Feynman integrals for a class of exponentially growing potentials

We construct the Feynman integrands for a class of exponentially growing time-dependent potentials as white noise functionals. We show that they solve the Schroedinger equation. The Morse potential is considered as a special case

Direct no-carrier-added 18F-labelling of arenes via nucleophilic substitution on aryl(2-thienyl)iodonium salts

For in vivo imaging of molecular processes via positron emission tomography (PET) radiotracers of high specific activity are demanded. In case of the most commonly used positron emitter fluorine-18, this is only achievable with no-carrier-added [18F]fluoride, which implies nucleophilic methods of 18F substitution. Whereas electron deficient aromatic groups can be labelled in one step using no-carrier-added [18F]fluoride, electron rich 18F-labelled aromatic molecules are only available by multi-step radiosyntheses or carrier-added electrophilic reactions. Here, diaryliodonium salts represent an alternative, since they have been proven as potent precursor for a direct nucleophilic 18F-introduction into aromatic molecules. Furthermore, as known from non-radioactive studies, the highly electron rich 2 thienyliodonium leaving group leads to a high regioselectivity in nucleophilic substitution reactions. Consequently, a direct nucleophilic no-carrier-added 18F-labelling of electron rich arenes via aryl¬(2 thienyl)iodonium precursors was developed in this work. The applicability of direct nucleophilic 18F labelling was examined in a systematic study on eighteen aryl(2-thienyl)iodonium salts. As electron rich precursors the ortho-, meta- and para-methoxyphenyl(2 thienyl)iodonium bromides, iodides, tosylates and triflates were synthesised. In addition, para-substituted (R = BnO, CH3, H, Cl, Br, I) aryl(2-thienyl)iodonium bromides were prepared as precursors with a systematically varying electron density. As first approach, the general reaction conditions of the nucleophilic 18F-substitution procedure were optimised. The best conditions for direct nucleophilic no-carrier-added 18F-labelling via aryl(2-thien¬yl)iodonium salts were found with dimethylformamide as solvent, a reaction temperature of 130 + 3 °C and 25 mmol/l as concentration of the precursor. For the effect of bromide, iodide, tosylate and triflate as counter anion on the radiochemical yield (RCY) the following order was obtained: tosylate < iodide < triflate < bromide. However, based on the kinetics a different order was observed for the initial reaction rates with: tosylate < bromide < iodide < triflate. The influence of the substitution pattern in ortho-, meta- and para-methoxyphenyl(2-thienyl)iodonium bromide showed an expected strong ortho-effect, which led with 60 % of 2-[18F]fluoroanisole to the highest RCY. Also under no-carrier-added conditions, the 2-thienyl group directed to a regiospecific radiofluorination, thus in all 18F-substitutions no 2-[18F]fluorothiophene, but only the desired [18F]fluoroarenes were formed. With the intention of a systematic examination of electronic factors, the kinetics of the 18F-substitution on substituted aryl(2-thienyl)iodonium bromides were investigated and the determined relative reactivities were compared with the Hammett constants of the corresponding substituents. As result a good linear Hammett correlation and a reaction parameter of &#61554; = + 1.16 + 0.2 were obtained. This confirms the SNAr-mechanism and a consistent mechanism over the whole range of investigated substituents. In order to demonstrate the applicability of this method, the 18F-labelling of two pharmacological relevant molecules was carried out. First, n.c.a. 4-[18F]fluorophenol was synthesised via 4-benzyl¬oxyphenyl(2-thienyl)iodonium bromide within 40 min and an overall RCY of 34 to 36 %. Second, a complex AMPA receptor antagonist was 18F-labelled via iodonium precursors; however only with low RCY of 1.2 to 3.6 %. For comparison, the radioiodine analogue was labelled via a trimethyltin precursor and [131I]iodide with a very high RCY of 97 + 2 % within 2 min, thus it was available for preliminary pharmacological evaluation studies. In conclusion, the 2-thienyliodonium leaving group proved as highly effective for direct nucleophilic no-carrier-added 18F-labelling even of nucleophilically non-activated arenes. Concerning the 18F-label¬ling of complex molecules, further optimisation, however, is necessary for this method

Tradable SO-2-permits in the European Union: a practicable scheme for public utilities

In this paper, a practicable scheme of SO2-emission permits for European power producers is developed. Background is the second UN-ECE Sulphur Protocol from 1994 (Protocol of Oslo). After discussing some theoretical models of spatially differentiated permit schemes, evaluating the U.S. Acid Rain and RECLAIM Program, and considering the setting in the EU-15 countries, a scheme of locally undifferentiated emission permits is proposed which is distinguished by a high degree of both economic efficiency and market functioning. However, as our model simulations indicate, national deposition targets will be violated in all probability due to the scheme?s missing differentiation regarding the receptors. The risk of hot spots is addressed adequately by a differentiated bundle of countermeasures. The general economic impact of an EU-wide permit scheme is low, and, in terms of change in GDP, lower compared to a non-coordinated SO2 policy. The proposed mode of the initial permit allocation allows for early price signals and guarantees maximum static and dynamic efficiency. Balancing the interests of existing and new emitters, a long-term transition from the grandfathering to the free auction procedure is chosen. --

Fingolimod for Multiple Sclerosis: Mechanism of Action, Clinical Outcomes, and Future Directions

The oral sphingosine 1-phosphate receptor (S1PR) modulator fingolimod functionally antagonizes S1PR hereby blocking lymphocyte egress from secondary lymphoid organs to the peripheral blood circulation. This results in a reduction in peripheral lymphocyte counts, including potentially encephalitogenic T cells. In patients with relapsing multiple sclerosis fingolimod has been shown to be an effective treatment. In phase 2 and phase 3 studies fingolimod-treated patients had reduced disease activity clinically and in MRI. Although severe infectious complications occurred in single cases treated with fingolimod, the frequency of overall infections was comparable in fingolimod-treated patients and controls. Overall, in clinical studies fingolimod was well tolerated and had a favorable safety profile. In follow-up studies with continuous fingolimod, treatment showed sustained efficacy while being well tolerate

Cryogenic Propellant Tank and Feedline Design Studies in the Framework of the CHATT Project

The EU-funded project CHATT (Cryogenic Hypersonic Advanced Tank Technologies) has been initiated early 2012 and is part of the European Commission’s Seventh Framework Programme (FP7). CHATT focuses on the development of novel cryogenic tank and propellant supply technologies. One of the tasks within the project is the investigation of adequate propellant crossfeed systems. Propellant crossfeed principally allows large mass savings for parallel burn vehicles such as the visionary passenger transport concept “SpaceLiner” which has been proposed by the Space Launcher Systems Analysis Department of the German Aerospace Center DLR. Therefore the tank and feedline systems of the SpaceLiner concept are studied by means of reference data and the results of simulations conducted with in-house and commercial tools

Hydrodynamic limits for the free Kawasaki dynamics of continuous particle systems

An infinite particle system of independent jumping particles is considered. Their constructions is recalled, further properties are derived, the relation with hierarchical equations, Poissonian analysis, and second quantization are discussed. The hydrodynamic limit for a general initial distribution satisfying a mixing condition is derived. The large time asymptotic is computed under an extra assumption