The glycosylation pattern of baculovirus expressed envelope protein E2 affects its ability to prevent infection with bovine viral diarrhoea virus

We have investigated the role of glycosylation of the envelope glycoprotein E2 of bovine viral diarrhoea virus (BVDV), produced in insect cells, in BVDV infection. When amino acids predicated to code for the C-terminal N-linked glycosylation site were mutated the resulting protein was less efficient than wild type protein at preventing infection of susceptible cells with BVDV. In addition, mutational analysis showed that a further two predicted N-terminal N-linked glycosylation sites of E2 are required for efficient production of recombinant protein. (c) 2005 Elsevier B.V. All rights reserved.

A novel Bayesian approach to drug design with simple and complex enzymes: Use with lens aldehyde dehydrogenase and the glyoxalase pathway

Purpose: Acquiring details of kinetic parameters of enzymes is crucial to biochemical understanding, drug development, and clinical diagnosis in ocular diseases. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. Methods: We have developed Bayesian utility functions to minimise kinetic parameter variance involving differentiation of model expressions and matrix inversion. These have been applied to the simple kinetics of the enzymes in the glyoxalase pathway (of importance in posttranslational modification of proteins in cataract), and the complex kinetics of lens aldehyde dehydrogenase (also of relevance to cataract). Results: Our successful application of Bayesian statistics has allowed us to identify a set of rules for designing optimum kinetic experiments iteratively. Most importantly, the distribution of points in the range is critical; it is not simply a matter of even or multiple increases. At least 60 % must be below the KM (or plural if more than one dissociation constant) and 40% above. This choice halves the variance found using a simple even spread across the range.With both the glyoxalase system and lens aldehyde dehydrogenase we have significantly improved the variance of kinetic parameter estimation while reducing the number and costs of experiments. Conclusions: We have developed an optimal and iterative method for selecting features of design such as substrate range, number of measurements and choice of intermediate points. Our novel approach minimises parameter error and costs, and maximises experimental efficiency. It is applicable to many areas of ocular drug design, including receptor-ligand binding and immunoglobulin binding, and should be an important tool in ocular drug discovery.

Application of neural network to hybrid systems with binary inputs

Boolean input systems are in common used in the electric industry. Power supplies include such systems and the power converter represents these. For instance, in power electronics, the control variable are the switching ON and OFF of components as thyristors or transistors. The purpose of this paper is to use neural network (NN) to control continuous systems with Boolean inputs. This method is based on classification of system variations associated with input configurations. The classical supervised backpropagation algorithm is used to train the networks. The training of the artificial neural network and the control of Boolean input systems are presented. The design procedure of control systems is implemented on a nonlinear system. We apply those results to control an electrical system composed of an induction machine and its power converter.

Using Doppler radar with a simple explicit microphysics model to diagnose problems with ice sublimation depth-scales in forecast models

Several previous studies have attempted to assess the sublimation depth-scales of ice particles from clouds into clear air. Upon examining the sublimation depth-scales in the Met Office Unified Model (MetUM), it was found that the MetUM has evaporation depth-scales 2–3 times larger than radar observations. Similar results can be seen in the European Centre for Medium-Range Weather Forecasts (ECMWF), Regional Atmospheric Climate Model (RACMO) and Météo-France models. In this study, we use radar simulation (converting model variables into radar observations) and one-dimensional explicit microphysics numerical modelling to test and diagnose the cause of the deep sublimation depth-scales in the forecast model. The MetUM data and parametrization scheme are used to predict terminal velocity, which can be compared with the observed Doppler velocity. This can then be used to test the hypothesis as to why the sublimation depth-scale is too large within the MetUM. Turbulence could lead to dry air entrainment and higher evaporation rates; particle density may be wrong, particle capacitance may be too high and lead to incorrect evaporation rates or the humidity within the sublimating layer may be incorrectly represented. We show that the most likely cause of deep sublimation zones is an incorrect representation of model humidity in the layer. This is tested further by using a one-dimensional explicit microphysics model, which tests the sensitivity of ice sublimation to key atmospheric variables and is capable of including sonde and radar measurements to simulate real cases. Results suggest that the MetUM grid resolution at ice cloud altitudes is not sufficient enough to maintain the sharp drop in humidity that is observed in the sublimation zone.

