A nonantisense sequence-selective effect of a phosphorothioate oligodeoxynucleotide directed against the epidermal growth factor receptor in A431 cells

The overexpression of epidermal growth factor receptor (EGFr) has been implicated as a causative factor and a poor prognostic marker in a number of carcinomas. Therefore, strategies that down-regulate EGFr expression may be therapeutically useful. We designed antisense ODNs complementary to the initiation codon region of the EGFr mRNA and evaluated their efficacy in several tumor-derived cells, including the A431 cell line that express amplified levels of EGFr. A 15-mer phosphorothioate (PS) antisense ODN (erbB1AS15) induced a concentration-dependent reduction in proliferation that was accompanied by a change in the morphology of A431 cells into more tightly clustered and discrete colonies. A 15-mer sense (PS) control oligodeoxynucleotide (ODN) and a phosphodiester (PO) version of erbB1AS15 had little or no effect on cell number of morphology, and erbB1AS15 (PS) did not induce these effects in control cell lines expressing lower levels of EGFr. The effects of erbB1AS15 (PS) on A431 cells were not mediated by a true antisense mechanism in that there was no reduction in the level of EGFr mRNA or protein over a 24-hr period, as determined by Northern and Western blotting, respectively. However, autophosphorylation of the receptor was significantly reduced by erbB1AS15 (PS) and not by control ODNs. The results of further studies suggested that this effect was mediated by a direct, dose-dependent inhibition of the EGFr tyrosine kinase enzyme and was not due to impairment of either ligand-binding or receptor dimerization. These data suggest that erbB1AS15 (PS) can inhibit proliferation and alter the morphology of A431 cells by a sequence-selective, but nonantisense mechanism affecting receptor tyrosine kinase activity.

Time series analysis in the assessment of ICT impact at the aggregate level – lessons and implications for the new economy

The major role of information and communication technology (ICT) in the new economy is well documented: countries worldwide are pouring resources into their ICT infrastructure despite the widely acknowledged “productivity paradox”. Evaluating the contribution of ICT investments has become an elusive but important goal of IS researchers and economists. But this area of research is fraught with complexity and we have used Solow's Residual together with time-series analysis tools to overcome some methodological inadequacies of previous studies. Using this approach, we conduct a study of 20 countries to determine if there was empirical evidence to support claims that ICT investments are worthwhile. The results show that ICT contributes to economic growth in many developed countries and newly industrialized economies (NIEs), but not in developing countries. We finally suggest ICT-complementary factors, in an attempt to rectify possible flaws in ICT policies as a contribution towards improvement in global productivity.

International and intranational technological spillovers and productivity growth in China

Technological spillovers from foreign direct investment (FDI) have been regarded as a major source of technical progress and productivity growth. This paper explores the role of international and intranational technological spillovers from FDI in technical change, efficiency improvement, and total factor productivity growth in Chinese manufacturing firms using a recent Chinese manufacturing firm-level panel data set over the 2001–05 period. International industry-specific research and development (R&D) stock is linked to the Chinese firm-level data, international R&D spillovers from FDI and intranational technological spillovers of R&D activities by foreign invested firms in China are examined as well. Policy implications are discussed.

‘O convergence, where art thou?’ Regional growth and industrialization in Italy

This paper shows that the Italian economy has two long-run equilibria, which are due to the different level of industrialization between the centre-north and the south of the country. These equilibria converge until 1971 but diverge afterwards; the end of the convergence process coincides with the slowing down of Italy's industrialization policy in the South. In this paper we argue that to address this problem effectively, an economic policy completely different from that in place in needed. However, such a policy is unlikely to be implemented given the scarcity of resources and the short run nature of the political cycle.

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.

Mixed communities: a new approach to spatially-concentrated poverty in England

This article examines the adoption, by the New Labour government, of a mixed communities approach to the renewal of disadvantaged neighbourhoods in England. It argues that while there are continuities with previous policy, the new approach represents a more neoliberal policy turn in three respects: its identification of concentrated poverty as the problem; its faith in market-led regeneration; and its alignment with a new urban policy agenda in which cities are gentrified and remodelled as sites for capital accumulation through entrepreneurial local governance. The article then draws on evidence from the early phases of the evaluation of the mixed community demonstration projects to explore how the new policy approach is playing out at a local level, where it is layered upon existing policies, politics and institutional relationships. Tensions between neighbourhood and strategic interests, community and capital are evident as the local projects attempt neighbourhood transformation, while seeking to protect the rights and interests of existing residents. Extensive community consultation efforts run parallel with emergent governance structures, in which local state and capital interests combine and communities may effectively be disempowered. Policies and structures are still evolving and it is not yet entirely clear how these tensions will be resolved, especially in the light of a collapsing housing market, increased poverty and demand for affordable housing, and a shortage of private investment.

