Beyond Procedural Fairness and Reciprocity

Most research in economics models agents somehow motivated by outcomes. Here, we model agents motivated by procedures instead, where procedures are defined independently of an outcome. To that end, we design procedures which yield the same expected outcomes or carry the same information on other's intentions while they have different outcome-invariant properties. Agents are experimentally confirmed to exhibit preferences over these which link to psychological attributes of their moral judgment.procedural preferences; experiment; procedural fairness

Identification of substrate requirements for γ-secretase cleavage of the amyloid precursor protein

Intramembrane proteolysis is of vital importance for numerous cellular processes and its dysfunction has repeatedly been associated with various diseases, such as Alzheimer’s disease (AD) and cancer. γ-Secretase is an intramembrane-cleaving protease complex involved in the production of the amyloid-β peptide (Aβ), one of the neuropathological hallmarks of AD. To date, a vast number of γ secretase substrates have been identified with C99, the precursor of Aβ, being one of the best studied substrates. Yet, despite recent advances in the field, the factors determining substrate recognition and efficient cleavage remain largely elusive. No specific consensus sequence motif for the discrimination between substrates and non substrates is currently known to exist. However, several lines of evidence suggested that the presence of a flexible region (e.g., a glycine-glycine (GG)-hinge motif) within the transmembrane domain (TMD) of a substrate might be critical for substrate recruitment and cleavage by γ secretase and intramembrane proteases in general, although, conflicting data existed. The cleavage of a γ-secretase substrate (substrate processing) can be divided into two stages: the initial cleavage and the subsequent trimming, also referred to as processivity. To illuminate the principles of substrate recognition and cleavage by γ-secretase, this thesis combined biophysical studies with biochemical data on the cleavability of various C99-based constructs. The work presented here, demonstrated that the GG-hinge motif in C99 conveys a flexibility necessary for the interaction with γ-secretase. A certain flexibility appears to be critical for the translocation from the exosites (distal binding sites) to the active site and correct positioning of the scissile bond at the active site. Indeed, the presence of a flexible motif in the N terminal half of the TMD (TM N) of C99 proved to be a sufficient substrate requirement for cleavage of C99 and may even be a substrate requirement for a subgroup of γ secretase substrates. The cleavage region, in the C terminal TMD (TM-C), turned out to be equally important for substrate cleavage by γ secretase. It appears that specific interactions between the substrate’s TM-C and the enzyme are far more important than a flexible motif in this region of C99. It is possible, that the TM C is vital for docking of the scissile bond at the active center, as well as for the formation of a β sheet, which has been shown to stabilize the substrate and to bring the scissile bond into position. Intriguingly, both the flexible motif and the cleavage region must cooperate to enable efficient cleavage of C99. After the initial cleavage, however, a helical TMD promoted further trimming. Altogether, these data indicate that cleavage of C99 is determined by the presence of a flexible region in the TM N, facilitating the translocation to the active site, and the cleavage region in the TM-C, crucial for the formation of a cleavage competent state, while a helical TMD is required for efficient trimming. Overall, this work further illuminated the principles of substrate recognition and cleavage by γ secretase, helping to advance our understanding of the structurally and functionally most complex intramembrane protease known.Die Intramembranproteolyse ist