Showing papers by "University of Bath published in 1995"

Model uncertainty, data mining and statistical inference

Abstract: This paper takes a broad, pragmatic view of statistical inference to include all aspects of model formulation. The estimation of model parameters traditionally assumes that a model has a prespecified known form and takes no account of possible uncertainty regarding the model structure. This implicitly assumes the existence of a 'true' model, which many would regard as a fiction. In practice model uncertainty is a fact of life and likely to be more serious than other sources of uncertainty which have received far more attention from statisticians. This is true whether the model is specified on subject-matter grounds or, as is increasingly the case, when a model is formulated, fitted and checked on the same data set in an iterative, interactive way. Modern computing power allows a large number of models to be considered and data-dependent specification searches have become the norm in many areas of statistics. The term data mining may be used in this context when the analyst goes to great lengths to obtain a good fit. This paper reviews the effects of model uncertainty, such as too narrow prediction intervals, and the non-trivial biases in parameter estimates which can follow data-based modelling. Ways of assessing and overcoming the effects of model uncertainty are discussed, including the use of simulation and resampling methods, a Bayesian model averaging approach and collecting additional data wherever possible. Perhaps the main aim of the paper is to ensure that statisticians are aware of the problems and start addressing the issues even if there is no simple, general theoretical fix.

The Unmanaged Organization: Stories, Fantasies and Subjectivity

Abstract: This paper argues that within every organization there is a terrain which is not and cannot be managed, in which people, both individually and in groups, can engage in unsupervised, spontaneous activity This is referred to as the unmanaged organization, a kind of organizational dreamworld in which desires, anxieties and emotions find expressions in highly irrational construc tions The chief force in this terrain is fantasy and its landmarks include stories, myths, jokes, gossip, nicknames, graffiti and cartoons In the organizational dreamworld, emotions prevail over rationality and pleasure over reality The paper argues that fantasy offers a third possibility to organizational members, which amounts to neither conformity nor rebellion, but to a grudging material acceptance accompanied by a symbolic refashioning of events and official stor ies Far from being a marginal terrain, it is suggested that the unmanaged organisation is rich, multidimensional and the natural habitat of subjectivity Four diffe

Growth of necrotic tumors in the presence and absence of inhibitors.

Abstract: A mathematical model is presented for the growth of a multicellular spheroid that comprises a central core of necrotic cells surrounded by an outer annulus of proliferating cells. The model distinguishes two mechanisms for cell loss: apoptosis and necrosis. Cell loss due to apoptosis is defined to be programmed cell death, occurring, for example, when a cell exceeds its natural lifespan, whereas cell death due to necrosis is induced by changes in the cell's microenvironment, occurring, for example, in nutrient-depleted regions. Mathematically, the problem involves tracking two free boundaries, one for the outer tumor radius, the other for the inner necrotic radius. Numerical simulations of the model are presented in an inhibitor-free setting and an inhibitor-present setting for various parameter values. The effects of nutrients and inhibitors on the existence and stability of the time-independent solutions of the model are studied using a combination of numerical and asymptotic techniques.

Flexible AC transmission systems

Abstract: This is the first of four tutorials on the general subject of flexible AC transmission systems (FACTS). This tutorial gives an overview of the area and explains why FACTS devices are needed. Future tutorials will describe methods of controlling and compensating AC transmission lines, FACTS based on thyristors and FACTS devices based on GTOs.

Fabrication of hollow porous shells of calcium carbonate from self-organizing media

Abstract: A RICH variety of elaborate microscopic skeletal structures composed of inorganic materials are produced in nature1. Such complex, three-dimensional structures, if produced synthetically, could find important applications as light-weight ceramics, catalyst supports, biomedical implants and robust membranes for high-temperature separation technology. Here we describe a method for synthesizing hollow porous shells of crystalline calcium carbonate (aragonite) that resemble the coccospheres of certain marine algae. We show that thin cellular frameworks of either mesoporous or macroporous aragonite can be formed from oil–water–surfactant microemulsions supersaturated with calcium bicarbonate, with the pore size determined by the relative concentrations of water and oil. Using micrometre-sized polystyrene beads as the substrate for the microemulsion, hollow spherical shells of the honeycomb architecture can be produced. We propose that these cellular frameworks originate from rapid mineralization of aragonite, with a self-organized foam of oil droplets acting as a structural template, and suggest that similar processes could be of general importance in materials chemistry.

Synthesis and Structure of an Iron(III) Sulfide-Ferritin Bioinorganic Nanocomposite.