Military spending and economic growth in South Africa

This paper undertakes an empirical analysis of the economic effects of military spending on the South African economy. It estimates a neo-classical model common in the literature at the level of the macroeconomy and at the level of the manufacturing sector. An attempt is made to improve upon the model by allowing the data to determine the dynamic structure of the model through an ARDL procedure. No significant impact of military spending is found in aggregate, but there is a significant negative impact for the manufacturing sector. This suggests that the cuts in domestic military procurement that have occurred since 1989 could lead to improved economic performance in South Africa through their impact on the manufacturing sector.

Glycogen, the preferred energy source for extracellular protein formation and growth of Aeromonas salmonicida

A study was made of the effect of supplementing a rich 3% (w/v) tryptone soya broth (TSB) medium and a poorer 1.7% (w/v) tryptone-based medium with glucose, maltose and glycogen, as carbon sources, on growth and exoprotein formation by Aeromonas salmonicida. In TSB, glucose inhibited growth and repressed exoprotein formation whilst maltose and glycogen had little effect, up to 20 h, when compared with an unsupplemented control. By contrast, in the poorer medium, over a 24-h incubation period, growth was stimulated three-fold by glycogen, and whilst exoprotein formation was low in comparison with that observed in TSB, the greatest production was observed in the presence of glycogen. Extracellular alpha-amylase was measured in the tryptone medium in the presence of the three carbon sources and the highest level, produced in the presence of glycogen, was 1.6 times that with added maltose whilst none was detectable with glucose present. This pattern was repeated in the case of the maltose-inducible porin, LamB, of the outer membrane.

Do changes in transglutaminase activity alter latent transforming growth factor beta activation in experimental diabetic nephropathy?

Background. Diabetic nephropathy is the leading cause of end-stage kidney failure worldwide. It is characterized by excessive extracellular matrix accumulation. Transforming growth factor beta 1 (TGF-ß1) is a fibrogenic cytokine playing a major role in the healing process and scarring by regulating extracellular matrix turnover, cell proliferation and epithelial mesanchymal transdifferentiation. Newly synthesized TGF-ß is released as a latent, biologically inactive complex. The cross-linking of the large latent TGF-ß to the extracellular matrix by transglutaminase 2 (TG2) is one of the key mechanisms of recruitment and activation of this cytokine. TG2 is an enzyme catalyzing an acyl transfer reaction leading to the formation of a stable e(?-glutamyl)-lysine cross-link between peptides.Methods. To investigate if changes in TG activity can modulate TGF-ß1 activation, we used the mink lung cell bioassay to assess TGF-ß activity in the streptozotocin model of diabetic nephropathy treated with TG inhibitor NTU281 and in TG2 overexpressing opossum kidney (OK) proximal tubular epithelial cells.Results. Application of the site-directed TG inhibitor NTU281 caused a 25% reduction in kidney levels of active TGF-ß1. Specific upregulation of TG2 in OK proximal tubular epithelial cells increased latent TGF-ß recruitment and activation by 20.7% and 19.7%, respectively, in co-cultures with latent TGF-ß binding protein producing fibroblasts.Conclusions. Regulation of TG2 directly influences the level of active TGF-ß1, and thus, TG inhibition may exert a renoprotective effect by targeting not only a direct extracellular matrix deposition but also TGF-ß1 activation and recruitment.

Radial growth and carbohydrate levels in the lichen Parmelia conspersa on north and south facing rock surfaces

Parmelia conspersa (Ehrh. Ex Ach.)Ach. is a foliose lichen found more frequently on south facing compared with north facing rock surfaces in South Gwynedd, Wales, UK. The radial growth of thalli of P. conspersa from a north and a south facing rock surface was measured in situ at intervals of two months for 1 yr during 1990/1991. Mean annual radial growth rates were greater on the south compared with the north facing rock surface. In addition, the pattern of radial growth varied during the year with maximum growth recorded in the Feb/Mar. period especially on the south facing rock surface. The levels of ribitol, arabitol and mannitol were measured in individual lobes of P. conspersa collected from the same rock surfaces on 4 days (2 Jun; 7 July and 30 Nov. 1990 and 29 Mar. 1991) during 1990/1991. The total of the three carbohydrates varied between days; the levels of arbitol and ribitol being significantly lower in the 7 July sample on both north and south facing rock surfaces. In addition, the levels ribitol, arabitol and mannitol were higher on the south facing rock surface especially in the summer samples. The ratio of arabitol plus mannitol to ribitol and the mannitol/arabitol ratio varied more between days sampled than between north and south facing rock surfaces. The level of ribitol in individual thalli was positively correlated with arabitol on the north facing and with mannitol on the south facing slope. These results suggest that differences in the radial growth of P. conspersa thalli with aspect are more likely to reflect higher rates of photosynthesis on the south facing rock surface rather than large difference in the way carbohydrates were partitioned on the different surfaces. Lower radial growth rates may place P. conspersa at a competitive disadvantage on north facing rock surfaces.

Excess leverage and productivity growth in emerging economies:is there a threshold effect?

This paper studies the relationship between leverage and growth, focusing on a large sample of firms in emerging economies of central and eastern Europe (CEE). Contrary to the general wisdom, we find that deviation from optimal leverage, especially, excess leverage is common among firms in many CEE countries. Using firm-level panel data from a group of transition countries, the paper provides support to the hypothesis that leverage positively affects productivity growth but only below an endogenously determined threshold level.

