Size frequency distributions of the florid prion protein aggregates in variant Creutzfeldt-Jakob disease follow a power-law function

The objective was to test the hypothesis that the size frequency distributions of the prion protein (PrP) plaques in cases of variant Creutzfeldt-Jakob disease (vCJD) follow a power-law function. The design was a retrospective neuropathological study. The patients were 11 cases of clinically and neuropathologically verified vCJD. Size distributions of the diffuse and florid-type plaques were measured in several areas of the cerebral cortex and hippocampus from each case and a power-law function fitted to each distribution. The size distributions of the florid and diffuse plaques were fitted successfully by a powerlaw function in 100% and 42% of brain areas investigated respectively. Processes of aggregation/disaggregation may be more important than surface diffusion in the pathogenesis of the florid plaques. By contrast, surface diffusion may be a more significant factor in the development of the diffuse plaques. © Springer-Verlag Italia 2006.

Molecular phase space transport in water:non-stationary random walk model

Molecular transport in phase space is crucial for chemical reactions because it defines how pre-reactive molecular configurations are found during the time evolution of the system. Using Molecular Dynamics (MD) simulated atomistic trajectories we test the assumption of the normal diffusion in the phase space for bulk water at ambient conditions by checking the equivalence of the transport to the random walk model. Contrary to common expectations we have found that some statistical features of the transport in the phase space differ from those of the normal diffusion models. This implies a non-random character of the path search process by the reacting complexes in water solutions. Our further numerical experiments show that a significant long period of non-stationarity in the transition probabilities of the segments of molecular trajectories can account for the observed non-uniform filling of the phase space. Surprisingly, the characteristic periods in the model non-stationarity constitute hundreds of nanoseconds, that is much longer time scales compared to typical lifetime of known liquid water molecular structures (several picoseconds).

Introduction: improving manufacturing performance through technology diffusion, implementation and management

The role of technology management in achieving improved manufacturing performance has been receiving increased attention as enterprises are becoming more exposed to competition from around the world. In the modern market for manufactured goods the demand is now for more product variety, better quality, shorter delivery and greater flexibility, while the financial and environmental cost of resources has become an urgent concern to manufacturing managers. This issue of the International Journal of Technology Management addresses the question of how the diffusion, implementation and management of technology can improve the performance of manufacturing industries. The authors come from a large number of different countries and their contributions cover a wide range of topics within this general theme. Some papers are conceptual, others report on research carried out in a range of different industries including steel production, iron founding, electronics, robotics, machinery, precision engineering, metal working and motor manufacture. In some cases they describe situations in specific countries. Several are based on presentations made at the UK Operations Management Association's Sixth International Conference held at Aston University at which the conference theme was 'Achieving Competitive Edge: Getting Ahead Through Technology and People'. The first two papers deal with questions of advanced manufacturing technology implementation and management. Firstly Beatty describes a three year longitudinal field study carried out in ten Canadian manufacturing companies using CADICAM and CIM systems. Her findings relate to speed of implementation, choice of system type, the role of individuals in implementation, organization and job design. This is followed by a paper by Bessant in which he argues that a more a strategic approach should be taken towards the management of technology in the 1990s and beyond. Also considered in this paper are the capabilities necessary in order to deploy advanced manufacturing technology as a strategic resource and the way such capabilities might be developed within the firm. These two papers, which deal largely with the implementation of hardware, are supplemented by Samson and Sohal's contribution in which they argue that a much wider perspective should be adopted based on a new approach to manufacturing strategy formulation. Technology transfer is the topic of the following two papers. Pohlen again takes the case of advanced manufacturing technology and reports on his research which considers the factors contributing to successful realisation of AMT transfer. The paper by Lee then provides a more detailed account of technology transfer in the foundry industry. Using a case study based on a firm which has implemented a number of transferred innovations a model is illustrated in which the 'performance gap' can be identified and closed. The diffusion of technology is addressed in the next two papers. In the first of these, by Lowe and Sim, the managerial technologies of 'Just in Time' and 'Manufacturing Resource Planning' (or MRP 11) are examined. A study is described from which a number of factors are found to influence the adoption process including, rate of diffusion and size. Dahlin then considers the case of a specific item of hardware technology, the industrial robot. Her paper reviews the history of robot diffusion since the early 1960s and then tries to predict how the industry will develop in the future. The following two papers deal with the future of manufacturing in a more general sense. The future implementation of advanced manufacturing technology is the subject explored by de Haan and Peters who describe the results of their Dutch Delphi forecasting study conducted among a panel of experts including scientists, consultants, users and suppliers of AMT. Busby and Fan then consider a type of organisational model, 'the extended manufacturing enterprise', which would represent a distinct alternative pure market-led and command structures by exploiting the shared knowledge of suppliers and customers. The three country-based papers consider some strategic issues relating manufacturing technology. In a paper based on investigations conducted in China He, Liff and Steward report their findings from strategy analyses carried out in the steel and watch industries with a view to assessing technology needs and organizational change requirements. This is followed by Tang and Nam's paper which examines the case of machinery industry in Korea and its emerging importance as a key sector in the Korean economy. In his paper which focuses on Venezuela, Ernst then considers the particular problem of how this country can address the problem of falling oil revenues. He sees manufacturing as being an important contributor to Venezuela's future economy and proposes a means whereby government and private enterprise can co-operate in development of the manufacturing sector. The last six papers all deal with specific topics relating to the management manufacturing. Firstly Youssef looks at the question of manufacturing flexibility, introducing and testing a conceptual model that relates computer based technologies flexibility. Dangerfield's paper which follows is based on research conducted in the steel industry. He considers the question of scale and proposes a modelling approach determining the plant configuration necessary to meet market demand. Engstrom presents the results of a detailed investigation into the need for reorganising material flow where group assembly of products has been adopted. Sherwood, Guerrier and Dale then report the findings of a study into the effectiveness of Quality Circle implementation. Stillwagon and Burns, consider how manufacturing competitiveness can be improved individual firms by describing how the application of 'human performance engineering' can be used to motivate individual performance as well as to integrate organizational goals. Finally Sohal, Lewis and Samson describe, using a case study example, how just-in-time control can be applied within the context of computer numerically controlled flexible machining lines. The papers in this issue of the International Journal of Technology Management cover a wide range of topics relating to the general question of improving manufacturing performance through the dissemination, implementation and management of technology. Although they differ markedly in content and approach, they have the collective aim addressing the concepts, principles and practices which provide a better understanding the technology of manufacturing and assist in achieving and maintaining a competitive edge.

