The dynamics of firm profitability, growth, and exit.

This thesis analyses the dynamics of firm profitability, growth, and exit across different industries. Chapter 1 documents a striking empirical regularity in the joint distribution of firm profitability and firm size which varies systematically across industries: In industries with a high intensity of R&D investments, there is a strong, systematic "negative tail" of small loss-making firms in the profits-size distribution, whereas this "negative tail" is much less pronounced in industries with low R&D intensity. The chapter also proposes a simple reduced form dynamic model which explains the main empirical features by combining two key mechanisms: a real option effect at the business level and a diversification effect at the firm level. The second part of the thesis takes a structural approach. Its focus is on estimating the dynamic evolution of firm productivity which is an unobserved state variable in an underlying structural model. In this model, firms make exit decisions and investment decisions in physical capital and in R&D. Chapter 2 extends the model in Olley & Pakes (1996) to include R&D decisions that stochastically affect future productivity realisations and proves that their invertibility approach still applies. It estimates the distribution of future productivity conditional on current productivity and R&D investments, which is the key stochastic primitive in theoretical models of firm dynamics. Chapter 3 introduces knowledge capital as a second unobserved state variable into the model and extends the invertibility idea and the estimation strategy to the case of two unobserved state variables. Knowledge allows for lagged effects of R&D on productivity while simultaneously accounting for the stochastic nature of R&D. This reconciles the knowledge capital view in the tradition of Griliches (e.g. 1998) with the stochastic approach in the recent literature on firm dynamics

Has the HIV epidemic peaked?

This working paper reviews the highly diverse regional and country patterns of HIV epidemics and discusses possible causes of the geographic variation in epidemic sizes. The main finding of this analysis is that the HIV epidemic reached a major turning point over the past decade. The peak years of HIV incidence rates are past for all regions, and the peaks of prevalence rates are mostly in the past except in Eastern Europe, where it is expected to peak in 2008. But owing in part to the life-prolonging effect of antiretroviral therapy and to sustained population growth, the absolute number of infected individuals is expected to keep growing slowly in sub-Saharan Africa and remain near current levels worldwide, thus posing a continuing challenge to public health programs. No country is expected to see a decline in its population size between 2005 and 2050 that is attributable to high mortality related to AIDS

The kinetics of the reaction of superoxide radical with Fe(III) complexes of EDTA, DETAPAC and HEDTA

AbstractTo gain an understanding of the mechanism by which the hydroxyl free radical can arise in superoxide generating systems and learn how different chelaters of iron can inhibit this reaction, a pulse radiolysis kinetic study of the reaction of O−2 with Fe(III)EDTA, Fe(III)HEDTA and Fe(III)DETAPAC (or DTPA) was undertaken. Superoxide reacts readily with Fe(III)EDTA and Fe(III)HEDTA with a pH-dependent second-order rate constant having values of 1.9 × 106 M−1.s−1 and 7.6 × 105 M−1.s−1 at pH 7, respectively. However, the rate constant for the reaction of O−2 with Fe(III)DETAPAC was found to be much slower, the upper limit for the rate constant being 104 M−1.s−1. These results in conjunction with spin-trapping experiments with Fe(II)EDTA, Fe(II)HEDTA, Fe(II)DETAPAC and H2O2 suggests that DETAPAC inhibits the formation of OH by slowing the reduction of Fe(III) to Fe(II) and not by inhibiting the Fenton reaction

The Use of Quantitative Economic Techniques in EU Merger Control

In some recent merger cases the European Commission has relied on quantitative economic techniques in the competitive assessment of horizontal mergers. These techniques have ranged from the use of merger simulation models (for both differentiated and homogenous goods), to the deployment of direct estimation methods to study the effects of relevant events in the past. This article describes the appropriate use of these quantitative techniques, and it explains the rationale for the reliance on these methods. It also explains why the evidence from economic modelling is complementary to more traditional qualitative evidence on the expected impact of horizontal mergers

