A study of observations of Ionospheric upwelling made by theEISCAT Svalbard Radar during the International Polar Year campaign of 2007

We have used EISCAT Svalbard Radar data, obtained during the International Polar Year 2007 campaign, to study ionospheric upflow events with fluxes exceeding 1013 m−2 s−1. In this study, we have classified the upflow events into low, medium, and high flux upflows, and we report on the incidence and seasonal distribution of these different classes. It is observed that high upflow fluxes are comparatively rare and low flux upflow events are a frequent phenomenon. Analysis shows that occurrence peaks around local noon at 31%, 16%, and 2% for low, medium, and high‐flux upflow, respectively, during geomagnetically disturbed periods. In agreement with previous studies on vertical and field‐aligned flows, ion upflow is observed to take place over a wide range of geomagnetic conditions, with downflow flux occurrence being lower than upflow occurrence. In contrast to previous observations, however, the upflow occurrence is greater around noon during highly disturbed geomagnetic conditions than for moderate geomagnetic conditions. Analysis of the seasonal distribution reveals that, while high‐flux upflow has its peak around local noon in the summer, with its occurrence being driven predominantly by high geomagnetic disturbance, the occurrence of low‐flux upflow is broadly distributed across all seasons, geomagnetic activity conditions, and times of day. The medium‐flux upflow events, although distributed across all seasons, show an occurrence peak strongly related to high Kp. Furthermore, during highly disturbed conditions, the low‐flux and medium‐flux upflow events show a minimum occurrence during the winter, whereas minimum occurrence for the high‐flux upflow events occurs in autumn

Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic

The accumulation of senescent cells has an important role in the phenotypical changes observed in ageing and in many age-related pathologies. Thus, the strategies designed to prevent these effects, collectively known as senotherapies, have a strong clinical potential. Senolytics are a type of senotherapy aimed at specifically eliminating senescent cells from tissues. Several small molecule compounds with senolytic properties have already been identified, but their specificity and range of action are variable. Because of this, potential novel senolytics are being actively investigated. Given the involvement of HDACs and the PI3K pathway in senescence, we hypothesized that the dual inhibitor CUDC-907, a drug already in clinical trials for its antineoplastic effects, could have senolytic effects. Here, we show that CUDC-907 was indeed able to selectively induce apoptosis in cells driven to senesce by p53 expression, but not when senescence happened in the absence of p53. Consistent with this, CUDC-907 showed senolytic properties in different models of stress-induced senescence. Our results also indicate that the senolytic functions of CUDC-907 depend on the inhibitory effects of both HDACs and PI3K, which leads to an increase in p53 and a reduction in BH3 pro-survival proteins. Taken together, our results show that CUDC-907 has the potential to be a clinically relevant senolytic in pathological conditions in which stress-induced senescence is involved.</p