Cognition, ocular accommodation, and cardiovascular function in emmetropes and late-onset myopes

PURPOSE. To investigate objectively and noninvasively the role of cognitive demand on autonomic control of systemic cardiovascular and ocular accommodative responses in emmetropes and myopes of late-onset. METHODS. Sixteen subjects (10 men, 6 women) aged between 18 and 34 years (mean ± SD: 22.6 ± 4.4 years), eight emmetropes (EMMs; mean spherical equivalent [MSE] refractive error ± SD: 0.05 ± 0.24 D) and eight with late-onset myopia (LOMs; MSE ± SD: -3.66 ± 2.31 D) participated in the study. Subjects viewed stationary numerical digits monocularly within a Badal optical system (at both 0.0 and -3.0 D) while performing a two-alternative, forced-choice paradigm that matched cognitive loading across subjects. Five individually matched cognitive levels of increasing difficulty were used in random order for each subject. Five 20-second, continuous-objective recordings of the accommodative response measured with an open-view infrared autorefractor were obtained for each cognitive level, whereas simultaneous measurement of heart rate was continuously recorded with a finger-mounted piezoelectric pulse transducer for 5 minutes. Fast Fourier transformation of cardiovascular function allowed the relative power of the autonomic components to be assessed in the frequency domain, whereas heart period gave an indication of the time-domain response. RESULTS. Increasing the cognitive demand led to a significant reduction in the accommodative response in all subjects (0.0 D: by -0.35 ± 0.33 D; -3.0 D: by -0.31 ± 0.40 D, P < 0.001). The greater lag of LOMs compared with EMMs was not significant (P = 0.07) at both distance (0.38 ± 0.35 D) and near (0.14 ± 0.42 D). Mean heart period reduced with increasing levels of workload (P < 0.0005). LOMs exhibited a relative elevation in sympathetic system activity compared to EMMs. Within refractive groups, however, accommodative shifts with increasing cognition correlated with parasympathetic activity (r = 0.99, P < 0.001), more than with sympathetic activity (r = 0.62, P > 0.05). CONCLUSIONS. In an equivalent workload paradigm, increasing cognitive demand caused a reduction in accommodative response that was attributable principally to a concurrent reduction in the relative power of the parasympathetic component of the autonomic nervous system (ANS). The disparity in accommodative response between EMMs and LOMs, however, appears to be augmented by changes in the sympathetic nervous component of the systemic ANS. Copyright © Association for Research in Vision and Ophthalmology.

