Structure and regulation of type 2 transglutaminase in relation to its physiological functions and pathological roles

This chapter contains sections titled: Introduction Structure and Regulation Physiologic Functions of TG2 Disruption of TG2 Functions in Pathologic Conditions Perspectives for Pharmacologic Interventions Concluding Comments Acknowledgements References

Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10-9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development. © 2013 Brandler et al.

A survey of some small firms in the rural areas of England: their structure and functions, with special reference to factors that affect their development

This study was concerned with the structure, functions and development, especially the performance, of some rural small firms associated with the Council for Small Industries in Rural Areas (C?SIRA) of England. Forty firms were used as the main basis of analysis. For some aspects of the investigation, however, data from another 54 firms, obtained indirectly through nine CoSIRA Organisers, were also used. For performance-analysis, the 40 firms were firstly ranked according to their growth and profitability rates which were calculated from their financial data. Then each of the variables hypothesised to be related to performance was tested to ascertain its relationship with performance, using the Spearman's Rank Correlation technique. The analysis indicated that each of the four factors .. the principal, the firm itself, its management, and the environment - had a bearing upon the performance of the firm. Within the first factor, the owner-manager's background and attitudes were found to be most important; in the second, the firm's size, age and scope of activities were also found to be correlated with performance; with respect to the third, it was revealed that firms which practised some forms of systems in planning, control and costing performed better than those which did not and, finally with respect to the fourth factor, it was found that some of the services provided by CoSIRA, especially credit finance, were facilitative to the firm's performance. Another significant facet of the firms highlighted by the study was their multifarious roles. These, meeting economic, psychological, sociological and political needs, were considered to be most useful to man and his society. Finally, the study has added light to the structural characteristics of the sampled firms, including various aspects of their development, orientation and organisation, as well as their various structural strengths and weakness. ' .

Splines and vector splines

The thrust of this report concerns spline theory and some of the background to spline theory and follows the development in (Wahba, 1991). We also review methods for determining hyper-parameters, such as the smoothing parameter, by Generalised Cross Validation. Splines have an advantage over Gaussian Process based procedures in that we can readily impose atmospherically sensible smoothness constraints and maintain computational efficiency. Vector splines enable us to penalise gradients of vorticity and divergence in wind fields. Two similar techniques are summarised and improvements based on robust error functions and restricted numbers of basis functions given. A final, brief discussion of the application of vector splines to the problem of scatterometer data assimilation highlights the problems of ambiguous solutions.

South Africa and the global game:football, apartheid and beyond

Firmly situating South African teams, players, and associations in the international framework in which they have to compete, South Africa and the Global Game: Football, Apartheid, and Beyond presents an interdisciplinary analysis of how and why South Africa underwent a remarkable transformation from a pariah in world sport to the first African host of a World Cup in 2010. Written by an eminent team of scholars, this special issue and book aims to examine the importance of football in South African society, revealing how the black oppression transformed a colonial game into a force for political, cultural and social liberation. It explores how the hosting of the 2010 World Cup aims to enhance the prestige of the post-apartheid nation, to generate economic growth and stimulate Pan-African pride. Among the themes dealt with are race and racism, class and gender dynamics, social identities, mass media and culture, and globalization. This collection of original and insightful essays will appeal to specialists in African Studies, Cultural Studies, and Sport Studies, as well as to non-specialist readers seeking to inform themselves ahead of the 2010 World Cup. This book was published as a special issue of Soccer and Society. 1. Introduction Peter Alegi and Chris Bolsmann Part 1: Past is Prologue – History of Football in South Africa 2. Football as Code: The Social Diffusion of ‘Soccer’ in South Africa Lloyd Hill 3. White Football in South Africa: Empire, Apartheid and Change, 1892 – 1977 Chris Bolsmann 4. A Biography of Darius Dhlomo: Transnational Footballer in the Era of Apartheid Peter Alegi 5. Women and Gender in South African Soccer Cynthia Fabrizio Pelak Part 2: Football Culture after Apartheid: Local and Transnational Dynamics 6. "You Must Support Chiefs: Pirates Already Have Two White Fans!" Race and Racial Discourse in South African Football Fandom Marc Fletcher 7. "It wasn’t that I did not like South African Football": Media, History, and Biography Sean Jacobs 8. Soccer in a Rugby Town: Restructuring Football in Stellenbosch Sylvain Cubizolles 9. Differing Trajectories: Football Development and Patterns of Player Migration in South Africa and Ghana Paul Darby and Eirik Solberg Part 3: The 2010 World Cup: Challenges and Opportunities 10. Football's Tsars: Proprietorship, Corporatism and Politics in the 2010 FIFA World Cup Scarlett Cornelissen 11. Sports as Cultural Diplomacy: The 2010 FIFA World Cup in South Africa’s Foreign Policy Sifiso Mxolisi Ndlovu 12. World Cup 2010: Africa’s Turn or the Turn on Africa? Ashwin Desai and Goolam Vahed 13. The 2010 FIFA World Cup: Critical Voices From Below Percy Ngonyama.

Monetary models of exchange rates and sweep programs

Numerous studies find that monetary models of exchange rates cannot beat a random walk model. Such a finding, however, is not surprising given that such models are built upon money demand functions and traditional money demand functions appear to have broken down in many developed countries. In this article, we investigate whether using a more stable underlying money demand function results in improvements in forecasts of monetary models of exchange rates. More specifically, we use a sweep-adjusted measure of US monetary aggregate M1 which has been shown to have a more stable money demand function than the official M1 measure. The results suggest that the monetary models of exchange rates contain information about future movements of exchange rates, but the success of such models depends on the stability of money demand functions and the specifications of the models.

