Regulatory mechanisms in cross-presentation <i>in vivo</i>

Dendritic cells can present exogenous antigen to CD8 T cells using a mechanism termed cross-presentation. This mechanism is important for immune responses against tumors, viruses, intracellular pathogens and autoantigens expressed in peripheral tissues. However, the physiological mechanisms that regulate cross-presentation in vivo in particular the endocytosis mechanisms involved in this process are not well understood. The first aim of this study was to elucidate the role of the mannose receptor (MR), a C-type lectin in cross-presentation. MR deficient mice showed reduced uptake of soluble OVA and diminished activation of CD8 T cells. This was due to the reduced cross-presentation ability of DCs in MR deficient mice, as the MR was only present in the cross-presenting CD8α+ DCs. As opposed to soluble OVA, the cell-associated form of this model antigen did not use the MR to enter the cross-presentation pathways. These data provide first formal evidences that a particular antigen uptake receptor, here the MR can specifically introduce antigen into the cross-presentation pathway. Furthermore, they identify this receptor as a further marker of cross-presenting DCs. The second aim of the present study was to identify the mechanisms by which soluble antigens are transported from the peripheral organs to draining LNs for subsequent cross-presentation. Proteins smaller than the molecular weight of albumin, such as soluble OVA theoretically may pass the kidney glomerular filter and be concentrated in the tubular compartment. It appeared possible that this physiological process might increase the availability of antigen for the cross-presenting APC. Therefore the kidney - renal lymph node (rLN) system was choosen to investigate antigen transport from organ to draining LN. Several lines of independent evidence indicated that soluble OVA was concentrated in the kidney DCs but was transported in a cell-independent fashion to DC resident in the rLN. Further studies showed that these DCs tolerized specific T cells. This tolerization was independent from steady-state migration of kidney DC to draining LN. These findings identify the rLN as a unique site where antigen is rapidly enriched for T cell activation; provided it is small enough to pass the glomerular filter. This mechanism may contribute avoiding unwanted immune responses against innocuous circulating antigens, for example self-serum or food proteins. In conclusion the present study revealed new in vivo mechanisms in regulating cross-presentation of soluble molecules such as antigen uptake via MR and antigen presentation occurring in the kidney – renal LN system

The strategic dimension of financing global public goods

One challenge in addressing transboundary problems such as climate change is the incentive to free-ride. Transfers from multilateral compensation funds are often used to counteract such incentives, albeit with varying success. We examine how such funds can change the incentive to free-ride in a global public-goods game. In our game, self-interested countries choose their own preferred course, deciding their voluntary public good provision, whether to join a fund that offers compensation for providing the public good and the volume of compensatory payments. We show that (i) total public-good provision is higher when those contributing are given more compensation; and (ii) non-participation in the fund can be punished if the remaining members decrease their public-good provision sufficiently. We then examine three specific fund designs. In the first, the compensation paid to each country is equal to the percentage of above-average total costs for public-goods provision. This design is best able to deter free-riding and can establish the social optimum as the equilibrium. In the second, the compensation paid to each country is a function of the marginal cost of their public-good provision. Here there are significant incentives to free-ride. In the third case, the monetary resources provided by the fund are fixed, a design frequently encountered in international funds. This design is the one least able to deter free-riding. © 2020 The Author(s

Comparison of methods for broadband electromagnetic characterization of Molded Interconnect Device materials

Combining the Molded Interconnect Device technology with the Laser Direct Structuring technology exhibits the potential of designing electrical and mechanical components on three-dimensional surfaces to increase functionality, level of integration and to reduce costs. When taking advantage of this technology especially in the design of RF devices, a precise knowledge of the electromagnetic parameters of the MID material is required, as the complex permeability and permittivity strongly influence the device performance. At present time, these materials are not electromagnetically characterized in the RF frequency range. In this paper different methods are therefore presented and compared with respect to their potentials for broadband electromagnetic characterization of Molded Interconnect Device materials

Anwendung von Maximum-Likelihood Expectation-Maximization und Origin Ensemble zur Rekonstruktion von Aktivitätsverteilungen beim Single Plane Compton Imaging (SPCI)

