Marketing innovative service solutions with inter-organizational service networks: opportunities and threats

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Radical-containing particles activate dendritic cells and enhance Th17 inflammation in a mouse model of asthma

We identified a previously unrecognized component of airborne particulate matter (PM) formed in combustion and thermal processes, namely, environmentally persistent free radicals (EPFRs). The pulmonary health effects of EPFRs are currently unknown. In the present study, we used a model EPFR-containing pollutant-particle system referred to as MCP230. We evaluated the effects of MCP230 on the phenotype and function of bone marrow - derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. We also investigated the adjuvant role of MCP230 on airway inflammation in a mouse model of asthma. MCP230 decreased intracellular reduced glutathione (GSH) and the GSH/oxidized glutathione ratio in BMDCs, and up-regulated the expression of costimulatory molecules CD80 and CD86 on DCs. The maturation of DCs was blocked by inhibiting oxidative stress or the uptake of MCP230. BMDCs exposed to MCP230 increased their antigen-specific T-cell proliferation in vitro. In a model of asthma, exposure to MCP230 exacerbated pulmonary inflammation, which was attributed to the increase of neutrophils and macrophages but not eosinophils. This result correlated with an increase in Th17 cells and cytokines, compared with non - MCP230-treated but ovalbumin (OVA) - challenged mice. The percentage of Th2 cells was comparable between OVA and OVA + MCP230 mice. Our data demonstrate that combustion-generated, EPFR-containing PM directly induced the maturation of DCs in an uptake-dependent and oxidative stress - dependent manner. Furthermore, EPFR-containing PM induced a Th17-biased phenotype in lung, accompanied by significant pulmonary neutrophilia. Exposure to EPFR-containing PM may constitute an important and unrecognized risk factor in the exacerbation and development of a severe asthma phenotype in humans

Inchoate CD8\u3csup\u3e+\u3c/sup\u3e T cell responses in neonatal mice permit influenza-induced persistent pulmonary dysfunction

Influenza infection remains a significant cause of pulmonary morbidity and mortality worldwide, with the highest hospitalization and mortality rates occurring in infants and elder adults. The mechanisms inducing this considerable morbidity and mortality are largely unknown. To address this question, we established a neonatal mouse model of influenza infection to test the hypothesis that the immaturity of the neonatal immune system is responsible for the severe pulmonary disease observed in infants. Seven-day-old mice were infected with influenza A virus (H1N1) and allowed to mature. As adults, these mice showed enhanced airway hyperreactivity, chronic pulmonary inflammation, and diffuse emphysematous-type lesions in the lungs. The adaptive immune responses of the neonates were much weaker than those of adults. This insufficiency appeared to be in both magnitude and functionality and was most apparent in the CD8 + T cell population. To determine the role of neonatal CD8 + T cells in disease outcome, adult, naive CD8+ T cells were adoptively transferred into neonates before infection. Neonatal mice receiving the adult CD8+ T cells had significantly lower pulmonary viral titers and greatly improved pulmonary function as adults (airway resistance similar to SHAM). Additional adoptive transfer studies using adult CD8+ T cells from IFN-γ-deficient mice demonstrated the importance of IFN-γ from CD8+ T cells in controlling the infection and in determining disease outcome. Our data indicate that neonates are more vulnerable to severe infections due to immaturity of their immune system and emphasize the importance of vaccination in infants. Copyright © 2008 by The American Association of Immunologists, Inc

Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs

<p>Abstract</p> <p>Background</p> <p>Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM). The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs), in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma.</p> <p>Methods</p> <p>Neonatal rats (7-days of age) were exposed to EPFR-containing combustion generated ultrafine particles (CGUFP), non-EPFR containing CGUFP, or air for 20 minutes per day for one week. Pulmonary function was assessed in exposed rats and age matched controls. Lavage fluid was isolated and assayed for cellularity and cytokines and <it>in vivo </it>indicators of oxidative stress. Pulmonary histopathology and characterization of differential protein expression in lung homogenates was also performed.</p> <p>Results</p> <p>Neonates exposed to EPFR-containing CGUFP developed significant pulmonary inflammation, and airway hyperreactivity. This correlated with increased levels of oxidative stress in the lungs. Using differential two-dimensional electrophoresis, we identified 16 differentially expressed proteins between control and CGUFP exposed groups. In the rats exposed to EPFR-containing CGUFP; peroxiredoxin-6, cofilin1, and annexin A8 were upregulated.</p> <p>Conclusions</p> <p>Exposure of neonates to EPFR-containing CGUFP induced pulmonary oxidative stress and lung dysfunction. This correlated with alterations in the expression of various proteins associated with the response to oxidative stress and the regulation of glucocorticoid receptor translocation in T lymphocytes.</p