The past, present and future of observational research in marketing

Purpose - To introduce the contents of the special issue, and provide an integrative overview of the development of observational methodologies in marketing research, as well as some directions for the future. Design/methodology/approach - A historical review of the development of observational methods, beginning with philosophical foundations, is provided. Key philosophical debates are summarized, and trends in observational methods are described and analyzed, with particular reference to the impact of technology. Following this, the contributions to the special issue are summarized and brought together. Findings - Observational research in marketing is more than the well-known method of "participant-observation." In fact, technology has the potential to revolutionize observational research, and move it beyond a solely "qualitative" method. The internet, video, scanner-tracking, and neuroimaging methods are all likely to have a big impact on the development of traditional and innovative observation methods in the future. The articles in the special issue provide a good overview of these developments. Research limitations/implications - The views of the authors may differ from those of others. Practical implications - Observation is a far more wide-ranging strategy than many perceive. There is a need for more expertise in all types of observational methodologies within marketing research schools and departments, in order to take account of the vast opportunities which are currently emerging. Originality/value - Provides an original perspective on observational methods, and serves as a useful overview of trends and developments in the field.

Binocular combination at threshold: temporal filtering and summation of signals in separate ON and OFF channels

How does the brain combine spatio-temporal signals from the two eyes? We quantified binocular summation as the improvement in 2AFC contrast sensitivity for flickering gratings seen by two eyes compared with one. Binocular gratings in-phase showed sensitivity up to 1.8 times higher, suggesting nearly linear summation of contrasts. The binocular advantage decreased to 1.4 at lower spatial and higher temporal frequencies (0.25 cycle deg-1, 30 Hz). Dichoptic, antiphase gratings showed only a small binocular advantage, by a factor of 1.1 to 1.2, but no evidence of cancellation. We present a signal-processing model to account for the contrast-sensitivity functions and the pattern of binocular summation. It has linear sustained and transient temporal filters, nonlinear transduction, and half-wave rectification that creates ON and OFF channels. Binocular summation occurs separately within ON and OFF channels, thus explaining the phase-specific binocular advantage. The model also accounts for earlier findings on detection of brief antiphase flashes and the surprising finding that dichoptic antiphase flicker is seen as frequency-doubled (Cavonius et al, 1992 Ophthalmic and Physiological Optics 12 153 - 156). [Supported by EPSRC project GR/S74515/01].

Contrast discrimination and pattern masking: contrast gain control with fixed additive noise

We studied the visual mechanisms that serve to encode spatial contrast at threshold and supra-threshold levels. In a 2AFC contrast-discrimination task, observers had to detect the presence of a vertical 1 cycle deg-1 test grating (of contrast dc) that was superimposed on a similar vertical 1 cycle deg-1 pedestal grating, whereas in pattern masking the test grating was accompanied by a very different masking grating (horizontal 1 cycle deg-1, or oblique 3 cycles deg-1). When expressed as threshold contrast (dc at 75% correct) versus mask contrast (c) our results confirm previous ones in showing a characteristic 'dipper function' for contrast discrimination but a smoothly increasing threshold for pattern masking. However, fresh insight is gained by analysing and modelling performance (p; percent correct) as a joint function of (c, dc) - the performance surface. In contrast discrimination, psychometric functions (p versus logdc) are markedly less steep when c is above threshold, but in pattern masking this reduction of slope did not occur. We explored a standard gain-control model with six free parameters. Three parameters control the contrast response of the detection mechanism and one parameter weights the mask contrast in the cross-channel suppression effect. We assume that signal-detection performance (d') is limited by additive noise of constant variance. Noise level and lapse rate are also fitted parameters of the model. We show that this model accounts very accurately for the whole performance surface in both types of masking, and thus explains the threshold functions and the pattern of variation in psychometric slopes. The cross-channel weight is about 0.20. The model shows that the mechanism response to contrast increment (dc) is linearised by the presence of pedestal contrasts but remains nonlinear in pattern masking.

Experimental and theoretical characterisation of tunable fibre gratings

This thesis presents details on both theoretical and experimental aspects of UV written fibre gratings. The main body of the thesis deals with the design, fabrication and testing of telecommunication optical fibre grating devices, but also an accurate theoretical analysis of intra-core fibre gratings is presented. Since more than a decade, fibre gratings have been extensively used in the telecommunication field (as filters, dispersion compensators, and add/drop multiplexers for instance). Gratings for telecommunication should conform to very high fabrication standards as the presence of any imperfection raises the noise level in the transmission system compromising its ability of transmitting intelligible sequence of bits to the receiver. Strong side lobes suppression and high and sharp reflection profile are then necessary characteristics. A fundamental part of the theoretical and experimental work reported in this thesis is about apodisation. The physical principle of apodisation is introduced and a number of apodisation techniques, experimental results and numerical optimisation of the shading functions and all the practical parameters involved in the fabrication are detailed. The measurement of chromatic dispersion in fibres and FBGs is detailed and an estimation of its accuracy is given. An overview on the possible methods that can be implemented for the fabrication of tunable fibre gratings is given before detailing a new dispersion compensator device based on the action of a distributed strain onto a linearly chirped FBG. It is shown that tuning of second and third order dispersion of the grating can be obtained by the use of a specially designed multipoint bending rig. Experiments on the recompression of optical pulses travelling long distances are detailed for 10 Gb/s and 40 Gb/s. The characterisation of a new kind of double section LPG fabricated on a metal-clad coated fibre is reported. The fabrication of the device is made easier by directly writing the grating through the metal coating. This device may be used to overcome the recoating problems associated with standard LPGs written in step-index fibre. Also, it can be used as a sensor for simultaneous measurements of temperature and surrounding medium refractive index.

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.