bcl-x is expressed in embryonic and postnatal neural tissues and functions to prevent neuronal cell death.

Previous studies have implicated the bcl-2 protooncogene as a potential regulator of neuronal survival. However, mice lacking functional bcl-2 exhibited normal development and maintenance of the central nervous system (CNS). Since bcl-2 appears dispensable for neuronal survival, we have examined the expression and function of bcl-x, another member of the bcl-2 family of death regulatory genes. Bcl-2 is expressed in neuronal tissues during embryonic development but is down-regulated in the adult CNS. In contrast, Bcl-xL expression is retained in neurons of the adult CNS. Two different forms of bcl-x mRNA and their corresponding products, Bcl-xL and Bcl-x beta, were expressed in embryonic and adult neurons of the CNS. Microinjection of bcl-xL and bcl-x beta cDNAs into primary sympathetic neurons inhibited their death induced by nerve growth factor withdrawal. Thus, Bcl-x proteins appear to play an important role in the regulation of neuronal survival in the adult CNS.

Growth and carbon metabolism of the seaweed Fucus vesiculosus in the western Baltic Sea ("Kiel Outdoor Benthocosms")

Warming and acidification of the oceans as a consequence of increasing CO2-concentrations occur at large scales. Numerous studies have shown the impact of single stressors on individual species. However, studies on the combined effect of multiple stressors on a multi-species assemblage, which is ecologically much more realistic and relevant, are still scarce. Therefore, we orthogonally crossed the two factors warming and acidification in mesocosm experiments and studied their single and combined impact on the brown alga Fucus vesiculosus associated with its natural community (epiphytes and mesograzers) in the Baltic Sea in all seasons (from April 2013 to April 2014). We superimposed our treatment factors onto the natural fluctuations of all environmental variables present in the Benthocosms in so-called delta-treatments. Thereby we compared the physiological responses of F. vesiculosus (growth and metabolites) to the single and combined effects of natural Kiel Fjord temperatures and pCO2 conditions with a 5 °C temperature increase and/or pCO2 increase treatment (1100 ppm in the headspace above the mesocosms). Responses were also related to the factor photoperiod which changes over the course of the year. Our results demonstrate complex seasonal pattern. Elevated pCO2 positively affected growth of F. vesiculosus alone and/or interactively with warming. The response direction (additive, synergistic or antagonistic), however, depended on season and daylength. The effects were most obvious when plants were actively growing during spring and early summer. Our study revealed for the first time that it is crucial to always consider the impact of variable environmental conditions throughout all seasons. In summary, our study indicates that in future F. vesiculosus will be more affected by detrimental summer heat-waves than by ocean acidification although the latter consequently enhances growth throughout the year. The mainly negative influence of rising temperatures on the physiology of this keystone macroalga may alter and/or hamper its ecological functions in the shallow coastal ecosystem of the Baltic Sea.

Hyposulfatemia, growth retardation, reduced fertility, and seizures in mice lacking a functional NaSi-1 gene

inorganic sulfate is required for numerous functions in mammalian physiology, and its circulating levels are proposed to be maintained by the Na+-SO42- cotransporter, (NaSi-1). To determine the role of NaSi-1 in sulfate homeostasis and the physiological consequences in its absence, we have generated a mouse lacking a functional NaSi-1 gene, Nas1. Serum sulfate concentration was reduced by >75% in Nas1(-/-) mice when compared with Nas1(+/+) mice. Nas1(-/-) mice exhibit increased urinary sulfate excretion, reduced renal and intestinal Na+-SO42- cotransport, and a general growth retardation. Nas1(-/-) mouse body weight was reduced by >20% when compared with Nas1(+/+) and Nas1(+/-) littermates at 2 weeks of age and remained so throughout adulthood. Nas1(-/-) females had a lowered fertility, with a 60% reduction in litter size. Spontaneous clonic seizures were observed in Nas1(-/-) mice from 8 months of age. These data demonstrate NaSi-1 is essential for maintaining sulfate homeostasis, and its expression is necessary for a wide range of physiological functions.

