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The 53BP1-RIF1 pathway antagonizes resection of DNA broken ends and confers PARP inhibitor sensitivity on BRCA1-mutated tumors. However, it is unclear how this pathway suppresses initiation of resection. Here, we identify ASF1 as a partner of RIF1 via an interacting manner similar to its interactions with histone chaperones CAF-1 and HIRA. ASF1 is recruited to distal chromatin flanking DNA breaks by 53BP1-RIF1 and promotes non-homologous end joining (NHEJ) using its histone chaperone activity. Epistasis analysis shows that ASF1 acts in the same NHEJ pathway as RIF1, but via a parallel pathway with the shieldin complex, which suppresses resection after initiation. Moreover, defects in end resection and homologous recombination (HR) in BRCA1-deficient cells are largely suppressed by ASF1 deficiency. Mechanistically, ASF1 compacts adjacent chromatin by heterochromatinization to protect broken DNA ends from BRCA1-mediated resection. Taken together, our findings identify a RIF1-ASF1 histone chaperone complex that promotes changes in high-order chromatin structure to stimulate the NHEJ pathway for DSB repair.

The 53BP1-RIF1 pathway antagonizes resection of DNA broken ends and confers PARP inhibitor sensitivity on BRCA1-mutated tumors. However, it is unclear how this pathway suppresses initiation of resection. Here, we identify ASF1 as a partner of RIF1 via an interacting manner similar to its interactions with histone chaperones CAF-1 and HIRA. ASF1 is recruited to distal chromatin flanking DNA breaks by 53BP1-RIF1 and promotes non-homologous end joining (NHEJ) using its histone chaperone activity. Epistasis analysis shows that ASF1 acts in the same NHEJ pathway as RIF1, but via a parallel pathway with the shieldin complex, which suppresses resection after initiation. Moreover, defects in end resection and homologous recombination (HR) in BRCA1- deficient cells are largely suppressed by ASF1 deficiency. Mechanistically, ASF1 compacts adjacent chromatin by heterochromatinization to protect broken DNA ends from BRCA1-mediated resection. Taken together, our findings identified a RIF1-ASF1 histone chaperone complex that promotes changes in high-order chromatin structure to stimulate the NHEJ pathway for DSB repair.

Maintaining the stability of the modern power grid is becoming increasingly difficult due to fluctuating power consumption, unstable power supply coming from renewable energies, and unpredictable accidents such as man-made and natural disasters. As the operation on the power grid must consider its impact on future stability, reinforcement learning (RL) has been employed to provide sequential decision-making in power grid management. However, existing methods have not considered the environmental constraints. As a result, the learned policy has risk of selecting actions that violate the constraints in emergencies, which will escalate the issue of overloaded power lines and lead to large-scale blackouts. In this work, we propose a novel method for this problem, which builds on top of the search-based planning algorithm. At the planning stage, the search space is limited to the action set produced by the policy. The selected action strictly follows the constraints by testing its outcome with the simulation function provided by the system. At the learning stage, to address the problem that gradients cannot be propagated to the policy, we introduce Evolutionary Strategies (ES) with black-box policy optimization to improve the policy directly, maximizing the returns of the long run. In NeurIPS 2020 Learning to Run Power Network (L2RPN) competition, our solution safely managed the power grid and ranked first in both tracks.

To study the effect of weld and defects on the corrosion behavior of nickel aluminum bronze (UNS C95810) in 3.5% NaCl solution, the weight loss, X-ray diffraction, optical microscope, scanning electron microscope and electrochemical test of the specimen with weld and defects were investigated. The results show that the presence of weld and defects increases the corrosion rate of bronze. Weld does not change the structure of the corrosion product film, but defects induce a lack of the protective outermost corrosion product in bronze. Weld makes the corrosion product film in the early stage more porous. Defects always produce an increase in the dissolution rate of the bronze.

53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) and promotes non-homologous end joining (NHEJ) in an unclear manner. Here we show that REV7 forms a complex with two proteins, FAM35A and C20ORF196. We demonstrate that FAM35A preferentially binds single-strand DNA (ssDNA) in vitro, and is recruited to DSBs as a complex with C20ORF196 and REV7 downstream of RIF1 in vivo. Epistasis analysis shows that both proteins act in the same pathway as RIF1 in NHEJ. The defects in HR pathway to repair DSBs and the reduction in resection of broken DNA ends in BRCA1-mutant cells can be largely suppressed by inactivating FAM35A or C20ORF196, indicating that FAM35A and C20ORF196 prevent end resection in these cells. Together, our data identified a REV7–FAM35A–C20ORF196 complex that binds and protects broken DNA ends to promote the NHEJ pathway for DSB repair.

Waterborne silicate composite coatings were prepared to replace existing solvent-based coatings for ships. A series of complex coatings were prepared by adding anticorrosive pigments to the silicate resin. Adhesion, pencil hardness, and impact resistance were investigated, and corrosion performance in 3.5% NaCl solution was measured by electrochemical impedance spectroscopy (EIS). The results show that adhesion and impact resistance are high, and that pencil hardness can reach 4H. The curing mechanism for the coatings were investigated by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The mechanism of curing reaction in the studied waterborne silicate paint was found to be different from that reported in the literature. When the coatings were immersed in 3.5% NaCl solution for 8 h, there is only one time constant in the Bode plot, and coating capacitance (Qc) gradually increases while coating resistance (Rc) gradually decreases. Glass flake composite coatings have better corrosion resistance by comprehensive comparison of Qc and Rc.

The anticorrosive composite coatings based on waterborne silicate were prepared to replace existing solvent-based coatings suitable for ships. A series of composite coatings were prepared by adding zinc powder and micaceous iron oxide to the waterborne silicate resin. The adhesion, pencil hardness and impact resistance of the coatings were investigated and corrosion performance in seawater is characterized by electrochemical impedance spectroscopy (EIS). The results show that coatings have excellent adhesion and impact resistance and their pencil hardness can reach up to 4H. During the immersion of composite coatings in seawater for 8 h, only one time constant appears in the Bode plot, coating capacitance (Qc) gradually increases but dispersion coefficient (n) and coating resistance (Rc) gradually decrease. The breakpoint frequency formula was deduced, considering the dispersion effect. With the increase of micaceous iron oxide, the fluctuation of breakpoint frequency with immersion time is weakened. It can be used to evaluate the corrosion resistance of inorganic anticorrosive coatings in seawater. In addition, different penetration models of corrosive media were proposed for the coatings with low or high content of micaceous iron oxide.