Churn, Baby, Churn: Strategic Dynamics Among Dominant and Fringe Firms in a Segmented Industry

This paper integrates and extends the literatures on industry evolution and dominant firms to develop a dynamic theory of dominant and fringe competitive interaction in a segmented industry. It argues that a dominant firm, seeing contraction of growth in its current segment(s), enters new segments in which it can exploit its technological strengths, but that are sufficiently distant to avoid cannibalization. The dominant firm acts as a low-cost Stackelberg leader, driving down prices and triggering a sales takeoff in the new segment. We identify a “churn” effect associated with dominant firm entry: fringe firms that precede the dominant firm into the segment tend to exit the segment, while new fringe firms enter, causing a net increase in the number of firms in the segment. As the segment matures and sales decline in the segment, the process repeats itself. We examine the predictions of the theory with a study of price, quantity, entry, and exit across 24 product classes in the desktop laser printer industry from 1984 to 1996. Using descriptive statistics, hazard rate models, and panel data methods, we find empirical support for the theoretical predictions

Activated CD4(+) T cells and highly differentiated alloreactive CD4(+) T cells distinguish operationally tolerant liver transplantation recipients

Spontaneous operational tolerance to the allograft develops in a proportion of liver transplantation (LT) recipients weaned off immunosuppressive (IS) drugs. Several studies have investigated whether peripheral blood circulating T cells could play a role in the development or identify operational tolerance, but never characterized alloreactive T cells in detail due to the lack of a marker for these T cells. In this study, we comprehensively investigated phenotypic and functional characteristics of alloreactive circulating T cell subsets in tolerant LT recipients (n = 15) using multiparameter flow cytometry and compared these with LT recipients on IS drugs (n = 23) and healthy individuals (n = 16). Activation-induced CD137 was used as a marker for alloreactive T cells upon allogenic stimulation. We found that central and effector memory CD4+ T cells were hyporesponsive against donor and third-party splenocyte stimulation in tolerant LT recipients, whereas an overall hyperresponsiveness was observed in alloreactive terminally differentiated effector memory CD4+ T cells. In addition, elevated percentages of circulating activated T helper cells were observed in these recipients. Lastly, tolerant and control LT recipients did not differ in donor-specific antibody formation. In conclusion, a combination of circulating hyperresponsive highly differentiated alloreactive CD4+ T cells and circulating activated T helper cells could discriminate tolerant recipients from a larger group of LT recipients.Transplantation and autoimmunit

Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase

BACKGROUND: For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally.The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. CONCLUSION: These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons

Regaining momentum for international climate policy beyond Copenhagen

The 'Copenhagen Accord' fails to deliver the political framework for a fair, ambitious and legally-binding international climate agreement beyond 2012. The current climate policy regime dynamics are insufficient to reflect the realities of topical complexity, actor coalitions, as well as financial, legal and institutional challenges in the light of extreme time constraints to avoid 'dangerous' climate change of more than 2°C. In this paper we analyze these stumbling blocks for international climate policy and discuss alternatives in order to regain momentum for future negotiations

The dynamics of entry, exit and profitability: an error correction approach for the retail industry

We develop a two equation error correction model to investigate determinants of and dynamic interaction between changes in profits and number of firms in retailing. An explicit distinction is made between the effects of actual competition among incumbants, new firms competition and potential competition from firms outside the market. Effects of cost, demand and general income changes on profitability are investigated to gain insight in the role of retailing in the cost, demand and wage inflationary processes. The relative importance of profitability, growth and unemployment as determinants of net entry are studied. The model is tested using a panel data set of 36 Dutch shoptypes covering the 1977–1988 period

Validation of a Combined Transcriptome and T Cell Receptor Alpha/Beta (TRA/TRB) Repertoire Assay at the Single Cell Level for Paucicellular Samples

Transcriptomics can be combined with TRA and TRB clonotype analysis at the single cell level. The aim of this study was to validate this approach on the ICELL8 Single-Cell system and to evaluate its usefulness to analyse clinical paucicellular samples. For this purpose, we carefully select

Determining how internal and external process connectivity affect supply chain agility: a life-cycle theory perspective

This paper examines how organizations connect internal and external processes to enable an agile response to continuous change. Drawing on life cycle theory, a hypothetical model is developed regarding the independent and combinative effects of internal and external process connectivity on supply chain agility and the moderating effect of product and supply complexity. The model is tested using hierarchical regression analysis based on survey data from 143 managers at German manufacturing firms. Our findings suggest that internal and external process connectivity have a positive effect on supply chain agility independently and collectively, with complexity having a moderating effect in particular instances. The findings build on prior research regarding the process-related enablers of supply chain agility; research that has yet to clearly differentiate between internal and external processes or uses the terms interchangeably. The theoretical contribution of the paper rests on its extension of life cycle theory to the supply chain

ICRH operations and experiments during the JET-ILW tritium and DTE2 campaigns

2021 has culminated with the completion of the JET-ILW DTE2 experimental campaign. This contribution summarizes Ion Cyclotron Resonance Heating (ICRH) operations from system and physics point of view. Improvements to the (ICRH) system, to operation procedures and to real time RF power control were implemented to address specific constraints from tritium and deuterium-tritium operations and increase the system reliability and power availability during D-T pulses. ICRH was operated without the ITER-Like Antenna (ILA) because water leaked from an in-vessel capacitor into the vessel on day-2 of the D-T campaign. Three weeks were required to identify and isolate the leak and resume plasma operations. Dedicated RF-Plasma Wall Interaction (PWI) experiments were conducted; tritium plasmas exhibit a higher level of Be sputtering on the outer wall and impurity content when compared to deuterium or hydrogen plasmas. The JET-DTE2 campaigns provided the opportunity to characterize ICRH schemes foreseen for the ITER operation, in the ITER like wall environment in ELMy H-mode scenarios aiming at maximizing fusion performance. The second harmonic tritium resonance heating and to a lesser extent minority 3He heating (ITER D-T ICRH reference schemes) lead to improved ion temperature and fusion performance when compared to hydrogen minority ICRH. However, these discharges suffered from a lack of stationarity and gradual impurity accumulation potentially because of a deficit of ICRH power when using JET antennas at lower frequencies. Fundamental deuterium ICRH was used in tritium-rich plasmas and with deuterium Neutral Beam Heating; this ICRH scheme proved to be very efficient boosting ion temperature and fusion performance in these plasmas