Spatial and temporal variability in somatic growth of green sea turtles (Chelonia mydas) resident in the Hawaiian Archipelago

The somatic growth dynamics of green turtles ( Chelonia mydas) resident in five separate foraging grounds within the Hawaiian Archipelago were assessed using a robust non-parametric regression modelling approach. The foraging grounds range from coral reef habitats at the north-western end of the archipelago, to coastal habitats around the main islands at the southeastern end of the archipelago. Pelagic juveniles recruit to these neritic foraging grounds from ca. 35 cm SCL or 5 kg ( similar to 6 years of age), but grow at foraging-ground-specific rates, which results in quite different size- and age-specific growth rate functions. Growth rates were estimated for the five populations as change in straight carapace length ( cm SCL year) 1) and, for two of the populations, also as change in body mass ( kg year) 1). Expected growth rates varied from ca. 0 - 2.5 cm SCL year) 1, depending on the foraging-ground population, which is indicative of slow growth and decades to sexual maturity, since expected size of first-time nesters is greater than or equal to 80 cm SCL. The expected size- specific growth rate functions for four populations sampled in the southeastern archipelago displayed a non-monotonic function, with an immature growth spurt at ca. 50 - 53 cm SCL ( similar to 18 - 23 kg) or ca. 13 - 19 years of age. The growth spurt for the Midway atoll population in the northwestern archipelago occurs at a much larger size ( ca. 65 cm SCL or 36 kg), because of slower immature growth rates that might be due to a limited food stock and cooler sea surface temperature. Expected age-at-maturity was estimated to be ca. 35 - 40 years for the four populations sampled at the south-eastern end of the archipelago, but it might well be > 50 years for the Midway population. The Hawaiian stock comprises mainly the same mtDNA haplotype, with no differences in mtDNA stock composition between foraging-ground populations, so that the geographic variability in somatic growth rates within the archipelago is more likely due to local environmental factors rather than genetic factors. Significant temporal variability was also evident, with expected growth rates declining over the last 10 - 20 years, while green turtle abundance within the archipelago has increased significantly since the mid-1970s. This inverse relationship between somatic growth rates and population abundance suggests a density-dependent effect on somatic growth dynamics that has also been reported recently for a Caribbean green turtle stock. The Hawaiian green turtle stock is characterised by slow growth rates displaying significant spatial and temporal variation and an immature growth spurt. This is consistent with similar findings for a Great Barrier Reef green turtle stock that also comprises many foraging-ground populations spanning a wide geographic range.

Modelling the effect of fibropapilloma disease on the somatic growth dynamics of Hawaiian green sea turtles

The effect of the tumour-forming disease, fibropapillomatosis, on the somatic growth dynamics of green turtles resident in the Pala'au foraging grounds (Moloka'i, Hawai'i) was evaluated using a Bayesian generalised additive mixed modelling approach. This regression model enabled us to account for fixed effects (fibropapilloma tumour severity), nonlinear covariate functional form (carapace size, sampling year) as well as random effects due to individual heterogeneity and correlation between repeated growth measurements on some turtles. Somatic growth rates were found to be nonlinear functions of carapace size and sampling year but were not a function of low-to-moderate tumour severity. On the other hand, growth rates were significantly lower for turtles with advanced fibropapillomatosis, which suggests a limited or threshold-specific disease effect. However, tumour severity was an increasing function of carapace size-larger turtles tended to have higher tumour severity scores, presumably due to longer exposure of larger (older) turtles to the factors that cause the disease. Hence turtles with advanced fibropapillomatosis tended to be the larger turtles, which confounds size and tumour severity in this study. But somatic growth rates for the Pala'au population have also declined since the mid-1980s (sampling year effect) while disease prevalence and severity increased from the mid-1980s before levelling off by the mid-1990s. It is unlikely that this decline was related to the increasing tumour severity because growth rates have also declined over the last 10-20 years for other green turtle populations resident in Hawaiian waters that have low or no disease prevalence. The declining somatic growth rate trends evident in the Hawaiian stock are more likely a density-dependent effect caused by a dramatic increase in abundance by this once-seriously-depleted stock since the mid-1980s. So despite increasing fibropapillomatosis risk over the last 20 years, only a limited effect on somatic growth dynamics was apparent and the Hawaiian green turtle stock continues to increase in abundance.

