1850. We show that it arises as a 0-limit of three-dimensional nonlinear elasticity theory as the thickness of a plate goes to zero. A key ingredient in the proof is a sharp rigidity estimate for maps v V U ! R n , U R n . We show that the L 2 -distance of rv from a single rotation matrix is bounded by a multiple of the L 2 -distance from

748 citations


Journal ArticleDOI
TL;DR: The current understanding of the mechanisms by which plants control senescence and the processes that are involved is presented.
Abstract: Senescence in green plants is a complex and highly regulated process that occurs as part of plant development or can be prematurely induced by stress. In the last decade, the main focus of research has been on the identification of senescence mutants, as well as on genes that show enhanced expression during senescence. Analysis of these is beginning to expand our understanding of the processes by which senescence functions. Recent rapid advances in genomics resources, especially for the model plant species Arabidopsis, are providing scientists with a dazzling array of tools for the identification and functional analysis of the genes and pathways involved in senescence. In this review, we present the current understanding of the mechanisms by which plants control senescence and the processes that are involved.

704 citations


Journal ArticleDOI
TL;DR: This paper presents the key ingredients, which are essential for Six Sigma implementation, generated from a pilot survey conducted in the UK manufacturing and service organisations.
Abstract: Six Sigma is a business strategy and a systematic methodology, use of which leads to breakthrough in profitability through quantum gains in product/service quality, customer satisfaction and productivity. The concept of implementing Six Sigma processes was pioneered at Motorola in the 1980s and the objective was to reduce the number of defects to as low as 3.4 parts per million opportunities. For the effective implementation of Six Sigma projects in organisations, one must understand the critical success factors that will make the application successful. This paper presents the key ingredients, which are essential for Six Sigma implementation. These ingredients are generated from a pilot survey conducted in the UK manufacturing and service organisations.

Journal ArticleDOI
03 May 2002-Cell
TL;DR: The data indicate that highly complex neoplastic lesions can be both induced and maintained in vivo by a simple combination of two interlocking molecular lesions.

Journal ArticleDOI
TL;DR: In this paper, the ergodicity of SDEs is established by using techniques from the theory of Markov chains on general state spaces, such as that expounded by Meyn-Tweedie.

Journal ArticleDOI
TL;DR: This paper reviews the literature related to the critical success factors for the effective implementation of six sigma projects in organisations.
Abstract: Six sigma is a popular approach to drive out variability from processes using powerful statistical tools and techniques. Although originally introduced by Motorola in 1986 as a quality performance measurement, six sigma has evolved into a statistically oriented approach to process and product quality improvement. Many organisations have reported significant benefits as a result of six sigma project implementation, though not all are yet success stories. This paper reviews the literature related to the critical success factors for the effective implementation of six sigma projects in organisations.

Journal ArticleDOI
TL;DR: It is demonstrated that, as shown previously for CCA1, inactivation of LHY shortens the period of circadian rhythms in gene expression and leaf movements, and it is concluded that LHY and C CA1 appear to be negative regulatory elements required for central oscillator function.

Journal ArticleDOI
TL;DR: DL_POLY as discussed by the authors is a general-purpose molecular dynamics simulation package, which was developed by Daresbury Laboratory in the mid-1990s for the molecular simulation community in the United Kingdom.
Abstract: DL_POLY is a general-purpose molecular dynamics simulation package, which was developed by Daresbury Laboratory in the mid-1990s for the molecular simulation community in the United Kingdom. The package now has a world-wide user base and applications in many areas of molecular simulation. In this article we briefly review the history and design of the package and highlight some recent applications in the areas of; liquids and solutions; spectroscopy; ionic solids; molecular crystals; polymers; glasses; membranes; proteins; solid and liquid interfaces; catalysis; liquid crystals; intercalation and clathrates; and novel systems. The strengths and weaknesses of the code and its future in the near term are also discussed.

