Protective and Aggravating Effects of Nlrp3 Inflammasome Activation in IBD Models: Influence of Genetic and Environmental Factors

Background: Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation due to dysregulation of the mucosal immune system. The cytokines IL-1 beta and IL-18 appear early in intestinal inflammation and their pro-forms are processed via the caspase-1-activating multiprotein complex, the Nlrp3 inflammasome. Previously, we reported that the uptake of dextran sodium sulfate (DSS) by macrophages activates the Nlrp3 inflammasome and that Nlrp3(-/-) mice are protected in the acute DSS colitis model. Of note, other groups have reported opposing effects in regards to DSS susceptibility in Nlrp3(-/-) mice. Recently, mice lacking inflammasomes were found to develop a distinct intestinal microflora. Methods: To reconcile the contradicting observations, we investigated the role of Nlrp3 deficiency in two different IBD models: acute DSS colitis and TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced colitis. In addition, we in-vestigated the impact of the intestinal flora on disease severity by performing cohousing experiments of wild-type and Nlrp3(-/-) mice, as well as by antibiotic treatment. Results: Nlrp3(-/-) mice treated with either DSS or TNBS exhibited attenuated colitis and lower mortality. This protective effect correlated with an increased frequency of CD103+ lamina propria dendritic cells expressing a tolerogenic phenotype in Nlrp3(-/-) mice in steady state conditions. Interestingly, after cohousing, Nlrp3(-/-) mice were as susceptible as wild-type mice, indicating that transmission of endogenous bacterial flora between the two mouse strains might increase susceptibility of Nlrp3(-/-) mice towards DSS-induced colitis. Accordingly, treatment with antibiotics almost completely prevented colitis in the DSS model. Conclusions: The composition of the intestinal microflora significantly influences disease severity in IBD models comparing wild-type and Nlrp3(-/-) mice. This observation may - at least in part - explain contradictory results concerning the role of the inflammasome in different labs. Further studies are required to define the role of the Nlrp3 inflammasome in noninflamed mucosa under steady state conditions and in IBD. Copyright (C) 2012 S. Karger AG, Base

Die Modellierung des sportlichen Erfolges : Implikationen für das Sponsoring

Die Auswahl von geeigneten Sponsoring-Engagements mit dem Ziel einer Verbesserung des Unternehmensergebnisses nimmt einen immer wichtigeren Stellenwert im Marketing von Unternehmen ein. Da gerade im Sportsponsoring der finanzielle Erfolg des Sponsors entscheidend vom Erfolg des Gesponserten abhängt, stehen Marketingmanager vor der Herausforderung, den sportlichen Erfolg verlässlich abzuschätzen. Diese Untersuchung stellt daher ein Modell zur Prognose von sowohl kurzfristigem als auch langfristigem sportlichen Erfolg vor. Als primäre Erkenntnisse lassen sich dabei festhalten, dass der kurzfristige sportliche Erfolg durch Leistungs-, situative und Marketingfaktoren relativ gut prognostiziert werden kann und dass die Ergebnisse der kurzfristigen Perspektive ausreichen, um den langfristigen sportlichen Erfolg gut (r = 0,61) vorherzusagen. Die Untersuchung umfasst dabei mehr als 34.000 Spiele des deutschen Profifußballs und berücksichtigt damit mehr als 150 Mannschaften in 35 Jahren. Eine Analyse mittels ordinaler LogitRegression und Markov-Chain-Monte-Carlo-Simulationen zeigt, dass neben der Teamstärke insbesondere die Bedeutung des Spiels für die sportlichen Ziele den größten Einfluss auf den sportlichen Erfolg ausübt. Zudem zeigt sich, dass der sportliche Erfolg positiv durch Fan Commitment und Markenstärke, allerdings negativ durch die Rivalität zwischen den Teams beeinflusst wird. Das kalibrierte Modell, welches auf Basis öffentlich zugänglicher und größtenteils objektiver Informationen ermittelt wird, kann Managern als Tool zur Festlegung des optimalen SponsoringEngagements dienen