Nuclear translocation of cell-surface receptors: Lessons from fibroblast growth factor

The nuclear localization of a number of growth factors, cytokine ligands and their receptors has been reported in various cell lines and tissues. These include members of the fibroblast growth factor (FGF), epidermal growth factor and growth hormone families. Accordingly, a number of nuclear functions have begun to emerge for these protein families. The demonstration of functional interactions of these proteins with the nuclear import machinery has further supported their functions as nuclear signal transducers. Here, we review the membrane- trafficking machinery and pathways demonstrated to regulate this cell surface to nucleus-trafficking event and highlight the many remaining unanswered questions. We focus on the FGF family, which is providing many of the clues as to the process of this unusual phenomenon.

A Bayesian approach to imposing curvature on distance functions

The estimated parameters of output distance functions frequently violate the monotonicity, quasi-convexity and convexity constraints implied by economic theory, leading to estimated elasticities and shadow prices that are incorrectly signed, and ultimately to perverse conclusions concerning the effects of input and output changes on productivity growth and relative efficiency levels. We show how a Bayesian approach can be used to impose these constraints on the parameters of a translog output distance function. Implementing the approach involves the use of a Gibbs sampler with data augmentation. A Metropolis-Hastings algorithm is also used within the Gibbs to simulate observations from truncated pdfs. Our methods are developed for the case where panel data is available and technical inefficiency effects are assumed to be time-invariant. Two models-a fixed effects model and a random effects model-are developed and applied to panel data on 17 European railways. We observe significant changes in estimated elasticities and shadow price ratios when regularity restrictions are imposed. (c) 2004 Elsevier B.V. All rights reserved.

Regulation of endocytosis, nuclear translocation, and signaling of fibroblast growth factor receptor 1 by E-cadherin

Fibroblast growth factor (FGF) receptors (FGFRs) signal to modulate diverse cellular functions, including epithelial cell morphogenesis. In epithelial cells, E-cadherin plays a key role in cell-cell adhesion, and its function can be regulated through endocytic trafficking. In this study, we investigated the location, trafficking, and function of FGFR1 and E-cadherin and report a novel mechanism, based on endocytic trafficking, for the coregulation of E-cadherin and signaling from FGFR1. FGF induces the internalization of surface FGFR1 and surface E-cadherin, followed by nuclear translocation of FGFR1. The internalization of both proteins is regulated by common endocytic machinery, resulting in cointernalization of FGFR1 and E-cadherin into early endosomes. By blocking endocytosis, we show that this is a requisite, initial step for the nuclear translocation of FGFR1. Overexpression of E-cadherin blocks both the coendocytosis of E-cadherin and FGFR1, the nuclear translocation of FGFR1 and FGF-induced signaling to the mitogen-activated protein kinase pathway. Furthermore, stabilization of surface adhesive E-cadherin, by overexpressing p120(ctn), also blocks internalization and nuclear translocation of FGFR1. These data reveal that conjoint endocytosis and trafficking is a novel mechanism for the coregulation of E-cadherin and FGFR1 during cell signaling and morphogenesis.

Yield functions for porous materials with cubic symmetry using different definitions of yield

Plastic yield criteria for porous ductile materials are explored numerically using the finite-element technique. The cases of spherical voids arranged in simple cubic, body-centred cubic and face-centred cubic arrays are investigated with void volume fractions ranging from 2 % through to the percolation limit (over 90 %). Arbitrary triaxial macroscopic stress states and two definitions of yield are explored. The numerical data demonstrates that the yield criteria depend linearly on the determinant of the macroscopic stress tensor for the case of simple-cubic and body-centred cubic arrays - in contrast to the famous Gurson-Tvergaard-Needleman (GTN) formula - while there is no such dependence for face-centred cubic arrays within the accuracy of the finite-element discretisation. The data are well fit by a simple extension of the GTN formula which is valid for all void volume fractions, with yield-function convexity constraining the form of the extension in terms of parameters in the original formula. Simple cubic structures are more resistant to shear, while body-centred and face-centred structures are more resistant to hydrostatic pressure. The two yield surfaces corresponding to the two definitions of yield are not related by a simple scaling.

Adaptive economic growth

This paper develops an evolutionary theory of adaptive growth, understood as a product of structural change and economic self-transformation, based upon processes that are closely connected with but not reducible to the growth of knowledge. The dominant connecting theme is enterprise, the innovative variations it generates and the multiple connections between investment, innovation, demand and structural transformation in the market process. The paper explores the dependence of macroeconomic productivity growth on the diversity of technical progress functions and income elasticities of demand at the industry level, and the resolution of this diversity into patterns of economic change through market processes. It is shown how industry growth rates are constrained by higher-order processes of emergence that convert an ensemble of industry growth rates into an aggregate rate of growth. The growth of productivity, output and employment are determined mutually and endogenously, and their values depend on the variation in the primary causal influences in the system.

