Showing papers by "Cardiff University published in 2004"

Genome sequence of the Brown Norway rat yields insights into mammalian evolution

Abstract: The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

Learning to evolve: A review of contemporary lean thinking

Abstract: The application of lean thinking has made a significant impact both in academic and industrial circles over the last decade. Fostered by a rapid spread into many other industry sectors beyond the automotive industry, there has been a significant development and “localisation” of the lean concept. Despite successful “lean” applications in a range of settings however, the lean approach has been criticised on many accounts, such as the lack of human integration or its limited applicability outside high‐volume repetitive manufacturing environments. The resulting lack of definition has led to confusion and fuzzy boundaries with other management concepts. Summarising the lean evolution, this paper comments on approaches that have sought to address some of the earlier gaps in lean thinking. Linking the evolution of lean thinking to the contingency and learning organisation schools of thought, the objective of this paper is to provide a framework for understanding the evolution of lean not only as a concept, but also its implementation within an organisation, and point out areas for future research.

Reconsidering Political and Popular Understandings of the Digital Divide

Abstract: This article presents a theoretical examination of the digital divide, tracing its origins in the centre–Left social inclusion policy agenda of the 1980s and 1990s to its current status of political ‘hot topic’. It then moves on to outline four conceptual limitations to conventional dichotomous notions of the digital divide and individuals’ ‘access’ to information and communications technology (ICT): what is meant by ICT; what is meant by ‘access’; the relationship between ‘access to ICT’ and ‘use of ICT’; and a lack of consideration of the consequences of engagement with ICT. The article outlines a more sophisticated, hierarchical model of the digital divide based around these conceptual ‘stages’ while recognizing the mediating role of economic, cultural and social forms of capital in shaping individuals’ engagements with ICT. It concludes by developing a set of research themes and questions for future examination of inequalities in individuals’ use of ICT.

The psychometric properties of the internet addiction test.

Abstract: There is growing concern about excessive Internet use and whether this can amount to an addiction. In researching this topic, a valid and reliable assessment instrument is essential. In her survey of Internet addiction, Young1,2 designed the Internet Addiction Test (IAT), which provides a basis for developments. The IAT has high face validity, but it has not been subjected to systematic psychometric testing. This study sought to replicate and expand Young's1 survey, and to examine the IAT more systematically. A questionnaire that existed as a Web page was devised, consisting of the IAT and 15 other questions regarding the respondents' demographic information and Internet usage. Participants were recruited through the Internet, yielding 86 valid responses (29 males and 57 females). Factor analysis of the IAT revealed six factors—salience, excessive use, neglecting work, anticipation, lack of control, and neglecting social life. These factors showed good internal consistency and concurrent validity, with sa...

Antecedents of Export Venture Performance: A Theoretical Model and Empirical Assessment

Abstract: Both the size and the rapid growth of global exporting have focused the attention of marketing researchers on the factors associated with firms’ export performance. However, knowledge of this increasingly important domain of marketing activity remains limited. To address this knowledge gap, the authors draw on the strategy and marketing literature to develop an integrative theory of the antecedents of export venture performance. The interplay among available resources and capabilities, competitive strategy decisions, and competitive intensity determines export venture positional advantages and performance outcomes in the theoretical model. The authors empirically assess predicted relationships using survey data from 287 export ventures. Results broadly support the theoretical model, indicating that resources and capabilities affect export venture competitive strategy choices and the positional advantages achieved in the export market, which in turn affect export venture performance outcomes. In c...

The surface of articular cartilage contains a progenitor cell population.

Abstract: It is becoming increasingly apparent that articular cartilage growth is achieved by apposition from the articular surface. For such a mechanism to occur, a population of stem/progenitor cells must reside within the articular cartilage to provide transit amplifying progeny for growth. Here, we report on the isolation of an articular cartilage progenitor cell from the surface zone of articular cartilage using differential adhesion to fibronectin. This population of cells exhibits high affinity for fibronectin, possesses a high colony-forming efficiency and expresses the cell fate selector gene Notch 1. Inhibition of Notch signalling abolishes colony forming ability whilst activated Notch rescues this inhibition. The progenitor population also exhibits phenotypic plasticity in its differentiation pathway in an embryonic chick tracking system, such that chondroprogenitors can engraft into a variety of connective tissue types including bone, tendon and perimysium. The identification of a chondrocyte subpopulation with progenitor-like characteristics will allow for advances in our understanding of both cartilage growth and maintenance as well as provide novel solutions to articular cartilage repair.