A new variational radial basis function approximation for inference in multivariate diffusions

In this paper we present a radial basis function based extension to a recently proposed variational algorithm for approximate inference for diffusion processes. Inference, for state and in particular (hyper-) parameters, in diffusion processes is a challenging and crucial task. We show that the new radial basis function approximation based algorithm converges to the original algorithm and has beneficial characteristics when estimating (hyper-)parameters. We validate our new approach on a nonlinear double well potential dynamical system.

A longitudinal study of the diffusion of the ISO/IEC information resource dictionary system standard (IRDS.)

The IRDS standard is an international standard produced by the International Organisation for Standardisation (ISO). In this work the process for producing standards in formal standards organisations, for example the ISO, and in more informal bodies, for example the Object Management Group (OMG), is examined. This thesis examines previous models and classifications of standards. The previous models and classifications are then combined to produce a new classification. The IRDS standard is then placed in a class in the new model as a reference anticipatory standard. Anticipatory standards are standards which are developed ahead of the technology in order to attempt to guide the market. The diffusion of the IRDS is traced over a period of eleven years. The economic conditions which affect the diffusion of standards are examined, particularly the economic conditions which prevail in compatibility markets such as the IT and ICT markets. Additionally the consequences of the introduction of gateway or converter devices into a market where a standard has not yet been established is examined. The IRDS standard did not have an installed base and this hindered its diffusion. The thesis concludes that the IRDS standard was overtaken by new developments such as object oriented technologies and middleware. This was partly because of the slow development process of developing standards in traditional organisations which operate on a consensus basis and partly because the IRDS standard did not have an installed base. Also the rise and proliferation of middleware products resulted in exchange mechanisms becoming dominant rather than repository solutions. The research method used in this work is a longitudinal study of the development and diffusion of the ISO/EEC IRDS standard. The research is regarded as a single case study and follows the interpretative epistemological point of view.

The effects of nitrogen mustard on plasma membrane function

The antitumour bifunctional alkylating agent nitrogen mustard (HN2) inhibited the unidirectional influx of the potassium congener, 86 rubidium, into murine PC6A plasmacytoma cells and L1210 leukaemia cells. The proliferation of L1210 cells in vitro was characterised and shown to be sentitive to HN2. 86Rubidium influx into cells from rapidly-dividing cultures was more sensitive to inhibition by HN2 than that of cells from stationary cultures. Three components of unidirectional 86Rb+ & K+ influx into proliferating L1210 cells were identified pharmacologically: approximately 40% was active to the Na+ K+ ATPase inhibitor ouabain (10-3M), 40% was sensitive to the `loop' diuretics bumetanide (10-4M) and furosemide (10-3M) and the remainder was insensitive to both ouabain and furosemide. HN2 (10-5M) selectively inhibited the diuretic-sensitive component, which was entirely dependent upon extracellular Na+ and Cl- ions, and was presumed to represent Na+ K+ Cl- cotransport activity. The system did not mediate K+ /K+ exchange or unidirectional 86Rb+ efflux; accordingly, 86Rb+ efflux was insensitive to HN2. Inhibition of 86Rb & K+ influx by 10-5M HN2 was accompanied by approximately 35% of cell volume under isosmotic conditions; thus intracellular Na+ and K+ concentrations remained unchanged. These effects followed lethal damage to the cells but preceded actual cell death; other cellular functions were maintained including accumulation of cycloleucine, transmembrane potential, permeability to trypan blue, intracellular pH, total intracellular glutathione and calcium concentrations. No evidence was found that elevated cAMP levels or reduced ATP levels were involved in modulation of 86Rb+ & K+ influx. However, the Na+ - depedent transport of an amino acid was inhibited in a manner which appeared to be independent of 86Rb & K+ influx. An HN2-resistant L1210R cell line was also resistant to furosemide, and lacked a component of 86Rb+ & K+ influx which was sensitive to furosemide (10-3M). The results strongly suggest that the Na+ K+ Cl- costransporter of L1210 cells is a cellular target for HN2. This lesion is discussed with reference to the cytotoxic effects of the agent.

