Synergistic Stimulation with Different TLR7 Ligands Modulates Gene Expression Patterns in the Human Plasmacytoid Dendritic Cell Line CAL-1

Objective. TLR7 ligation in plasmacytoid dendritic cells is promising for the treatment of cancer, allergy, and infectious diseases; however, high doses of ligands are required. We hypothesized that the combination of structurally different TLR7 ligands exponentiates the resulting immune response. Methods. CAL-1 (human pDC line) cells were incubated with the TLR7-specific adenine analog CL264 and single-stranded 9.2s RNA. Protein secretion was measured by ELISA. Microarray technique was used to detect modified gene expression patterns upon synergistic stimulation, revealing underlying functional groups and networks. Cell surface binding properties were studied using FACS analysis. Results. CL264 in combination with 9.2s RNA significantly enhanced cytokine and interferon secretion to supra-additive levels. This effect was due to a stronger stimulation of already regulated genes (by monostimulation) as well as to recruitment of thus far unregulated genes. Top scoring canonical pathways referred to immune-related processes. Network analysis revealed IL-1β, IL-6, TNF, and IFN-β as major regulatory nodes, while several minor regulatory nodes were also identified. Binding of CL264 to the cell surface was enhanced by 9.2s RNA. Conclusion. Structurally different TLR7 ligands act synergistically on gene expression patterns and on the resulting inflammatory response. These data could impact future strategies optimizing TLR7-targeted drug design

Assessing Shipping Induced Emissions Impact on Air Quality with Various Techniques : Initial Results of the SCIPPER project

This paper presents the methods deployed by the Horizon 2O2O SCIPPER project to characterize emission performance of vebels, mainly under the perspective of checking compliance to new emissions regulations. Various on-board and remote measurement techniques have been demonstrated within five experimental campaigns conducted at Europe's main sea areas and ports. Almost a thousand of ship plumes has been measured and crobed checked with various instrumentation, revealing the emission profile of ships during actual operation Accuracy of each measurement technique was also tested. Emission measurements are further exploited to abess the impact of shipping on air quality of coastal areas, by identifying the transformations of pollutants performed in the atmosphere as plume evolves and quantifying onshore pollutants concentrations attributed to shipping activity.Peer reviewe

Neue Werkstoffkonzepte für erhöhte Standzeiten und verbesserte Funktionalität von Werkzeugen und Formen

Der Werkzeug- und Formenbau für urformende und umformende Verfahren steht in Deutschland großen Herausforderungen gegenüber. Einerseits drängen asiatische Werkzeugbauer auf den europäischen Markt und andererseits erwarten die Kunden eine immer komplexere Funktionalität (z. B. lokal unterschiedliches Wärmemanagement, oder lokal unterschiedliche Anforderungen an Verschleiß- und Korrosionsschutz) und kürzere Zykluszeiten bei höherer Werkzeugverfügbarkeit. Zudem steigt die Geometriekomplexität der Bauteile, die umgeformt, gegossen oder gespritzt werden sollen, um z. B. spätere Fügeoperationen zu vermeiden

Graded layers for wear and corrosion protection produced by laser cladding

Graded layers on the basis of Fe- and Ni-alloys were developed for applications in the tool making industry. The graded materials are formed layer by layer with a continuous change of the composition in each layer using the technology of laser beam cladding with powder feeding. The composition of the graded layers aims at the improvement of wear and corrosion resistance as well as thermal shock resistance. Depending on the composition a surface hardness up to 65 HRC can be achieved. The layers on steel substrates are crack free up to 60 HRC. The graded materials can also be clad on a Cu substrate using the bonding layer Fe33Ni. The hardness should be limited to values around 50 HRC to ensure crack free cladding. Machining of the materials using milling, grinding, EDM and polishing was proved. A thermal shock test and a wear test process have shown promising results regarding the applicability ofthe various graded layers for the injection moulding process