Soft or hard ionization of molecules in helium nanodroplets? An electron impact investigation of alcohols and ethers

Electron impact (70 eV) mass spectra of a series of C[subscript 1]-C[subscript 6] alcohols encased in large superfluid liquid helium nanodroplets (approximately 60,000 helium atoms) have been recorded. The presence of helium alters the fragmentation patterns when compared with the gas phase, with some ion product channels being more strongly affected than others, most notably cleavage of the C[subscript α]-H bond in the parent ion to form the corresponding oxonium ion. Parent ion intensities are also enhanced by the helium, but only for the two cyclic alcohols studied, cyclopentanol and cyclohexanol, is this effect large enough to transform the parent ion from a minor product (in the gas phase) into the most abundant ion in the helium droplet experiments. To demonstrate that these findings are not unique to alcohols, we have also investigated several ethers. The results obtained for both alcohols and ethers are difficult to explain solely by rapid cooling of the excited parent ions by the surrounding superfluid helium, although this undoubtedly takes place. A second factor also seems to be involved, a cage effect which favors hydrogen atom loss over other fragmentation channels. The set of molecules explored in this work suggest that electron impact ionization of doped helium nanodroplets does not provide a sufficiently large softening effect to be useful in analytical mass spectrometry

Effect of Heterogeneous Microstructure on Refining Austenite Grain Size in Low Alloy Heavy-Gage Plate

The present work introduces the role of heterogeneous microstructure in enhancing the nucleation density of reversed austenite. It was found that the novel pre-annealing produced a heterogeneous microstructure consisting of alloying elements-enriched martensite and alloying-depleted intercritical ferrite. The shape of the martensite at the prior austenite grain boundary was equiaxed and acicular at inter-laths. The equiaxed reversed austenite had a K-S orientation with adjacent prior austenite grain, and effectively refined the prior austenite grain that it grew into. The alloying elements-enriched martensite provided additional nucleation sites to form equiaxed reversed austenite at both prior austenite grain boundaries and intragranular inter-lath boundaries during re-austenitization. It was revealed that prior austenite grain size was refined to ~12 μm by pre-annealing and quenching, while it was ~30 μm by conventional quenching. This is a practical way of refining transformation products by refining prior austenite grain size to improve the strength, ductility and low temperature toughness of heavy-gage plate steel

Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency

Autophagy is a lysosome-dependent degradative process that protects cancer cells from multiple stresses. In preclinical models, autophagy inhibition with chloroquine (CQ) derivatives augments the efficacy of many anticancer therapies, but CQ has limited activity as a single agent. Clinical trials are underway combining anticancer agents with hydroxychloroquine (HCQ), but concentrations of HCQ required to inhibit autophagy are not consistently achievable in the clinic. We report the synthesis and characterization of bisaminoquinoline autophagy inhibitors that potently inhibit autophagy and impair tumor growth in vivo. The structural motifs that are necessary for improved autophagy inhibition compared with CQ include the presence of two aminoquinoline rings and a triamine linker and C-7 chlorine. The lead compound, Lys01, is a 10-fold more potent autophagy inhibitor than HCQ. Compared with HCQ, Lys05, a water-soluble salt of Lys01, more potently accumulates within and deacidifies the lysosome, resulting in impaired autophagy and tumor growth. At the highest dose administered, some mice develop Paneth cell dysfunction that resembles the intestinal phenotype ofmice and humanswith genetic defects in the autophagy gene ATG16L1, providing in vivo evidence that Lys05 targets autophagy. Unlike HCQ, significant single-agent antitumor activity is observed without toxicity in mice treated with lower doses of Lys05, establishing the therapeutic potential of this compound in cancer