Evidence of Sulfur Non-Innocence in [CoII(dithiacyclam)]2+-Mediated Catalytic Oxygen Reduction Reactions

In many metalloenzymes, sulfur-containing ligands participate in catalytic processes, mainly via the involvement in electron transfer reactions. In a biomimetic approach, we now demonstrate the implication of S-ligation in cobalt mediated oxygen reduction reactions (ORR). A comparative study between the catalytic ORR capabilities of the four-nitrogen bound [Co(cyclam)]2+ (1; cyclam=1,5,8,11-tetraaza-cyclotetradecane) and the S-containing analog [Co(S2N2-cyclam)]2+ (2; S2N2-cyclam=1,8-dithia-5,11-diaza-cyclotetradecane) reveals improved catalytic performance once the chalcogen is introduced in the Co coordination sphere. Trapping and characterization of the intermediates formed upon dioxygen activation at the CoII centers in 1 and 2 point to the involvement of sulfur in the O2 reduction process as the key for the improved catalytic ORR capabilities of 2

Microservice Transition and its Granularity Problem: A Systematic Mapping Study

Microservices have gained wide recognition and acceptance in software industries as an emerging architectural style for autonomic, scalable, and more reliable computing. The transition to microservices has been highly motivated by the need for better alignment of technical design decisions with improving value potentials of architectures. Despite microservices' popularity, research still lacks disciplined understanding of transition and consensus on the principles and activities underlying "micro-ing" architectures. In this paper, we report on a systematic mapping study that consolidates various views, approaches and activities that commonly assist in the transition to microservices. The study aims to provide a better understanding of the transition; it also contributes a working definition of the transition and technical activities underlying it. We term the transition and technical activities leading to microservice architectures as microservitization. We then shed light on a fundamental problem of microservitization: microservice granularity and reasoning about its adaptation as first-class entities. This study reviews state-of-the-art and -practice related to reasoning about microservice granularity; it reviews modelling approaches, aspects considered, guidelines and processes used to reason about microservice granularity. This study identifies opportunities for future research and development related to reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table

Models of <i>KPTN</i>-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.</p

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models.Kptn−/− mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants.Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1.By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.Genetics of disease, diagnosis and treatmen

Entwicklung und Erprobung eines neuen Fertigungsverfahrens von Rotorblaettern fuer Windkraftanlagen Abschlussbericht ueber die Herstellung von Rotorblaettern in Wickel- und Presstechnik

Conventional rotor blades are produced in parts and glued together. The new process is based on a CNC-controlled winding technology which is more accurate, produces no failure-prone glued seams, and avoids glues that may be environmentally harmful and affect human health.Bei der herkoemmlichen Rotorblattherstellung werden Fluegelober- und unterseite getrennt im Handlaminierverfahren produziert. Auch die Stuetzelemente werden so in einer eigenen Form gefertigt. In den weiteren Fertigungsschritten werden dann Fluegeloberseite, Stuetzelement und Fluegelunterseite unter Einsatz entsprechender Klebstoffe miteinander verklebt. Im Vergleich dazu ergeben sich mit dem CNC-gesteuerten Wickelverfahren wesentliche Vorteile sowohl fuer den Herstellprozess als auch fuer das fertige Rotorblatt. Es ermoeglicht eine genauere und reproduzierbare Fluegelfertigung. In die Blattwurzel des Fluegels wird ein faserverbundgerechtes Krafteinleitungselement integriert mit einer optimalen Anbindung an den Holm der spaeter die Festigkeits- und Steifigkeits-Anforderungen sicherstellt. Infolge der wickeltechnischen Fertigung koennen die sicherheiskritischen Klebenaehte an der Blattvorder- und Hinterkante, wie bei Blaettern in Schalenbauweise vorhanden, vermieden werden. Die mechanische Bearbeitung zum Anbringen von Krafteinleitungselementen entfaellt. Der Verzicht auf den Einsatz von Klebstoffen entlastet die Umwelt und verringert gesundheitliche Belastungen der Mitarbeiter. (orig.)In cooperation with: Ventis Energietechnik GmbH, Braunschweig (DE); Deutsches Zentrum fuer Luft- und Raumfahrt e.V., Braunschweig (DE)SIGLEAvailable from TIB Hannover: F02B1265 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDeutsche Bundesstiftung Umwelt, Osnabrueck (Germany)DEGerman