Quantitative Magnetresonanztomografie: Einfluss von Mikrostruktur auf die Bestimmung der Relaxationszeiten und der magnetischen Suszeptibilität

Die Magnetresonanztomografie ermöglicht die Bestimmung quantitativer Probenparameter aus dem gemessenen Kernresonanzsignal, wie beispielsweise den Relaxationszeiten oder der magnetischen Suszeptibilität. Im ersten Teil dieser Arbeit wird eine lexikonbasierte Methode zur Kartierung der T2 Relaxationszeit mittels einer Multi-Echo-Turbo-Spinechosequenz vorgestellt. Durch Berücksichtigung der Inhomogenitäten des Anregungsfeldes B1 und des Schichtprofils wird hiermit auch an Ultra-Hochfeldgeräten eine zuverlässige Bestimmung der transversalen Relaxationszeit ermöglicht. Diese Methode wurde in Phantomexperimenten bei 1,5 T und 7 T validiert, wobei bei 7 T und einem Refokussierungswinkel von 120° eine mittlere Abweichung der T2-Zeiten von (5,4 ± 5,8) % relativ zur Referenzmessung erreicht wurde. Bei in vivo Messungen an vier gesunden Probanden konnte bei einer Feldstärke von 7 T in der grauen Substanz ein Mittelwert von T2 = (55 ± 2) ms und in der weißen Substanz von T2 = (39 ± 5) ms bestimmt werden. Im zweiten Teil dieser Arbeit wird der Einfluss von mikroskopischen Suszeptibilitätsquellen unterschiedlichen Vorzeichens innerhalb desselben Voxels auf die Änderung der Relaxationsrate ΔR2* untersucht. Unter der Annahme von vernachlässigbaren Diffusionseinflüssen wurde in Simulationen und Phantomexperimenten erstmals die Linearität der Relaxationsrate bestätigt. Diese Eigenschaft wurde zusammen mit der Linearität der gemessenen Suszeptibilität für die Entwicklung eines Algorithmus zur Trennung der Einflüsse von positiven und negativen Suszeptibilitätsquellen innerhalb desselben Voxels verwendet. Im Softwarephantom und in Phantomexperimenten wurde die Anwendbarkeit der Trennung von Susuzeptibilitätsquellen verifiziert und erste in vivo Messungen durchgeführt

Climate targets in European timber-producing countries conflict with goals on forest ecosystem services and biodiversity

The role of increased timber harvests in reaching climate mitigation targets for European countries will be limited if the protection of forest ecosystem services and biodiversity is to be achieved, suggests an empirical forest model driven by future scenarios to limit warming to 1.5 degrees C in 2100.The European Union (EU) set clear climate change mitigation targets to reach climate neutrality, accounting for forests and their woody biomass resources. We investigated the consequences of increased harvest demands resulting from EU climate targets. We analysed the impacts on national policy objectives for forest ecosystem services and biodiversity through empirical forest simulation and multi-objective optimization methods. We show that key European timber-producing countries - Finland, Sweden, Germany (Bavaria) - cannot fulfil the increased harvest demands linked to the ambitious 1.5 degrees C target. Potentials for harvest increase only exists in the studied region Norway. However, focusing on EU climate targets conflicts with several national policies and causes adverse effects on multiple ecosystem services and biodiversity. We argue that the role of forests and their timber resources in achieving climate targets and societal decarbonization should not be overstated. Our study provides insight for other European countries challenged by conflicting policies and supports policymakers

Mechanisms of CD8+ T cell failure in chronic hepatitis E virus infection

Background and aims In immunosuppressed patients, persistent hepatitis E virus (HEV) infection is common and may lead to cirrhosis and liver failure. HEV clearance depends on an effective virus-specific CD8+ T cell response, however, the knowledge gap of HEV-specific CD8+ T cell epitopes hindered analysis of the mechanisms of T cell failure in persistent infection thus far. Methods We comprehensively studied HEV-specific CD8+ T cell responses in 46 patients with self-limiting (n=34) or chronic HEV infection (n=12), by epitope-specific expansion, functional testing, ex vivo peptide HLA class I tetramer multi-parametric staining, and viral sequence analysis. Results We identified 25 HEV-specific CD8+ T cell epitopes restricted by 9 different HLA class I alleles. In self-limiting HEV infection, HEV-specific CD8+ T cells were vigorous, contracted after resolution of infection, and formed functional memory responses. In contrast, in chronic infection, the HEV-specific CD8+ T cell response was diminished, declined over time, and displayed phenotypic features of exhaustion. However, improved proliferation and interferon-γ production of HEV-specific CD8+ T cells and evolution of a memory-like phenotype was observed upon reduction of immunosuppression and/or ribavirin treatment and was associated with viral clearance. In one patient, mutational viral escape in a targeted CD8+ T cell epitope contributed to CD8+ T cell failure. Conclusion Chronic HEV infection is associated with HEV-specific CD8+ T cell exhaustion, indicating that T cell exhaustion driven by persisting antigen recognition also occurs in severely immunosuppressed hosts. Functional reinvigoration of virus-specific T cells is at least partially possible when antigen is cleared. In a minority of patients, viral escape also contributes to HEV-specific CD8+ T cell failure and thus needs to be taken into account in personalized immunotherapeutic approaches. Lay Summary In immunosuppressed patients, chronic HEV infection is common. For resolution of infection a functional HEV-specific CD8+ T cell response is essential, however, in immunosuppressed individuals CD8+ T cell exhaustion and viral escape contribute to CD8+ T cell failure

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements