Neural modelling, control and optimisation of an industrial grinding process

This paper describes the development of neural model-based control strategies for the optimisation of an industrial aluminium substrate disk grinding process. The grindstone removal rate varies considerably over a stone life and is a highly nonlinear function of process variables. Using historical grindstone performance data, a NARX-based neural network model is developed. This model is then used to implement a direct inverse controller and an internal model controller based on the process settings and previous removal rates. Preliminary plant investigations show that thickness defects can be reduced by 50% or more, compared to other schemes employed. (c) 2004 Elsevier Ltd. All rights reserved.

Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2

Explaining the uniqueness of the acquired somatic JAK2 V617F mutation, which is present in more than 95% of polycythemia vera patients, has been a challenge. The V617F mutation in the pseudokinase domain of JAK2 renders the unmutated kinase domain constitutively active. We have performed random mutagenesis at position 617 of JAK2 and tested each of the 20 possible amino acids for ability to induce constitutive signaling in Ba/F3 cells expressing the erythropoietin receptor. Four JAK2 mutants, V617W, V617M, V617I, and V617L, were able to induce cytokine independence and constitutive downstream signaling. Only V617W induced a level of constitutive activation comparable with V617F. Also, only V617W stabilized tyrosine-phosphorylated suppressor of cytokine signaling 3 ( SOCS3), a mechanism by which JAK2 V617F overcomes inhibition by SOCS3. The V617W mutant induced a myeloproliferative disease in mice, mainly characterized by erythrocytosis and megakaryocytic proliferation. Although JAK2 V617W would predictably be pathogenic in humans, the substitution of the Val codon, GTC, by TTG, the codon for Trp, would require three base pair changes, and thus it is unlikely to occur. We discuss how the predicted conformations of the activated JAK2 mutants can lead to better screening assays for novel small molecule inhibitors.

The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognition.

T cell immune responses to central nervous system-derived and other self-antigens are commonly described in both healthy and autoimmune individuals. However, in the case of the human prion protein (PrP), it has been argued that immunologic tolerance is uncommonly robust. Although development of an effective vaccine for prion disease requires breaking of tolerance to PrP, the extent of immune tolerance to PrP and the identity of immunodominant regions of the protein have not previously been determined in humans. We analyzed PrP T cell epitopes both by using a predictive algorithm and by measuring functional immune responses from healthy donors. Interestingly, clusters of epitopes were focused around the area of the polymorphic residue 129, previously identified as an indicator of susceptibility to prion disease, and in the C-terminal region. Moreover, responses were seen to PrP peptide 121-134 containing methionine at position 129, whereas PrP 121-134 [129V] was not immunogenic. The residue 129 polymorphism was also associated with distinct patterns of cytokine response: PrP 128-141 [129M] inducing IL-4 and IL-6 production, which was not seen in response to PrP 128-141 [129V]. Our data suggest that the immunogenic regions of human PrP lie between residue 107 and the C-terminus and that, like with many other central nervous system antigens, healthy individuals carry responses to PrP within the T cell repertoire and yet do not experience deleterious autoimmune reactions.

Industrial applications of ionic liquids

The potential to use Ionic Liquids (ILs) as novel solvents or fluids for a diverse range of applications has become increasingly rent as researchers in academia and try respond to challenges from atmospheric emissions and disposal of many common solvents by evaluating novel reaction media. The intrinsic non-volatile nature of ILs provides an opportunity to reduce, or even completely eliminate, hazardous and toxic emissions to the atmosphere, thus providing the promise for significant environmental benefits. In synthesis and catalysis, ILs have been used as solvents (or solvents and catalysts), with the greatest current effort on using the ILs as alternatives to VOCs. In contrast, electrochemical studies hove utills'ed the fact that ILs are liquid rather than solids to provide liquid electrolytes without needing to odd an additional solvent. is overview appraiso an appraisal of potential to use ILs in industrial applications, illustrating some areas where practical uses are being developed, and how, throuqh understanding ionic liquids in a conceptuo level, new opportunities ore continuing to evolve.

Nature as historical protagonist: environment and society in pre-industrial England

This article compares chronologies reconstructed from historical records of prices, wages, grain harvests, and population with corresponding chronologies of growing conditions and climatic variations derived from dendrochronology and Greenland ice-cores. It demonstrates that in pre-industrial, and especially late medieval, England, short-term environmental shocks and more enduring shifts in environmental conditions (sometimes acting in concert with biological agencies) exercised a powerful influence upon the balance struck between population and available resources via their effects upon the reproduction, health and life expectancy of humans, crops, and livestock. Prevailing socio-economic conditions and institutions, in turn, shaped society's susceptibility to these environmental shocks and shifts.

Will attracting the creative class boost economic growth in old industrial regions? A case study of Scotland

Attracting in-migration of the creative class has been argued by Florida (2002) to be a route to higher economic growth in the era of the knowledge economy. This paper critically evaluates this proposition in relation to old industrial regions using the example of Scotland. The paper presents an assessment of, in the first instance, to what extent there is a shortage of skilled, talented and entrepreneurial individuals and, in the second instance, whether a talent attraction strategy alone can hope to attract such people to Scotland. It is proposed that for most migrants the availability of appropriate economic opportunities is a prerequisite for mobility. However, despite uncertain evidence that place attractiveness is a catalyst to mobility among the so-called creative class, this is not a reason for dismissing talent attraction programmes. Instead it is argued that talent attraction programmes have the potential to contribute to old industrial economies, but their success will be greatest when talent attraction is carefully targeted and based on economic realities rather than the marketing of ethereal conceptions of place attractiveness.