Empirical analysis of human capital development and economic growth in Europe

Recent discussion of the knowledge-based economy draws increasingly attention to the role that the creation and management of knowledge plays in economic development. Development of human capital, the principal mechanism for knowledge creation and management, becomes a central issue for policy-makers and practitioners at the regional, as well as national, level. Facing competition both within and across nations, regional policy-makers view human capital development as a key to strengthening the positions of their economies in the global market. Against this background, the aim of this study is to go some way towards answering the question of whether, and how, investment in education and vocational training at regional level provides these territorial units with comparative advantages. The study reviews literature in economics and economic geography on economic growth (Chapter 2). In growth model literature, human capital has gained increased recognition as a key production factor along with physical capital and labour. Although leaving technical progress as an exogenous factor, neoclassical Solow-Swan models have improved their estimates through the inclusion of human capital. In contrast, endogenous growth models place investment in research at centre stage in accounting for technical progress. As a result, they often focus upon research workers, who embody high-order human capital, as a key variable in their framework. An issue of discussion is how human capital facilitates economic growth: is it the level of its stock or its accumulation that influences the rate of growth? In addition, these economic models are criticised in economic geography literature for their failure to consider spatial aspects of economic development, and particularly for their lack of attention to tacit knowledge and urban environments that facilitate the exchange of such knowledge. Our empirical analysis of European regions (Chapter 3) shows that investment by individuals in human capital formation has distinct patterns. Those regions with a higher level of investment in tertiary education tend to have a larger concentration of information and communication technology (ICT) sectors (including provision of ICT services and manufacture of ICT devices and equipment) and research functions. Not surprisingly, regions with major metropolitan areas where higher education institutions are located show a high enrolment rate for tertiary education, suggesting a possible link to the demand from high-order corporate functions located there. Furthermore, the rate of human capital development (at the level of vocational type of upper secondary education) appears to have significant association with the level of entrepreneurship in emerging industries such as ICT-related services and ICT manufacturing, whereas such association is not found with traditional manufacturing industries. In general, a high level of investment by individuals in tertiary education is found in those regions that accommodate high-tech industries and high-order corporate functions such as research and development (R&D). These functions are supported through the urban infrastructure and public science base, facilitating exchange of tacit knowledge. They also enjoy a low unemployment rate. However, the existing stock of human and physical capital in those regions with a high level of urban infrastructure does not lead to a high rate of economic growth. Our empirical analysis demonstrates that the rate of economic growth is determined by the accumulation of human and physical capital, not by level of their existing stocks. We found no significant effects of scale that would favour those regions with a larger stock of human capital. The primary policy implication of our study is that, in order to facilitate economic growth, education and training need to supply human capital at a faster pace than simply replenishing it as it disappears from the labour market. Given the significant impact of high-order human capital (such as business R&D staff in our case study) as well as the increasingly fast pace of technological change that makes human capital obsolete, a concerted effort needs to be made to facilitate its continuous development.

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. ' .

Growth, sporulation and spore properties of bacillus stearothemophilus produced in chemically defined media