The development of calibration and adaptive filtering procedures for neuromagnetic studies of human visual function

This thesis first considers the calibration and signal processing requirements of a neuromagnetometer for the measurement of human visual function. Gradiometer calibration using straight wire grids is examined and optimal grid configurations determined, given realistic constructional tolerances. Simulations show that for gradiometer balance of 1:104 and wire spacing error of 0.25mm the achievable calibration accuracy of gain is 0.3%, of position is 0.3mm and of orientation is 0.6°. Practical results with a 19-channel 2nd-order gradiometer based system exceed this performance. The real-time application of adaptive reference noise cancellation filtering to running-average evoked response data is examined. In the steady state, the filter can be assumed to be driven by a non-stationary step input arising at epoch boundaries. Based on empirical measures of this driving step an optimal progression for the filter time constant is proposed which improves upon fixed time constant filter performance. The incorporation of the time-derivatives of the reference channels was found to improve the performance of the adaptive filtering algorithm by 15-20% for unaveraged data, falling to 5% with averaging. The thesis concludes with a neuromagnetic investigation of evoked cortical responses to chromatic and luminance grating stimuli. The global magnetic field power of evoked responses to the onset of sinusoidal gratings was shown to have distinct chromatic and luminance sensitive components. Analysis of the results, using a single equivalent current dipole model, shows that these components arise from activity within two distinct cortical locations. Co-registration of the resulting current source localisations with MRI shows a chromatically responsive area lying along the midline within the calcarine fissure, possibly extending onto the lingual and cuneal gyri. It is postulated that this area is the human homologue of the primate cortical area V4.

Technical and economic study of plantain food products

Plantain (Banana-Musa AAB) is a widely growing but commercially underexploited tropical fruit. This study demonstrates the processing of plantain to flour and extends its use and convenience as a constituent of bread, cake and biscuit. Plantain was peeled, dried and milled to produce flour. Proximate analysis was carried out on the flour to determine the food composition. Drying at temperatures below 70ºC produced light coloured plantain flour. Experiments were carried out to determine the mechanism of drying, the heat and mass transfer coefficients, effect of air velocity, temperature and cube size on the rate of drying of plantain cubes. The drying was diffusion controlled. Pilot scale drying of plantain cubes in a cabinet dryer showed no significant increase of drying rate above 70ºC. In the temperature range found most suitable for plantain drying (ie 60 to 70ºC) the total drying time was adequately predicted using a modified equation based on Fick's Law provided the cube temperature was taken to be about 5ºC below the actual drying air temperature. Studies of baking properties of plantain flour revealed that plantain flour can be substituted for strong wheat flour up to 15% for bread making and up to 50% for madeira cake. A shortcake biscuit was produced using 100% plantain flour and test-marketed. Detailed economic studies showed that the production of plantain fruit and its processing into flour would be economically viable in Nigeria when the flour is sold at the wholesale price of NO.65 per kilogram provided a minimum sale of 25% plantain suckers. There is need for government subsidy if plantain flour is to compete with imported wheat flour. The broader economic benefits accruing from the processing of plantain fruit into flour and its use in bakery products include employment opportunity, savings in foreign exchange and stimulus to home agriculture.

Show bizz becomes show buzz:how viral diffusion changes the traditional meaning-making process of a rising star

Studying the case of a young French rapper called Kamini, the authors show how the viral diffusion of a new creative product, such as a song, radically changes traditional meaning-making processes. Instead of the top-down approach in which product positioning is carefully constructed and transferred to consumers, marketers are faced with a bottom-up trend in which consumers increasingly participate in blogs and online forums to talk about products (thus, creating and diffusing meaning) before any marketing action is undertaken. Our study aims to understand the interactions and tensions between market forces that result from this pro-active role of the consumer.

The slope of the psychometric function and non-stationarity of thresholds in spatiotemporal contrast vision

The slope of the two-interval, forced-choice psychometric function (e.g. the Weibull parameter, ß) provides valuable information about the relationship between contrast sensitivity and signal strength. However, little is known about how or whether ß varies with stimulus parameters such as spatiotemporal frequency and stimulus size and shape. A second unresolved issue concerns the best way to estimate the slope of the psychometric function. For example, if an observer is non-stationary (e.g. their threshold drifts between experimental sessions), ß will be underestimated if curve fitting is performed after collapsing the data across experimental sessions. We measured psychometric functions for 2 experienced observers for 14 different spatiotemporal configurations of pulsed or flickering grating patches and bars on each of 8 days. We found ß ˜ 3 to be fairly constant across almost all conditions, consistent with a fixed nonlinear contrast transducer and/or a constant level of intrinsic stimulus uncertainty (e.g. a square law transducer and a low level of intrinsic uncertainty). Our analysis showed that estimating a single ß from results averaged over several experimental sessions was slightly more accurate than averaging multiple estimates from several experimental sessions. However, the small levels of non-stationarity (SD ˜ 0.8 dB) meant that the difference between the estimates was, in practice, negligible.