The exaggerated death of geography: learning, proximity and territorial innovation systems

Abstract: Globalization and digitalization have been presented as ineluctable forces which signal the ‘death of geography’. The paper takes issue with this fashionable narrative. The argument that ‘geography matters’ is pursued in three ways: first, by questioning the ‘distance-destroying’ capacity of information and communication technologies where social depth is conflated with spatial reach; second, by arguing that physical proximity may be essential for some forms of knowledge exchange; and third, by charting the growth of territorial innovation systems.

Solution-Processed, Organophilic Membrane Derived from a Polymer of Intrinsic Microporosity

Abstract: A polymer with a rigid, randomly contorted molecular structure (see Figure), incorporating fused rings connected by spiro-centres, may be precipitated or cast from solution to give microporous powders and membranes stable up to temperatures of 350 °C, with apparent surface areas > 600 m2 g–1. Organophilic membranes may be formed, as demonstrated by the separation of phenol from water by pervaporation.

Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.

Abstract: Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of β-catenin Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a “crypt progenitor-like” phenotype Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting

Bipolar coagulating instrument

Abstract: A bipolar coagulating instrument includes a blade-like electrode assembly comprising an upper planar face and a lower planar face separated by an intermediate portion of insulating material therebetween. The upper face includes first and second electrodes separated by a first insulating member, and the lower face includes third and fourth electrodes separated by a second insulating member. The first and second insulating members are out of correlation one with respect to the other, such that there is at least one region in which the first electrode overlies the third electrode, and at least one other region in which the first electrode overlies the fourth electrode. A cutting electrode is provided between the upper and lower faces, extending marginally beyond the periphery thereof.

A Critique of Conventional CSR Theory: An SME Perspective

Abstract: Over the last couple of decades Small and Medium Sized Enterprises [1] (SMEs) have become more important both numerically and economically, a trend that is set to be maintained. SMEs make up over 90 per cent of businesses worldwide and account for between 50 and 60 per cent of employment [2]. A report by the Global Entrepreneurship Monitor shows that Chile, Korea, New Zealand, Uganda and Venezuela are emerging as among the most entrepreneurial countries in the world, and that more than 80 per cent of entrepreneurs throughout the 41 countries studied expect to create new jobs within the next five years [3]. Given the significant scale of small business in nearly every economy, their aggregate achievements have a major effect worldwide. SMEs have multiple roles; they may be seen as innovators (or laggards) in the life-cycle of particular technologies, as a mechanism for privatisation of state-owned enterprises, as a response to global competition, or as a device for economic regeneration [4].

New paradigms for modelling species distributions

Abstract: 1The management of both desirable and undesirable species requires an understanding of the factors determining their distribution. Quantitative distribution models offer simple methods for formulating the species–habitat link and the means not only for predicting where species should occur, but also for understanding the factors involved. Generalized linear modelling, in particular, links the incidence of species to habitat variables, and has increasingly formed the backbone of the modelling approaches used. New ‘data technologies’, such as remote sensing and geographical information systems, have further broadened these modelling applications to almost any ecological system and any species for which there are distribution data.2Many previous approaches have aimed to identify the most parsimonious model with the best suite of predictors, selected on the basis of null hypothesis testing. However, information-theoretic approaches based on Akaike's information criterion allow the selection of a best approximating model or a subset of models from a set of candidates. Information-theoretic approaches require a deeper understanding of the biology of the system modelled and may well become an improved paradigm for species distribution modelling.3Synthesis and applications. This special profile of six papers demonstrates the development in methodology used in species distribution modelling. The papers show how information-theoretic approaches can be coupled with emerging data technologies to address issues of conservation significance. With conservation biology and applied ecology at the forefront of many of the basic science developments so far, we expect these methods to pervade other areas of ecological research more fully in future.

