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- Fakultät II - Maschinenbau und Bioverfahrenstechnik (153) (remove)
A novel method has been implemented to prepare metal oxide nanopowders covered with known quantities of adsorbed water; we subsequently studied the γ-radiolysis of ZrO2 nanopowders covered with H2O layers. H2 yields from the adsorbed water radiolysis are of importance in multiple industrial contexts – the nuclear industry being a prime example. Measured H2 yields at water coverages of just below and above one monolayer are around 350 times greater than for neat water, but these yields decrease rapidly with increasing water loading of the ZrO2 nanoparticles, approaching the yield of bulk water at coverages of tens of water layers. The observed plateau of the yields at 0.5 to 2.0 monolayers coverage can be explained by the ease with which electronic excitations in the ZrO2 can be transferred across the interface to the first one or two adsorbed water layers. However, with increasing water loading, energy transfer to water layers further away from the interface becomes less efficient, and above ~30 water layers, most of the water is not affected by any exciton formation in the ZrO2.
HOXA9 and MEIS1 are frequently upregulated in acute myeloid leukemia (AML), including those with MLL‐rearrangement. Because of their pivotal role in hemostasis, HOXA9 and MEIS1 appear non‐druggable. We, thus, interrogated gene expression data of pre‐leukemic (overexpressing Hoxa9) and leukemogenic (overexpressing Hoxa9 and Meis1; H9M) murine cell lines to identify cancer vulnerabilities. Through gene expression analysis and gene set enrichment analyses, we compiled a list of 15 candidates for functional validation. Using a novel lentiviral multiplexing approach, we selected and tested highly active sgRNAs to knockout candidate genes by CRISPR/Cas9, and subsequently identified a H9M cell growth dependency on the cytosolic phospholipase A2 (PLA2G4A). Similar results were obtained by shRNA‐mediated suppression of Pla2g4a. Remarkably, pharmacologic inhibition of PLA2G4A with arachidonyl trifluoromethyl ketone (AACOCF3) accelerated the loss of H9M cells in bulk cultures. Additionally, AACOCF3 treatment of H9M cells reduced colony numbers and colony sizes in methylcellulose. Moreover, AACOCF3 was highly active in human AML with MLL rearrangement, in which PLA2G4A was significantly higher expressed than in AML patients without MLL rearrangement, and is sufficient as an independent prognostic marker. Our work, thus, identifies PLA2G4A as a prognostic marker and potential therapeutic target for H9M‐dependent AML with MLL‐rearrangement.
This paper proposes an extended Petri net formalism as a suitable language for composing optimal scheduling problems of industrial production processes with real and binary decision variables. The proposed approach is modular and scalable, as the overall process dynamics and constraints can be collected by parsing of all atomic elements of the net graph. To conclude, we demonstrate the use of this framework for modeling the moulding sand preparation process of a real foundry plant.