Zur Regioselektivität der Umsetzung von Methallylisothiocyanat mit monosubstituierten Hydrazinen

Regioselectivity of the Reaction of Methallyl Isothiocyanate with Monosubstituted Hydrazines Methallyl isothiocyanate 1 reacts with substituted aryl hydrazines to 1,4- respectively 2,4-disubstituted thiosemicarbazides 4 and 5 in dependence on the reaction conditions and the nature of the aryl group. The influence of the substituents is discussed. The novel N′-mono- and disubstituted N-methallylic thioureas 2 and 3 are synthesized.     

Defective smooth muscle regulation in cGMP kinase I-deficient mice

Regulation of smooth muscle contractility is essential for many important biological processes such as tissue perfusion, cardiovascular haemostasis and gastrointestinal motility. While an increase in calcium initiates smooth muscle contraction, relaxation can be induced by cGMP or cAMP. cGMP-dependent protein kinase I (cGKI) has been suggested as a major mediator of the relaxant effects of both nucleotides. To study the biological role of cGKI and its postulated cross-activation by cAMP, we inactivated the gene coding for cGKI in mice. Loss of cGKI abolishes nitric oxide (NO)/cGMP-dependent relaxation of smooth muscle, resulting in severe vascular and intestinal dysfunctions. However, cGKI-deficient smooth muscle responded normally to cAMP, indicating that cAMP and cGMP signal via independent pathways, with cGKI being the specific mediator of the NO/cGMP effects in murine smooth muscle.     

Application of a modified polytetrafluoroethylene powder in diaphragms for alkali chloride electrolysis

A shape retaining asbestos diaphragm which is well suited for alkali chloride solution electrolysis can be obtained from sintering of a mixture of asbestos and a modified polytetrafluoroethylene powder. The usual different polymers of tetrafluoroethylene are not suitable as additives to asbestos diaphragms, whereas an irradiation process permits the production of a modified polytetrafluoroethylene powder which has proved its worth as a component in the diaphragm composition. With reactants present during the irradiation process, functional groups which reduce the water repellency of the polytetrafluoroethylene are incorporated into the polymer. The parallel process of partial polymer chain degradation simultaneously provides an intense reduction of the melt viscosity of the polytetrafluoroethylene so that a composite structure with asbestos can be formed by sintering.     

A Multiplex CRISPR-Screen Identifies PLA2G4A as Prognostic Marker and Druggable Target for HOXA9 and MEIS1 Dependent AML

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.     

Ordering of nitric acid (HNO3) intercalated in graphite

X-ray studies of intercalation compounds of single crystals of natural graphite have enabled us to settle essential features of the in-plane ordering of α-HNO₃-graphite. A low temperature superstructure with $\textcolor{red}{}\text{= 17}\textcolor{red}{}{}_{\mathrm{<mtext>G</mtext>}}\text{,}\textcolor{red}{}\text{= 2}\textcolor{red}{}{}_{\mathrm{<mtext>G</mtext>}}\text{+ 9}\textcolor{red}{}{}_{\mathrm{<mtext>G</mtext>}}$ is found below 210 K. Above this temperature, the structure is incommensurate with the graphite lattice, with $\textcolor{red}{}\text{～- 17}\textcolor{red}{}{}_{\mathrm{<mtext>G</mtext>}}\text{/12}$. In stage 8 sample this structure persists until the disordering temperature at about 250 K, whereas fresh stage 2 samples show an intermediate phase strongly incommensurate and quite different from the low temperature phase. The X-ray pattern from the liquid phase above 250 K shows pronounced hexagonal modulation.     

Speech understanding systems: Report of a steering committee

A five-year interdisciplinary effort by speech scientists and computer scientists has demonstrated the feasibility of programming a computer system to “understand” connected speech, i.e., translate it into operational form and respond accordingly. An operational system (HARPY) accepts speech from five speakers, interprets a 1000-word vocabulary, and attains 91 percent sentence accuracy. This Steering Committee summary report describes the project history, problem, goals, and results.