Expression of luminal and basal cytokeratins in human breast carcinoma

Abstract: We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14 Additionally, assessment of alpha-smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed The vast majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age Multivariate analysis showed that CK 5/6 was an independent indicator for relapse free interval We were able to subgroup the cases into four distinct phenotype categories (pure luminal, mixed luminal/basal, pure basal and null), which had significant differences in relation to the biological features and the clinical course of the disease Tumours classified as expressing a basal phenotype (the combined luminal plus basal and the pure basal) were in a poor prognostic subgroup, typically ER negative in most cases These findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance

Peer relations in childhood

Abstract: We present a developmental model that describes normal peer relations and highlights processes that underlie the emergence of problems with peers in childhood. We propose that children's relationships with peers begin in the first years of life, with stable individual differences and preferences for particular peers emerging by three years of age. Social skills that facilitate peer relationships consolidate in the preschool years, during which time peer groups become structured with respect to friendship groups, gender, and dominance relations; some children begin to be rejected by their peers. In later childhood some children develop entrenched problems with peer relationships, in terms of loneliness, bullying and victimisation. Underlying cognitive and emotional processes that facilitate successful peer relationships at all ages are identified, and the extent to which peer relations play a causal role in the genesis of disorder is evaluated. A review of the evidence suggests that, rather than a simple pathway from problematic peer relations to disorder, there is a reciprocal relationship between children's problems with peers and their psychological problems from infancy to adolescence.

The HIPASS catalogue - I. Data presentation

Abstract: The H I Parkes All-Sky Survey (HIPASS) catalogue forms the largest uniform catalogue of H I sources compiled to date, with 4315 sources identified purely by their H I content. The catalogue data comprise the southern region δ< + 2 ◦ of HIPASS, the first blind H I survey to cover the entire southern sky. The rms noise for this survey is 13 mJy beam −1 and the velocity range is −1280 to 12 700 km s −1 . Data search, verification and parametrization methods are discussed along with a description of measured quantities. Full catalogue data are made available to the astronomical community including positions, velocities, velocity widths, integrated fluxes and peak flux densities. Also available are on-sky moment maps, position‐velocity moment maps and spectra of catalogue sources. A number of local large-scale features are observed in the space distribution of sources, including the super-Galactic plane and the Local Void. Notably, large-scale structure is seen at low Galactic latitudes, a region normally obscured at optical wavelengths.

Heterogeneous enantioselective catalysts: strategies for the immobilisation of homogeneous catalysts

Abstract: Enantioselective formation of C–H, C–C, C–O and C–N bonds has been extensively studied using homogeneous asymmetric catalysts for many years. However, these catalysts have yet to make a significant impact in the industrial synthesis of fine chemicals. A central reason is that homogeneous asymmetric catalyst design requires relatively bulky ligands and catalyst re-use through recovery and recycle often causes problems. One mechanism to overcome this problem is to immobilise the asymmetric catalyst onto a support and the resulting heterogeneous asymmetric catalyst can, in principle, be readily re-used. This tutorial review covers the different methodologies for immobilisation, including: adsorption, encapsulation, tethering using a covalent bond and electrostatic interaction and is aimed at both researchers new to the field and those with a wider interest in the immobilisation of homogeneous catalysts. Most importantly, recent studies will be highlighted that demonstrate that immobilised catalysts can give higher enantioselection when compared with their non-immobilised counterparts and the question of how high enantioselection can be achieved is addressed.

A Transgenic Mouse with a Deletion in the Collagenous Domain of Adiponectin Displays Elevated Circulating Adiponectin and Improved Insulin Sensitivity

Abstract: Adiponectin is a plasma protein expressed exclusively in adipose tissue. Adiponectin levels are linked to insulin sensitivity, but a direct effect of chronically elevated adiponectin on improved insulin sensitivity has not yet been demonstrated. We identified a dominant mutation in the collagenous domain of adiponectin that elevated circulating adiponectin values in mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and suppressed insulin-mediated endogenous glucose production. The induction of adiponectin during puberty and the sexual dimorphism in adult adiponectin values were preserved in these transgenic animals. As a result of elevated adiponectin, serum PRL values and brown adipose mass both increased. The effects on carbohydrate and lipid metabolism were associated with elevated phosphorylation of 5′-AMP-activated protein kinase in liver and elevated expression of peroxisomal proliferator-activated receptor γ2, caveolin-1, and mitochondrial markers in white adip...

