Expression in Escherichia coli of a cloned DNA sequence encoding the pre-S2 region of hepatitis B virus

A DNA sequence encoding the entire pre-S2 region (amino acids 120-174; serotype ayw) of human hepatitis B virus envelope protein has been inserted into the lacZ gene of the plasmid pSKS105 yielding a recombinant, pWS3. Lac+ colonies of the Escherichia coli M182 (lacIOPZYA), isolated after transformation with pWS3, produced a pre-S2 peptide-ß-galactosidase fusion protein. This fusion protein, which comprised as much as 3% of the total bacterial protein, was purified to >90% homogeneity by affinity chromatography on p-aminophenyl-ß-D-thiogalactoside-Sepharose. It is immunoprecipitable with rabbit antibodies to a synthetic peptide corresponding to amino acids 120-145 of the pre-S2 region of serotype adw [pre-S(120-145)] or with antibodies to hepatitis B virus. pre-S(120-145) completely blocked the binding of either antibody to the pre-S2 peptide-ß-galactosidase fusion protein. These results indicate that there are antigenic determinants on the fusion protein that are closely related to, if not identical to, determinants on synthetic pre-S(120-145) and on pre-S2 sequences of native hepatitis B virus particles. Thus, bacteria transformed with pWS3 can provide an abundant source of pre-S2-ß-galactosidase fusion protein, which may prove useful either as a diagnostic reagent possessing marker enzyme activity suitable for ELISA tests or as an immunogen with potential to contribute to active prophylaxis of hepatitis B

Public policy to promote entrepreneurship: a call to arms

We debate the motivation for and effectiveness of public policies to encourage individuals to become entrepreneurs. Reviewing established evidence we find that most Western world policies do not greatly reduce or solve any market failures but instead waste taxpayers’ money, encourage those already intent on becoming entrepreneurs, and mostly generate one-employee businesses with low-growth intentions and a lack of interest in innovating. Most policy initiatives that would have the effect of promoting valuable entrepreneurship would not be recognizable as such, because they would primarily address other market failures: A central-payer health care would remove healthcare-related distortions affecting employment choices; greater STEM education would produce more engineers of which some start valuable new firms; and labor market reform to encourage hiring immigrants in jobs they have been educated for would reduce inefficient allocation of talent to entrepreneurship

Testing the Schumpeterian Hypothesis

The late Joseph Schumpeter had opposing views about economic development. In his earlier work, he argued that innovation is promoted by the presence of entrepreneurs outside the firm. Later, he argued that innovation activity is promoted by large firms, for whom the innovation process in endogenous. This paper uses a direct measure of innovation to test the later Schumpeterian hypothesis. The authors find support for bo th the early and later Schumpeterian hypotheses about innovation.

Recent developments in the Dutch firm-size distribution

This study investigates the development of the firm-size distribution in the Netherlands using various measures. Data are used for the period 1978 through 1989 covering practically the entire Dutch private sector. The results show a general tendency towards smaller firm sizes in manufacturing industries until 1986, but indicate an opposite development after that year. This tendency towards larger firm sizes after 1986 is also encountered for non-manufacturing industries. This study is part of a research program carried out at the Centre for Advanced Small Business Economics (CASBEC) of the Erasmus University Rotterdam. The authors are grateful to Jan van Dalen, Aad Kleijweg, Jeroen Potjes and Wim Verhoeven for helpful comments and Herman van Schaik for elaborating the original data files. The authors acknowledge a research grant from the Stichting KMO-fonds

Evaluation of canonical siRNA and Dicer substrate RNA for inhibition of hepatitis C virus genome replication - a comparative study

