The BRCA2 tumor suppressor protects genome integrity by promoting homologous recombination-based repair of DNA breaks, stability of stalled DNA replication forks and DNA damage-induced cell cycle ...checkpoints. BRCA2 deficient cells display the radio-resistant DNA synthesis (RDS) phenotype, however the mechanism has remained elusive. Here we show that cells without BRCA2 are unable to sufficiently restrain DNA replication fork progression after DNA damage, and the underrestrained fork progression is due primarily to Primase-Polymerase (PRIMPOL)-mediated repriming of DNA synthesis downstream of lesions, leaving behind single-stranded DNA gaps. Moreover, we find that BRCA2 associates with the essential DNA replication factor MCM10 and this association suppresses PRIMPOL-mediated repriming and ssDNA gap formation, while having no impact on the stability of stalled replication forks. Our findings establish an important function for BRCA2, provide insights into replication fork control during the DNA damage response, and may have implications in tumor suppression and therapy response.
In order to improve the working performance of linear metro, the multistep model predictive control (MMPC) is applied to linear induction machine (LIM) in this paper. However, due to the maximum ...current and voltage limitations, the optimal problem of multistep model predictive control (MMPC) becomes difficult to handle in practice. For simplifying the optimal problem of an MMPC with constraints, first, the optimal problem of MMPC is solved off-line, with the assumption that the input voltage of the LIM is continuous without limitations. And, the expression of current constraint is expressed by voltage variables through the mathematical model of the LIM to simultaneously consider both the voltage and current limitations. Then, according to the solved optimal value without constraints, one iterative algorithm is proposed to search a suboptimal value, which satisfies both the current and voltage limitations. Finally, the proposed strategy is applied to two 3-kW arc induction motors to verify its effectiveness.
Homopolar inductor machines (HIMs) are promising candidates of the pulsed alternator for the application of high power pulsed supplies. However, a single HIM can hardly serve as both a pulsed ...alternator and a motor, because the voltage and frequency of the pulsed alternator are usually much higher than those of the motor. Thus, a prime motor is needed to drag the pulsed alternator, which makes the pulsed alternator system rather complex. To simplify the structure of the system, this paper proposes a novel four-stator-core HIM (FSCHIM) consisting of an alternator and a motor. First, both the configuration and operation principle of the FSCHIM are introduced. Second, the sizing equations of the FSCHIM are deduced to obtain its primary size parameters. Third, the armature reaction is investigated and the influences of main structure parameters on key output indices are studied by using finite-element analysis (FEA). Finally, the optimized scheme is validated by three-dimensional FEA and experimental results on the subelectrical machines. The results demonstrate that the FSCHIM can serve as a combination of the motor and the pulsed alternator, which enjoys the merits of high-voltage and high-frequency discharge performance with a lower voltage and lower frequency driving system.
Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence ...are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The deadbeat control (DBC) can track current reference closely, depending on the model of a linear induction machine (LIM). However, the DBC has to consider both the voltage and current constraints ...for staying in the safe working region of LIM, when calculating the input voltage vector of LIM. To solve such a challenge, one improved DBC with an iterative algorithm is proposed in this paper to solve the voltage and current constraints problem in the traditional DBC. Finally, the improved DBC is applied to 3 kW arc induction motors to verify its effectiveness.
The high power pulsed charging power supply is usually necessary for the pulsed power devices with high power repetitive discharge. This paper first introduces a new topology structure of a charge ...and discharge system for high voltage capacitor and its operating principle, then comes up with technical requirements for the pulsed alternator. Afterward, design features of the inductor pulsed alternator, including the structure, main dimensions, and sizes of rotor teeth and slots are studied, and the main parameters of homopolar inductor pulsed alternator (HIPA) prototype are provided. The choice of rotor material and bearing failure phenomenon are also investigated to find a responsible solution. Finally, the experimental waveforms of HIPA prototype without and rated load when charging capacitor are given. The research shows that the pulsed power supply based on the inductor pulsed alternator is competitive for its high energy storage density, moderate power density, and high reliability, which is suited to the charging power supply of pulsed capacitor.
