Design and properties of lanthanoid chelating tags

The work presented in this thesis is centred around the magnetic anisotropy of lanthanoids and how it can be harnessed for the study of bio macromolecules. Following the introduction about paramagnetic NMR spectroscopy, lanthanoids and lanthanoid chelating tags are three individual chapters regarding the properties, design and synthesis of lanthanoid chelating tags. The first chapter comprises a published study concerning the anisotropy of the magnetic susceptibility exhibited by lanthanoid (III) ions within lanthanoid chelating tags (LCTs). LCTs are widely used to induce pseudocontact shifts (PCSs) or residual dipolar couplings (RDCs) on bio macromolecules. The size of the observed PCSs or RDCs is dependent on the anisotropy of the magnetic susceptibility of the lanthanoid (III) ion. The anisotropy of the magnetic susceptibility can be described by the anisotropy parameters, which are for LCTs commonly determined from PCS observed on a conjugated protein. Because the PCS observed on the protein are inevitably reduced by motional averaging, the anisotropy parameters determined from them describe always only a fraction of the anisotropy of the magnetic susceptibility a lanthanoid ion exhibits within an LCT. This study presents for the first time the intrinsic anisotropy parameters for the full lanthanoid series determined from shifts observed on the LCT itself. The strongly shifted proton spectra could no longer be assigned using conventional 2D- NMR assignment strategies, due to the extremely short T2 times. Instead, the 1D proton spectra were fully assigned using extensive, site-specific 2H and 13C labelling in combination with combinatorial methods. The full assignments were used to determine the anisotropy parameters, which deliver an upper limit for future PCS applications relying on this coordination polyhedron as well as new insights into future LCT designs. Surprisingly, we observed an, at least at room temperature, unprecedented correlation between the oblate or prolate f-electron distribution of the lanthanoid and the orientation of the main magnetic axis. Furthermore, a comparison of different ligands revealed that the size of the anisotropy parameters depends on the interaction between the ligand and the lanthanoid ion. In the second chapter, the focus lies on the development of a new single-arm LCT, which could provide predictable anisotropy parameters. For current single-arm LCTs the averaging of the observed PCS on a conjugated protein is not only dependent on the LCT but also on the tagging site. Therefore, the averaging of the PCS is different for each tagging site, requiring the determination of the anisotropy parameters in each case. It would greatly ease the application of PCS NMR spectroscopy if a single-arm LCT would provide predictable anisotropy parameters. A priori knowledge of the anisotropy parameters would allow the choice of the best-suited tagging site for a given application and facilitate the assignment of paramagnetic signals. Based on the insights gained from determining the intrinsic anisotropy parameters it was hypothesized that coaxiality between the rotation axis and z-axis of the tensor frame could provide predictable anisotropy parameters. The sought coaxiality can be achieved with a symmetric LCT that is tethered via a thioether to the protein. In order to develop a new LCT, two scaffolds were tested for their suitability as an LCT. The second scaffold provided a new symmetric LCT, which was successfully tethered to ubiquitin S57C. Determination of the anisotropy parameters and comparison to the estimated intrinsic anisotropy parameters showed that the PCS induced by the new LCT are barely affected by averaging. The current results were not sufficient to ascertain whether the new LCT is able to provide predictable anisotropy parameters but they hold great promise for further research. The third chapter describes the synthesis of a new building block for DOTA-M8-based LCTs. DOTA-M8 provides excellent properties for the development of lanthanoid chelating tags but has the inherent problem that it is difficult to synthesize. The main challenge in the synthesis towards DOTA-M8 is the synthesis of M4-cyclen. In this chapter, a new cyclen building block is presented, which should be simpler to synthesise but still provides all the necessary properties for high performance LCTs. A convenient synthetic route towards the new building block was tested. The encountered obstacles revealed which changes would be necessary for the future success of the proposed synthetic strategy

Survey-Welten

Die Open-Access-Studie nimmt eine plurale Perspektive auf Survey-Qualität ein und untersucht empirisch unterschiedliche Logiken der Survey-Produktion. Wie aufgezeigt wird, gehen die vier identifizierten Survey-Welten mit unterschiedlichen Koordinationsprozessen und Qualitätskonventionen einher. Survey-Qualität wird dabei auf einer pragmatischen Basis im Hinblick auf unterschiedliche Nutzungskontexte von statistischen Daten konzipiert. Durch die Verknüpfung der Qualitätsthematik mit der praktischen Organisation des Produktionsprozesses von surveybasierten Daten wird eine engere Verbindung zwischen den Arbeiten der normativen Survey-Methodologie und den Herausforderungen der empirischen Survey-Praxis angestrebt. Die Arbeit präsentiert die Pluralität der Praxisformen von Umfragen, sie identifiziert die Vielfalt der Qualitätskriterien und sie leistet eine konzeptionelle Grundlage für reflexives Survey-Management. Der Inhalt Perspektiven auf Survey-Qualität ● Die erweiterte Perspektive der Economie des conventions ● Methodologische Grundlegung und methodisches Vorgehen ● Die vier Survey-Welten im Überblick ● Survey-Projekte aus einer survey-weltlichen Perspektive ● Eine vertiefte survey-weltliche Perspektive auf Surveys ● Skizze einer Systematisierung von Relationen zwischen Regimen des Engagements und Rechtfertigungsordnungen Der Autor Dr. Raphael Vogel war bis Juni 2018 Mitarbeiter am Soziologischen Seminar der Universität Luzern