Serotonin 5-HT\u3csub\u3e2\u3c/sub\u3e receptor activation prevents allergic asthma in a mouse model

© 2015 the American Physiological Society. Asthma is an inflammatory disease of the lung characterized by airways hyper-responsiveness (AHR), inflammation, and mucus hyperproduction. Current main-stream therapies include bronchodilators that relieve bronchoconstriction and inhaled glucocorticoids to reduce inflammation. The small molecule hormone and neurotransmitter serotonin has long been known to be involved in inflammatory processes; however, its precise role in asthma is unknown. We have previously established that activation of serotonin 5-hydroxytryptamine (5-HT)2A receptors has potent anti-inflammatory activity in primary cultures of vascular tissues and in the whole animal in vasculature and gut tissues. The 5-HT2A receptor agonist, (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] is especially potent. In this work, we have examined the effect of (R)-DOI in an established mouse model of allergic asthma. In the ovalbumin mouse model of allergic inflammation, we demonstrate that inhalation of (R)-DOI prevents the development of many key features of allergic asthma, including AHR, mucus hyperproduction, airways inflammation, and pulmonary eosinophil recruitment. Our results highlight a likely role of the 5-HT2 receptors in allergic airways disease and suggest that 5-HT2 receptor agonists may represent an effective and novel small molecule-based therapy for asthma

Sport in the city: measuring economic significance at the local level

In many cities throughout Europe, sport is increasingly being used as a tool for economic revitalisation. While there has been a growth in literature relating to the specific economic impacts of sports-led development, including professional sport facilities, teams, and sport events, limited research has been undertaken on the contribution of the whole sport sector to output and employment. In the United Kingdom (UK), studies have focused on evaluating sport-related economic activity at the national level, yet despite the increasing use of sport for local economic development little research has been undertaken at the city level. To address this situation, this article uses the National Income Accounting framework to measure the economic importance of sport in Sheffield, UK. It shows that the value-added in 1996/97 was 165.61m or 4.11% of Gross Domestic Product (GDP), approximately twice the amount predicted from current national estimates. It is argued that this can primarily be explained by previous studies under-estimating the economic importance of sport, largely due to methodological differences. It goes on to suggest that future research on the significance of sport should be undertaken at the local level to provide policymakers with information at the spatial level where regeneration programmes are being implemented.</p

Franchising as a Strategy for Combining Small and Large Group Advantages (Logics) in Social Entrepreneurship:A Hayekian Perspective

This article develops a Hayekian perspective on social franchising that distinguishes between the end-connected logic of the small group and the rule-connected logic of the big group. Our key claim is that mission-driven social entrepreneurs often draw on the small-group logic when starting their social ventures and then face difficulties when the process of scaling shifts their operations toward a big-group logic. In this situation, social franchising offers a strategy to replicate the small group despite systemwide scaling, to mobilize decentrally accessible social capital, and to reduce agency costs through mechanisms of self-selection and self-monitoring. By employing a Hayekian perspective, we are thus able to offer an explanation as to why social franchising is a suitable scaling strategy for some social entrepreneurship organizations and not for others. We illustrate our work using the Ashoka Fellow Wellcome

Does the perception of fairness and standard of care in the health system depend on the field of study? Results of an empirical analysis

Background: The main challenge in the context of health care reforms and priority setting is the establishment and/or maintenance of fairness and standard of care. For the political process and interdisciplinary discussion, the subjective perception of the health care system might even be as important as potential objective criteria. Of special interest are the perceptions of academic disciplines, whose representatives act as decision makers in the health care sector. The aim of this study is to explore and compare the subjective perception of fairness and standard of care in the German health care system among students of medicine, law, economics, philosophy, and religion. Methods: Between October 2011 and January 2012, we asked freshmen and advanced students of the fields mentioned above to participate in a paper and pencil survey. Prior to this, we formulated hypotheses. The data were analysed by micro econometric regression techniques. Results: Data from 1,088 students were included in the study. Medical students, freshmen, and advanced students perceive the standard of care significantly as being better than non-medical students. Differences in the perception of fairness are not significant between the freshmen of the academic disciplines; however, they increase with the number of study terms. Besides the field of study, further variables such as gender and health status have a significant impact on perceptions. Conclusions: Our results show that there are differences in the perception of fairness and standard of care between academic disciplines, which might influence the interdisciplinary discussion on health care reforms and priority setting.Leibniz University Hannover/Wege in die Forschung I