In this paper, one novel heteropolar radial hybrid magnetic bearing (HRHMB) is proposed for flywheel energy storage system. First, its structure and working principle are introduced in detail. Then, ...its fundamental equations are derived based on magnetic circuit model, such as displacement stiffness, current stiffness, and load capacity. Furthermore, its suspension performance and magnetic coupling are analyzed based on the 2-D finite-element analysis. Finally, the comparison of main performance indexes between the proposed HRHMB and conventional one under the same constraints is made. It indicates that the displacement stiffness can be reduced by the novel structure. In addition, the rotor core loss of the novel HRHMB is just 22.53 W, which is only 41.6% of the conventional eight-pole HRHMB with the same load capacity.
While having various desired merits of high structural robustness and thus reliability, high thrust density, low fabrication cost, and so on, the stator-magnet moving-iron transverse-flux linear ...oscillatory machine suffers from high consumption of rare-earth magnetic material (high material cost) and heavy flux leakage at the stator outer region (underutilization of permanent magnets). To mitigate the demerits, a novel stator-magnet moving-iron transversal-flux hybrid-flux-path linear oscillatory machine (SMTHLOM), with additional back iron and auxiliary radially magnetized ferrite magnets, is proposed in this paper. The topology and operational principle of the proposed SMTHLOM are explained in detail. The 3-D finite-element analysis is introduced to investigate the sensitivities of main structural parameters, which enables the selection of optimal dimensions. Based on a set of comparison rules, a comprehensive comparison was conducted between these two topologies on various key indicators, such as the back electromotive force, thrust, and thermal distribution. The simulation results show that the SMTHLOM is low cost and small stator outer flux leakage, and thus is more suitable for some applications, e.g., fridge compressors, requiring low cost and high thrust density.
Active magnetic bearing (AMB) has been widely applied for flywheel system due to the excellent characteristics at high speed. However, limited by processing technology, rotor eccentricity will bring ...unbalanced vibration which will endanger the whole system. Vibration suppression is an important and unavoidable topic for the further development of AMB. In this paper, sliding mode active disturbance rejection control (SMADRC) strategy based on inverse system decoupling is proposed. Firstly, coupling phenomenon between four degrees of freedom (DOF) in radial direction of the system is analyzed, and a decoupling controller based on the inverse system method is designed. Then, considering the unbalanced force caused by rotor eccentricity, dynamic model of AMB flywheel system under high speed operation is established. Later, conventional nonlinear feedback control law is replaced by sliding mode control and external disturbance will be suppressed by SMADRC. Lastly, tracking performance of extended state observer (ESO) is analyzed, and stability of the system is realized by adjusting control parameters in SMADRC. Simulation results show that the inverse system control (ISC) can realize complete decoupling of radial four DOF and ESO has excellent tracking performance. Compared with conventional control strategy, SMADRC-ISC has better dynamic performance and can effectively suppress the unbalanced vibration caused by rotor eccentricity, which amplitude is reduced by 40.9% compared with PID-ISC.
The occurrence of distant tumor metastases is a major barrier in non-small cell lung cancer (NSCLC) therapy, and seriously affects clinical treatment and patient prognosis. Recently, long non-coding ...RNAs (lncRNAs) have been demonstrated to be crucial regulators of metastasis in lung cancer. The aim of this study was to reveal the underlying mechanisms of a novel lncRNA LNC CRYBG3 in regulating NSCLC metastasis. Experimental results showed that LNC CRYBG3 was upregulated in NSCLC cells compared with normal tissue cells, and its level was involved in these cells' metastatic ability. Exogenously overexpressed LNC CRYBG3 increased the metastatic ability and the protein expression level of the metastasis-associated proteins Snail and Vimentin in low metastatic lung cancer HCC827 cell line. In addition, LNC CRYBG3 contributed to HCC827 cell metastasis in vivo. Mechanistically, LNC CRYBG3 could directly combine with eEF1A1 and promote it to move into the nucleus to enhance the transcription of MDM2. Overexpressed MDM2 combined with MDM2 binding protein (MTBP) to reduce the binding of MTBP with ACTN4 and consequently increased cell migration mediated by ACTN4. In conclusion, the LNC CRYBG3/eEF1A1/MDM2/MTBP axis is a novel signaling pathway regulating tumor metastasis and may be a potential therapeutic target for NSCLC treatment.
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