Hepatitis C virus (HCV) frequently establishes persistent infections in the liver, leading to the development of chronic hepatitis and, potentially, to liver cirrhosis and hepatocellular carcinoma at later stages. The objective of this study was to test the ability of five Dicer substrate siRNAs (DsiRNA) to inhibit HCV replication and to compare these molecules to canonical 21 nt siRNA. DsiRNA molecules were designed to target five distinct regions of the HCV genome - the 5′ UTR and the coding regions for NS3, NS4B, NS5A or NS5B. These molecules were transfected into Huh7.5 cells that stably harboured an HCV subgenomic replicon expressing a firefly luciferase/neoR reporter (SGR-Feo-JFH-1) and were also tested on HCVcc-infected cells. All of the DsiRNAs inhibited HCV replication in both the subgenomic system and HCVcc-infected cells. When DsiRNAs were transfected prior to infection with HCVcc, the inhibition levels reached 99.5%. When directly compared, canonical siRNA and DsiRNA exhibited similar potency of virus inhibition. Furthermore, both types of molecules exhibited similar dynamics of inhibition and frequencies of resistant mutants after 21 days of treatment. Thus, DsiRNA molecules are as potent as 21 nt siRNAs for the inhibition of HCV replication and may provide future approaches for HCV therapy if the emergence of resistant mutants can be addressed

Introduction: innovation and small business

This paper introduces the special issue of Small Business Economics on Innovation. What binds the papers together is either their focus on the effect of firm size on the causes and consequences of innovation or their focus on the role small firms play in reshaping the industrial landscape

Regional innovation and spillover effects of foreign direct investment in China: a threshold approach

Using a data set on twenty-nine Chinese provinces for the period 1985–2008, this paper establishes a threshold model to analyse the relationship between spillover effects of foreign direct investment (FDI) and regional innovation in China. There is clear evidence of double-threshold effects of regional innovation on productivity spillovers from FDI. Specifically, only when the level of regional innovation reaches the minimum innovation threshold will FDI in the region begin to produce positive productivity spillovers. Furthermore, positive productivity spillovers from FDI will be substantial only when the level of regional innovation attains a higher threshold. The double threshold divides Chinese provinces into three super-regions in terms of innovation, with most provinces positioned within the middle-level innovation super-region. Policy implications are discussed

Semi-analytical approach to magnetized temperature autocorrelations

The cosmic microwave background (CMB) temperature autocorrelations, induced by a magnetized adiabatic mode of curvature inhomogeneities, are computed with semi-analytical methods. As suggested by the latest CMB data, a nearly scale-invariant spectrum for the adiabatic mode is consistently assumed. In this situation, the effects of a fully inhomogeneous magnetic field are scrutinized and constrained with particular attention to harmonics which are relevant for the region of Doppler oscillations. Depending on the parameters of the stochastic magnetic field a hump may replace the second peak of the angular power spectrum. Detectable effects on the Doppler region are then expected only if the magnetic power spectra have quasi-flat slopes and typical amplitude (smoothed over a comoving scale of Mpc size and redshifted to the epoch of gravitational collapse of the protogalaxy) exceeding 0.1 nG. If the magnetic energy spectra are bluer (i.e. steeper in frequency) the allowed value of the smoothed amplitude becomes, comparatively, larger (in the range of 20 nG). The implications of this investigation for the origin of large-scale magnetic fields in the Universe are discussed. Connections with forthcoming experimental observations of CMB temperature fluctuations are also suggested and partially explored.Comment: 40 pages, 13 figure

Business experience and start-up size: buying more lottery tickets next time around?

This paper explores the determinants of start-up size by focusing on a cohort of 6247 businesses that started trading in 2004, using a unique dataset on customer records at Barclays Bank. Quantile regressions show that prior business experience is significantly related with start-up size, as are a number of other variables such as age, education and bank account activity. Quantile treatment effects (QTE) estimates show similar results, with the effect of business experience on (log) start-up size being roughly constant across the quantiles. Prior personal business experience leads to an increase in expected start-up size of about 50%. Instrumental variable QTE estimates are even higher, although there are concerns about the validity of the instrument

National business regulations and city entrepreneurship in Europe: a multilevel nested analysis

This article provides and tests a theoretical framework with a multilevel (country–city) nested model to analyze the relationship between national business regulations (NBRs) and city level entrepreneurship. While public interest theory predicts a positive relationship between NBR and city level entrepreneurship, public choice theory predicts the opposite, a negative relationship. Based on multilevel analysis for a matched country–city panel of 228 cities across 20 European countries for the years 2004 to 2009, the empirical evidence from panel data estimation explains how changes in NBRs influence changes in city level entrepreneurial activity over time