First Direct Detection Constraints on Planck-Scale Mass Dark Matter with Multiple-Scatter Signatures Using the DEAP-3600 Detector.

Dark matter with Planck-scale mass (≃10^{19} GeV/c^{2}) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×10^{6} and 1.2×10^{19} GeV/c^{2}, and ^{40}Ar-scattering cross sections between 1.0×10^{-23} and 2.4×10^{-18} cm^{2}. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings.

Biodistribution and Tumors MRI Contrast Enhancement of Magnetic Nanocubes, Nanoclusters, and Nanorods in Multiple Mice Models.

Magnetic resonance imaging (MRI) is a powerful technique for tumor diagnostics. Iron oxide nanoparticles (IONPs) are safe and biocompatible tools that can be used for further enhancing MR tumor contrasting. Although numerous IONPs have been proposed as MRI contrast agents, low delivery rates to tumor site limit its application. IONPs accumulation in malignancies depends on both IONPs characteristics and tumor properties. In the current paper, three differently shaped Pluronic F-127-modified IONPs (nanocubes, nanoclusters, and nanorods) were compared side by side in three murine tumor models (4T1 breast cancer, B16 melanoma, and CT26 colon cancer). Orthotopic B16 tumors demonstrated more efficient IONPs uptake than heterotopic implants. Magnetic nanocubes (MNCb) had the highest r2-relaxivity in vitro (300 mM-1·s-1) compared with magnetic nanoclusters (MNCl, 104 mM-1·s-1) and magnetic nanorods (MNRd, 51 mM-1·s-1). As measured by atomic emission spectroscopy, MNCb also demonstrated better delivery efficiency to tumors (3.79% ID) than MNCl (2.94% ID) and MNRd (1.21% ID). Nevertheless, MNCl overperformed its counterparts in tumor imaging, providing contrast enhancement in 96% of studied malignancies, whereas MNCb and MNRd were detected by MRI in 73% and 63% of tumors, respectively. Maximum MR contrasting efficiency for MNCb and MNCl was around 6-24 hours after systemic administration, whereas for MNRd maximum contrast enhancement was found within first 30 minutes upon treatment. Presumably, MNRd poor MRI performance was due to low r2-relaxivity and rapid clearance by lungs (17.3% ID) immediately after injection. MNCb and MNCl were mainly captured by the liver and spleen without significant accumulation in the lungs, kidneys, and heart. High biocompatibility and profound accumulation in tumor tissues make MNCb and MNCl the promising platforms for MRI-based tumor diagnostics and drug delivery.

On the mechanism of biosynthesis of divinyl ether oxylipins by enzyme from garlic bulbs.

The microsomal fraction of homogenate of garlic (Allium sativum L.) bulbs contains a divinyl ether synthase which catalyzes conversion of (9Z,11E,13S)-13-hydroperoxy-9, 11-octadecadienoic acid and (9Z,11E,13S,15Z)-13-hydroperoxy-9,11,15-octadecatri eno ic acid into (9Z,11E,1'E,)-12-(1'-hexenyloxy)-9,11-dodecadienoic acid (etherolenic acid) and (9Z,11E,1'E,3'Z)-12-(1',3'-hexadienyloxy)-9,11-dode cadienoic acid (etherolenic acid), respectively. Two isomers of etherolenic acid were isolated. As shown by NMR spectrometry, the double bond configurations of these compounds were (9E,11E,1'E) and (9Z,11Z,1'E). Experiments with linoleic acid (13R,S)-hydroperoxide demonstrated that the S enantiomer was a much better substrate for the divinyl ether synthase compared to the R enantiomer. Incubation of (9Z,11E,13S)-[18O2]hydroperoxy-9,11-octadecadienoic acid led to the formation of etherolenic acid which retained 18O in the ether oxygen. An intermediary role of an epoxyallylic cation in etherolenic acid biosynthesis is postulated.

Formation of ketols from linolenic acid 13-hydroperoxide via allene oxide. Evidence for two distinct mechanisms of allene oxide hydrolysis.