Abstract: Amorphous iron sulfide minerals containing either 500 or 3000 iron atoms in each cluster have been synthesized in situ within the nanodimensional cavity of horse spleen ferritin. Iron-57 Mossbauer spectroscopy indicated that most of the iron atoms in the 3000-iron atom cores are trivalent, whereas in the 500-iron atom clusters, approximately 50 percent of the iron atoms are Fe(III), with the remaining atoms having an effective oxidation state of about +2.5. Iron K-edge extended x-ray absorption fine structure data for the 500-iron atom nanocomposite are consistent with a disordered array of edge-shared FeS4 tetrahedra, connected by Fe(S)2Fe bridges with bond lengths similar to those of the cubane-type motif of iron-sulfur clusters. The approach used here for the controlled synthesis of bioinorganic nanocomposites could be useful for the nanoscale engineering of dispersed materials with biocompatible and bioactive properties.

Classical and quantum magnetic phenomena in natural and artificial ferritin proteins

Abstract: Artificial ferritin has been synthesized with control of both the magnetic state (antiferromagnetic or ferrimagnetic) and the particle size over an ofer of magnitude in the number of iron atoms. The magnetic properties of the artificial ferritin were compared with those of natural horse spleen ferritin in a range of temperatures (20 millikelvin to 300 kelvin) and fields (1 nanotesla to 27 tesla). In the classical regime, the blocking temperature was found to correlate with the average particle size. A correlation was also observed in the quantum regime between the resonance frequency of macroscopic quantum tunneling of the Neel vector and the particle size. At high magnetic fields (to 27 tesla), a spin flop transition with a strong dependence on orientation was seen in the natural ferritin, providing evidence of antiferromagnetism in this system.

Spatial holeburning effects on the dynamics of vertical cavity surface-emitting laser diodes

Abstract: Calculations are reported of the dynamic evolution of transverse modes in vertical cavity surface emitting lasers (VCSEL's). It is shown that the spatial distribution of the modal fields plays an important role in determining the steady-state operating characteristics of the device. It is found that spatially separated modes can coexist by sharing the available gain, whereas strong competition occurs between modes that have a strong spatial overlap. The influence of carrier diffusion and spatial holeburning during the turn-on transient of the laser is elucidated, and the implications for the steady-state modal properties of the device are indicated. >

A taxonomy of information systems applications: the benefits' evaluation ladder

Abstract: One of the prime reasons for the deployment of information technology in organizations is the expectation of a positive return on the investment. But the returns from different types of application vary both in terms of the ability to provide straightforward measurement of the costs and benefits, and in the degree of certainty with which estimates of costs and benefits will be realised. This paper provides a framework for classifying applications in the form of an eight-rung ladder, each rung of which represents a class of application. The way in which applications need to be handled and the methods by which their impact can be evaluated changes from rung to rung. Moving up the ladder increases the complexity of evaluation and the degree of risk and uncertainty, but at the same time also increases the potential returns on the investments. The ladder is different from conventional ‘strategic IT’ frameworks: it is a framework for action as well as understanding; it specifically relates to evaluation; and it does not imply any predetermined or time-based sequence of progress.

Cloning of an Enterococcus faecalis endocarditis antigen: homology with adhesins from some oral streptococci.

Abstract: Serum from a patient with Enterococcus faecalis endocarditis was used to identify the gene efaA cloned in Lambda ZapII in Escherichia coli. Nucleotide sequence analysis revealed a 924-bp open reading frame encoding a protein with a predicted molecular weight of 34,768. The amino acid sequence of EfaA shows 55 to 60% homology to a group of streptococcal proteins, FimA from Streptococcus parasanguis, SsaB from Streptococcus sanguis, ScaA from Streptococcus gordonii, and PsaA from Streptococcus pneumoniae. Members of this group have been shown to be adhesins, and we hypothesize that EfaA may function as an adhesin in endocarditis.

Marketing higher education: the MBA experience

Abstract: Given the increasing competition in higher education, including that on MBA degrees, it is surprising that more attention has not been paid to marketing issues, such as are educational institutions really “customer‐oriented”?; do they choose the most appropriate market segments?; the complexities of the decision processes of the “buyers”. Looks first at general issues facing educational marketers, and then examines the marketing of MBA degrees in the light of theory, of previous survey data and of evidence arising from their collective experience. Concludes that, whether the “customer” is an individual student or a company, a greater understanding of buyer behaviour is needed; business schools should improve their marketing or stand accused of not practising what they preach.

The attentional control of pain: Methodological and theoretical concerns.