Journal ArticleDOI
TL;DR: In this paper, the authors developed a model, the TSIR (Time-series Suscep- tible-Infected-Recovered) model, that can capture both endemic cycles and episodic out-breaks in measles.
Abstract: Before the development of mass-vaccination campaigns, measles exhibited persistent fluctuations (endemic dynamics) in large British cities, and recurrent outbreaks (episodic dynamics) in smaller communities. The critical community size separating the two regimes was ;300 000-500 000. We develop a model, the TSIR (Time-series Suscep- tible-Infected-Recovered) model, that can capture both endemic cycles and episodic out- breaks in measles. The model includes the stochasticity inherent in the disease transmission (giving rise to a negative binomial conditional distribution) and random immigration. It is thus a doubly stochastic model for disease dynamics. It further includes seasonality in the transmission rates. All parameters of the model are estimated on the basis of time series data on reported cases and reconstructed susceptible numbers from a set of cities in England and Wales in the prevaccination era (1944-1966). The 60 cities analyzed span a size range from London (3.3 3 10 6 inhabitants) to Teignmouth (10 500 inhabitants). The dynamics of all cities fit the model well. Transmission rates scale with community size, as expected from dynamics adhering closely to frequency dependent transmission (''true mass action''). These rates are further found to reveal strong seasonal variation, corresponding to high transmission during school terms and lower transmission during the school holidays. The basic reproductive ratio, R0, is found to be invariant across the observed range of host community size, and the mean proportion of susceptible individuals also appears to be constant. Through the epidemic cycle, the susceptible population is kept within a 3% interval. The disease is, thus, efficient in ''regulating'' the susceptible population—even in small cities that undergo recurrent epidemics with frequent extinction of the disease agent. Recolonization is highly sensitive to the random immigration process. The initial phase of the epidemic is also stochastic (due to demographic stochasticity and random immigration). However, the epidemic is nearly ''deterministic'' through most of the growth and decline phase.

Book
06 Sep 2002
TL;DR: In this article, the authors present a true teaching text complete with pedagogical features to support learning, which will provide a rigorous yet accessible approach to the new area of knowledge management.
Abstract: From the Publisher: Designed as a true teaching text complete with pedagogical features to support learning, this book will provide a rigorous yet accessible approach to the new area of knowledge management. Based on empirical research rather than anecdotal evidence, the text is written specifically for a student audience rather than an academic one.

Journal ArticleDOI
TL;DR: In this paper, the authors identify communities of practice as playing a critical role in the promotion of learning and innovation in organizations, yet, while innovation may be facilitated within communities of...
Abstract: Communities of practice have been identified as playing a critical role in the promotion of learning and innovation in organizations. Yet, while innovation may be facilitated within communities of ...

Journal ArticleDOI
TL;DR: It is concluded that clinical lameness has a significant impact on milk production and the importance of early identification and the urgency of techniques to improve the definition of this highly subjective diagnosis is added.

Journal ArticleDOI
05 Sep 2002-Nature
TL;DR: The gene EARLY FLOWERING 4 (ELF4), which is involved in photoperiod perception and circadian regulation, is described, which promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles.
Abstract: Many plants use day length as an environmental cue to ensure proper timing of the switch from vegetative to reproductive growth. Day-length sensing involves an interaction between the relative length of day and night, and endogenous rhythms that are controlled by the plant circadian clock. Thus, plants with defects in circadian regulation cannot properly regulate the timing of the floral transition. Here we describe the gene EARLY FLOWERING 4 (ELF4), which is involved in photoperiod perception and circadian regulation. ELF4 promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles. elf4 mutants show attenuated expression of CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a gene that is thought to function as a central oscillator component. In addition, elf4 plants transiently show output rhythms with highly variable period lengths before becoming arrhythmic. Mutations in elf4 result in early flowering in non-inductive photoperiods, which is probably caused by elevated amounts of CONSTANS (CO), a gene that promotes floral induction.

Journal ArticleDOI
TL;DR: In this article, an institutionalist and yet social constructivist understanding of the appeal to external economic constraints (such as globalization and European integration) within contemporary European public policy and political economy is presented.
Abstract: While studies of globalization proliferate, we remain relatively under-informed about discourses of globalization and associated issues of power and knowledge. These issues come to the fore in the light of the intensive deployment of particular rhetorics of globalization and European integration within policy-making, journalistic and corporate communities. This paper seeks to contribute to the development of an institutionalist and yet social constructivist understanding of the appeal to external economic constraints (such as globalization and European integration) within contemporary European public policy and political economy. Through an attempt first to map the range of discourses of globalization and European integration in contemporary Europe and then to chart the (frequently) strategic deployment of such discourses in Britain, France, Germany and Italy, the paper attempts to move beyond an understanding of globalization discourse as the linguistic expression of exogenous interests. It shows how ide...

