Search

A sustained increase in spring discharges was monitored after the 2016 Central Italy seismic sequence in the fractured carbonate aquifer of Valnerina–Sibillini Mts. The groundwater surplus recorded between August 2016 and November 2017 was determined to be between 400 and 500 × 106 m3. In fractured aquifers, the post-seismic rise in spring discharges is generally attributed to an increase in bulk permeability caused by the fracture cleaning effect, which is induced by pore pressure propagation. In the studied aquifers, the large amount of additional discharge cannot only be attributed to the enhanced permeability, which was evaluated to be less than 20% after each main seismic event. A detailed analysis of the spring discharge hydrographs and of the water level at five gauging stations was carried out to determine the possible causes of this sudden increase in groundwater outflow. Taking into account the geological and structural framework, a conceptual model of a basin-in-series has been adopted to describe the complex hydrogeological setting, where the thrusts and extensional faults have clearly influenced the groundwater flow directions before and after the seismic sequence. The prevalent portion of the total post-seismic discharge surplus not explained by the increase in permeability has been attributed to changes in the hydraulic gradient that caused seismogenic fault rupture and the disruption in the upgradient sector of the aquifer. The additional flow calculated through the breach of the pre-existing hydrostructural barrier corresponds to approximately 470 × 106 m3. This value is consistent with the total discharge increase measured in the whole study area, validating the proposed conceptual model. Consequently, a shift in the piezometric divide of the hydrogeological system has been induced, causing a potentially permanent change that lowers the discharge amount of the eastern springs.

Gemcitabine (2',2'-difluoro-2'-deoxycytidine, or dFdC) is a promising anticancer agent with demonstrated clinical activity in solid tumours currently undergoing clinical trials. Despite extensive studies on the biochemical mechanism of action, cell cycle perturbations induced by dFdC have not yet been thoroughly investigated, apart from the expected inhibition of DNA synthesis. The aim of our study was to clarify whether cell population kinetics is a vital factor in the cytotoxicity of dFdC in single or repeated treatments and in the dFdC-cisplatin combination. Ovarian cancer cells growing in vitro were treated with dFdC for 1 hr in a range of concentrations from 10 nM to 10 microM. Cell kinetics was investigated by DNA-bromodeoxyuridine flow cytometry, using different experimental protocols to measure either the time course of DNA-synthesis inhibition or the fate of cells in G(1), S or G(2)M at the time of dFdC treatment or 24 hr later. A modified sulforhodamine B test was used to assess the growth inhibition caused by dFdC given alone or with cisplatin. Although dFdC promptly inhibited DNA synthesis, cytotoxicity on proliferating cells was not specific for cells initially in the S phase. DNA synthesis was restored after a G(1) block of variable, dose-dependent length, but recycling cells were intercepted at the subsequent checkpoints, resulting in delays in the G(2)M and G(1) phases. The activity of repeated treatment with dFdC + dFdC or dFdC + cisplatin was highly dependent on the interval length between them. These results suggest that the kinetics of cell recycling from a first dFdC treatment strongly affects the outcome of a second treatment with either dFdC itself or cisplatin.