In der nuklearmedizinischen Bildgebung mit Anger-Kameras wird ein höheres Auflösungsvermögen durch Limitierung der Nachweiseffizienz erreicht. Compton Cameras können die Nachweiseffizienz mittels elektronischer Kollimation, die zur Ortsbestimmung die Compton-Kinematik anwendet, erhöhen. Ein alternativer Ansatz für die Konstruktion einer Compton Camera, die Streu- und Absorptionsebenen in einer Ebene kombiniert, wurde in der Vergangenheit untersucht. Die sogenannte Single Plane Compton Camera ist in der Lage, Punktquellen im Vakuum getrennt aufzulösen. Zur Darstellung komplexerer Bildinhalte wird die Optimierung der Bildrekonstruktion angestrebt. Diese umfasst ein umfängliches Verständnis des Messprinzips, das in dieser Arbeit dargelegt wird. Jeweils ein 3D-Rekonstruktionsalgorithmus wurde für konventionell gebinnte und List-Mode-Daten implementiert. Anhand eines vorliegenden Simulationsdatensatzes einer einfachen Detektorkonfiguration wurden Messdaten generiert und rekonstruiert. Es konnte gezeigt werden, dass aufgrund der hohen Zählstatistik ein robustes Signal-to-Noise-Ratio erhalten wird. List-Mode-Verfahren eignen sich aufgrund eines höheren Rechenaufwandes nicht. Die mittlere Ortsinformation der Ereignisse ist systembedingt gering und beeinträchtigt die Ortsauflösung, welche für E = 662 keV etwa 15 mm in einem Abstand von 50cmm beträgt. Eine Verbesserung der Auflösung ist durch die Algorithmen nicht möglich, sondern umfasst technische Maßnahmen, welche anhand dieser Arbeit in weiteren Studien umgesetzt werden können.:1 Einleitung 2 Single Plane Compton Imaging 3 Bildrekonstruktion beim Single Plane Compton Imaging 4 Materialien und Methoden 5 Ergebnisse 6 Diskussion 7 Zusammenfassung und Ausblick Literaturverzeichnis Abkürzungsverzeichnis Abbildungsverzeichnis Tabellenverzeichnis Selbstständigkeitserklärung A Herleitung des ML-EM Algorithmus B Tiefergehende Informationen zu OE C C++-Code für die Bildrekonstruktion beim SPCIIn nuclear medicine imaging, the Anger camera imposes a limit on the detection efficiency in order to improve the spatial resolution. The detection efficiency can be increased with electronically collimated systems known as Compton Cameras, which use the kinematics of Compton scattering to locate the detected events. An alternative approach to the design of a Compton Camera combining scatter and absorption planes was investigated in the past. It was shown that the so-called Single Plane Compton Camera is able to separately reconstruct two point sources in empty space. Further optimization is required to reconstruct more complex images. Thus, an extensive understanding of the measurement principle is provided. Two 3D-algorithms were implemented for binned data and list mode data. Measurement data were generated by means of an existing simulated data set of a simple detector design and reconstructed. It is shown that a robust signal-to-noise ratio can be achieved due to high numbers of detected counts. List mode algorithms produce high computational costs and binned algorithms may be used instead. The average position information is low and imposes a negative impact on the spatial resolution, which is about 15mm at a distance of 50mm for E = 662 keV. The implemented algorithms cannot increase the spatial resolution due to lack of precise position information. Therefore, future studies should focus on technical measures, which are given in this thesis.:1 Einleitung 2 Single Plane Compton Imaging 3 Bildrekonstruktion beim Single Plane Compton Imaging 4 Materialien und Methoden 5 Ergebnisse 6 Diskussion 7 Zusammenfassung und Ausblick Literaturverzeichnis Abkürzungsverzeichnis Abbildungsverzeichnis Tabellenverzeichnis Selbstständigkeitserklärung A Herleitung des ML-EM Algorithmus B Tiefergehende Informationen zu OE C C++-Code für die Bildrekonstruktion beim SPC

The social cost of carbon and inequality: When local redistribution shapes global carbon prices

The social cost of carbon is a central metric for optimal carbon prices. Previous literature shows that inequality significantly influences the social cost of carbon, but mostly omits heterogeneity below the national level. We present an optimal taxation model of the social cost of carbon that accounts for inequality between and within countries. We find that climate and distributional policy can generally not be separated. If only one country does not compensate low-income households for disproportionate damages, the social cost of carbon tends to increase globally. Optimal carbon prices remain roughly unchanged if national redistribution leaves inequality between households unaffected by climate change and if the utility of households is approximately logarithmic in consumption

Konzeption und Realisierung einer Supply-Chain-Management-orientierten Anwendungsintegration im mittelständischen Automotive-Umfeld

