Complement in neurological disorders and emerging complement-targeted therapeutics

The complement system consists of a network of plasma and membrane proteins that modulate tissue homeostasis and contribute to immune surveillance by interacting with the innate and adaptive immune systems. Dysregulation, impairment or inadvertent activation of complement components contribute to the pathogenesis of some autoimmune neurological disorders and could even contribute to neurodegenerative diseases. In this Review, we summarize current knowledge about the main functions of the complement pathways and the involvement of complement in neurological disorders. We describe the complex network of complement proteins that target muscle, the neuromuscular junction, peripheral nerves, the spinal cord or the brain and discuss the autoimmune mechanisms of complement-mediated myopathies, myasthenia, peripheral neuropathies, neuromyelitis and other CNS disorders. We also consider the emerging role of complement in some neurodegenerative diseases, such as Alzheimer disease, amyotrophic lateral sclerosis and even schizophrenia. Finally, we provide an overview of the latest complement-targeted immunotherapies including monoclonal antibodies, fusion proteins and peptidomimetics that have been approved, that are undergoing phase I–III clinical trials or that show promise for the treatment of neurological conditions that respond poorly to existing immunotherapies. © 2020, Springer Nature Limited

Evaluation of Complement Activation on Cardiopulmonary Bypass and in Retransfused Oxygenator and Shed Mediastinal Blood

Several methods of blood salvage are used in cardiac surgery. Our aim was to study, on the basis of complement activation, the quality of autologous blood products reinfused to the patient. Eleven patients with elective myocardial revascularisation were studied for: operative and cardiopulmonary bypass (CPB) data, hematology, blood chemistry and complement activation (C3a [des Arg] and terminal complement complex [TCC] or C5b-9 complex). Centrifugated oxygenator blood (COB) and shed mediastinal blood (SMB) samples were examined before reinfusion into the patient and the effect of this retransfusion on the systemic values. The activation pattern for C3a [des Arg] and TCC was similar. Thus only evaluation of C3a [des Arg] is reported. Anesthesia increased C3a [des Arg] two fold over baseline (85 +/- 64 vs. 161 +/-103 ng/ml [standardised]; ns)

Methoden und Programmwerkzeuge fuer die Planung von photonischen Backbone-Netzen Abschlussbericht

Due to the increasing use of WDM technology, we can expect the realisation of optical networks including optical transmission and optical switching functionality in addition to optical point-to-point links in the near future. In recent literature, much work is reported concerning planning and evaluation tasks for such networks. This project however includes some new aspects. The work focuses on the investigation of network architectures and evolution paths for optical networks, on an integrated planning approach which considers the optical layer as well as the electrical layer, and on performance evaluation of optical networks. The latter has to consider dynamic traffic conditions which will occur for real network operation. The solve these tasks, numerous models were developed and transformed into appropriate software tools. These include network planning tools as well as simulation tools for performance evaluation tasks under dynamic conditions. The studies performed by using these tools allow for example the analysis of performance improvements in WDM networks by using wavelength converters, the comparison of resource requirements for different protection and restoration mechanisms, or the investigation of network behaviour for different routing strategies. Results like the examples given above are important to show the advantages of optical technology compared to established network technologies and to determine functional requirements for network operation. This influences the system and component requirements and can therefore be helpful for technological research by providing some kind of guideline. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(70,17) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Magnetic properties of a Kramers doublet. An univocal bridge between experimental results and theoretical predictions

The magnetic response of a Kramers doublet is analyzed in a general case taking into account only the formal properties derived from time reversal operation. It leads to a definition of a matrix G (gyromagnetic matrix) whose expression depends on the chosen reference frame and on the Kramers conjugate basis used to describe the physical system. It is shown that there exists a reference frame and a suitable Kramers conjugate basis that gives a diagonal form for the G-matrix with all non-null elements having the same sign. A detailed procedure for obtaining this canonical expression of G is presented when the electronic structure of the KD is known regardless the level of the used theory. This procedure provides a univocal way to compare the theoretical predictions with the experimental results obtained from a complete set of magnetic experiments. In this way the problems arising from ambiguities in the g-tensor definition are overcome. This procedure is extended to find a spin-Hamiltonian suitable for describing the magnetic behavior of a pair of weakly coupled Kramers systems in the multispin scheme when the interaction between the two moieties as well as the individual Zeeman interaction are small enough as compared with ligand field splitting. Explicit relations between the physical interaction and the parameters of such a spin-Hamiltonian are also obtained.This work was supported by Spanish Ministry of Economy and Competitively (MINECO), Projects no. MAT2011-23861 to JIM and by ‘‘Grupos de investigación’’ Program of the Aragon Autonomous Government, refs. B18 and E33.Peer reviewe

Quasifree π+ production studied using the C12(γ, π+n)B11 reaction in the Δ(1232) resonance region

Results are presented from a coincidence study of the C<sup>12</sup>(γ, π+n) <sup>11</sup>B quasifree pion production reaction made in the Δ-resonance region using tagged photons. Cross sections for reactions originating on 1p-shell protons are found to be significantly larger than predicted by calculations based on quasifree pion production. It is suggested that more sophisticated calculations, perhaps including medium effects, may be required to reproduce the data