An introduction to medical imaging with coherent terahertz frequency radiation

Methods have recently been developed that make use of electromagnetic radiation at terahertz (THz) frequencies, the region of the spectrum between millimetre wavelengths and the infrared, for imaging purposes. Radiation at these wavelengths is non-ionizing and subject to far less Rayleigh scatter than visible or infrared wavelengths, making it suitable for medical applications. This paper introduces THz pulsed imaging and discusses its potential for in vivo medical applications in comparison with existing modalities.

To what extent do pupils perceive science to be inconsistent with religious faith? An exploratory survey of 13-14 year-old English pupils

Scientists hold a wide range of beliefs on matters of religion, although popular media coverage in the UK commonly suggests that atheism is a core commitment for scientists. Considering the relationship between religion and science is a recommended topic in the English National Curriculum for lower secondary pupils (11-14 year-olds), and it is expected that different perspectives will be considered. However it is well established that many pupils may have difficulty accessing sophisticated ideas about the nature of science, and previous research suggests some may identify science with scientism. To explore pupil impressions of the relationship between science and religion, 13-14 year old pupils were surveyed in one class from each of four English secondary schools, by asking them to rate a set of statements about the relationship between science and religion, and scientific and religious perspectives on the origins of the world, and of life on earth, on the value of prayer and on the status of miracles. The survey revealed diverse views on these issues, reflecting the wider society. However it was found that a considerable proportion of the pupils in the sample considered religious beliefs and scientific perspectives to be opposed. The basis and potential consequences of such views are considered, and the need for more attention to this area of student thinking is highlighted.

Inferring convective responses to El Niño with atmospheric electricity measurements at Shetland

Pacific ocean temperature anomalies associated with the El Niño–Southern Oscillation (ENSO) modulate atmospheric convection and hence thunderstorm electrification. The generated current flows globally via the atmospheric electric circuit, which can be monitored anywhere on Earth. Atmospheric electricity measurements made at Shetland (in Scotland) display a mean global circuit response to ENSO that is characterized by strengthening during 'El Niño' conditions, and weakening during 'La Niña' conditions. Examining the hourly varying response indicates that a potential gradient (PG) increase around noon UT is likely to be associated with a change in atmospheric convection and resultant lightning activity over equatorial Africa and Eastern Asia. A secondary increase in PG just after midnight UT can be attributed to more shower clouds in the central Pacific ocean during an 'El Niño'.

How not to do things with words

If philosophy and poetry are to illuminate each other, we should first understand their tendencies to mutual antipathy. Examining (and, where possible, correcting) mutual misapprehension is part of this task. J. L. Austin's remarks on poetry offer one such point of entry: they are often cited by poets and critics as an example of philosophy's blindness to poetry (I). These remarks are complex and their purpose obscure—more so than those who take exception to them usually allow or admit (II). But it is reasonable to think that, for all his levity at their expense, what Austin offers poets is exemption from forms of commitment. Since such exemption is precisely what poets and critics have sought, this diagnosis is eirenic (III). This exemption has a price, but it may be affordable (IV).

Sparse polynomial approximation in positive order Sobolev spaces with bounded mixed derivatives and applications to elliptic problems with random loading

In the present paper we study the approximation of functions with bounded mixed derivatives by sparse tensor product polynomials in positive order tensor product Sobolev spaces. We introduce a new sparse polynomial approximation operator which exhibits optimal convergence properties in L2 and tensorized View the MathML source simultaneously on a standard k-dimensional cube. In the special case k=2 the suggested approximation operator is also optimal in L2 and tensorized H1 (without essential boundary conditions). This allows to construct an optimal sparse p-version FEM with sparse piecewise continuous polynomial splines, reducing the number of unknowns from O(p2), needed for the full tensor product computation, to View the MathML source, required for the suggested sparse technique, preserving the same optimal convergence rate in terms of p. We apply this result to an elliptic differential equation and an elliptic integral equation with random loading and compute the covariances of the solutions with View the MathML source unknowns. Several numerical examples support the theoretical estimates.

