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The multi-layer computing model is developed to calculate wide-angle neutron spectra, in the range from 0° to 180° with a 5° step, produced by bombarding a thick beryllium target with deuterons. The double-differential cross-sections (DDCSs) for the 9Be(d, xn) reaction are calculated using the TALYS-1.8 code. They are in agreement with the experimental data, and are much better than the PHITS-JQMD/GEM results at 15° , 30° , 45° and 60° neutron emission angles for deuteron energy of 10.0 MeV. In the TALYS-1.8 code, neutron contributions from direct reactions (break-up, stripping and knock-out reactions) are controlled by adjustable parameters, which describe the basic characteristics of typical direct reactions and control the relative intensity and the position of the ridgy hillock at the tail of DDCSs. It is found that the typical calculated wide-angle neutron spectra for different neutron emission angles and neutron angular distributions agree quite well with the experimental data for 13.5 MeV deuterons. The multi-layer computing model can reproduce the experimental data reasonably well by optimizing the adjustable parameters in the TALYS-1.8 code. Given the good agreement with the experimental data, the multi-layer computing model could provide better predictions of wide-angle neutron energy spectra, neutron angular distributions and neutron yields for the 9Be(d, xn) reaction neutron source.

The covalent attachment of ubiquitin (Ub) to various intracellular proteins plays important roles in altering the function, localization, processing, and degradation of the modified target. A minimal ubiquitylation pathway uses a three-enzyme cascade (E1, E2, and E3) to activate Ub and select target proteins for modification. Although diverse E3 families provide much of the target specificity, several factors have emerged recently that coordinate the subcellular localization of the ubiquitylation machinery. Here, we show that the family of membrane-anchored ubiquitin-fold (MUB) proteins recruits and docks specific E2s to the plasma membrane. Protein interaction screens with Arabidopsis MUBs revealed that interacting E2s are limited to a well defined subgroup that is phylogenetically related to human UbcH5 and yeast Ubc4/5 families. MUBs appear to interact noncovalently with an E2 surface opposite the active site that forms a covalent linkage with Ub. Bimolecular fluorescence complementation demonstrated that MUBs bind simultaneously to the plasma membrane via a prenyl tail and to the E2 in planta. These findings suggest that MUBs contribute subcellular specificity to ubiquitylation by docking the conjugation machinery to the plasma membrane.

As a therapeutic target for antitumor necrosis factor (TNF)-α interventions, UbcH5c is one of the key ubiquitin-conjugating enzymes catalyzing ubiquitination during TNF-α-triggered nuclear factor kappa B (NF-κB) activation. In the present study, three series of analogues were designed and synthesized from α-santonin, and their UbcH5c inhibitory activities were screened by Western blotting and NF-κB luciferase assay. Further BIAcore, in-gel fluorescence imaging, and immunoprecipitation assays demonstrated that compound 6d exhibited robust and specific inhibition of UbcH5c, exceeding that of the positive compound 1 (IJ-5). Mechanistic investigations revealed that compound 6d preferentially bound to and inactivated UbcH5c by forming a covalent adduct with its active site Cys85. Furthermore, compound 6d exhibited potent anti-inflammatory activity against complete Freund's adjuvant-induced adjuvant arthritis in vivo. These findings suggest that the novel α-santonin-derived UbcH5c inhibitor 6d is a promising lead compound for the development of new antirheumatoid arthritis (RA) agent.

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We demonstrate thermal noise limited and shot noise limited performance of ultra-stable diode laser systems. The measured heterodyne beat linewidth between such two independent diode lasers reaches 0.74 Hz. The frequency instability of one single laser approaches 1.0 × 10 for averaging time between 0.3 s and 10 s, which is close to the thermal noise limit of the reference cavity. Taking advantage of these two ultra-stable laser systems, we systematically investigate the ultimate electrical noise contributions, and derive expressions for the closed-loop spectral density of laser frequency noise. The measured power spectral density of the beat frequency is compared with the theoretically calculated closed-loop spectral density of the laser frequency noise, and they agree very well. It illustrates the power and generality of the derived closed-loop spectral density formula of the laser frequency noise. Our result demonstrates that a 10 level locking in a wide frequency range is feasible with careful design.