Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy

Gastro-oesophageal cancer is associated with a high incidence of cachexia. Proteolysis-inducing factor (PIF) has been identified as a possible cachectic factor and studies suggest that PIF is produced exclusively by tumour cells. We investigated PIF core peptide (PIF-CP) mRNA expression in tumour and benign tissue from patients with gastro-oesophageal cancer and in gastro-oesophageal biopsies for healthy volunteers. Tumour tissue and adjacent benign tissue were collected from patients with gastric and oesophageal cancer (n = 46) and from benign tissue only in healthy controls (n = 11). Expression of PIF-CP mRNA was quantified by real-time PCR. Clinical and pathological information along with nutritional status was collected prospectively. In the cancer patients, PIF-CP mRNA was detected in 27 (59%) tumour samples and 31 (67%) adjacent benign tissue samples. Four (36%) gastro-oesophageal biopsies from healthy controls also expressed PIF-CP mRNA. Expression was higher in tumour tissue (P = 0.031) and benign tissue (P = 0.022) from cancer patients compared with healthy controls. In the cancer patients, tumour and adjacent benign tissue PIF-CP mRNA concentrations were correlated with each other (P<0.0001, r = 0.73) but did not correlate with weight loss or prognosis. Although PIF-CP mRNA expression is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy, expression does not relate to prognosis or cachexia. Post-translational modification of PIF may be a key step in determining the biological role of PIF in the patient with advanced cancer and cachexia. © 2006 Cancer Research.

A sensory-linguistic approach to normal and impaired reading development

In this chapter we outline a sensory-linguistic approach to the, study of reading skill development. We call this a sensory-linguistic approach because the focus of interest is on the relationship between basic sensory processing skills and the ability to extract efficiently the orthographic and phonological information available in text during reading. Our review discusses how basic sensory processing deficits are associated with developmental dyslexia, and how these impairments may degrade word-decoding skills. We then review studies that demonstrate a more direct relationship between sensitivity to particular types of auditory and visual stimuli and the normal development of literacy skills. Specifically, we suggest that the phonological and orthographic skills engaged while reading are constrained by the ability to detect and discriminate dynamic stimuli in the auditory and visual systems respectively.

Contrast masking in strabismic amblyopia: attenuation, noise, interocular suppression and binocular summation

To investigate amblyopic contrast vision at threshold and above we performed pedestal-masking (contrastdiscrimination) experiments with a group of eight strabismic amblyopes using horizontal sinusoidal gratings (mainly 3 c/deg) in monocular, binocular and dichoptic configurations balanced across eye (i.e. five conditions). With some exceptions in some observers, the four main results were as follows. (1) For the monocular and dichoptic conditions, sensitivity was less in the amblyopic eye than in the good eye at all mask contrasts. (2) Binocular and monocular dipper functions superimposed in the good eye. (3) Monocular masking functions had a normal dipper shape in the good eye, but facilitation was diminished in the amblyopic eye. (4) A less consistent result was normal facilitation in dichoptic masking when testing the good eye, but a loss of this when testing the amblyopic eye. This pattern of amblyopic results was replicated in a normal observer by placing a neutral density filter in front of one eye. The two-stage model of binocular contrast gain control [Meese, T.S., Georgeson, M.A. & Baker, D.H. (2006). Binocular contrast vision at and above threshold. Journal of Vision 6, 1224--1243.] was `lesioned' in several ways to assess the form of the amblyopic deficit. The most successful model involves attenuation of signal and an increase in noise in the amblyopic eye, and intact stages of interocular suppression and binocular summation. This implies a behavioural influence from monocular noise in the amblyopic visual system as well as in normal observers with an ND filter over one eye.

