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Laura Ascherl, C. Evangelisti, T. Klapötke, B. Krumm, J. Nafe, A. Nieder, S. Rest, Christian L Schütz et al.

An investigation of the structures and chemistry of substituted hexamethyl disiloxanes ((XCH2)3Si)2O; X=F, Cl, Br, I, N3 , and ONO2) is reported. New synthetic routes to the precursor hexakis(chloromethyl)disiloxane are presented. The products with X=Cl, Br, I, and N3 were characterized by NMR, IR, and Raman spectroscopy. In addition, the single-crystal structures of the products with X=Cl, Br, and I are discussed in detail. The compounds with X=F and ONO2 were not obtained in their pure form; instead investigations of the decomposition products revealed their conversion into intermediates. Theoretical calculations of the gas-phase structures at the B3LYP/cc-pVDZ, B3LYP/3-21G, MP2/6-31G*, and MP2/3-21G levels of theory are used to explain the chemical and physical behavior of the compounds with X=Cl, Br, I, N3, and ONO2. A new decomposition pathway of hexakis(nitratomethyl)disiloxane is presented and is used to explain their remarkable instability. The energetic properties and values of the nitrate and azide derivatives were calculated at the CBS-4M level of theory by using the improved EXPLO5 computer code version 6.01.

C. Blanchetot, D. Verzijl, Azra Mujić-Delić, Leontien Bosch, Louise Rem, R. Leurs, C. Verrips, M. Saunders et al.

Background: Chemokines play a prominent role in inflammatory diseases. Results: Nanobodies targeting chemokines display high affinity and potently neutralize chemokine-induced receptor binding and signaling. Conclusion: Neutralizing Nanobodies targeting chemokines effectively inhibit chemokine function. Significance: Nanobodies directed against inflammatory and homeostatic chemokines form a promising new class of potent and specific inhibitors of chemokine function, to be used for research and therapeutic purposes. Chemokine receptors and their ligands play a prominent role in immune regulation but many have also been implicated in inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, allograft rejection after transplantation, and also in cancer metastasis. Most approaches to therapeutically target the chemokine system involve targeting of chemokine receptors with low molecular weight antagonists. Here we describe the selection and characterization of an unprecedented large and diverse panel of neutralizing Nanobodies (single domain camelid antibodies fragment) directed against several chemokines. We show that the Nanobodies directed against CCL2 (MCP-1), CCL5 (RANTES), CXCL11 (I-TAC), and CXCL12 (SDF-1α) bind the chemokines with high affinity (at nanomolar concentration), thereby blocking receptor binding, inhibiting chemokine-induced receptor activation as well as chemotaxis. Together, we show that neutralizing Nanobodies can be selected efficiently for effective and specific therapeutic treatment against a wide range of immune and inflammatory diseases.

D. Haller, A. Meynard, D. Pejic, A. Sredic, S. Huseinagic, D. Courvoisier, N. Perone, L. Sanci et al.

Coordinate measuring machines (CMMs) are widely used to check dimensions of manufactured parts, especially in the automotive industry. The major obstacles in automation of these measurements are fixturing and clamping assemblies, which are required in order to position the measured object within the CMM. This paper describes how an industrial robot can be used to manipulate the measured object within the CMM work space, in order to enable automation of complex geometry measurement.

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