Sich verändernde Märkte führen in der Automobilindustrie gemeinsam mit geopolitischen Entwicklungen seit einigen Jahren zu einer Situation, in der sich die Unternehmen mit den Folgen von Globalisierung, Konsolidierung und verschärftem Wettbewerb auseinandersetzen müssen. Insbesondere an die überwiegend mittelständisch geprägte Automobilzulieferindustrie werden dadurch Herausforderungen gestellt, denen mit neuen Prozessmodellen begegnet werden muss. Als zielführend herausgestellt haben sich dabei die Prozesse innerhalb der Lieferketten (Supply Chains), die im Rahmen des Supply Chain Managements (SCM) die Prozesselemente entlang der Wertschöpfungskette betrachten. Das Ziel ist dabei die Optimierung des zugrundeliegenden logistischen Gesamtprozesses, wobei die Sichtweise von der unternehmensinternen auf die unternehmensexterne Perspektive wechselt. Da heute nahezu alle Unternehmensprozesse über IT-Systeme abgebildet oder gesteuert werden, müssen auch auf IT-Infrastrukturebene Voraussetzungen geschaffen werden, damit das Ziel der optimierten Supply Chain erreicht werden kann. Insbesondere sind die oftmals heterogenen Systemstrukturen, die bisher eine durchgängige Prozesskommunikation verhindern, durch geeignete Integrationslösungen zu erweitern, damit die System- und Prozesskommunikation zwischen den beteiligten Systemen in Echtzeit erfolgen kann. Erst dadurch wird ein effizientes Supply Chain Management ermöglicht. Diese Integrationsfunktion nehmen Enterprise Application Integration (EAI-)Systeme wahr, die Unternehmensanwendungen zusammenführen und die erforderlichen Prozessdaten integrieren. Die heute am Markt erhältlichen EAI-Systeme zeichnen sich durch ein umfangreiches Leistungsspektrum aus, was sie allerdings gleichermaßen teuer wie administrationsintensiv macht und damit ungeeignet für den Mittelstand erscheinen lässt. Daher ist es das Ziel der Arbeit, eine mittelstandstaugliche EAI-Lösung zu beschreiben, um damit im mittelständischen Automotive-Bereich typische SCM-Szenarien umzusetzen. Als EAI-Basis wird dabei die aus dem Bereich der Webservices bekannte LAMP-Umgebung herangezogen, die ein Anwendungssystem aus den vier open source Softwarekomponenten Linux, Apache, MySQL und PHP darstellt. Mit Hilfe der LAMP-Umgebung werden die Verbindungen zwischen einzelnen Unternehmensanwendungen und prozessen hergestellt und eine webbasierte Anwendungsintegration konzeptionell beschrieben sowie exemplarisch anhand von branchentypischen SCM-Szenarien (VMI, ATP, Portal, Prozessdatenaustausch) umgesetzt

What is important for achieving 2 °C? UNFCCC and IPCC expert perceptions on obstacles and response options for climate change mitigation

Global mitigation efforts remain insufficient to limit the global temperature increase to well below 2 °C. While a growing academic literature analyzes this problem, perceptions of which obstacles inhibit goal attainment and which responses might be most effective seem to differ widely. This makes prioritization and agreement on the way forward difficult. To inform prioritization in global climate policy and research agendas, we present quantitative data on how 917 experts from the IPCC and the UNFCCC perceive the importance of different obstacles and response options for achieving 2 °C. On average, respondents consider opposition from special interest groups the most important obstacle and technological R&D the most important response. Our survey also finds that the majority of experts perceives a wide range of issues as important, supporting an agenda that is inclusive in terms of coverage. Average importance ratings differ between experts from the Global North and South, suggesting that balanced representation in global fora and regionally differentiated agendas are important. In particular, opposition from special interest groups is a top priority among experts from North America, Europe and Oceania. Investigating the drivers of individual importance ratings, we find little difference between experts from the IPCC and the UNFCCC, while expert's perceptions correlate with their academic training and their national scientific, regulatory, and financial contexts

Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?

The terms microparticles (MPs) and microvesicles (MVs) refer to large extracellular vesicles (EVs) generated from a broad spectrum of cells upon its activation or death by apoptosis. The unique surface antigens of MPs/MVs allow for the identification of their cellular origin as well as its functional characterization. Two basic aspects of MP/MV functions in physiology and pathological conditions are widely considered. Firstly, it has become evident that large EVs have strong procoagulant properties. Secondly, experimental and clinical studies have shown that MPs/MVs play a crucial role in the pathophysiology of inflammation-associated disorders. A cardinal feature of these disorders is an enhanced generation of platelets-, endothelial-, and leukocyte-derived EVs. Nevertheless, anti-inflammatory effects of miscellaneous EV types have also been described, which provided important new insights into the large EV-inflammation axis. Advances in understanding the biology of MPs/MVs have led to the preparation of this review article aimed at discussing the association between large EVs and inflammation, depending on their cellular origin

The Dynamics of Coalition Formation on Complex Networks

Acknowledgements This work was carried out within the framework of PIK’s COPAN project. We gratefully acknowledge funding by the German Federal Ministry of Education and Research (BMBF) via the CoNDyNet project, grant no. 03SF0472A, and of the Government of the Russian Federation (Agreement No. 14.Z50.31.0033 with Institute of Applied Physics RAS). We thank Jonathan Donges for helpful discussions on this manuscript.Peer reviewedPublisher PD