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A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/ cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged

Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability. Here we provide evidence that hyper-activation of DNA ligase III (LIG3) is crucial for genomic instability and survival of MM cells. LIG3 mRNA expression in MM patients correlates with shorter survival and even increases with more advanced stage of disease. Knockdown of LIG3 impairs MM cells viability in vitro and in vivo, suggesting that neoplastic plasmacells are dependent on LIG3-driven repair. To investigate the mechanisms involved in LIG3 expression, we investigated the post-transcriptional regulation. We identified miR-22-3p as effective negative regulator of LIG3 in MM. Enforced expression of miR-22 in MM cells downregulated LIG3 protein, which in turn increased DNA damage inhibiting in vitro and in vivo cell growth. Taken together, our findings demonstrate that myeloma cells are addicted to LIG3, which can be effectively inhibited by miR-22, promoting a novel axis of genome stability regulation.

Woody plant encroachment over the past 140 years has substantially changed grasslands in western North American. We studied encroachment of western juniper (Juniperus occidentalis var. occidentalis) into a previously mixed shrub–grassland site in central Oregon (USA) using a modified version of Cellular Automata Tree–Grass–Shrub Simulator (CATGraSS) ecohydrological model. We developed simple algorithms to simulate three encroachment factors (grazing, fire frequency reduction, and seed dispersal by herbivores) in CATGraSS. Local ecohydrological dynamics represented by the model were first evaluated using satellite-derived leaf area index and measured evapotranspiration data. Reconstructed pre-encroachment vegetation cover percentages and the National Land Cover Database (NLCD 2006) vegetation map were used to estimate parameters for encroachment factors to represent juniper encroachment in CATGraSS. Model sensitivity experiments examined the influence of each encroachment factor and their combinations on trajectories of modeled percent cover of each plant functional type and emergent spatial vegetation patterns in the modeled domain. Simulation results identified grazing as the key factor leading to juniper encroachment, by reducing shrub and grass cover and promoting the formation of juniper tree clusters. Reduced fire frequency and increased seed dispersal by grazers further amplified juniper encroachment into grassland patches between clusters of juniper trees. Each encroachment factor showed different consequences on modeled vegetation patterns. Time series of modeled plant cover and spatial patterns of plant functional types were found to be consistent with an existing conceptual model described in the literature. The proposed model provides a tool that can be used to improve our understanding of the drivers and processes of woody plant encroachment and vegetation response to global change.

Critical rainfall thresholds for landslides are powerful tools for preventing landslide hazard. The thresholds are commonly estimated empirically starting from rainfall events that triggered landslides in the past. The creation of the appropriate rainfall–landslide database is one of the main efforts in this approach. In fact, an accurate agreement between the landslide and rainfall information, in terms of location and timing, is essential in order to correctly estimate the rainfall–landslide relationships. A further issue is taking into account the average moisture conditions prior the triggering event, which reasonably may be crucial in determining the sufficient amount of precipitation. In this context, the aim of this paper is exploiting historical landslide and rainfall data in a spatial database for the derivation of critical rainfall thresholds for landslide occurrence in Sicily, southern Italy. The hourly rainfall events that caused landslides occurred in the twentieth century were specifically identified and reconstructed. A procedure was proposed to automatically convert rain guages charts recorded on paper tape into digital format and then to provide the cumulative rainfall hyetograph in digital format. This procedure is based on a segmentation followed by signal recognition techniques which allow to digitalize and to recognize the hyetograph automatically. The role of rainfall prior to the landslide events was taken into account by including in the analysis the rainfall occurred 5, 15 and 30 days before each landslide. Finally, cumulated rainfall duration thresholds for different exceedance probability levels were determined. The obtained thresholds resulted in agreement with the regional curves proposed by other authors for the same area; antecedent rainfall turned out to be particularly important in triggering landslides.