Phase equilibrium studies at normal pressures

A total pressure apparatus has been developed to measure vapour-liquid equilibrium data on binary mixtures at atmospheric and sub-atmospheric pressures. The method gives isothermal data which can be obtained rapidly. Only measurements of total pressure are made as a direct function of composition of synthetic liquid phase composition, the vapour phase composition being deduced through the Gibbs-Duhem relationship. The need to analyse either of the phases is eliminated. As such the errors introduced by sampling and analysis are removed. The essential requirements are that the pure components be degassed completely since any deficiency in degassing would introduce errors into the measured pressures. A similarly essential requirement was that the central apparatus would have to be absolutely leak-tight as any leakage of air either in or out of the apparatus would introduce erroneous pressure readings. The apparatus was commissioned by measuring the saturated vapour pressures of both degassed water and ethanol as a function of temperature. The pressure-temperature data on degassed water measured were directly compared with data in the literature, with good agreement. Similarly the pressure-temperature data were measured for ethanol, methanol and cyclohexane and where possible a direct comparison made with the literature data. Good agreement between the pure component data of this work and those available in the literature demonstrates firstly that a satisfactory degassing procedure has been achieved and that secondly the measurements of pressure-temperature are consistent for any one component; since this is true for a number of components, the measurements of both temperature and pressure are both self-consistent and of sufficient accuracy, with an observed compatibility between the precision/accuracy of the separate means of measuring pressure and temperature. The liquid mixtures studied were of ethanol-water, methanol-water and ethanol-cyclohexane. The total pressure was measured as the composition inside the equilibrium cell was varied at a set temperature. This gave P-T-x data sets for each mixture at a range of temperatures. A standard fitting-package from the literature was used to reduce the raw data to yield y-values to complete the x-y-P-T data sets. A consistency test could not be applied to the P-T-x data set as no y-values were obtained during the experimental measurements. In general satisfactory agreement was found between the data of this work and those available in the literature. For some runs discrepancies were observed, and further work recommended to eliminate the problems identified.

A methodology for the generation and evaluation of biorefinery process chains, in order to identify the most promising biorefineries for the EU

The topic of bioenergy, biofuels and bioproducts remains at the top of the current political and research agenda. Identification of the optimum processing routes for biomass, in terms of efficiency, cost, environment and socio-economics is vital as concern grows over the remaining fossil fuel resources, climate change and energy security. It is known that the only renewable way of producing conventional hydrocarbon fuels and organic chemicals is from biomass, but the problem remains of identifying the best product mix and the most efficient way of processing biomass to products. The aim is to move Europe towards a biobased economy and it is widely accepted that biorefineries are key to this development. A methodology was required for the generation and evaluation of biorefinery process chains for converting biomass into one or more valuable products that properly considers performance, cost, environment, socio-economics and other factors that influence the commercial viability of a process. In this thesis a methodology to achieve this objective is described. The completed methodology includes process chain generation, process modelling and subsequent analysis and comparison of results in order to evaluate alternative process routes. A modular structure was chosen to allow greater flexibility and allowing the user to generate a large number of different biorefinery configurations The significance of the approach is that the methodology is defined and is thus rigorous and consistent and may be readily re-examined if circumstances change. There was the requirement for consistency in structure and use, particularly for multiple analyses. It was important that analyses could be quickly and easily carried out to consider, for example, different scales, configurations and product portfolios and so that previous outcomes could be readily reconsidered. The result of the completed methodology is the identification of the most promising biorefinery chains from those considered as part of the European Biosynergy Project.

An investigation into the nature, determinants, and dynamics of service quality expectations

On the basis of a review of the substantive quality and service marketing literature current knowledge regarding service quality expectations was found either absent or deficient. The phenomenon is of increasing importance to both marketing researchers and management and was therefore judged worthy of scholarly consideration. Because the service quality literature was insufficiently rich when embarking on the thesis three basic research issues were considered namely the nature, determinants, and dynamics of service quality expectations. These issues were first conceptually and then qualitatively explored. This process generated research hypotheses mainly relating to a model which were subsequently tested through a series of empirical investigations using questionnaire data from field studies in a single context. The results were internally consistent and strongly supported the main research hypotheses. It was found that service quality expectations can be meaningfully described in terms of generic/service-specific, intangible/tangible, and process/outcome categories. Service-specific quality expectations were also shown to be determined by generic service quality expectations, demographic variables, personal values, psychological needs, general service sophistication, service-specific sophistication, purchase motives, and service-specific information when treating service class involvement as an exogenous variable. Subjects who had previously not directly experienced a particular service were additionally found to revise their expectations of quality when exposed to the service with change being driven by a sub-set of identified determinants.

Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

Priority evaluation in transportation policies and programmes

This work is concerned with the development of techniques for the evaluation of large-scale highway schemes with particular reference to the assessment of their costs and benefits in the context of the current transport planning (T.P.P.) process. It has been carried out in close cooperation with West Midlands County Council, although its application and results are applicable elsewhere. The background to highway evaluation and its development in recent years has been described and the emergence of a number of deficiencies in current planning practise noted. One deficiency in particular stood out, that stemming from inadequate methods of scheme generation and the research has concentrated upon improving this stage of appraisal, to ensure that subsequent stages of design, assessment and implementation are based upon a consistent and responsive foundation. Deficiencies of scheme evaluation were found to stem from inadequate development of appraisal methodologies suffering from difficulties of valuation, measurement and aggregation of the disparate variables that characterise highway evaluation. A failure to respond to local policy priorities was also noted. A 'problem' rather than 'goals' based approach to scheme generation was taken, as it represented the current and foreseeable resource allocation context more realistically. A review of techniques with potential for highway problem based scheme generation, which would work within a series of practical and theoretical constraints were assessed and that of multivariate analysis, and classical factor analysis in particular, was selected, because it offerred considerable application to the difficulties of valuation, measurement and aggregation that existed. Computer programs were written to adapt classical factor analysis to the requirements of T.P.P. highway evaluation, using it to derive a limited number of factors which described the extensive quantity of highway problem data. From this, a series of composite problem scores for 1979 were derived for a case study area of south Birmingham, based upon the factorial solutions, and used to assess highway sites in terms of local policy issues. The methodology was assessed in the light of its ability to describe highway problems in both aggregate and disaggregate terms, to guide scheme design, coordinate with current scheme evaluation methods, and in general to improve upon current appraisal. Analysis of the results was both in subjective, 'common-sense' terms and using statistical methods to assess the changes in problem definition, distribution and priorities that emerged. Overall, the technique was found to improve upon current scheme generation methods in all respects and in particular in overcoming the problems of valuation, measurement and aggregation without recourse to unsubstantiated and questionable assumptions. A number of deficiencies which remained have been outlined and a series of research priorities described which need to be reviewed in the light of current and future evaluation needs.

Developing and evaluating a methodology for business process improvement

Purpose – There appears to be an ever-insatiable demand from markets for organisations to improve their products and services. To meet this, there is a need to provide business process improvement (BPI) methodologies that are holistic, structured and procedural. Therefore, this paper describes research that has formed and tested a generic and practical methodology termed model-based and integrated process improvement (MIPI) to support the implementation of BPI; and to validate its effectiveness in organisations. This methodology has been created as an aid for practitioners within organisations. Design/methodology/approach – The research objectives were achieved by: reviewing and analysing current methodologies, and selecting a few frameworks against key performance indicators. Using a refined Delphi approach and semi-structured interview with the “experts” in the field. Intervention, case study and process research approach to evaluating a methodology. Findings – The BPI methodology was successfully formed and applied by the researcher and directly by the companies involved against the criteria of feasibility, usability and usefulness. Research limitations/implications – The paper has demonstrated a new knowledge on how to systematically assess a BPI methodology in practice. Practical implications – Model-based and integrated process improvement methodology (MIPI) methodology offers the practitioner (experienced and novice) a set of step-by-step aids necessary to make informed, consistent and efficient changes to business processes. Originality/value – The novelty of this research work is the creation of a holistic workbook-based methodology with relevant tools and techniques. It extends the capabilities of existing methodologies.

Growth expectations of business owners:impact of human capital, firm characteristics and environmental transition

This paper presents an empirical study based on a survey of 399 owners of small and medium size companies in Lithuania. Applying bivariate and ordered probit estimators, we investigate why some business owners expect their firms to expand, while others do not. Our main findings provide evidence that SME owner's generic and specific human capital matter. Those with higher education and 'learning by doing' attributes, either through previous job experience or additional entrepreneurial experience, expect their businesses to expand. The expectations of growth are positively related to exporting and non-monotonically to enterprise size. In addition, we analyse the link between the perceptions of constraints to business activities and growth expectations and find that the factors, which are perceived as main business barriers, are not necessary those which are associated with reduced growth expectations. In particular, perceptions of both corruption and of inadequate tax systems seem to affect growth expectations the most.

Development of areolae and growth of the peripheral prothallus in the crustose lichen Rhizocarpon geographicum:an image analysis study

Areolae of the crustose lichen Rhizocarpon geographicum (L.) DC., are present on the peripheral prothallus (marginal areolae) and also aggregate to form confluent masses in the centre of the thallus (central areolae). To determine the relationships between these areolae and whether growth of the peripheral prothallus is dependent on the marginal areolae, the density, morphology, and size frequency distributions of marginal areolae were measured in 23 thalli of R. geographicum in north Wales, UK using image analysis (Image J). Size and morphology of central areolae were also studied across the thallus. Marginal areolae were small, punctate, and occurred in clusters scattered over the peripheral prothallus while central areolae were larger and had a lobed structure. The size-class frequency distributions of the marginal and central areolae were fitted by power-law and log-normal models respectively. In 16 out of 23 thalli, central areolae close to the outer edge were larger and had a more complex lobed morphology than those towards the thallus centre. Neither mean width nor radial growth rate (RaGR) of the peripheral prothallus were correlated with density, diameter, or area fraction of marginal areolae. The data suggest central areolae may develop from marginal areolae as follows: (1) marginal areolae develop in clusters at the periphery and fuse to form central areolae, (2) central areolae grow exponentially, and (3) crowding of central areolae results in constriction and fragmentation. In addition, growth of the peripheral prothallus may be unrelated to the marginal areolae. © 2013 Springer Science+Business Media Dordrecht.