The Use of Quantitative Economic Techniques in EU Merger Control

In some recent merger cases the European Commission has relied on quantitative economic techniques in the competitive assessment of horizontal mergers. These techniques have ranged from the use of merger simulation models (for both differentiated and homogenous goods), to the deployment of direct estimation methods to study the effects of relevant events in the past. This article describes the appropriate use of these quantitative techniques, and it explains the rationale for the reliance on these methods. It also explains why the evidence from economic modelling is complementary to more traditional qualitative evidence on the expected impact of horizontal mergers

Automated evaluation of autoantibodies on human epithelial-2 cells as an approach to standardize cell-based immunofluorescence tests

INTRODUCTION: Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) is a basic tool for the serological diagnosis of systemic rheumatic disorders. Automation of autoantibody IIF reading including pattern recognition may improve intra- and inter-laboratory variability and meet the demand for cost-effective assessment of large numbers of samples. Comparing automated and visual interpretation, the usefulness for routine laboratory diagnostics was investigated. METHODS: Autoantibody detection by IIF on human epithelial-2 (HEp-2) cells was conducted in a total of 1222 consecutive sera of patients with suspected systemic rheumatic diseases from a university routine laboratory (n = 924) and a private referral laboratory (n = 298). IIF results from routine diagnostics were compared with a novel automated interpretation system. RESULTS: Both diagnostic procedures showed a very good agreement in detecting AAB (kappa = 0.828) and differentiating respective immunofluorescence patterns. Only 98 (8.0%) of 1222 sera demonstrated discrepant results in the differentiation of positive from negative samples. The contingency coefficients of chi-square statistics were 0.646 for the university laboratory cohort with an agreement of 93.0% and 0.695 for the private laboratory cohort with an agreement of 90.6%, P < 0.0001, respectively. Comparing immunofluorescence patterns, 111 (15.3%) sera yielded differing results. CONCLUSIONS: Automated assessment of AAB by IIF on HEp-2 cells using an automated interpretation system is a reliable and robust method for positive/negative differentiation. Employing novel mathematical algorithms, automated interpretation provides reproducible detection of specific immunofluorescence patterns on HEp-2 cells. Automated interpretation can reduce drawbacks of IIF for AAB detection in routine diagnostics providing more reliable data for clinicians

Borane-Catalysed Hydroboration of Alkynes and Alkenes

Simple, commercially available borane adducts, H 3 B·THF and H 3 B·SMe 2, have been used to catalyse the hydroboration of alkynes and alkenes with pinacolborane to give the alkenyl and alkyl boronic esters, respectively. Alkynes and terminal alkenes underwent highly regioselective hydroboration to give the linear boronic ester products. Good functional group tolerance was observed for substrates bearing ester, amine, ether and halide substituents. This catalytic process shows comparable reactivity to transition-metal-catalysed hydroboration protocols

Biomechanical comparison of menisci from different species and artificial constructs

Background: Loss of meniscal tissue is correlated with early osteoarthritis but few data exist regarding detailed biomechanical properties (e. g. viscoelastic behavior) of menisci in different species commonly used as animal models. The purpose of the current study was to biomechanically characterize bovine, ovine, and porcine menisci (each n = 6, midpart of the medial meniscus) and compare their properties to that of normal and degenerated human menisci (n = 6) and two commercially available artificial scaffolds (each n = 3). Methods: Samples were tested in a cyclic, minimally constraint compression-relaxation test with a universal testing machine allowing the characterization of the viscoelastic properties including stiffness, residual force and relative sample compression. T-tests were used to compare the biomechanical parameters of all samples. Significance level was set at p &lt; 0.05. Results: Throughout cyclic testing stiffness, residual force and relative sample compression increased significantly (p &lt; 0.05) in all tested meniscus samples. From the tested animal meniscus samples the ovine menisci showed the highest biomechanical similarity to human menisci in terms of stiffness (human: 8.54 N/mm +/- 1.87, cycle 1; ovine: 11.24 N/mm +/- 2.36, cycle 1, p = 0.0528), residual force (human: 2.99 N +/- 0.63, cycle 1 vs. ovine 3.24 N +/- 0.13, cycle 1, p = 0.364) and relative sample compression (human 19.92\% +/- 0.63, cycle 1 vs. 18.72\% +/- 1.84 in ovine samples at cycle 1, p = 0.162). The artificial constructs - as hypothesized- revealed statistically significant inferior biomechanical properties. Conclusions: For future research the use of ovine meniscus would be desirable showing the highest biomechanical similarities to human meniscus tissue. The significantly different biomechanical properties of the artificial scaffolds highlight the necessity of cellular ingrowth and formation of extracellular matrix to gain viscoelastic properties. As a consequence, a period of unloading (at least partial weight bearing) is necessary, until the remodeling process in the scaffold is sufficient to withstand forces during weight bearing