Erfolgsfaktoren von Investmentfonds aus Nachfragersicht

Die vorliegende Arbeit dient der Untersuchung des Marketing von Investmentfondsgesellschaften in Deutschland. Ein erstes Hauptaugenmerk liegt auf der Beschreibung des Marketingverhaltens von Fondsgesellschaften. Dabei wird eine Vorgehensweise anhand der vier klassichen Marketing-Mix-Instrumente Preis, Produkt, Distribution und Kommunikation gewählt. Es werden die jeweiligen Besonderheiten in der Anwendung im Vergleich zu anderen Dienstleistungen und aktuelle Entwicklungen dargestellt. Danach wird als zweiter Schwerpunkt auf das Kaufverhalten von Fondskonsumenten eingegangen; ein bislang vollkommen unerforschtes Gebiet. Der Markt für Investmentfonds wird also neben der Betrachtung der Anbieterseite nun auch nachfragerseitig beleuchtet. Interessante Ergebnisse sind z.B. die steigende Wichtigkeit der Reputation der Fondsgesellschaft und die unbedeutende Stellung der Fondsmanager im Kaufentscheidungsprozess von Anlegern. Abschließend werden anhand der analysierten anbieter- als auch nachfragerseitigen Entwicklungen Handlungsempfehlungen für deutsche Fondsgesellschaften abgeleitet

Simulation of phase-controlled mode-beating lasers

Self-pulsations in Phase Controlled Mode Beating lasers (PhaseCOMB) are very attractive for all-optical clock recovery at ultra-high bit rates. In this paper we apply the comprehensive simulation tool LDSL that has been developed by us for studying the self-pulsation features of PhaseCOMB lasers considering the effects of spontaneous emission noise, longitudinal spatial hole burning, and gain dispersion. In particular the importance of mode control for adjusting the PhaseCOMB operating conditions is pointed out. The simulation results are confirmed by measurements on fabricated devices

Preisbündelung von Hotel-Dienstleistungen : Ergebnisse einer empirischen Studie

Bei der Gestaltung einer marktfähigen Leistung fassen immer mehr Anbieter ihre Erzeugnisse im Hinblick auf einen möglichen Verwendungszweck zu einem Paket zusammen und verkaufen dieses zu einem Bündelpreis. Zeitschriftenverlage bieten z.B. ihren Kunden verschiedene Titelkombinationen, während Hersteller von Industriegütern wie Werkzeugmaschinen, elektronische Bauteile und chemische Substanzen ihre Leistungen häufig im Verbund mit einem Dienstleistungskranz zu einem Systempreis offerieren. Eine besondere Relevanz besitzt die Preisbündelung auch in der Hotelindustrie. Dort bilden einzelne Dienstleistungen die Basis für die Konstruktion einer Vielzahl von Paketen, die z. B. unter den Begriffen "Schnupperwochenende" und "Musicalwochende" die Attraktivität der Hotels steigern. Vor der Entscheidung zugunsten dieses produktpolitischen Instruments bedarf es jedoch der Beantwortung der Fragen, welche Faktoren bei der Gestaltung eines Paketes zu berücksichtigen sind und wie sie einschließlich Preis auf das Kaufverhalten der Nachfrager wirken. Vor diesem Hintergrund besteht das Ziel der Studie zum einen darin, dem Leser einen Überblick über die Grundlagen der Bündelung von Dienstleistungen zu verschaffen. Zum anderen soll mit Hilfe der Conjoint-Analyse ein für den Nachfrager optimales Bündel von Hoteldienstleistungen generiert werden. Marktsimulationen tragen dazu bei, Reaktionen der Konkurrenz auf das Angebot eines solchen Bündels abzuschätzen

Quantitative precipitation estimation based on highresolution numerical weather prediction and data assimilation with WRF - a performance test