Journal ArticleDOI
TL;DR: This paper is one of a series exploring simple approaches for the estimation of lattice energy of ionic materials, avoiding elaborate computation, using the relationship that is developed arises from the dependence on the inverse cube root of the molar volume.
Abstract: This paper is one of a series exploring simple approaches for the estimation of lattice energy of ionic materials, avoiding elaborate computation. The readily accessible, frequently reported, and easily measurable (requiring only small quantities of inorganic material) property of density, rho(m), is related, as a rectilinear function of the form (rho(m)/M(m))(1/3), to the lattice energy U(POT) of ionic materials, where M(m) is the chemical formula mass. Dependence on the cube root is particularly advantageous because this considerably lowers the effects of any experimental errors in the density measurement used. The relationship that is developed arises from the dependence (previously reported in Jenkins, H. D. B.; Roobottom, H. K.; Passmore, J.; Glasser, L. Inorg. Chem. 1999, 38, 3609) of lattice energy on the inverse cube root of the molar volume. These latest equations have the form U(POT)/kJ mol(-1) = gamma(rho(m)/M(m))(1/3) + delta, where for the simpler salts (i.e., U(POT)/kJ mol(-1) 5000, gamma/kJ mol(-1) cm = 10(-7) AI(2IN(A))(1/3) and delta/kJ mol(-1) = 0 where A is the general electrostatic conversion factor (A = 121.4 kJ mol(-1)), I is the ionic strength = 1/2 the sum of n(i)z(i)(2), and N(A) is Avogadro's constant.

Journal ArticleDOI
TL;DR: Methods are described which improve upon a previously proposed method for estimating the log(HR) from survival curves and extend to life-tables.
Abstract: In a meta-analysis of randomized controlled trials with time-to-event outcomes, an aggregate data approach may be required for some or all included studies Variation in the reporting of survival analyses in journals suggests that no single method for extracting the log(hazard ratio) estimate will suffice Methods are described which improve upon a previously proposed method for estimating the log(HR) from survival curves These methods extend to life-tables In the situation where the treatment effect varies over time and the trials in the meta-analysis have different lengths of follow-up, heterogeneity may be evident In order to assess whether the hazard ratio changes with time, several tests are proposed and compared A cohort study comparing life expectancy of males and females with cerebral palsy and a systematic review of five trials comparing two anti-epileptic drugs, carbamazepine and sodium valproate, are used for illustration

Journal ArticleDOI
TL;DR: The hypothesis that the features of autism associated with weak central coherence result from a reduction in the integration of specialized local neural networks in the brain caused by a deficit in temporal binding is proposed.
Abstract: Frith has argued that people with autism show “weak central coherence,” an unusual bias toward piecemeal rather than configurational processing and a reduction in the normal tendency to process information in context. However, the precise cognitive and neurological mechanisms underlying weak central coherence are still unknown. We propose the hypothesis that the features of autism associated with weak central coherence result from a reduction in the integration of specialized local neural networks in the brain caused by a deficit in temporal binding. The visuoperceptual anomalies associated with weak central coherence may be attributed to a reduction in synchronization of high-frequency gamma activity between local networks processing local features. The failure to utilize context in language processing in autism can be explained in similar terms. Temporal binding deficits could also contribute to executive dysfunction in autism and to some of the deficits in socialization and communication.

Journal ArticleDOI
TL;DR: The research identified certain factors in IT outsourcing relationships not captured satisfactorily by the interaction approach, namely the centrality of the contract, the importance of formal processes, and the hidden costs of relationship management.
Abstract: Information technology (IT) outsourcing ventures have been termed successful or less successful in achieving their expected outsourcing objectives according to the operational effectiveness of the ...

Journal ArticleDOI
TL;DR: The economic returns to schooling are estimated using comparable microdata in 28 countries, worldwide as mentioned in this paper, and there is no evidence for a worldwide rising rate of return to education from 1985 through 1995.

Journal ArticleDOI
TL;DR: In this paper, a critique of instrumental cultural policies and social impact studies in the UK is presented, where the authors argue that art as a means of alleviating social exclusion does not really work.
Abstract: (2002). Art as a means of alleviating social exclusion: Does it really work? A critique of instrumental cultural policies and social impact studies in the UK. International Journal of Cultural Policy: Vol. 8, No. 1, pp. 91-106.

Posted Content
Abstract: Based on the estimation of a theoretically consistent gravity equation, together with a careful computation of transportation costs across countries and industries, the Paper first provides estimates of 'border effects' among EU countries. The second objective is to examine the reasons for border effects. Contrarily to the previous findings reported in the literature, we show that national trade barriers do provide an explanation. In particular, technical barriers to trade, together with firm and product-specific information costs, increase border effects, whereas non-tariff barriers are not significant. Our results however suggest that these barriers are not the only cause since the spatial clustering of firms is also shown to matter.

Journal ArticleDOI
TL;DR: In this paper, the authors identify deep democratic deficits that have emerged as a consequence of contemporary globalisation and discuss various ways that civil society can either enhance or undermine democracy in the governance of global relations.
Abstract: Recent years have witnessed substantial civil society mobilisation on questions of global governance. This paper considers the implications of this development for democracy. After specifying concepts of ‘civil society’, ‘democracy’, ‘globality’ and ‘governance’, the paper identifies deep democratic deficits that have emerged as a consequence of contemporary globalisation. The discussion then outlines various ways that civil society can either enhance or undermine democracy in the governance of global relations.