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A series of novel 4-Hydroxyquinazoline derivatives were designed and synthesized to enhance sensitivity in primary PARPi-resistant cells. Among them, the compound B1 has been found to have superior cytotoxicity in primary PARPi-resistant HCT-15 and HCC1937 cell lines, and dose-dependently suppressed the intracellular PAR formation and enhanced the γH2AX aggregation. Mechanistic study showed that B1 stimulated the formation of intracellular ROS and the depolarization of the mitochondrial membrane, which could increase apoptosis and cytotoxicity. An in vivo study showed that B1 significantly suppressed tumor growth at a dose of 25 mg/kg, and an acute toxicity study confirmed its safety. Molecular docking and dynamics simulations revealed that hydrogen bonding between B1 and ASP766 may be helpful to enhance anti-drug resistance ability. This study suggests that B1 is a potent PARP inhibitor that can overcome PARPi resistance and deserves further investigation. [ABSTRACT FROM AUTHOR]

Summary: Cold stress is a major limiting factor in grape (Vitis) productivity. In this study, we characterized a cold‐responsive ethylene response factor (ERF) transcription factor, VaERF092, from Amur grape (Vitis amurensis). VaERF092 expression was induced by both low temperatures and the ethylene precursor 1‐aminocyclopropane‐1‐carboxylate (ACC), but was suppressed by treatment with the ethylene inhibitor aminoethoxyvinylglycine (AVG) under cold conditions. Ectopic expression of VaERF092 in Arabidopsis thaliana enhanced cold tolerance. Co‐expression network analysis of V. vinifera genes indicated that WRKY33 might be a downstream target of VaERF092. This hypothesis was supported by the fact that VaWRKY33 was expressed temporally after VaERF092 expression and could also be induced by cold and ACC, and inhibited by AVG. Yeast one‐hybrid, transient β‐glucuronidase (GUS) and dual‐luciferase reporter assays provided evidence for an interaction between VaERF092 and a GCC‐box element in the VaWRKY33 promoter. In addition, heterologous overexpression of VaWRKY33 in A. thaliana resulted in enhanced cold tolerance. VaERF092‐ and VaWRKY33 overexpressing grape calli showed lower low‐temperature exothermic values than the empty vector (EV) calli, indicating enhanced tolerance to cold. Together, these results indicated that VaERF092 regulates VaWRKY33 through binding to its promoter GCC‐box, leading to enhanced cold stress tolerance. Significance Statement: Our study revealed that ethylene response factor VaERF092 regulated VaWRKY33 through binding to its promoter GCC‐box, leading to enhanced cold tolerance. This finding may provide a model responding to cold stress in plants. [ABSTRACT FROM AUTHOR]

Presents a theoretical investigation on the quantum field effect directional coupler. General formulation of the device; Calculation of the transfer length; Conductance of the device.

Discusses a study that proposed a mode selector to realize single modedness in the waveguidelike quantum devices. Application of a mode selector to quantum devices; Demonstration of the mode selecting function by the principle of resonant tunneling effect; Description of the mode selector on a typical electron waveguide.

Wu, Z.; Xiang, Y.; Li, M.; Iqbal, M., and Xu, G, 2019. Investigation of accumulator main parameters of hydraulic excitation system. In: Guido-Aldana, P.A. and Mulahasan, S. (eds.), Advances in Water Resources and Exploration. Journal of Coastal Research, Special Issue No. 93, pp. 613–622. Coconut Creek (Florida), ISSN 0749-0208. The accumulator is a special container which used for accumulate energy and its responsiveness plays an important role in improving hydraulic system performance. Therefore, it can be seen from the current research results that most scholars focus on the bladder-type accumulator owing to the reflection of the bladder-type accumulator is fast. The hydraulic system with a bladder-type accumulator is adapted to absorb shock pressure and eliminate pressure pulsations. However, due to the sudden change of the reversing valve or the sudden stop of the actuator, the pressure shock will occur in the hydraulic system, and the relief valve will not be able to move, which will cause the pipeline to vibrate. In severe cases, the hydraulic pipe will be broken and caused a safety accident. In actual use, the effect of absorbing pressure shock is not ideal due to improper selection of accumulator parameters. Therefore, the main objective of this study is to use theoretical analysis, computer simulation and experimental research to analyse the influence of accumulator parameters on the hydraulic system. [ABSTRACT FROM AUTHOR]