TY - CHAP A1 - Schlosser, Daniel A1 - Jarschel, Michael A1 - Duelli, Michael A1 - Hoßfeld, Tobias A1 - Hoffmann, Klaus A1 - Hoffmann, Marco A1 - Morper, Hans Jochen A1 - Jurca, Dan A1 - Khan, Ashiq T1 - A Use Case Driven Approach to Network Virtualization N2 - In today's Internet, services are very different in their requirements on the underlying transport network. In the future, this diversity will increase and it will be more difficult to accommodate all services in a single network. A possible approach to cope with this diversity within future networks is the introduction of support for running isolated networks for different services on top of a single shared physical substrate. This would also enable easy network management and ensure an economically sound operation. End-customers will readily adopt this approach as it enables new and innovative services without being expensive. In order to arrive at a concept that enables this kind of network, it needs to be designed around and constantly checked against realistic use cases. In this contribution, we present three use cases for future networks. We describe functional blocks of a virtual network architecture, which are necessary to support these use cases within the network. Furthermore, we discuss the interfaces needed between the functional blocks and consider standardization issues that arise in order to achieve a global consistent control and management structure of virtual networks. KW - Virtualisierung KW - Datenkommunikationsnetz KW - Internet KW - Rechnernetz KW - Anwendungsfall KW - Netzvirtualisierung KW - Standardisierung KW - Use case KW - network virtualization KW - future Internet architecture KW - standardization Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-55611 N1 - Accepted at IEEE Kaleidoscope 2010 ER - TY - JOUR A1 - Matera, Carlo A1 - Kauk, Michael A1 - Cirillo, Davide A1 - Maspero, Marco A1 - Papotto, Claudio A1 - Volpato, Daniela A1 - Holzgrabe, Ulrike A1 - De Amici, Marco A1 - Hoffmann, Carsten A1 - Dallanoce, Clelia T1 - Novel Xanomeline-containing bitopic ligands of muscarinic acetylcholine receptors: design, synthesis and FRET investigation JF - Molecules N2 - In the last few years, fluorescence resonance energy transfer (FRET) receptor sensors have contributed to the understanding of GPCR ligand binding and functional activation. FRET sensors based on muscarinic acetylcholine receptors (mAChRs) have been employed to study dual-steric ligands, allowing for the detection of different kinetics and distinguishing between partial, full, and super agonism. Herein, we report the synthesis of the two series of bitopic ligands, 12-Cn and 13-Cn, and their pharmacological investigation at the M\(_1\), M\(_2\), M\(_4\), and M\(_5\) FRET-based receptor sensors. The hybrids were prepared by merging the pharmacophoric moieties of the M\(_1\)/M\(_4\)-preferring orthosteric agonist Xanomeline 10 and the M\(_1\)-selective positive allosteric modulator 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone) 11. The two pharmacophores were connected through alkylene chains of different lengths (C3, C5, C7, and C9). Analyzing the FRET responses, the tertiary amine compounds 12-C5, 12-C7, and 12-C9 evidenced a selective activation of M\(_1\) mAChRs, while the methyl tetrahydropyridinium salts 13-C5, 13-C7, and 13-C9 showed a degree of selectivity for M\(_1\) and M\(_4\) mAChRs. Moreover, whereas hybrids 12-Cn showed an almost linear response at the M\(_1\) subtype, hybrids 13-Cn evidenced a bell-shaped activation response. This different activation pattern suggests that the positive charge anchoring the compound 13-Cn to the orthosteric site ensues a degree of receptor activation depending on the linker length, which induces a graded conformational interference with the binding pocket closure. These bitopic derivatives represent novel pharmacological tools for a better understanding of ligand-receptor interactions at a molecular level. KW - muscarinic acetylcholine receptors KW - Xanomeline KW - 77-LH-28-1 KW - bitopic hybrid ligands KW - synthesis KW - fluorescence resonance energy transfer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311249 SN - 1420-3049 VL - 28 IS - 5 ER -