A comprehensive test stand for high-intensity cyclotron development, a 10 MeV 430 μA cyclotron, has been successfully constructed at China Institute of Atomic Energy (CIAE) for the experimental ...verification of the viability of a 100 MeV high-intensity cyclotron (CYCIAE-100) being constructed at CIAE. The verification includes the overall design technology, detail design and engineering technology for the crucial parts of the machine, e.g. main magnet and beam diagnostics. It will also pave the way for future enhancement of the beam intensity. The test stand consists of a H− ion source, axial injection system, central region, main magnet and coil, RF resonator, stripping extraction, and auxiliary systems, which include the RF power amplifier, high voltage and DC power supplies, electric apparatus, beam diagnostics, control, vacuum, water cooling, pneumatic system, and safety interlock. This paper presents the work regarding the design and sub-system development of the test sand, and the results of the beam commissioning of the machine.
The BRCA1 tumor suppressor plays an important role in homologous recombination (HR)-mediated DNA double-strand-break (DSB) repair. BRCA1 is phosphorylated by Chk2 kinase upon γ-irradiation, but the ...role of Chk2 phosphorylation is not understood. Here, we report that abrogation of Chk2 phosphorylation on BRCA1 delays end resection and the dispersion of BRCA1 from DSBs but does not affect the assembly of Mre11/Rad50/NBS1 (MRN) and CtIP at DSBs. Moreover, we show that BRCA1 is ubiquitinated by SCF
Skp2
and that abrogation of Chk2 phosphorylation impairs its ubiquitination. Our study suggests that BRCA1 is more than a scaffold protein to assemble HR repair proteins at DSBs, but that Chk2 phosphorylation of BRCA1 also serves as a built-in clock for HR repair of DSBs. BRCA1 is known to inhibit Mre11 nuclease activity. SCF
Skp2
activity appears at late G1 and peaks at S/G2, and is known to ubiquitinate phosphodegron motifs. The removal of BRCA1 from DSBs by SCF
Skp2
-mediated degradation terminates BRCA1-mediated inhibition of Mre11 nuclease activity, allowing for end resection and restricting the initiation of HR to the S/G2 phases of the cell cycle.
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