A semantic solution to the problem with aesthetic testimony

There is something peculiar about aesthetic testimony. It seems more difficult to gain knowledge of aesthetic properties based solely upon testimony than it is in the case of other types of property. In this paper, I argue that we can provide an adequate explanation at the level of the semantics of aesthetic language, without defending any substantive thesis in epistemology or about aesthetic value/judgement. If aesthetic predicates are given a non-invariantist semantics, we can explain the supposed peculiar difficulty with aesthetic testimony.

The blended approach to real estate allocations: performance implications of combining an exposure to German Spezialfonds with Global Listed Real Estate Securities

This paper seeks to increase the understanding of the performance implications for investors who choose to combine an unlisted real estate portfolio (in this case German Spezialfonds) with a (global) listed real estate element. We call this a “blended” approach to real estate allocations. For the avoidance of doubt, in this paper we are dealing purely with real estate equity (listed and unlisted) allocations, and do not incorporate real estate debt (listed or unlisted) or direct property into the process. A previous paper (Moss and Farrelly 2014) showed the benefits of the blended approach as it applied to UK Defined Contribution Pension Schemes. The catalyst for this paper has been the recent attention focused on German pension fund allocations, which have a relatively low (real estate) equity content, and a high bond content. We have used the MSCI Spezialfonds Index as a proxy for domestic German institutional real estate allocations, and the EPRA Global Developed Index as a proxy for a global listed real estate allocation. We also examine whether a rules based trading strategy, in this case Trend Following, can improve the risk adjusted returns above those of a simple buy and hold strategy for our sample period 2004-2015. Our findings are that by blending a 30% global listed portfolio with a 70% allocation (as opposed to a typical 100% weighting) to Spezialfonds, the real estate allocation returns increase from 2.88% p.a. to 5.42% pa. Volatility increases, but only to 6.53%., but there is a noticeable impact on maximum drawdown which increases to 19.4%. By using a Trend Following strategy raw returns are improved from 2.88% to 6.94% p.a. , The Sharpe Ratio increases from 1.05 to 1.49 and the Maximum Drawdown ratio is now only 1.83% compared to 19.4% using a buy and hold strategy . Finally, adding this (9%) real estate allocation to a mixed asset portfolio allocation typical for German pension funds there is an improvement in both the raw return (from 7.66% to 8.28%) and the Sharpe Ratio (from 0.91 to 0.98).

Using computers to teach people with intellectual disabilities to perform some of the tasks used within cognitive behavioural therapy: a randomised experiment

Aims Training has been shown to improve the ability of people with intellectual disabilities (IDs) to perform some cognitive behavioural therapy (CBT) tasks. This study used a computerised training paradigm with the aim of improving the ability of people with IDs to: a) discriminate between behaviours, thoughts and feelings, and b) link situations, thoughts and feelings. Methods Fifty-five people with mild-to-moderate IDs were randomly assigned to a training or attention-control condition in a single-blind mixed experimental design. Computerised tasks assessed the participants’ skills in: (a) discriminating between behaviours, thoughts and feelings (separately and pooled together), and (b) cognitive mediation by selecting appropriate emotions as consequences to given thoughts, and appropriate thoughts as mediators of given emotions. Results Training significantly improved ability to discriminate between behaviours, thoughts and feelings pooled together, compared to the attention-control condition, even when controlling for baseline scores and IQ. Large within-group improvements in the ability to identify behaviours and feelings were observed for the training condition, but not the attention-control group. There were no significant between-group differences in ability to identify thoughts, or on cognitive mediation skills. Conclusions A single session of computerised training can improve the ability of people with IDs to understand and practise CBT tasks relating to behaviours and feelings. There is potential for computerised training to be used as a “primer” for CBT with people with IDs to improve engagement and outcomes, but further development on a specific computerised cognitive mediation task is needed.