Abstract: Although it is now well accepted that attention-based cognitive coping strategies are effective in altering pain perception and have potentially useful analgesic qualities, there exists contradiction and equivocation as to the role of various factors in the production of that analgesia. Cioffi (1991) has suggested that the response to this equivocation has been a ‘collective ennui’ on the part of researchers. This article seeks to explore methodological and theoretical reasons for this reigning equivocation and offers some suggestions for moving beyond it. In particular, critical attention is focussed upon four possible sources of variance in experimental pain procedures: the choice of the pain induction procedure, the instructions given, the measures taken and the content of the taught strategy.

RANTES-activated human T lymphocytes. A role for phosphoinositide 3-kinase.

Abstract: RANTES (regulated on activation, normal T cell expressed and secreted), a member of the chemokine family, is a potent chemoattractant for CD4+/CD45RO human T lymphocytes, but the signal-transduction mechanisms utilized by RANTES are poorly defined. In freshly isolated human T lymphocytes loaded with fura-2 acetoxymethyl, the CD3 mAb, UCHT-1, but not RANTES, elicited elevation of intracellular calcium levels. However, RANTES produced a bell-shaped chemotactic response and an increase in polarization of the T lymphocytes. Immunoprecipitates of phosphoinositide (PI) 3-kinase, derived from T lymphocytes stimulated with RANTES, contained increased in vitro PI 3-kinase activity compared with that present in immunoprecipitates derived from vehicle-treated cells. RANTES induction of PI 3-kinase activity was maximal at 10 to 100 ng/ml. Furthermore, the fungal metabolite, wortmannin, which is a potent PI 3-kinase inhibitor, inhibited RANTES-induced T lymphocyte migration, polarization, and increased PI 3-kinase activity. Our results show that RANTES activation of T lymphocytes seems to be independent of detectable elevation of cytosolic-free calcium, but the functional effects of chemotaxis and polarization, induced by RANTES, seem to involve the putative PI 3-kinase signal-transduction pathway.

Repeat Treatment of Obese Mice With BRL 49653, a New Potent Insulin Sensitizer, Enhances Insulin Action in White Adipocytes: Association With Increased Insulin Binding and Cell-Surface GLUT4 as Measured by Photoaffinity Labeling

Abstract: (±)-5-([4-[2-Methyl-2(pyridylamino)ethoxy]phenyl]methyl) 2,4-thiazolidinedione (BRL 49653) is a new potent antidiabetic agent that improves insulin sensitivity in animal models of NIDDM. In C57BL/6 obese ( ob/ob ) mice, BRL 49653, included in the diet for 8 days, improved glucose tolerance. The half-maximal effective dose was 3 μmol/kg diet, which is equivalent to ∼0.1 mg/kg body wt. Improvements in glucose tolerance were accompanied by significant reductions in circulating triacylglycerol, nonesterified fatty acids, and insulin. The insulin receptor number of epididymal white adipocytes prepared from obese mice treated with BRL 49653 (30 μmol/kg diet) for 14 days was increasedtwofold. The affinity of the receptor for insulin was unchanged. In the absence of added insulin, the rates of glucose transport in adipocytes from untreated and BRL 49653-treated obese mice were similar. Insulin (73 nmol/l) produced only a 1.5-fold increase in glucose transport in adipocytes from control obese mice, whereas after BRL 49653 treatment, insulin stimulated glucose transport 2.8-fold. BRL 49653 did not alter the sensitivity of glucose transport to insulin. The increase in insulin responsiveness was accompanied by a 2.5-fold increase in the total tissue content of the glucose transporter GLUT4. Glucose transport in adipocytes from lean littermates was not altered by BRL 49653. To establish the contribution of changes in glucose transporter trafficking to the BRL 49653-mediated increase in insulin action, the cell-impermeant bis-mannose photolabel 2- N -[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis-(D-mannos-4-yloxy)-2-[2- 3 H]-propylamine was used to measure adipocyte cell-surface–associated glucose transporters. In these experiments, the increase in maximal insulin-stimulated glucose transport (4.2-fold) produced after BRL 49653 treatment was correlated with a 2.6-fold increase in cell-surface–associated GLUT4. Photolabeled cell-sur-face GLUT1 was not detectable in any adipocyte preparation. These results suggest that the improvement in glycemic control produced by repeated administration of BRL 49653 to obese mice is mediated by increased insulin responsiveness of target tissues. BRL 49653 potentiates insulin-stimulated glucose transport in adipocytes from insulin-resistant obese mice, both by increasing insulin receptor number and by facilitating translocation of GLUT4, from an expanded intracellular pool, to the cell surface. In addition, the increased intrinsic activity of cell-surface glucose transporters may also contribute to an increased insulin responsiveness of adipose tissue.