Having your day in court:judicial opportunity and tactical choice in Anti-GMO campaigns in France and the United Kingdom

Investigating the recent direct action campaigns against genetically modified crops in France and the United Kingdom, the authors set out to understand how contrasting judicial systems and cultures affect the way that activists choose to commit ostensibly illegal actions and how they negotiate the trade-offs between effectiveness and public accountability. The authors find evidence that prosecution outcomes across different judicial systems are consistent and relatively predictable and consequently argue that the concept of a “judicial opportunity structure” is useful for developing scholars’ understanding of social movement trajectories. The authors also find that these differential judicial opportunities cannot adequately account for the tactical choices made by activists with respect to the staging of covert or overt direct action; rather, explanations of tactical choice are better accounted for by movement ideas, cultures, and traditions.

Fast reconstruction of harmonic functions from Cauchy data using the Dirichlet-to-Neumann map and integral equations

We propose and investigate a method for the stable determination of a harmonic function from knowledge of its value and its normal derivative on a part of the boundary of the (bounded) solution domain (Cauchy problem). We reformulate the Cauchy problem as an operator equation on the boundary using the Dirichlet-to-Neumann map. To discretize the obtained operator, we modify and employ a method denoted as Classic II given in [J. Helsing, Faster convergence and higher accuracy for the Dirichlet–Neumann map, J. Comput. Phys. 228 (2009), pp. 2578–2576, Section 3], which is based on Fredholm integral equations and Nyström discretization schemes. Then, for stability reasons, to solve the discretized integral equation we use the method of smoothing projection introduced in [J. Helsing and B.T. Johansson, Fast reconstruction of harmonic functions from Cauchy data using integral equation techniques, Inverse Probl. Sci. Eng. 18 (2010), pp. 381–399, Section 7], which makes it possible to solve the discretized operator equation in a stable way with minor computational cost and high accuracy. With this approach, for sufficiently smooth Cauchy data, the normal derivative can also be accurately computed on the part of the boundary where no data is initially given.

Modulation of interleukin-6 and matrix metalloproteinase 2 expression in human fibroblast-like synoviocytes by functional ionotropic glutamate receptors

Objective. Patients with rheumatoid arthritis (RA) have increased concentrations of the amino acid glutamate in synovial fluid. This study was undertaken to determine whether glutamate receptors are expressed in the synovial joint, and to determine whether activation of glutamate receptors on human synoviocytes contributes to RA disease pathology. Methods. Glutamate receptor expression was examined in tissue samples from rat knee joints and in human fibroblast-like synoviocytes (FLS). FLS from 5 RA patients and 1 normal control were used to determine whether a range of glutamate receptor antagonists influenced expression of the proinflammatory cytokine interleukin-6 (IL-6), enzymes involved in matrix degradation and cytokine processing (matrix metalloproteinase 2 [MMP-2] and MMP-9), and the inhibitors of these enzymes (tissue inhibitor of metalloproteinases 1 [TIMP-1] and TIMP-2). IL-6 concentrations were determined by enzyme-linked immunosorbent assay, MMP activity was measured by gelatin zymography, and TIMP activity was determined by reverse zymography. Fluorescence imaging of intracellular calcium concentrations in live RA FLS stimulated with specific antagonists was used to reveal functional activation of glutamate receptors that modulated IL-6 or MMP-2. Results. Ionotropic and metabotropic glutamate receptor subunit mRNA were expressed in the patella, fat pad, and meniscus of the rat knee and in human articular cartilage. Inhibition of N-methyl-D-aspartate (NMDA) receptors in RA FLS increased proMMP-2 release, whereas non-NMDA ionotropic glutamate receptor antagonists reduced IL-6 production by these cells. Stimulation with glutamate, NMDA, or kainate (KA) increased intracellular calcium concentrations in RA FLS, demonstrating functional activation of specific ionotropic glutamate receptors. Conclusion. Our findings indicate that activation of NMDA and KA glutamate receptors on human synoviocytes may contribute to joint destruction by increasing IL-6 expression. © 2007, American College of Rheumatology.