Quantitative precipitation estimation and forecasting (QPE and QPF) are among the most challenging tasks in atmospheric sciences. In this work, QPE based on numerical modelling and data assimilation is investigated. Key components are the Weather Research and Forecasting (WRF) model in combination with its 3D variational assimilation scheme, applied on the convection-permitting scale with sophisticated model physics over central Europe. The system is operated in a 1-hour rapid update cycle and processes a large set of in situ observations, data from French radar systems, the European GPS network and satellite sensors. Additionally, a free forecast driven by the ECMWF operational analysis is included as a reference run representing current operational precipitation forecasting. The verification is done both qualitatively and quantitatively by comparisons of reflectivity, accumulated precipitation fields and derived verification scores for a complex synoptic situation that developed on 26 and 27 September 2012. The investigation shows that even the downscaling from ECMWF represents the synoptic situation reasonably well. However, significant improvements are seen in the results of the WRF QPE setup, especially when the French radar data are assimilated. The frontal structure is more defined and the timing of the frontal movement is improved compared with observations. Even mesoscale bandlike precipitation structures on the rear side of the cold front are reproduced, as seen by radar. The improvement in performance is also confirmed by a quantitative comparison of the 24-hourly accumulated precipitation over Germany. The mean correlation of the model simulations with observations improved from 0.2 in the downscaling experiment and 0.29 in the assimilation experiment without radar data to 0.56 in the WRF QPE experiment including the assimilation of French radar data

Nonlinear dynamics of semiconductor lasers with active optical feedback

An in-depth theoretical as well as experimental analysis of the nonlinear dynamics in semiconductor lasers with active optical feedback is presented. Use of a monolithically integrated multi-section device of sub-mm total length provides access to the short-cavity regime. By introducing an amplifier section as novel feature, phase and strength of the feedback can be separately tuned. In this way, the number of modes involved in the laser action can be adjusted. We predict and observe specific dynamical scenarios. Bifurcations mediate various transitions in the device output, from single-mode steady-state to self-pulsation and between different kinds of self-pulsations, reaching eventually chaotic behavior in the multi-mode limit

High-frequency pulsations in DFB-lasers with amplified feedback

We describe the basic ideas behind the concept of DFB-lasers with short optical feedback for the generation of high-frequency self-pulsations (SPs) and show the theoretical background describing realized devices. It is predicted by theory that the SP frequency increases with increasing feedback strength. To provide evidence for this we propose a novel device design which employs an amplifier section in the integrated feedback cavity of a DFB-laser. We present results from numerical simulations and experiments. It has been shown experimentally that a continuous tuning of the SP frequency from 12 to 45GHz can be adjusted via the control of the feedback strength. The numerical simulations which are in good accordance with experimental investigations give an explanation for a self stabilizing effect of the SPs due to the additional carrier dynamic in the integrated feedback cavity

Investigation of Adjacent Lifted Flames Interaction in an Inline and Inclined Multi-Burner Arrangement

The main objective of this research is to assess an innovative, low nitrogen oxides emission combustor concept, which has the potential to achieve the long term European emissions goals for aircraft engines. Lean lifted spray flames and their very low nitrogen oxides emissions are combined with an inclination of burners in annular combustor leading to a more compact combustor with superior stability range. The presented combustor concept was developed in the frame of the European research project CHAIRLIFT (Compact Helical Arranged combustoRs with lean LIFTed flames). CHAIRLIFT combustor concept is based on “low swirl” lean lifted spray flames, which features a high degree of premixing and consequently significantly reduced nitrogen oxides emissions and flashback risk compared to conventional swirl stabilized flames. In the CHAIRLIFT combustor concept, the lifted flames are combined with Short Helical Combustors arrangement to attain stable combustion by tilting the axis of the flames relative to the axis of the turbine to enhance the interaction of adjacent flames in a circumferential direction. A series of experimental tests were conducted at a multi-burner array test rig consisting of up to five modular burners at different burner inclination angles (0° and 45°), equivalence ratios, and relative air pressure drop at ambient conditions. For all investigated configurations, a remarkable high lean blow out for non-piloted burners (ϕLBO = 0.29–0.37), was measured. The multi-burner configurations were observed having a superior stability range in contrast to the typical decrease in stability from single to high swirl multi-burner. The unwanted flow deflection of highly swirled flames in Short Helical Combustors arrangement, could be avoided with the investigated low swirl lifted flames. Moreover, the flame chemiluminescence (OH*) measurements were used to provide a qualitative characterization of the flame topology. Complementary numerical investigations were carried out using different numbers of burners to evaluate the effect of boundary conditions