Rapid Atlantification along the Fram Strait at the beginning of the 20th century.

The recent expansion of Atlantic waters into the Arctic Ocean represents undisputable evidence of the rapid changes occurring in this region. Understanding the past variability of this “Atlantification” is thus crucial in providing a longer perspective on the modern Arctic changes. Here, we reconstruct the history of Atlantification along the eastern Fram Strait during the past 800 years using precisely dated paleoceanographic records based on organic biomarkers and benthic foraminiferal data.

Testing the applicability of random forest modeling to examine benthic foraminiferal responses to multiple environmental parameters.

The main environmental variables controlling benthic foraminiferal distributions were identified and used to assess their influence on ecological indices developed as predictors of Ecological Quality Status (EcoQS) in marine ecosystems. Gradient forest and random forest models were applied to assess the predictive value of a selection of abiotic (environmental) and biotic (foraminifera) variables in a costal marine area in the central Adriatic Sea (Italy). This approach yields evidence that the predictor variables sand, silt, Pollution Load Index, and TN have the greatest influence on the distribution of benthic foraminifera in this area.

Fault-controlled deep hydrothermal flow in a back-arc tectonic setting, SE Tyrrhenian Sea.

Understanding magmatic systems and deep hydrothermal circulation beneath arc-volcanoes provides insights into deep processes associated with slab-subduction and mantle-wedge partial melting. Here we analyze hydrothermal flow below a structural high (Capo Vaticano Ridge, CVR) located offshore Capo Vaticano (western Calabria) and affected by magmatic intrusions generated from above the Ionian subducting-slab. In order to explain observations, we combine geophysical and numerical modelling results.

Detecting long-term temporal trends in sediment-bound metals in the western Adriatic (Mediterranean Sea).

Major and trace metal concentrations were determined in western Adriatic sediment cores. Based on sediment chronology, the earliest anthropogenic influence appeared as a Zn and Pb increase in the Po River prodelta starting from ~1914. The increasing contamination signal of these trace metals propagated southward as far as 450km with a growing delay, taking ~10years to reach the south Adriatic Sea.

Spatial patterns and temporal trends of trace metal mass budgets in the western Adriatic sediments (Mediterranean Sea).

Spatial patterns of major (Al, Fe and Ti) and trace metals (Cu, Cr, Mn, Ni, Pb and Zn) measured in surficial sediments collected within the Late-Holocene mud-wedge in the western Adriatic Sea were analyzed to elucidate their sources, transport and mass budgets. Distributions of sedimentary trace metals, their fluvial inputs and accumulation loads reveal along-shore transport towards the southern Adriatic. Pb and to a lower extent Zn accumulation loads over time decreased significantly since 1988 in the North Adriatic, consistently with the implementation of regulations in the Western Europe, whereas Zn accumulation in the Po River prodelta remained unchanged since 1995.

Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding.

Cdc7 serine/threonine kinase is a key regulator of DNA synthesis in eukaryotic organisms. Cdc7 inhibition through siRNA or prototype small molecules causes p53 independent apoptosis in tumor cells while reversibly arresting cell cycle progression in primary fibroblasts. This implies that Cdc7 kinase could be considered a potential target for anticancer therapy.

Polyfluorinated amino acids for sensitive 19F NMR-based screening and kinetic measurements.

Two novel series of polyfluorinated amino acids (PFAs) were designed and synthesized according to a very short and scalable synthetic sequence. The advantages and limitations of these moieties for screening purposes are presented and discussed. The potential applications of these PFAs were tested with their incorporation into small arginine-containing peptides that represent suitable substrates for the enzyme trypsin.

Sensitivity improvement in 19F NMR-based screening experiments: theoretical considerations and experimental applications.

NMR-based binding and functional screening performed with FAXS (fluorine chemical shift anisotropy and exchange for screening) and 3-FABS (three fluorine atoms for biochemical screening) represents a potential alternative approach to high-throughput screening for the identification of novel potential drug candidates. The major limitation of this method in its current status is its intrinsic low sensitivity that limits the number of tested compounds. One approach for overcoming this problem is the use of a cryogenically cooled (19)F probe that reduces the thermal noise in the receiver circuitry.

Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition.

Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC(50) of 0.027 microM in the enzymatic assay for Aur-A inhibition and IC(50)s between 0.

3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding.

Abnormal proliferation mediated by disruption of the normal cell cycle mechanisms is a hallmark of virtually all cancer cells. Compounds targeting complexes between cyclin-dependent kinases (CDK) and cyclins, such as CDK2/cyclin A and CDK2/cyclin E, and inhibiting their kinase activity are regarded as promising antitumor agents to complement the existing therapies. From a high-throughput screening effort, we identified a new class of CDK2/cyclin A/E inhibitors.