Better fiscal rules for Europe : reflections based on new empirical evidence

Die Fiskalregeln der Eurozone wurden in den letzten fünf Jahren reformiert und erweitert. Ob diese Veränderungen tatsächlich zu einem gesteigerten Maß an fiskalpolitischer Klugheit geführt haben und weitreichend genug waren, ist jedoch unklar. Dieses Grundsatzpapier fasst die jüngsten Forschungsergebnisse eines spanisch-deutsch-amerikanischen Forscherteams unter der Leitung des ZEW zusammen. In der Studie werden die allgemeine Wirksamkeit bisheriger fiskalischer Regelwerke sowie das Zusammenspiel zwischen Regeln, politischen Faktoren und dem Finanzausgleich untersucht. Eine Hauptempfehlung: Die Fiskalpolitik sollte Haushaltsentwicklungen in scheinbar guten Zeiten stärker im Auge behalten und explizit Vorsicht walten lassen bei der Nutzung unerwarteter Mehreinnahmen sowie dem Entstehen umfangreicher Bürokratien

NOEnet–Use of NOE networks for NMR resonance assignment of proteins with known 3D structure

Motivation: A prerequisite for any protein study by NMR is the assignment of the resonances from the 15N−1H HSQC spectrum to their corresponding atoms of the protein backbone. Usually, this assignment is obtained by analyzing triple resonance NMR experiments. An alternative assignment strategy exploits the information given by an already available 3D structure of the same or a homologous protein. Up to now, the algorithms that have been developed around the structure-based assignment strategy have the important drawbacks that they cannot guarantee a high assignment accuracy near to 100%

Robust structure-based resonance assignment for functional protein studies by NMR

High-throughput functional protein NMR studies, like protein interactions or dynamics, require an automated approach for the assignment of the protein backbone. With the availability of a growing number of protein 3D structures, a new class of automated approaches, called structure-based assignment, has been developed quite recently. Structure-based approaches use primarily NMR input data that are not based on J-coupling and for which connections between residues are not limited by through bonds magnetization transfer efficiency. We present here a robust structure-based assignment approach using mainly HN–HN NOEs networks, as well as 1H–15N residual dipolar couplings and chemical shifts. The NOEnet complete search algorithm is robust against assignment errors, even for sparse input data. Instead of a unique and partly erroneous assignment solution, an optimal assignment ensemble with an accuracy equal or near to 100% is given by NOEnet. We show that even low precision assignment ensembles give enough information for functional studies, like modeling of protein-complexes. Finally, the combination of NOEnet with a low number of ambiguous J-coupling sequential connectivities yields a high precision assignment ensemble. NOEnet will be available under: http://www.icsn.cnrs-gif.fr/download/nmr

Nitrogen Oxides and Reactive Nitrogen in the UTLS: Long Term Observations from CARIBIC

Nitrogen oxides measurements in the UTLS region within the CARIBIC project

MyPMFs: a simple tool for creating statistical potentials to assess protein structural models

International audienc

TEF 2.0: a graph-based method for decomposing protein structures into closed loops

International audienc

Exhaustive exploration of the conformational landscape of small cyclic peptides using a robotics approach

International audienceSmall cyclic peptides represent a promising class of therapeutic molecules with unique chemical properties. However, the poor knowledge of their structural characteristics makes their computational design and structure prediction a real challenge. In order to better describe their conformational space, we developed a method, named EGSCyP, for the exhaustive exploration of the energy landscape of small head-to-tail cyclic peptides. The method can be summarized by (i) a global exploration of the conformational space based on a mechanistic representation of the peptide and the use of robotics-based algorithms to deal with the closure constraint, (ii) an all-atom refinement of the obtained conformations. EGSCyP can handle D-form residues and N-methylations. Two strategies for the side-chains placement were implemented and compared. To validate our approach, we applied it to a set of three variants of cyclic RGDFV pentapeptides, including the drug candidate Cilengitide. A comparative 1 analysis was made with respect to replica exchange molecular dynamics simulations in implicit solvent. It results that the EGSCyP method provides a very complete characterization of the conformational space of small cyclic pentapeptides