The nutritional requirements for the vegetative growth of B. stearothermophilus strains NCIB 8919, NCTC lO,OO3 (wild) were found to be DL-methionine, biotin, nicotinic acid, thiamin, glucose and mineral salts. Strains NCIB 8920 required in addition L-tryptophan. B. stearothermophilus NCTC lO,OO3 (mutant) grew in a medium containing only glucose and mineral salts. Separate chemically defined media for the growth of Bacillus stearothermophilus strains NCIB 8919, 8920, NCTC lO,OO3 (wild) and NCTC lO,OO3 (mutant) were developed. Optimally aerated culture of B. stearothermonhilus NCTC lO,OO3(mutant) required 1.0 x 10-4 M. Mn2+ and 2.4 x 10-3 M. glutamic acid for optimal sporulation. Specific nutrient depletion of growth affected percentage sporulation. Spore suspensions of B. stearothermophilus NCTC 10,003 (mutant) were prepared from media in which sulphate (SO4-), nitrogen (N-),phosphate (Po4-), carbon (C-), magnesium-carbon simultaneously (Ng-C-) depleted growth. The heat resistance, dormancy and chemistry of these spores varied considerably. B. stearothermophilus NCTC 10,003 10,00310,00(mutant) spores prepared from carbon depleted cultures containing high and low concentrations of calcium, iron or manganese showed variations in heat resistance,dormancy and chemical composition. Progressive increase in the concentration of medium calciumfrom 1.0 X 10-5  M to 1.4 X 10-4 M. progressively increased theheat resistance of B. stearothermophilus NCTC 10,003 (mutant) spores prepared from nitrogen depleted cultures (N-). The thermodynamic functions for germination rate, magnesium and manganese release of N- and SO4- spores were within the range expected of enzymic reactions. The thermodynamic functions for the breaking of dormancy in SO4- spores and that for the release of D.P.A. were identical. Sublethal heating of SO4- spores (96.5°C and below) induced dormancy in these spores, whereas heating above 96.5°C gave rise to heat activation. Pooled results of the chemical analyses of all spore types studied showed that the concentration of D.P.A. and calcium were positively related to heat resistance whereas magnesium concentration and Mg/Ca molar ratio were inversely proportional to heat resistance.

The measurement and decomposition of economy-wide productivity growth:Assessing the accuracy and selecting between different approaches

Productivity at the macro level is a complex concept but also arguably the most appropriate measure of economic welfare. Currently, there is limited research available on the various approaches that can be used to measure it and especially on the relative accuracy of said approaches. This thesis has two main objectives: firstly, to detail some of the most common productivity measurement approaches and assess their accuracy under a number of conditions and secondly, to present an up-to-date application of productivity measurement and provide some guidance on selecting between sometimes conflicting productivity estimates. With regards to the first objective, the thesis provides a discussion on the issues specific to macro-level productivity measurement and on the strengths and weaknesses of the three main types of approaches available, namely index-number approaches (represented by Growth Accounting), non-parametric distance functions (DEA-based Malmquist indices) and parametric production functions (COLS- and SFA-based Malmquist indices). The accuracy of these approaches is assessed through simulation analysis, which provided some interesting findings. Probably the most important were that deterministic approaches are quite accurate even when the data is moderately noisy, that no approaches were accurate when noise was more extensive, that functional form misspecification has a severe negative effect in the accuracy of the parametric approaches and finally that increased volatility in inputs and prices from one period to the next adversely affects all approaches examined. The application was based on the EU KLEMS (2008) dataset and revealed that the different approaches do in fact result in different productivity change estimates, at least for some of the countries assessed. To assist researchers in selecting between conflicting estimates, a new, three step selection framework is proposed, based on findings of simulation analyses and established diagnostics/indicators. An application of this framework is also provided, based on the EU KLEMS dataset.

Localisation of members of the vascular endothelial growth factor (VEGF) family and their receptors in human atherosclerotic arteries

Background: Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. The existence of single or multiple VEGF isoforms and receptors suggests that these proteins may have overlapping but distinct functions, which may be reflected in their cell expression and distribution. Methods: The localisation of VEGFs A–C and their receptors (VEGFRs 1–3, respectively) in 30 fresh human atherosclerotic arteries, 15 normal uterine arteries, and 15 saphenous veins using immunohistochemistry and western blotting. Results: Saphenous veins showed no staining for VEGF-B or VEGFR-2. Smooth muscle cells (SMCs) showed the strongest staining for VEGF-A, VEGF-B, VEGFR-1, and VEGFR-2 in all specimens. Conversely, VEGFR-3 and VEGF-C were predominately localised to the endothelial vasa vasorum in normal arteries, whereas medial SMCs showed the strongest staining in atherosclerotic arteries. Western blotting showed variations in VEGF protein localisation, with lower amounts of VEGF-B and VEGF-C in saphenous veins, compared with arterial tissue. Amounts of VEGF-C were lower than those of VEGF-A and VEGF-B in all specimens. Conclusion: This study provides direct evidence of the presence of VEGF proteins and receptors in human physiology and pathology, with variations in both the amounts of VEGF proteins expressed and their cellular distribution in normal arteries compared with atherosclerotic arteries. The presence of VEGFs A–C and their receptors in normal arterial tissue implies that VEGF functions may extend beyond endothelial cell proliferation. Reduced VEGFR-2 staining in atherosclerotic arteries may have implications for the atherosclerosis process and the development of vascular disease and its complications.