H-D Substitution in Interstellar Solid Methanol: A Key Route for D Enrichment

Deuterium enrichment of interstellar methanol is reproduced experimentally for the first time via grain-surface H-D substitution in solid methanol at an atomic D/H ratio of 0.1. Although previous gas-grain models successfully reproduce the deuterium enrichments observed in interstellar methanol molecules (D/H of up to 0.4, compared to the cosmic ratio of $\sim 10^{-5})$, the models exclusively focus on deuterium fractionation resulting from the successive addition of atomic hydrogen/deuterium on CO. The mechanism proposed here represents a key route for deuterium enrichment that reproduces the high observed abundances of deuterated methanol, including multiple deuterations.Comment: 4 pages, 4 figures, Accepted to the ApJ

Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function

Single-fluorescent-molecule imaging tracking (SMT) is becoming an important tool to study living cells. However, photobleaching and photoblinking (hereafter referred to as photobleaching/photoblinking) of the probe molecules strongly hamper SMT studies of living cells, making it difficult to observe in vivo molecular events and to evaluate their lifetimes (e.g., off rates). The methods used to suppress photobleaching/photoblinking in vitro are difficult to apply to living cells because of their toxicities. Here using 13 organic fluorophores we found that, by combining low concentrations of dissolved oxygen with a reducing-plus-oxidizing system, photobleaching/photoblinking could be strongly suppressed with only minor effects on cells, which enabled SMT for as long as 12,000 frames (~7 min at video rate, as compared to the general 10-s-order durations) with ~22-nm single-molecule localization precisions. SMT of integrins revealed that they underwent temporary (<80-s) immobilizations within the focal adhesion region, which were responsible for the mechanical linkage of the actin cytoskeleton to the extracellular matrix

Forgeability of AZ Series Magnesium Alloy produced by Twin Roll Casting

Plastic forming of magnesium alloy is hardly reported because of its low forgeability. The productions of magnesium alloy are mainly produced by casting. Typical wrought magnesium alloy is AZ31. Magnesium-aluminum alloy indicates maximum elongation when the composition includes 3% aluminum. When the magnesium alloy includes over 3% aluminum, its elongation slightly decreases. Therefore, AZ31 that include 3% aluminum and 1% zinc is generally used for plastic forming. The more increasing aluminum composition, the larger 0.2% proof stress becomes. However its forgeability is decreasing because of precipitation of β phase such as Mg17Al12. It is supposed that the β phase is refined by rapid cooling casting process such as twin roll casting. In this paper, the magnesium alloy thick sheet of AZ91, AZ121 and AZ131 for hot forging, that include 9%, 12% and 13% aluminum composition respectively, was produced by twin roll strip casting process. And the forgeability of high aluminum containing magnesium alloy was investigated by die forging. As a result, it was possible to forge their magnesium alloys

Revisiting PFA-mediated tissue fixation chemistry: FixEL enables trapping of small molecules in the brain to visualize their distribution changes

ホルマリン漬けから着想した小分子可視化法 --医薬品開発効率化につながる新たな戦略--. 京都大学プレスリリース. 2022-12-05.Various small molecules have been used as functional probes for tissue imaging in medical diagnosis and pharmaceutical drugs for disease treatment. The spatial distribution, target selectivity, and diffusion/excretion kinetics of small molecules in structurally complicated specimens are critical for function. However, robust methods for precisely evaluating these parameters in the brain have been limited. Herein, we report a new method termed “fixation-driven chemical cross-linking of exogenous ligands (FixEL), ” which traps and images exogenously administered molecules of interest (MOIs) in complex tissues. This method relies on protein-MOI interactions and chemical cross-linking of amine-tethered MOI with paraformaldehyde used for perfusion fixation. FixEL is used to obtain images of the distribution of the small molecules, which addresses selective/nonselective binding to proteins, time-dependent localization changes, and diffusion/retention kinetics of MOIs such as the scaffold of PET tracer derivatives or drug-like small molecules

Observation of energetic-ion losses induced by various MHD instabilities in the Large Helical Device (LHD)

