The Effects of Self-Reinforcing Mechanisms on Firm Performance

This study empirically investigates the influence of the market-bound (i.e., interaction and network effects) on the firm-bound (i.e., scale and learning effects) self-reinforcing mechanisms, and their combined effect on product and organizational performance. The findings from a sample of 257 manufacturing firms reveal that interaction effects have a positive effect on network effects. Network effects have a positive impact on the potential for firms to realize scale and learning effects, which in turn, is positively related to their actual realization of these effects. The actual realization of scale and learning effects has a positive effect on product performance, which in turn positively influences organizational performance. These effects are robust across industries and provide ample opportunities for future research.management;economics;increasing returns;self-reinforcing mechanisms

A Managerial Perspective on the Logic of Increasing Returns

The focus of this study is on the challenges faced by managers in effectively dealing with the new management logic of increasing returns as the information and knowledge intensity of their transformation processes rises. Dealing with these challenges is especially relevant for companies currently making the transition from capital and physical labor intensive transformation processes (old economy) to information and knowledge intensive transformation processes (new economy). For these companies, this study provides a definition of increasing returns, explains the sources of increasing returns and develops tools for monitoring the realization of increasing returns. These tools are applied at the Randstad Group, a leading temporary employment agency based in the Netherlands, currently making the transition from the old to the new economy. The study concludes with a discussion of the management implications of the new logic of increasing returns and suggestions for further research.management;economics;interaction effects;increasing returns;network effects

A narrative review on spinal deformities in people with cerebral palsy: Measurement, norm values, incidence, risk factors and treatment

Spinal deformities are common in people with cerebral palsy (CP), and there is a concern of an increase during the adult ageing period. There is especially a worry about the increase of scoliosis, thoracic hyperkyphosis, lumbar hyperlordosis, spondylolysis and spondylolisthesis incidence, though supporting literature is lacking. Therefore, the aim of this narrative review is to provide a scientific overview of how spinal curvatures should be measured, what the norm values are and the incidence in people with CP, as well as a description of the risk factors and the treatment regimens for these spinal abnormalities. This review can be used as a guideline relevant for a range of clinicians, including orthopaedic and neurosurgeons, radiologists, physiotherapists, and biokineticists, as well as academics

A Managerial Perspective on the Logic of Increasing Returns

The focus of this study is on the challenges faced by managers in effectively dealing with the new management logic of increasing returns as the information and knowledge intensi

The Effects of Self-Reinforcing Mechanisms on Firm Performance

This study empirically investigates the influence of the market-bound (i.e., interaction and network effects) on the firm-bound (i.e., scale and learning effects) self-r

How to Determine the Increasing Returns Sensitivity of Your Industry?

Increasing returns means that self-reinforcing mechanisms are at work within firms and markets. These mechanisms come in four forms: scale effects, learning effects, network effects and social interaction effects. Some industries are more sensitive to increasing returns than others. It is important that managers are able to assess the increasing returns sensitivity of their industry. Therefore we have developed an analytical tool that allows managers to assess their industry’s sensitivity to increasing returns. Four case studies are used to illustrate this typology. The analytic tool shows that an industry has high increasing returns sensitivity if a combination of the following situations exists: 1) high fixed costs and low, or even zero, variable costs, indicating a high sensitivity to scale effects, 2) a high level of complexity of the business process and/or the products, indicating a high sensitivity to learning effects, 3) low product utility and high network utility, indicating a high sensitivity to network effects and finally, 4) a high degree of social involvement by customers and potential customers, indicating a high sensitivity to social interaction effects

PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells

Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the specialized polymerases to the damaged site through their ubiquitin-binding domain. In mammals, however, there is a debate on the requirement for ubiquitinated PCNA (PCNA-Ub) in TLS. We show that UV-induced Rpa foci, indicative of single-stranded DNA (ssDNA) regions caused by UV, accumulate faster and disappear more slowly in Pcna(K164R/K164R) cells, which are resistant to PCNA ubiquitination, compared to Pcna(+/+) cells, consistent with a TLS defect. Direct analysis of TLS in these cells, using gapped plasmids with site-specific lesions, showed that TLS is strongly reduced across UV lesions and the cisplatin-induced intrastrand GG crosslink. A similar effect was obtained in cells lacking Rad18, the E3 ubiquitin ligase which monoubiquitinates PCNA. Consistently, cells lacking Usp1, the enzyme that de-ubiquitinates PCNA exhibited increased TLS across a UV lesion and the cisplatin adduct. In contrast, cells lacking the Rad5-homologs Shprh and Hltf, which polyubiquitinate PCNA, exhibited normal TLS. Knocking down the expression of the TLS genes Rev3L, PolH, or Rev1 in Pcna(K164R/K164R) mouse embryo fibroblasts caused each an increased sensitivity to UV radiation, indicating the existence of TLS pathways that are independent of PCNA-Ub. Taken together these results indicate that PCNA-Ub is required for maximal TLS. However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity

特集 がん検診

Aims—To investigate whether the analysis of immunoglobulin (Ig)/T cell receptor (TCR) rearrangements is useful in the diagnosis of lymphoproliferative disorders. Methods—In a series of 107 consecutive cases with initial suspicion of non-Hodgkin's lymphoma (NHL), Southern blot (SB) analysis of Ig/TCR rearrangements was performed. Results—In 98 of 100 histopathologically conclusive cases, Ig/TCR gene results were concordant. In one presumed diffuse large B cell lymphoma (DLCL) and one follicular lymphoma (FL) case no clonality could be detected by SB analysis, or by polymerase chain reaction (PCR) at second stage. In the DLCL, sampling error might have occurred; the FL was revised after an initial diagnosis of reactivity. In many of the histopathologically inconclusive cases Ig/TCR gene SB analysis was helpful, giving support for the histopathological suspicion. However, because of a lack of (clinical) follow up data this could not be confirmed in a few cases. Conclusions—Experienced haematopathologists or a pathologist panel can diagnose malignant versus reactive lesions in most cases without the need for Ig/TCR gene analysis and can select the 5–10% of cases that might benefit from molecular clonality studies. Key Words: B cell lymphoma • immunoglobulin and T cell receptor genes • clonality analysis • Southern blottin