für zahlreiche grundlegende zelluläre Prozesse von entscheidender Bedeutung. Eine Dysfunktion dieses Prozesses wurde bereits mehrfach mit verschiedenen Krankheiten, wie der Alzheimer-Krankheit (AK) und Krebs, in Verbindung gebracht. Die γ Sekretase ist eine Intramembranprotease, welche an der Produktion von Aβ, Hauptbestandteil eines der neuropathologischen Merkmale der AK, beteiligt ist. Bis heute wurde eine Vielzahl von γ Sekretase Substraten identifiziert, wobei C99, das Vorläuferprotein von Aβ, eines der am besten untersuchten Substrate darstellt. Jedoch sind, trotz der jüngsten Fortschritte auf dem Gebiet der γ Sekretase Forschung, die Faktoren, die für die Erkennung und effiziente Spaltung der Substrate ausschlaggebend sind, nach wie vor weitgehend unbekannt. So wurde bisher kein spezifisches Erkennungsmotiv für die Unterscheidung von Substraten und Nicht-Substraten identifiziert. Diverse Hinweise deuten jedoch darauf hin, dass das Vorhandensein einer flexiblen Region (z. B.: ein Glycin Glycin- (GG ) Scharnier-Motiv) innerhalb der Transmembrandomäne (TMD) eines Substrats entscheidend für die Spaltung durch die γ Sekretase, und Intramembranproteasen im Allgemeinen, sein könnte. Die Datenlage bezüglich der Rolle einer flexiblen TMD für die Substratspaltung war allerdings nicht eindeutig. Die Spaltung eines γ-Sekretase-Substrats (Prozessierung) kann in zwei Abschnitte unterteilt werden: die initiale endoproteolytische Spaltung und die anschließende carboxyterminale Spaltung. Um die Prinzipien der Substraterkennung und -spaltung durch die γ-Sekretase besser verstehen zu können, wurden in dieser Arbeit biophysikalische Analysen mit biochemischen Daten zur Spaltbarkeit verschiedener C99 basierter Konstrukte kombiniert. Die hier vorgestellten Ergebnisse machen deutlich, dass das GG Motiv in C99 eine für die Interaktion zwischen dem Substrat und der γ Sekretase notwendige Flexibilität vermittelt. Eine gewisse Flexibilität scheint für die Translokation von den „Exosites“ (Bindestellen abseits des aktiven Zentrums) hin zu dem aktiven Zentrum, sowie die korrekte Positionierung der zu spaltenden Peptidbindung in dem aktiven Zentrum der γ-Sekretase entscheidend zu sein. Tatsächlich erwies sich das Vorhandensein eines flexiblen Motivs in dem N-terminalen Teil der TMD (TM N) von C99 als hinreichende Substratanforderung für die Spaltung durch die γ Sekretase. Möglicherweise stellt ein solches Motiv sogar eine Substratanforderung für eine Untergruppe von γ-Sekretase Substraten dar. Der C terminale Teil der Spaltregion, lokalisiert in der C terminalen Hälfte der TMD (TM-C), erwies sich als ebenso essenziell für die Spaltung durch die γ Sekretase. Es scheint, dass spezifische Interaktionen zwischen dem TM-C von C99 und dem Enzym viel wichtiger sind als ein flexibles Motiv in dieser Region des Substrats. Möglicherweise ist die TM-C entscheidend für das Andocken der zu spaltenden Bindung an das aktive Zentrum, sowie für die Bildung eines β-Faltblattes, welches das Substrat stabilisiert und die zu spaltende Bindung in Position bringt. Interessanterweise war ein Zusammenspiel zwischen dem flexiblen Motiv und der natürlichen Spaltregion notwendig, um eine effiziente Spaltung von C99 zu ermöglichen. Die weitere carboxyterminale Spaltung des Substrats, die im Anschluss an die initiale Spaltung erfolgt, wurde hingegen durch eine helikale Konformation der TMD des Substrats begünstigt. Folglich wird die Spaltung von C99 durch das Vorhandensein einer flexiblen Region im TM-N, welche die Translokation zum aktiven Zentrum ermöglicht, und der natürlichen Spaltregion im TM C, welche für die Positionierung des Substrats wichtig ist, bestimmt. Während eine helikale TMD für eine effiziente carboxyterminale Spaltung erforderlich ist. Insgesamt hat diese Arbeit dazu beigetragen, die Prinzipien der Substraterkennung und -spaltung durch die γ Sekretase aufzuklären und unser Verständnis der strukturell und funktionell komplexesten, bekannten Intramembranprotease, voranzutreiben

Competition on common value markets with naèive traders: a theoretical and experimental analysis

Theoretically and experimentally, we generalize the analysis of acquiring a company (Samuelson and Bazerman 1985) by allowing for competition of both, buyers and sellers. Naivety of both is related to the idea that higher prices exclude worse qualities. While competition of naive buyers increases prices, competition of naive sellers promotes effciency enhancing trade. Our predictions are tested experimentally

Beyond procedural equity and reciprocity

Most research in economics models agents somehow motivated by outcomes. Here, we model agents motivated by procedures instead, where procedures are defined independently of an outcome. To that end, we design procedures which yield the same expected outcomes or carry the same information on other's intentions while they have different outcome-invariant properties. Agents are experimentally confirmed to exhibit preferences over these which link to psychological attributes of their moral judgment

Militärinterventionen : verheerend und völkerrechtswidrig. Möglichkeiten friedlicher Konfliktlösung

The overall aim with this thesis is to create a broader understanding of how the EMS tool works in local authorities. This means to study whether EMS is a useful tool for managing the environmental impact from the local authorities' activities and by highlighting its strengths and weaknesses as a tool. EMS is a tool that is used on a voluntary basis that aims at improving organisations' environmental performance. There are several standards for designing EMSs; however, this thesis focuses on EMSs designed according to the principles of the international standard ISO 14001 and the EU regulation Eco-Management and Audit Scheme (EMAS). The standards are based on a wide range of requirements. If these requirements are fulfilled, the organisation can choose to get its EMS certified by a third party. The EMS tool is frequently used in the private sector, and it is sometimes argued that it is designed for private (industrial) organisations. However, local authorities worldwide have shown an increased interest in EMSs since the mid 1990s. The EMS use in the private sector has been subject to some critique. For example, there is a risk that the tool is used only to get another certificate in order to increase their legitimacy, which means that there is a risk that the environmental issues are neglected. Until now, little academic research has been conducted concerning EMS use in local authorities. Therefore, it is interesting to study what approaches local authorities have to EMSs. Mainly Swedish local authorities have been studied for this thesis. Many Swedish local authorities have been using EMSs for a fairly long time, which means that they have a certain amount of experience from this using tool. The local authorities' approaches to EMS use have been studied from several perspectives using postal surveys, interviews, and case study methodology. This means that the research has a strong empirical foundation. The EMS use in Swedish local authorities is fairly common, since almost half of them are in the process of implementing EMSs in all or some of their departments. The main reason for implementing EMSs is to improve the structure of their environmental management. The local authorities often use ISO 14001 and/or EMAS as inspiration and design the EMSs according to their local conditions and ambitions, thus certification of the EMSs is seldom an aim. Although many local authorities seem to use EMSs in a reflective and sensible way, several barriers or difficulties - for example, maintaining continuity and ensuring follow-up of the environmental improvements - have been discovered. Furthermore, the EMSs that are being implemented often exclude environmental impact related to their exercise of authority since it is difficult and abstract. Including environmental impact related to these activities is often seen as a matter of maturity. To develop the organisations' EMSs, internal and external communication and interaction is experienced as very important. Such issues contribute to the EMS maturity processes, since the local authorities find new inspiration, knowledge, and motivation to further develop the EMS processes and, as a consequence, improve their environmental performance

Temperate tree species show identical response in tree water deficit but different sensitivities in sap flow to summer soil drying

Temperate forests are expected to be particularly vulnerable to drought and soil drying because they are not adapted to such conditions and perform best in mesic environments. Here we ask (i) how sensitively four common temperate tree species (Fagus sylvatica, Picea abies, Acer pseudoplatanus and Fraxinus excelsior) respond in their water relations to summer soil drying and seek to determine (ii) if species-specific responses to summer soil drying are related to the onset of declining water status across the four species. Throughout 2012 and 2013 we determined tree water deficit (TWD) as a proxy for tree water status from recorded stem radius changes and monitored sap flow rates with sensors on 16 mature trees studied in the field at Lägeren, Switzerland. All tree species responded equally in their relative maximum TWD to the onset of declining soil moisture. This implies that the water supply of all tree species was affected by declining soil moisture and that none of the four species was able to fully maintain its water status, e.g., by access to alternative water sources in the soil. In contrast we found strong and highly species-specific responses of sap flow to declining soil moisture with the strongest decline in P. abies (92%), followed by F. sylvatica (53%) and A. pseudoplatanus (48%). F. excelsior did not significantly reduce sap flow. We hypothesize the species-specific responses in sap flow to declining soil moisture that occur despite a simultaneous increase in relative TWD in all species reflect how fast these species approach critical levels of their water status, which is most likely influenced by species-specific traits determining the hydraulic properties of the species tree

Forest canopy mortality during the 2018-2020 summer drought years in Central Europe: The application of a deep learning approach on aerial images across Luxembourg

Efficient monitoring of tree canopy mortality requires data that cover large areas and capture changes over time while being precise enough to detect changes at the canopy level. In the development of automated approaches, aerial images represent an under-exploited scale between high-resolution drone images and satellite data. Our aim herein was to use a deep learning model to automatically detect canopy mortality from high-resolution aerial images after severe drought events in the summers 2018–2020 in Luxembourg. We analysed canopy mortality for the years 2017–2020 using the EfficientUNet++, a state-of-the-art convolutional neural network. Training data were acquired for the years 2017 and 2019 only, in order to test the robustness of the model for years with no reference data. We found a severe increase in canopy mortality from 0.64 km2 in 2017 to 7.49 km2 in 2020, with conifers being affected at a much higher rate than broadleaf trees. The model was able to classify canopy mortality with an F1-score of 66%–71% and we found that for years without training data, we were able to transfer the model trained on other years to predict canopy mortality, if illumination conditions did not deviate severely. We conclude that aerial images hold much potential for automated regular monitoring of canopy mortality over large areas at canopy level when analysed with deep learning approaches. We consider the suggested approach a cost-efficient and -effective alternative to drone and field-based sampling

Thermophoresis of thermoresponsive polystyrene-poly(N-isopropylacrylamide) core-shell particles

We have investigated diffusion and thermodiffusion of thermosensitive core shell particles PS PNIPAM that consist of a poly styrene PS core and a poly N isopropyl acrylamide PNIPAM shell by means of an optical beam deflection technique. The results are compared to recent literature values for linear PNIPAM chains and cross linked PNIPAM microgel particles. The temperature dependence of the thermodiffusion coefficient of the core shell colloids resembles that of the linear polymer and a number of other aqueous systems. It is significantly different from one of the crosslinked microgel