Application of Paramagnetic Lanthanoid Chelating Tags in NMR Spectroscopy and Their Use for the Localization of Ligands Within Biomacromolecules

The application of paramagnetic lanthanoid chelating tags for the localization of ligands within biomacromolecules enables the elucidation of binding pockets and positioning of ligands within given targets of interest, a crucial prerequisite for rational drug design. This case study consists of an overview about lanthanoid chelating tags, a description of their structural properties, the induced anisotropy as well as approaches for the localization of ligands within biomacromolecules. The localization of sulfonamide inhibitors within human carbonic anhydrase II with an accuracy of up to 0.8 Å over distances of 22–38 Å using 19F pseudocontact shift is presented as a practical example

Unequal expenditure switching: Evidence from Switzerland

What are the unequal effects of changes in consumer prices on the cost of living? In the context of changes in import prices (driven by, e.g., changes in trade costs or exchange rates), most analyses focus on variation across households in initial expenditure shares on imported goods. However, the unequal welfare effects of non-marginal foreign price changes also depend on differences in how consumers substitute between imported and domestic goods, on which there is scant evidence. Using data from Switzerland surrounding the 2015 appreciation of the Swiss franc, we provide evidence that lower-income households have higher price elasticities. We quantify the contribution of heterogeneous elasticities for the unequal welfare effects of observed price changes between 2014–15 and for counterfactual shocks to the mean and dispersion of import price changes

Sedimentological imprints of environmental variability at the Balkan Peninsula on the sediment sequence of Lake Ohrid (Macedonia, Albania) between the Mid Pleistocene Transition and present days: the ICDP SCOPSCO project

The UNESCO World Heritage site of Lake Ohrid in the Balkans is thought to be the oldest, continuously existing lake in Europe. In order to unravel the geological and evolutionary history of the lake, a deep drilling campaign was conducted in spring 2013 under the umbrella of the ICDP SCOPSCO project. At the coring site “DEEP” in central parts of the lake, more than 1,500 m of sediments were recovered down to a penetration depth of 569 m blf. This sediment sequence is assumed to be more than 1.2 Ma old and likely covers the entire lacustrine deposits of the Lake Ohrid Basin

PowerDynamics.jl—An experimentally validated open-source package for the dynamical analysis of power grids

PowerDynamics.jl is a Julia package for time-domain modeling of power grids that is specifically designed for the stability analysis of systems with high shares of renewable energies. It makes use of Julia’s state-of-the-art differential equation solvers and is highly performant even for systems with a large number of components. Further, it is compatible with Julia’s machine learning libraries and allows for the utilization of these methods for dynamical optimization and parameter fitting. The package comes with a number of predefined models for synchronous machines, transmission lines and inverter systems. However, the strict open-source approach and a macro-based user-interface also allows for an easy implementation of custom-built models which makes it especially interesting for the design and testing of new control strategies for distributed generation units. This paper presents how the modeling concept, implemented component models and fault scenarios have been experimentally tested against measurements in the microgrid lab of TECNALIA.This research has been performed using the ERIGrid Research Infrastructure and is part of a project that has received funding from the European Union’s Horizon 2020 Research and Innova-tion Programme under the Grant Agreement No. 654113. The support of the European Research Infrastructure ERIGrid and its partner TECNALIA is very much appreciated. We further acknowl-edge the Support by BMBF(CoNDyNet2FK.03EK3055A), the DFG (ExSyCo-Grid, 410409736), the Leibniz competition (T42/2018) and the Federal Ministry of Economics (MAriE, FK. 03Ei4012B)

A Tris(diisocyanide)chromium(0) Complex Is a Luminescent Analog of [Fe(2,2'-Bipyridine)3]2+