The 1000 Brightest HIPASS Galaxies: H I Properties

Abstract: We present the HIPASS Bright Galaxy Catalog (BGC), which contains the 1000 H I brightest galaxies in the southern sky as obtained from the H i Parkes All-Sky Survey ( HIPASS). The selection of the brightest sources is based on their H I peak flux density (S-peak greater than or similar to116 mJy) as measured from the spatially integrated HIPASS spectrum. The derived H I masses range from similar to10(7) to 4 x 10(10) M-.. While the BGC ( z 10degrees. Therefore, the BGC yields no evidence for a population of free-floating'' intergalactic H I clouds without associated optical counterparts. HIPASS provides a clear view of the local large-scale structure. The dominant features in the sky distribution of the BGC are the Supergalactic Plane and the Local Void. In addition, one can clearly see the Centaurus Wall, which connects via the Hydra and Antlia Clusters to the Puppis Filament. Some previously hardly noticable galaxy groups stand out quite distinctly in the H I sky distribution. Several new structures, including some not behind the Milky Way, are seen for the first time.

Talking whilst walking: a geographical archaeology of knowledge

Abstract: This paper explores how understandings of the knowledge and lives of individuals can be gained through making geographical context more explicit within qualitative research methods. The paper will focus on ‘conversations in place’. More particularly, it will suggest that conversations held whilst walking through a place have the potential to generate a collage of collaborative knowledge. Drawing on the work of Casey, the paper builds upon the notion of the ‘constitutive co-ingredience’ of place and human identity, and, through using documentary and empirical examples, will argue that ‘talking whilst walking’ can harness place as an active trigger to prompt knowledge recollection and production.

Large–scale geographical variation confirms that climate change causes birds to lay earlier

Abstract: Advances in the phenology of organisms are often attributed to climate change, but alternatively, may reflect a publication bias towards advances and may be caused by environmental factors unrelated to climate change. Both factors are investigated using the breeding dates of 25 long-term studied populations of Ficedula flycatchers across Europe. Trends in spring temperature varied markedly between study sites, and across populations the advancement of laying date was stronger in areas where the spring temperatures increased more, giving support to the theory that climate change causally affects breeding date advancement.

Hemoxygenase-2 Is an Oxygen Sensor for a Calcium-Sensitive Potassium Channel

Abstract: Modulation of calcium-sensitive potassium (BK) channels by oxygen is important in several mammalian tissues, and in the carotid body it is crucial to respiratory control. However, the identity of the oxygen sensor remains unknown. We demonstrate that hemoxygenase-2 (HO-2) is part of the BK channel complex and enhances channel activity in normoxia. Knockdown of HO-2 expression reduced channel activity, and carbon monoxide, a product of HO-2 activity, rescued this loss of function. Inhibition of BK channels by hypoxia was dependent on HO-2 expression and was augmented by HO-2 stimulation. Furthermore, carotid body cells demonstrated HO-2–dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation.

Do biomedical models of illness make for good healthcare systems

Abstract: Current medical models assume that all illness is secondary to disease. Revision is needed to explain illnesses without disease and improve organisation of health care

Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor

Abstract: Ghrelin promotes fat accumulation, despite potent stimulation of the lipolytic hormone, GH. The function of the major circulating isoform of ghrelin, des-octanoyl ghrelin, is unclear, because it does not activate the GH secretagogue receptor (GHS-R1a) and lacks the endocrine activities of ghrelin. We have now addressed these issues by infusing ghrelin, des-octanoyl ghrelin, or synthetic GHS-R1a agonists into three rat models with moderate, severe, or total GH deficiency. We show that in the context of significant GH secretion, the adipogenic effect of systemic ghrelin infusion is pattern dependent. However, this adipogenic action is not mediated by the pituitary hormones. Using a novel unilateral local infusion strategy, we demonstrate that ghrelin promotes bone marrow adipogenesis in vivo by a direct peripheral action. Surprisingly, this effect was also observed with des-octanoyl ghrelin, whereas a potent synthetic GHS-R1a agonist was ineffective. Thus, these adipogenic effects are mediated by a receptor other than GHS-R1a. This is the first in vivo demonstration of a direct adipogenic effect of des-octanoyl ghrelin, a major circulating form of ghrelin that lacks GH-releasing activity. We suggest that the ratio of ghrelin and des-octanoyl ghrelin production could help regulate the balance between adipogenesis and lipolysis in response to nutritional status.