Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53

E2F/DP complexes were originally identified as potent transcriptional activators required for cell proliferation. However, recent studies revised this notion by showing that inactivation of total E2F/DP activity by dominant-negative forms of E2F or DP does not prevent cellular proliferation, but rather abolishes tumor suppression pathways, such as cellular senescence. These observations suggest that blockage of total E2F/DP activity may increase the risk of cancer. Here, we provide evidence that depletion of DP by RNA interference, but not overexpression of dominant-negative form of E2F, efficiently reduces endogenous E2F/DP activity in human primary cells. Reduction of total E2F/DP activity results in a dramatic decrease in expression of many E2F target genes and causes a senescence-like cell cycle arrest. Importantly, similar results were observed in human cancer cells lacking functional p53 and pRB family proteins. These findings reveal that E2F/DP activity is indeed essential for cell proliferation and its reduction immediately provokes a senescence-like cell cycle arrest

Effects of core stochastization on particle and momentum transport

The effects of the stochastic magnetic field in a plasma center produced by electron cyclotron current drive (ECCD) on transport have been revealed. Because the electron temperature profile is flat in the core region, in the case of counter-directed ECCD (ctr-ECCD) against the toroidal magnetic field, the magnetic field is stochastic in the core region with rotational transform ᵼ ∼ 1/3. The particle diffusion coefficient of the ctr-ECCD plasma is approximately 20 times as large as that of the plasma without the stochastic magnetic field produced by co-directed ECCD (co-ECCD) at the maximum. Furthermore, in the stochastic magnetic field with ctr-ECCD, counter-directed intrinsic rotation is observed in the plasma with balanced NBI discharge

Isotope effects on energy, particle transport and turbulence in electron cyclotron resonant heating plasma of the Large Helical Device

Positive isotope effects have been found in electron cyclotron resonant heating plasma of the Large Helical Device (LHD). The global energy confinement time (τE) in deuterium (D) plasma is 16% better than in hydrogen (H) plasma for the same line-averaged density and absorption power. The power balance analyses showed a clear reduction in ion energy transport, while electron energy transport does not change dramatically. The global particle confinement time (τp) is degraded in D plasma; τp in D plasma is 20% worse than in H plasma for the same line-averaged density and absorption power. The difference in the density profile was not due to the neutral or impurity sources, but rather was due to the difference in the transport. Ion scale turbulence levels show isotope effects. The core turbulence (ρ  =  0.5–0.8) level is higher in D plasma than in H plasma in the low collisionality regime and is lower in D plasma than in H plasma. The density gradient and collisionality play a role in the core turbulence level

Extended investigations of isotope effects on ECRH plasma in LHD

Isotope effects of ECRH plasma in LHD were investigated in detail. A clear difference of transport and turbulence characteristics in H and D plasmas was found in the core region, with normalized radius ρ < 0.8 in high collisionality regime. On the other hand, differences of transport and turbulence were relatively small in low collisionality regime. Power balance analysis and neoclassical calculation showed a reduction of the anomalous contribution to electron and ion transport in D plasma compared with H plasma in the high collisionality regime. In core region, density modulation experiments also showed more reduced particle diffusion in D plasma than in H plasma, in the high collisionality regime. Ion scale turbulence was clearly reduced at ρ < 0.8 in high collisionality regime in D plasma compared with H plasma. The gyrokinetic linear analyses showed that the dominant instability ρ = 0.5 and 0.8 were ion temperature gradient mode (ITG). The linear growth rate of ITG was reduced in D plasma than in H plasma in high collisionality regime. This is due to the lower normalized ITG and density gradient. More hollowed density profile in D plasma is likely to be the key control parameter. Present analyses suggest that anomalous process play a role to make hollower density profiles in D plasma rather than neoclassical process. Electron scale turbulence were also investigated from the measurements and linear gyrokinetic simulations

Isotope effects on transport in LHD

Isotope effects are one of the most important issues for predicting future reactor operations. Large helical device (LHD) is the presently working largest stellarator/helical device using super conducting helical coils. In LHD, deuterium experiments started in 2017. Extensive studies regarding isotope effects on transport have been carried out. In this paper, the results of isotope effect studies in LHD are reported. The systematic studies were performed adjusting operational parameters and nondimensional parameters. In L mode like normal confinement plasma, where internal and edge transport barriers are not formed, the scaling of global energy confinement time (τE) with operational parameters shows positive mass dependence (M0.27; where M is effective ion mass) in electron cyclotron heating plasma and no mass dependence (M0.0) in neutral beam injection heating plasma. The non-negative ion mass dependence is anti-gyro-Bohm scaling. The role of the turbulence in isotope effects was also found by turbulence measurements and gyrokinetic simulation. Better accessibility to electron and ion internal transport barrier (ITB) plasma is found in deuterium (D) plasma than in hydrogen (H). Gyro kinetic non-linear simulation shows reduced ion heat flux due to the larger generation of zonal flow in deuterium plasma. Peaked carbon density profile plays a prominent role in reducing ion energy transport in ITB plasma. This is evident only in plasma with deuterium ions. New findings on the mixing and non-mixing states of D and H particle transports are reported. In the mixing state, ion particle diffusivities are higher than electron particle diffusivities and D and H ion density profiles are almost identical. In the non-mixing state, ion particle diffusivity is much lower than electron diffusivity. Deuterium and hydrogen ion profiles are clearly different. Different turbulence structures were found in the mixing and non-mixing states suggesting different turbulence modes play a role

A Heuristic Approach for Integrated Nesting and Scheduling in Sheet Metal Processing

Part 3: Knowledge Based Production ManagementInternational audienceIn recent years, sustainable and agile manufacturing is aimed at in many manufacturing industries. Reducing the waste of raw materials and managing the production schedule are important factors for such manufacturing. Nesting is an activity designing a cutting layout while scheduling is one managing operational procedures. Noting such nesting and scheduling in sheet metal processing, we need to consider those simultaneously for increasing the entire efficiency. This is because there often occurs a trade-off between them. To resolve such problem, we previously proposed an integrated method of nesting and scheduling. In order to enhance the scheduling ability that was insufficient in our method, this study extends the idea through a heuristic approach. Actually, we apply a local search to update the initial schedule which is decided by EDD based dispatching rule and manage it in terms of the criteria referring to the bottleneck process. Computational experiment is provided to validate the effectiveness of the proposed method

Temporal evolution of momentum transport in JT-60U H-mode plasma

JT-60Uの運動量変調実験に対して、新たに開発した解析手法を適用することで拡散係数・対流速度の空間分布の時間発展を評価した。解析したH-modeプラズマにおいて、拡散係数・対流速度が変調実験を行っている時間で変化していること、及び、変調周期の時間スケールでは運動量フラックスと運動量勾配の間に非線形性は見られないが、変調実験を行っている時間スケールでは変化することを見いだした。Asia-Pacific Transport Working Group Meeting US-EU Transport Task Force Workshop, 202