NAD+ protects against EAE by regulating CD4+ T-cell differentiation

CD4+ T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD+) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4+IFNγ+IL-10+ T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD+ regulates CD4+ T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD+, the frequency of T-bet−/− CD4+IFNγ+ T cells was twofold higher than wild-type CD4+ T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4+ T-cell differentiation and demonstrate that NAD+ may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases

Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy

Targeted eradication of transformed or otherwise dysregulated cells using monoclonal antibodies (mAb), antibody-drug conjugates (ADC), T cell engagers (TCE), or chimeric antigen receptor (CAR) cells is very effective for hematologic diseases. Unlike the breakthrough progress achieved for B cell malignancies, there is a pressing need to find suitable antigens for myeloid malignancies. CD123, the interleukin-3 (IL-3) receptor alpha-chain, is highly expressed in various hematological malignancies, including acute myeloid leukemia (AML). However, shared CD123 expression on healthy hematopoietic stem and progenitor cells (HSPCs) bears the risk for myelotoxicity. We demonstrate that epitope-engineered HSPCs were shielded from CD123-targeted immunotherapy but remained functional, while CD123-deficient HSPCs displayed a competitive disadvantage. Transplantation of genome-edited HSPCs could enable tumor-selective targeted immunotherapy while rebuilding a fully functional hematopoietic system. We envision that this approach is broadly applicable to other targets and cells, could render hitherto undruggable targets accessible to immunotherapy, and will allow continued posttransplant therapy, for instance, to treat minimal residual disease (MRD)

Entwicklung und Herstellung von metallgestützten Festelektrolyt-Brennstoffzellen mit Hilfe des Hohlkathoden-Gasflusssputterns

In this work the electrolyte manufacturing of metal supported solid oxide fuel cells (MSC) by a gas flow sputtering (GFS) process is discussed. This GFS process was developed at Fraunhofer Institute for Surface Engineering and Thin Films (Fraunhofer IST) in Braunschweig, Germany. Based on a porous metal substrate (tradename: ITM, Plansee, Austria) a screen printed anode was developed in cooperation with Plansee and Forschungszentrum Jülich, Germany. On this anode a thin and gas-tight electrolyte is brought up by this physical vapour deposition (PVD) GFS process. The electrolyte was widely developed on a research facility in cooperation with Fraunhofer IST whereby a permanent matching with anode development in Jülich was realized. On the one hand, a first milestone was to find an anode with a structure to enable a gas-tight thin film electrolyte and on the other hand the anode should handle high residual compressive stresses of that electrolyte. A further component in this work lied in treatment of occurred electrolyte coating errors which will increase the leakage rate of that layer. Hereby different methods were evaluated which were able to locate coating errors and make them visible. On the research facility at Fraunhofer IST coating parameters were worked out and have been transferred to a manufacturing facility, whereas with this step a first industrialization was realized. Hereby it was necessary to ensure a consistent coating thickness and homogeneity of the electrolyte over the whole coating area. Different MSCs which were manufactured by an electrolyte depicted within this work were characterized electrochemically. Hereby single cell tests in planar design were performed at Karlsruhe Institute of Technology (KIT), whereas stack tests of MSCs in cassette design were made in Jülich

Accident scenarios with environmental impact of the TRIGA Mark II reactor Vienna

Zsfassung in dt. SpracheDer Sicherheitsbericht des TRIGA Mark II Reaktors in Wien umfasst drei Unfallszenarien und deren deterministische Dosisauswirkung auf die Umgebung. Es wurden der Bruch des höchstbelasteten Brennelements, der Bruch aller Brennelemente und ein Flugzeugabsturz als mögliche Szenarien betrachtet. Die Berechnungen stammen aus dem Jahr 1978 und wurden mit dem Programm STRISK durchgeführt.Die Aufgabe dieser Diplomarbeit umfasste die Anwendung des Programmpakets PC COSYMA auf den TRIGA Mark II Reaktor in Wien und die Aktualisierung der deterministischen Auswirkung der Unfallszenarien auf die Umgebung. Das Inventar der Spaltprodukte aller Brennelemente wurde aus einer Berechnung mit ORIGEN2 entnommen.Um meteorologische Daten für das Freisetzungsareal zu bekommen, wurde eine Wetterstation installiert. Die Parameter für die Freisetzung wurden aus dem Sicherheitsbericht übernommen oder durch Worst-Case Parameter ersetzt. Des Weiteren wurde ein viertes Szenario für den Fall des Absturzes eines kleinen Flugzeuges hinzugefügt.Die Szenarien wurden deterministisch betrachtet, d.h. eine konstante Atmosphärenbedingung wurde angenommen. Es wurde die Effektive Dosis innerhalb eines Radius von 5km um den Freisetzungspunkt berechnet und ausgewertet. Der Vollständigkeit halber sind die Szenarien mit verschiedenen meteorologischen Bedingungen berechnet worden. Die Diplomarbeit startete im Februar 2009 und dauerte bis August 2009The safety report of the TRIGA Mark II Reactor in Vienna includes three accident scenarios and their deterministic dose consequence to the environment. The destruction of the most activated fuel element, the destruction of all fuel elements and a plane crash were treated scenarios in that report. The calculations were made in 1978 with the computer program STRISK.In this diploma theses, the program package PC COSYMA was applied on the TRIGA Mark II Reactor in Vienna and the deterministic consequences of the scenarios to the environment were updated. The fission product inventories of all fuel elements were taken from a calculation with ORIGEN2.To get meteorological data of the atmospheric condition around the release area, a weather station was installed. The release parameters were taken from the safety report or were replaced by worst case parameters. Further on, a fourth scenario for the case of a small plane crash was added. The calculation of the scenarios was deterministic, which means the atmosphere was temporal stable. The effective dose was calculated within 5km from the release point. For the sake of completeness all scenarios were calculated with different atmospheric conditions. The diploma theses started in February 2009 and was finished in August 2009 .13

Advances beyond traditional SOFC cell designs

Research and development of Solid Oxide Fuel Cell (SOFC) technology has been carried out at the Jülich research center for more than 20 years. A standard cell design based on a porous nickel cermet has been established and tested with stationary conditions, for which a power density of 1.25 W/cm2 at 800°C in H2 was obtained. In order to broaden the field of possible applications, new cell designs have been developed. Among those are metal-supported SOFCs (MSC), which promise increased robustness against thermal-, mechanical and chemical stresses, as well as cheaper production costs. While the MSC development may find an application in mobile devices another cell design concept aims at much lower operating temperatures. For this cell type a very thin zirconia membrane is deposited on top of a standard anode support via a multi-step sol/gel-route. With this setup a reduction of the operating temperature to 600°C with a power output of 1.25 W/cm2 could be demonstrated