“Zur Neuen Welt” — Towards the New World. Ludwig Mies and his Architectural Youth in Aachen

Ludwig Mies van der Rohe's personal and professional connections to his hometown Aachen in Germany are mostly unknown today. Through the analysis of both old and new written and graphic sources, the authors give an insight into Mies van der Rohe's lifelong bond to his hometown. In the personal friendships, his friends Ferdinand Goebbels and Franz Dominick play a key role. Furthermore, the paper presents previously unknown buildings that young Mies was working on in the office of Albert Schneiders around 1905. One of the buildings, the house “Zur Neuen Welt” for client Joseph Oeben, is still standing and represents a lively example of the stylistic search in architecture after the turn of the millennium, and an early step towards Mies van der Rohe's architectural maturity

Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the oxidative inactivation of calcineurin

AbstractApproximately 10% of all familial cases of amyotrophic lateral sclerosis (fALS) are linked to mutations in the SOD1 gene, which encodes the copper/zinc superoxide dismutase (CuZnSOD). Recently, wild-type CuZnSOD was shown to protect calcineurin, a calcium/calmodulin-regulated phosphoprotein phosphatase, from inactivation by reactive oxygen species. We asked whether the protective effect of CuZnSOD on calcineurin is affected by mutations associated with fALS. For this, we monitored calcineurin activity in the presence of mutant and wild-type SOD. We found that the degree of protection against inactivation of calcineurin by different SOD mutants correlates with the severity of the phenotype associated with the different mutations, suggesting a potential role for calcineurin–SOD1 interaction in the etiology of fALS

AI Lifecycle Zero-Touch Orchestration within the Edge-to-Cloud Continuum for Industry 5.0

The advancements in human-centered artificial intelligence (HCAI) systems for Industry 5.0 is a new phase of industrialization that places the worker at the center of the production process and uses new technologies to increase prosperity beyond jobs and growth. HCAI presents new objectives that were unreachable by either humans or machines alone, but this also comes with a new set of challenges. Our proposed method accomplishes this through the knowlEdge architecture, which enables human operators to implement AI solutions using a zero-touch framework. It relies on containerized AI model training and execution, supported by a robust data pipeline and rounded off with human feedback and evaluation interfaces. The result is a platform built from a number of components, spanning all major areas of the AI lifecycle. We outline both the architectural concepts and implementation guidelines and explain how they advance HCAI systems and Industry 5.0. In this article, we address the problems we encountered while implementing the ideas within the edge-to-cloud continuum. Further improvements to our approach may enhance the use of AI in Industry 5.0 and strengthen trust in AI systems

A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study

The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m(2) doxorubicin or equivalent were allowed. Left ventricular ejection fraction of > 50 % was required. Patients received PLD 50 mg/m(2) every 28 days or capecitabine 1250 mg/m(2) twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838-1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %;P = 0.31). Both PLD and capecitabine are effective first-line agents for MBC

The expanding functional roles and signaling mechanisms of adhesion G protein–coupled receptors

The adhesion class of G protein–coupled receptors (GPCRs) is the second largest family of GPCRs (33 members in humans). Adhesion GPCRs (aGPCRs) are defined by a large extracellular N‐terminal region that is linked to a C‐terminal seven transmembrane (7TM) domain via a GPCR‐autoproteolysis inducing (GAIN) domain containing a GPCR proteolytic site (GPS). Most aGPCRs undergo autoproteolysis at the GPS motif, but the cleaved fragments stay closely associated, with the N‐terminal fragment (NTF) bound to the 7TM of the C‐terminal fragment (CTF). The NTFs of most aGPCRs contain domains known to be involved in cell–cell adhesion, while the CTFs are involved in classical G protein signaling, as well as other intracellular signaling. In this workshop report, we review the most recent findings on the biology, signaling mechanisms, and physiological functions of aGPCRs

ARTEFACTS: How do we want to deal with the future of our one and only planet?

The European Commission’s Science and Knowledge Service, the Joint Research Centre (JRC), decided to try working hand-in-hand with leading European science centres and museums. Behind this decision was the idea that the JRC could better support EU Institutions in engaging with the European public. The fact that European Union policies are firmly based on scientific evidence is a strong message which the JRC is uniquely able to illustrate. Such a collaboration would not only provide a platform to explain the benefits of EU policies to our daily lives but also provide an opportunity for European citizens to engage by taking a more active part in the EU policy making process for the future. A PILOT PROGRAMME To test the idea, the JRC launched an experimental programme to work with science museums: a perfect partner for three compelling reasons. Firstly, they attract a large and growing number of visitors. Leading science museums in Europe have typically 500 000 visitors per year. Furthermore, they are based in large European cities and attract local visitors as well as tourists from across Europe and beyond. The second reason for working with museums is that they have mastered the art of how to communicate key elements of sophisticated arguments across to the public and making complex topics of public interest readily accessible. That is a high-value added skill and a crucial part of the valorisation of public-funded research, never to be underestimated. Finally museums are, at present, undergoing something of a renaissance. Museums today are vibrant environments offering new techniques and technologies to both inform and entertain, and attract visitors of all demographics.JRC.H.2-Knowledge Management Methodologies, Communities and Disseminatio

Ausbau von Speicherkapazitäten für eine effiziente Stromversorgung mit erneuerbaren Energien in Deutschland und Europa bis 2050

In der Leitstudie 2010 [BMU 2010] wird die installierte Wind-, PV-, Wasserkraft- und Geothermie-Leistung in Deutschland bis zum Jahr 2050 auf ca. 153 GW gesteigert. Dahingegen beträgt die Spitzenlast, d. h. die maximal in einem Jahr benötigte Leistung, im Jahr 2050 nur noch rund 74 GW. Der Strombedarf wird dann in ca. einem Drittel des Jahres von der möglichen Stromerzeugung aus erneuerbaren Energien überstiegen. Pumpspeicher, Druckluftspeicher, Batterien und die chemischen Energieträger Wasserstoff und Methan können zur Anpassung der Stromeinspeisung durch erneuerbarer Erzeugungskapazitäten an den Strombedarf dienen und zur Netzstabilität beitragen. Um den Bedarf an Lastverlagerung zu ermitteln, müssen Strombedarf und fluktuierende Stromerzeugung in ihrem stündlichen Verlauf analysiert werden