Opinion leaders' role in innovation diffusion:a simulation study

This study investigates the critical role that opinion leaders (or influentials) play in the adoption process of new products. Recent existing reseach evidence indicates a limited effect of opinion leaders on diffusion processes, yet these studies take into account merely the network position of opinion leaders without addressing their influential power. Empirical findings of our study show that opinion leaders, in addition to having a more central network position, possess more accurate knowledge about a product and tend to be less susceptible to norms and more innovative. Experiments that address these attributes, using an agent-based model, demonstrate that opinion leaders increase the speed of the information stream and the adoption process itself. Furthermore, they increase the maximum adoption percentage. These results indicate that targeting opinion leaders remains a valuable marketing strategy.

Pre-attentive auditory sensory processing in autistic spectrum disorder:are electromagnetic measurements telling us a coherent story?

Sensory processing is a crucial underpinning of the development of social cognition, a function which is compromised in variable degree in patients with pervasive developmental disorders (PDD). In this manuscript, we review some of the most recent and relevant contributions, which have looked at auditory sensory processing derangement in PDD. The variability in the clinical characteristics of the samples studied so far, in terms of severity of the associated cognitive deficits and associated limited compliance, underlying aetiology and demographic features makes a univocal interpretation arduous. We hypothesise that, in patients with severe mental deficits, the presence of impaired auditory sensory memory as expressed by the mismatch negativity could be a non-specific indicator of more diffuse cortical deficits rather than causally related to the clinical symptomatology. More consistent findings seem to emerge from studies on less severely impaired patients, in whom increased pitch perception has been interpreted as an indicator of increased local processing, probably as compensatory mechanism for the lack of global processing (central coherence). This latter hypothesis seems extremely attractive and future trials in larger cohorts of patients, possibly standardising the characteristics of the stimuli are a much-needed development. Finally, specificity of the role of the auditory derangement as opposed to other sensory channels needs to be assessed more systematically using multimodal stimuli in the same patient group. (c) 2006 Elsevier B.V. All rights reserved.

Application of long period gratings sensors to respiratory function monitoring

A series of in-line curvature sensors on a garment are used to monitor the thoracic and abdominal movements of a human during respiration. These results are used to obtain volumetric tidal changes of the human torso showing reasonable agreement with a spirometer used simultaneously to record the volume at the mouth during breathing. The curvature sensors are based upon long period gratings written in a progressive three layered fibre that are insensitive to refractive index changes. The sensor platform consists of the long period grating laid upon a carbon fibre ribbon, which is encapsulated in a low temperature curing silicone rubber. An array of sensors is also used to reconstruct the shape changes of a resuscitation manikin during simulated respiration. The data for reconstruction is obtained by two methods of multiplexing and interrogation: firstly using the transmission spectral profile of the LPG's attenuation bands measured using an optical spectrum analyser; secondly using a derivative spectroscopy technique.

Can the Q Link Ally,® a form of sympathetic resonance technology (SRT™), sttenuate scute mobile phone-related changes to neural function?

OBJECTIVES: Exposure to active mobile phones (MP) has been shown to affect human neural function as shown by the electroencephalogram (EEG). Although it has not been determined whether such effects are harmful, a number of devices have been developed that attempt to minimize these MP-related effects. One such device, the Q Link Ally® (QL; Clarus Products, International, L.L.C., San Rafael, CA), is argued to affect the human organism in such a way as to attenuate the effect of MPs. The present pilot study was designed to determine whether there is any indication that QL does alter MP-related effects on the human EEG. DESIGN: Twenty-four (24) subjects participated in a single-blind, fully counterbalanced crossover design in which subjects' resting EEG and phase-locked neural responses to auditory stimuli were assessed under conditions of either active MP or active MP plus QL. RESULTS: The addition of QL to the MP condition increased resting EEG in the gamma range and did so as a function of exposure duration, and it attenuated MP-related effects in the delta and alpha range (at trend-level). The addition of the QL also affected phase-locked neural responses, with a laterality reversal in the alpha range and an alteration to changes over time in the delta range, a reduction of the MP-related beta decrease over time at fronto-posterior sites, and a global reduction in the gamma range that increased as a function of exposure duration. No unambiguous relations were found between these changes and either performance or psychologic state. CONCLUSIONS: This pilot study suggests that the addition of the QL to active MP-exposure does affect neural function in humans, altering both resting EEG patterns and the evoked neural response to auditory stimuli, and that there is a tendency for some MP-related changes to the EEG to be attenuated by the QL.