Modulation of GLO1 expression affects malignant properties of cells

The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect) characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO). Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1) that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed

Connecting the global H-mode power threshold to the local radial electric field at ASDEX Upgrade

The relation between the macroscopic input power required at ASDEX Upgrade to access the H-mode Pthr and the microscopic E x B shear has been investigated via fast charge-exchange recombination spectroscopy (CXRS) measurements at various toroidal magnetic fields, different electron densities, and in both hydrogen and deuterium plasmas. For the H-mode onset, a threshold in the v E x B minimum, an approximation of the E x B shear, has been found. This identifies v E x B and not Er as the important player for the L-H transition. A database of measurements including CXRS, Doppler reflectometry measurements and comparison to neoclassical approximations shows a threshold v E x B of (6.7 ± 1.0) km/s ranging over a factor of three in Pthr. Using these findings, a simple derivation of the Pthr scaling is proposed giving a physics interpretation of the Bt, density and surface dependence of Pthr.EUROfusion Consortium Grant Agreement No. 63305

Effects of strong density fluctuations at the plasma edge on ECEI measurements at ASDEX Upgrade

EUROfusion Consortium 63305

Effects of density gradients and fluctuations at the plasma edge on ECEI measurements at ASDEX Upgrade

Electron cyclotron emission imaging (ECEI) provides measurements of electron temperature (Te) and its fluctuations (δTe). However, when measuring at the plasma edge, in the steep gradient region, radiation transport effects must be taken into account. It is shown that due to these effects, the scrape-off layer region is not accessible to the ECEI measurements in steady state conditions and that the signal is dominated by the shine-through emission. Transient effects, such as filaments, can change the radiation transport locally, but cannot be distinguished from the shine-through. Local density measurements are essential for the correct interpretation of the electron cyclotron emission, since the density fluctuations influence the temperature measurements at the plasma edge. As an example, a low frequency 8 kHz mode, which causes 10%–15% fluctuations in the signal level of the ECEI, is analysed. The same mode has been measured with the lithium beam emission spectroscopy density diagnostic, and is very well correlated in time with high frequency magnetic fluctuations. With radiation transport modelling of the electron cyclotron radiation in the ECEI geometry, it is shown that the density contributes significantly to the radiation temperature (Trad) and the experimental observations have shown the amplitude modulation in both density and temperature measurements. The poloidal velocity of the low frequency mode measured by the ECEI is 3 km s–1. The calculated velocity of the high frequency mode measured with the magnetic pick-up coils is about 25 km s–1. Velocities are compared with the E × B background flow velocity and possible explanations for the origin of the low frequency mode are discussed.EUROfusion Consortium 63305