A meta-terphenyl unit was substituted with an isocyanide group on each of its two terminal aryls to afford a bidentate chelating ligand (CNtBuAr3NC) that is able to stabilize chromium in its zerovalent oxidation state. The homoleptic Cr(CNtBuAr3NC)3 complex luminesces in solution at room temperature, and its excited-state lifetime (2.2 ns in deaerated THF at 20 °C) is nearly 2 orders of magnitude longer than the current record lifetime for isoelectronic Fe(II) complexes, which are of significant interest as earth-abundant sensitizers in dye-sensitized solar cells. Due to its chelating ligands, Cr(CNtBuAr3NC)3 is more robust than Cr(0) complexes with carbonyl or monodentate isocyanides, manifesting in comparatively slow photodegradation. In the presence of excess anthracene in solution, efficient energy transfer and subsequent triplet–triplet annihilation upconversion is observed. With an excited-state oxidation potential of −2.43 V vs Fc+/Fc, the Cr(0) complex is a very strong photoreductant. The findings presented herein are relevant for replacement of precious metals in dye-sensitized solar cells and in luminescent devices by earth-abundant elements

Spatial Competition in Quality

Abstract The well-studied formalism of Hotelling's classic location paradigm does not apply to the case of good quality, which by its very definition requires that all individuals agree on the ranking of goods; therefore, the notion that goods are differentiated by a 'transportation cost' is inept in vertically differentiated markets. Motivated by this observation, we analyze the determinants of product differentiation in a general equilibrium model of monopolistic competition in good quality. The model features many firms, which each hold the monopoly to produce a unique quality level of an otherwise homogenous good, as well as consumers who are heterogeneous in their valuation for quality. We document that the analogue to the transportation cost in the Hotelling model arises if the marginal cost of production is convex with respect to quality. Firms' optimal prices depend on the latter convexity and on the prices of the competitors that are adjacent in the quality space. For given firm entry, average equilibrium markups are decreasing in the density of quality-competition, but are unaffected by average productivity. Endogenizing firm's entry decision, we demonstrate that the density of competition is increasing in the market size and decreasing in average productivity. Last, we apply these insights to analyze the effect of inter-and intra-industry trade on the toughness of quality-competition, firm entry and welfare. * We would like to than

Sedimentological processes and environmental variability at Lake Ohrid (Macedonia, Albania) between 637 ka and the present

Lake Ohrid (Macedonia, Albania) is thought to be more than 1.2 million years old and host more than 300 endemic species. As a target of the International Continental scientific Drilling Program (ICDP), a successful deep drilling campaign was carried out within the scope of the Scientific Collaboration on Past Speciation Conditions in Lake Ohrid (SCOPSCO) project in 2013. Here, we present lithological, sedimentological, and (bio-)geochemical data from the upper 247.8 m composite depth of the overall 569 m long DEEP site sediment succession from the central part of the lake. According to an age model, which is based on 11 tephra layers (first-order tie points) and on tuning of bio-geochemical proxy data to orbital parameters (second-order tie points), the analyzed sediment sequence covers the last 637 kyr. The DEEP site sediment succession consists of hemipelagic sediments, which are interspersed by several tephra layers and infrequent, thin (< 5 cm) mass wasting deposits. The hemipelagic sediments can be classified into three different lithotypes. Lithotype 1 and 2 deposits comprise calcareous and slightly calcareous silty clay and are predominantly attributed to interglacial periods with high primary productivity in the lake during summer and reduced mixing during winter. The data suggest that high ion and nutrient concentrations in the lake water promoted calcite precipitation and diatom growth in the epilimnion during MIS15, 13, and 5. Following a strong primary productivity, highest interglacial temperatures can be reported for marine isotope stages (MIS) 11 and 5, whereas MIS15, 13, 9, and 7 were comparably cooler. Lithotype 3 deposits consist of clastic, silty clayey material and predominantly represent glacial periods with low primary productivity during summer and longer and intensified mixing during winter. The data imply that the most severe glacial conditions at Lake Ohrid persisted during MIS16, 12, 10, and 6, whereas somewhat warmer temperatures can be inferred for MIS14, 8, 4, and 2. Interglacial-like conditions occurred during parts of MIS14 and 8

Time-ordering and a generalized Magnus expansion

Both the classical time-ordering and the Magnus expansion are well-known in the context of linear initial value problems. Motivated by the noncommutativity between time-ordering and time derivation, and related problems raised recently in statistical physics, we introduce a generalization of the Magnus expansion. Whereas the classical expansion computes the logarithm of the evolution operator of a linear differential equation, our generalization addresses the same problem, including however directly a non-trivial initial condition. As a by-product we recover a variant of the time ordering operation, known as T*-ordering. Eventually, placing our results in the general context of Rota-Baxter algebras permits us to present them in a more natural algebraic setting. It encompasses, for example, the case where one considers linear difference equations instead of linear differential equations