Incubations of [1-14C]13-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid (13-HPOT) with hydroperoxide dehydrase preparations from flax seeds lead to the formation of a novel ketol 2 along with the previously known 12-oxo-13-hydroxy-9(Z),15(Z)-octadecadienoic (12,13-alpha-ketol) and 9-hydroxy-12-oxo-10(E),15(Z)-octadecadienoic (gamma-ketol) acids. Compound 2 was identified as 11-hydroxy-12-oxo-9(Z),15(Z)-octadecadienoic acid (11,12-alpha-ketol) in accordance with the data of ultraviolet, mass (chemical ionization and electron impact) and 1H-NMR spectra. During long-term (30 min) incubations the yields of gamma-ketol and 11,12-alpha-ketol increased markedly and the yield of 12,13-alpha-ketol decreased in response to the pH change from basic (pH 7.4) to acidic (pH 5.8) conditions. Short-term (15 s) incubations of 13-HPOT with hydroperoxide dehydrase, terminated by HCl fixation, led to the formation of gamma-ketol and ketol 2. A similar incubation, followed by NaOH fixation, afforded only 12,13-alpha-ketol. The trapping of allene oxide (a primary product of hydroperoxide dehydrase) with pure methanol gives only compound 4 (12,13-alpha-ketol methyl ether). Products 5 (gamma-ketol methyl ether) and 6 (11,12-alpha-ketol methyl ether) were formed along with 4 as a result of trapping with acidified methanol. The results obtained indicate that: (a) the formation of 12,13-alpha-ketol is base-dependent; (b) the formation of gamma-ketol and ketol 2 is acid-dependent. Two distinct mechanisms of allene oxide hydrolysis are proposed: (1) nucleophilic (SN2 or SN1, OH- is an attacking group) substitution, resulting in formation of 12,13-alpha-ketol; (2) electrophilic (SE-like) reaction initiated by protonation of oxirane, affording gamma-ketol and 11,12-alpha-ketol.

Hydroperoxides of alpha-ketols. Novel products of the plant lipoxygenase pathway.

Metabolism of [1-14C]linolenic acid, 13-hydroperoxy-8(Z),11(E),15(Z)-[1-14C]octadecatrienoic acid (13-HPOT) and 9-hydroperoxy-10(E),12(Z),15(Z)-[1-14C]octadecatrienoic acid (9-HPOT) was studied by enzyme preparations from flax, wheat and corn seeds, containing two enzymes of fatty acid metabolism, namely, lipoxygenase and hydroperoxide dehydrase. Along with the previously known products of the hydroperoxide dehydrase pathway, the radiolabel was incorporated into some more polar metabolites. These polar products 1 and 4, formed from 13-HPOT and 9-HPOT, respectively, were purified by reversed-phase and normal-phase HPLC, and investigated by ultraviolet spectroscopy, chemical-ionization and electron-impact mass spectrometry, and 1H-NMR. The data obtained suggest that metabolites 1 and 4 are 9-hydroperoxy-12-oxo-13-hydroxy-10(E),15(Z)-octadecadienoic acid and 9-hydroxy-10-oxo-13-hydroperoxy-11(E),15(Z)-octadecadienoic acid, respectively. 12-oxo-13-hydroxy-9(Z),15(Z)-[1-14C]octadecadienoic acid (12,13-alpha-ketol) and 9-hydroxy-10-oxo-12(Z),15(Z)-[1-14C]octadecadienoic acid (9,10-alpha-keto) are the direct precursors of metabolites 1 and 4, respectively. Metabolites 1 and 4 are formed from the corresponding HPOT precursors in two stages; (a) conversion of hydroperoxide into the alpha-ketol by hydroperoxide dehydrase and (b) the lipoxygenase oxidation of the alpha-ketol. Different lipoxygenases were found to oxidize alpha-ketols. Oxidation of the 3(Z)-buten-1-onyl moiety of alpha-ketols presents an unusual and previously unknown type of lipoxygenase reaction.

Double hydroperoxidation of alpha-linolenic acid by potato tuber lipoxygenase.

The potato tuber lipoxygenase preparations convert alpha-linolenic acid not only to 9(S)-HPOTE, but also to some more polar metabolites. Two of these polar products, I and II, with ultraviolet absorbance maxima at 267 nm were purified by HPLC. It was found that metabolites I and II have, respectively, one and two hydroperoxy groups. Products of NaBH4 reduction of both I and II were identified by their chemical ionization and electron impact mass spectra and by 1H-NMR spectra as 9,16-dihydroxy-10(E), 12(Z), 14(E)-octadecatrienoic acid. The obtained results suggest that compound II is 9.16-dihydroperoxy-10(E), 12(Z), 14(E)-octadecatrienoic acid and product I is a mixture of two positional isomers, 9-hydroxy-16-hydroperoxy-10(E),12(Z),14(E)-octadecatrienoic and 9-hydroperoxy-16-hydroxy-10(E),12(Z),14(E)-octadecatrienoic acids. Lipoxygenase converts efficiently [14C]9-HOTE into product I. Also, both metabolites I and II are the products of double dioxygenation. The second oxygenation at C-16 position as well as the first one at C-9 is controlled by lipoxygenase.