An appraisal of employment problems and policies at the micro-economic level

This study has concentrated on the development of an impact simulation model for use at the sub-national level. The necessity for the development of this model was demonstrated by the growth of local economic initiatives during the 1970's, and the lack of monitoring and evaluation exercise to assess their success and cost-effectiveness. The first stage of research involved the confirmation that the potential for micro-economic and spatial initiatives existed. This was done by identifying the existence of involuntary structural unemployment. The second stage examined the range of employment policy options from the macroeconomic, micro-economic and spatial perspectives, and focused on the need for evaluation of those policies. The need for spatial impact evaluation exercise in respect of other exogenous shocks, and structural changes was also recognised. The final stage involved the investigation of current techniques of evaluation and their adaptation for the purpose in hand. This led to a recognition of a gap in the armoury of techniques. The employment-dependency model has been developed to fill that gap, providing a low-budget model, capable of implementation at the small area level and generating a vast array of industrially disaggregate data, in terms of employment, employment-income, profits, value-added and gross income, related to levels of United Kingdom final demand. Thus providing scope for a variety of impact simulation exercises.

The mechanics of creep crack growth in a Magnox alloy

Magnox AL80 has been used for a study of creep crack propagation. A number of variables have been considered such as specimen geometry,notch root radius, material thickness, creep prestrain and stress level.The work has covered the material behaving under two values of the creep exponent, n=3.5 and n=7, according to the stress level. As well as observing initiation times and crack growth rates, scribed grids have been used to examine the near crack tip strain levels and distributions. It was shown that estimations of COD from notch flank opening can give misleading indications of material behaviour and that a more informative method was to monitor displacements in the material surrounding the crack tip. Strong evidence was found for crack advance being displacement controlled, however it was shown that the COD approach should be considered geometry dependant. The summation of ∈xx and ∈yy provided the most successful description of crack advance as it produced a single value that described propagation in all the cases concidered. The strain distributions indicates that σyy was related to distance from a point ahead of the crack tip by the exponent - (l/n+l) and that σxx is proportional to σyy. The constraint stresses arising in the DEN and CN specimens were evaluated. Initiation time was found to be principally affected by the stress level but was modified by the constraints arising from specimen geometry. Crack growth was found not to obey either the empirical K or σpett relationships but was reviewed in context of the observed strain behaviour.

The economic impact of high growth start-ups:understanding the challenge for policy in the UK

Objectives The creation of more high-growth firms continues to be a key component of enterprise policy throughout the countries of the OECD. In the UK the developing enterprise policy framework highlights the importance of supporting businesses with growth potential. The difficulty, of course, is the ability of those delivering business support policies to accurately identify those businesses, especially at start-up, which will benefit from interventions and experiences an enhanced growth performance. This paper has a core objective of presenting new data on the number of high growth firms in the UK and providing an assessment of their economic significance. Approach This paper uses a specially created longitudinal firm-level database based on the Inter-Departmental Business Register (IDBR) held by the Office of National Statistics (ONS) for all private sector businesses in the UK for the period 1997-2008 to investigate the share of high-growth firms (including a sub-set of start-up more commonly referred to as gazelles) in successive cohorts of start-ups. We apply OECD definitions of high growth and gazelles to this database and are able to quantify for the first time their number (disaggregated by sector, region, size) and importance (employment and sales). Prior Work However, what is lacking at the core of this policy focus is any comprehensive statistical analysis of the scale and nature of high-growth firms in cohorts of new and established businesses. The evidence base in response to the question “Why do high-growth firms matter?” is surprisingly weak. Important work in this area has been initiated by Bartelsman et al., (2003),Hoffman and Jünge (2006) and Henreksen and Johansson (2009) but to date work in the UK has been limited (BERR, 2008b). Results We report that there are ~11,500 high growth firms in the UK in both 2005 and 2008. The share of high growth start-ups in the UK in 2005 (6.3%) was, contrary to the widely held perception in policy circles, higher than in the United States (5.2%). Of particular interest in the analysis are the growth trajectories (pattern of growth) of these firms as well as the extent to which they are restricted to technology-based or knowledge-based sectors. Implications and Value Using hitherto unused population data for the first time we have answered a fundamental research and policy question on the number and scale of high growth firms in the UK. We draw the conclusion that this ‘rare’ event does not readily lend itself to policy intervention on the grounds that the significant effort needed to identify such businesses ex ante would appear unjustified even if it was possible.

Firm size, source of finance, and growth:evidence from China

Using a comprehensive firm-level data set from China spanning the period 1998–2005, this study investigates the relationship between firm size, financing sources, and total factor productivity growth. Controlling for the endogeneity of financing sources, we find that firm size plays an important role in the way financial structure affects the growth process. Domestic bank loans are more effective for bigger firms, while self-raised finance is more beneficial to smaller firms’ growth. We also uncover evidence that ownership mediates the relationship between firm size, finance, and growth.