A sustained high fat diet for two years decreases IgM and IL-1 beta in ageing Wistar rats

Background The immune system undergoes several alterations of innate and adaptive immunity during ageing. The main features of the aged immune system are a reduced diversity of T cell receptors and a reduced activity of innate immune cells with subsequent changes in adaptive immunity resulting in a less effective, less specific, and dys-regulated immune response and in an increased susceptibility towards infection, malignancy, and autoimmunity. The process is referred to as immunosenescence and is also modulated by environmental modifiers, such as dietary factors. High fat diet (HFD), via direct modulation of immune cell function by fatty acids and/or increased body fat mass, influences immune function. However, it is not clear whether HFD is beneficial or detrimental for the functioning of the ageing immune system. Methods Male Wistar rats fed with either a high fat diet (HFD 43 en% of fat) or control diet (SD, 25 en% of fat) over up to 24 month and were analyzed for plasma IL-1β, IL-6, TNF, IgM, IgG1, IgA, IgG2a, IgG2b, IgG2c, light chains lambda and kappa, testosterone, prolactin and percentage of splenic B cells and apoptosis rate, respectively. Results In general, all analyzed immunoglobuline isotypes increased with age, except for IgA. This increase was attenuated by HFD. In HFD and SD rats the percentage of B cells in the spleen and also their apoptotic rate was lower in aged as compared to young animals with no additional diet-induced effect. Testosterone and prolactin levels were lower in old animals, as expected. There was a statistical trend towards an increased prolactin/testosterone ratio in middle aged (6–12 monthsnth) HFD rats as compared to SD. IL-6 was neither affected by HFD nor age. On the other hand, HFD rats showed a decrease in IL-1β as compared to SD, which correlated with the above-mentioned suppressive effect on immunoglobulin isotypes, especially IgM. Conclusion In Wistar rats, HFD reveals an immunosuppressive effect in ageing animals by decreasing immunoglobulins, especially IgM, and IL-1β when compared to SD

LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells

The epigenetic writer lysine-specific demethylase 1 (LSD1) is aberrantly upregulated in many cancer types and its overexpression correlates with poor survival and tumor progression. In this study, we analysed LSD1 function in non-small cell lung cancer adenocarcinomas. Expression profiling of 182 cases of lung adenocarcinoma proved a significant correlation of LSD1 overexpression with lung adenocarcinoma progression and metastasis. KRAS-mutated lung cancer cell clones were stably silenced for LSD1 expression. RNA-seq and comprehensive pathway analysis revealed, that genes related to a recently described non-canonical integrin β3 pathway, were significantly downregulated by LSD1 silencing. Hence, invasion and self-renewal capabilities were strongly decreased. Notably, this novel defined LSD1/integrin β3 axis, was also detected in human lung adenocarcinoma specimens. Furthermore, the linkage of LSD1 to an altered expression pattern of lung-lineage specific transcription factors and genes, which are involved in alveolar epithelial differentiation, was demonstrated. Thus, our findings point to a LSD1-integrin β3 axis, conferring attributes of invasiveness and tumor progression to lung adenocarcinoma