Energetic-ion losses induced by toroidicity-induced Alfvén eigenmodes (TAEs) and resistive interchange modes (RICs) were observed in neutral-beam heated plasmas of the Large Helical Device (LHD) at a relatively low toroidal magnetic field level (⩽0.75 T). The energy and pitch angle of the lost ions are detected using a scintillator-based lost-fast ion probe. Each instability increases the lost ions having a certain energy/pitch angle. TAE bursts preferentially induce energetic beam ions in co-passing orbits having energy from the injection energy E = 190 keV down to 130 keV, while RICs expel energetic ions of E = 190 keV down to ∼130 keV in passing–toroidally trapped boundary orbits. Loss fluxes induced by these instabilities increase with different dependences on the magnetic fluctuation amplitude: nonlinear and linear dependences for TAEs and RICs, respectively

Identification of 45 New Neutron-Rich Isotopes Produced by In-Flight Fission of a 238U Beam at 345 MeV/nucleon

A search for new isotopes using in-flight fission of a 345 MeV/nucleon 238U beam has been carried out at the RI Beam Factory at the RIKEN Nishina Center. Fission fragments were analyzed and identified by using the superconducting in-flight separator BigRIPS. We observed 45 new neutron-rich isotopes: 71Mn, 73,74Fe, 76Co, 79Ni, 81,82Cu, 84,85Zn, 87Ga, 90Ge, 95Se, 98Br, 101Kr, 103Rb, 106,107Sr, 108,109Y, 111,112Zr, 114,115Nb, 115,116,117Mo, 119,120Tc, 121,122,123,124Ru, 123,124,125,126Rh, 127,128Pd, 133Cd, 138Sn, 140Sb, 143Te, 145I, 148Xe, and 152Ba

Magnetic Configuration Effects on Fast Ion Losses Induced by Fast Ion Driven Toroidal Alfvén Eigenmodes in the Large Helical Device

Beam-ion losses induced by fast-ion-driven toroidal Alfvén eigenmodes (TAE) were measured with a scintillator-based lost fast-ion probe (SLIP) in the large helical device (LHD). The SLIP gave simultaneously the energy E and the pitch angle χ = arccos(υ///υ) distribution of the lost fast ions. The loss fluxes were investigated for three typical magnetic configurations of Rax_vac = 3.60 m, 3.75 m, and 3.90 m, where Rax_vac is the magnetic axis position of the vacuum field. Dominant losses induced by TAEs in these three configurations were observed in the E/χ regions of 50∼190 keV/40°, 40∼170 keV/25°, and 30∼190 keV/30°, respectively. Lost-ion fluxes induced by TAEs depend clearly on the amplitude of TAE magnetic fluctuations, Rax_vac and the toroidal field strength Bt. The increment of the loss fluxes has the dependence of (bTAE/Bt)s. The power s increases from s = 1 to 3 with the increase of the magnetic axis position in finite beta plasmas

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE

Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane.

The mechanisms by which the diffusion rate in the plasma membrane (PM) is regulated remain unresolved, despite their importance in spatially regulating the reaction rates in the PM. Proposed models include entrapment in nanoscale noncontiguous domains found in PtK2 cells, slow diffusion due to crowding, and actin-induced compartmentalization. Here, by applying single-particle tracking at high time resolutions, mainly to the PtK2-cell PM, we found confined diffusion plus hop movements (termed "hop diffusion") for both a nonraft phospholipid and a transmembrane protein, transferrin receptor, and equal compartment sizes for these two molecules in all five of the cell lines used here (actual sizes were cell dependent), even after treatment with actin-modulating drugs. The cross-section size and the cytoplasmic domain size both affected the hop frequency. Electron tomography identified the actin-based membrane skeleton (MSK) located within 8.8 nm from the PM cytoplasmic surface of PtK2 cells and demonstrated that the MSK mesh size was the same as the compartment size for PM molecular diffusion. The extracellular matrix and extracellular domains of membrane proteins were not involved in hop diffusion. These results support a model of anchored TM-protein pickets lining actin-based MSK as a major mechanism for regulating diffusion