Last improvements in the data assimilation scheme for the Mediterranean Analysis and Forecast system of the Copernicus Marine Service

The Mediterranean Forecasting System (MFS) is a numerical ocean prediction system that produces analyses, reanalyses and short term forecasts for the entire Mediterranean Sea and its Atlantic Ocean adjacent areas. The system is now part of the Copernicus Marine Environment Monitoring Service (CMEMS) providing regular and systematic information about the physical state and dynamics of the Mediterranean Sea through the Med-MFC (Mediterranean Monitoring and Forecasting Center). MFS has been implemented in the Mediterranean Sea with 1/16o horizontal resolution and 72 vertical levels and is composed by the hydrodynamic model NEMO (Nucleus for European Modelling of the Ocean) 2-way online coupled with the third generation wave model WaveWatchIII (Clementi et al., 2017a) and forced by ECMWF atmospheric fields at 1/8° horizontal resolution. The model solutions are corrected by the data assimilation system (3D variational scheme, Dobricic and Pinardi, 2008) with a daily assimilation cycle of along track satellite Sea Level Anomaly (SLA) and vertical profiles of Temperature and Salinity from ARGO and gliders. In this study we present a new estimate of the background error covariance matrix with vertical Empirical Orthogonal Functions (EOFs) that are defined at each grid point of the model domain in order to better account for the error covariance between temperature and salinity in the shelf and open ocean areas. Moreover the Observational error covariance matrix is z-dependent and varies in each month. This new dataset has been tested and validated for more than 2 years against a background error correlation matrix varying only seasonally and in thirteen sub-regions of the Mediterranean Sea (Dobricic et al. 2005).PublishedBergen, Norway3SR. AMBIENTE - Servizi e ricerca per la Societ

Last improvements in the data assimilation scheme for the Mediterranean Analysis and Forecast system of the Copernicus Marine Service

The Mediterranean Forecasting System (MFS) is a numerical ocean prediction system that produces analyses, reanalyses and short term forecasts for the entire Mediterranean Sea and its Atlantic Ocean adjacent areas. The system is now part of the Copernicus Marine Environment Monitoring Service (CMEMS) providing regular and systematic information about the physical state and dynamics of the Mediterranean Sea through the Med-MFC (Mediterranean Monitoring and Forecasting Center). MFS has been implemented in the Mediterranean Sea with 1/16o horizontal resolution and 72 vertical levels and is composed by the hydrodynamic model NEMO (Nucleus for European Modelling of the Ocean) 2-way online coupled with the third generation wave model WW3 (WaveWatchIII) and forced by ECMWF atmospheric fields at 1/8o horizontal resolution. The model solutions are corrected by the data assimilation system (3D variational-3Dvar scheme adapted to the oceanic assimilation problem, Dobricic and Pinardi, 2008) with a daily assimilation cycle of satellite Sea Level Anomaly (SLA) and vertical profiles of Temperature and Salinity. In this study we present a new estimate the of the background error covariance matrix with vertical Empirical Orthogonal Functions (EOFs) that are defined at each grid point of the model domain in order to better account for the error covariance between temperature and salinity in the shelf and open ocean areas. Moreover the Error covariance matrix is z-dependent and varies in each month. This new dataset has been tested and validated for more than 2 years against a background error correlation matrix varying only seasonally and in thirteen sub-regions of the Mediterranean Sea. Latest developments include the implementation of an upgraded 3Dvar (Storto et al. 2012) for a high-resolution model, 1/24o in the horizontal and 141 vertical levelsPublishedBergen, Norway3SR. AMBIENTE - Servizi e ricerca per la Societ

Structure-activity relationships of novel substituted naphthalene diimides as anticancer agents

Novel 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) derivatives were synthesized and evaluated for their antiproliferative activity on a wide number of different tumor cell lines. The prototypes of the present series were derivatives 1 and 2 characterized by interesting biological profiles as anticancer agents. The present investigation expands on the study of structure-activity relationships of prototypes 1 and 2, namely, the influence of the different substituents of the phenyl rings on the biological activity. Derivatives 3-22, characterized by a different substituent on the aromatic rings and/or a different chain length varying from two to three carbon units, were synthesized and evaluated for their cytostatic and cytotoxic activities. The most interesting compound was 20, characterized by a linker of three methylene units and a 2,3,4-trimethoxy substituent on the two aromatic rings. It displayed antiproliferative activity in the submicromolar range, especially against some different cell lines, the ability to inhibit Taq polymerase and telomerase, to trigger caspase activation by a possible oxidative mechanism, to downregulate ERK 2 protein and to inhibit ERKs phosphorylation, without acting directly on microtubules and tubuline. Its theoretical recognition against duplex and quadruplex DNA structures have been compared to experimental thermodynamic measurements and by molecular modeling investigation leading to putative binding modes. Taken together these findings contribute to define this compound as potential Multitarget-Directed Ligands interacting simultaneously with different biological targets.This research was supported by a grant from MIUR, Rome (PRIN), University of Bologna (RFO) and Polo Scientifico-Didattico di Rimini (to V.T.). We thank the National Cancer Institute (Bethesda, MD) for the anticancer assays. MICINN (Spanish Government) is acknowledged for grant BIO2010-16351 (to J.F.D.). Lizzia Raffaghello is a recipient of MFAG Grant. Giovanna Bianchi is a recipient of a FIRC fellowship

A 1/24 degree resolution Mediterranean analysis and forecast modeling system for the Copernicus Marine Environment Monitoring Service

The Mediterranean Forecasting System (MFS) is a numerical ocean prediction system that operationally produces analyses, reanalyses and short-term forecasts of the main physical parameters for the entire Mediterranean Sea and its Atlantic Ocean adjacent areas. This work is specifically focused on the description and evaluation of the analysis and forecast modeling system that covers the analysis of the current situation and produces daily updates of the following 10 days forecast. The system has been recently upgraded in the framework of the Copernicus Marine Environment Monitoring Service (CMEMS) by increasing the grid resolution from 1/16o to 1/24o in the horizontal and from 72 to 141 vertical levels, by increasing the number of fresh water river inputs and by updating the data assimilation scheme. The model has a non-linear explicit free surface and it is forced by surface pressure, interactive heat, momentum and water fluxes at the air-sea interface. In order to validate the modeling system and to estimate the accuracy of the model products, a quality assessment is regularly performed including both pre-operational qualification and near real time (NRT) validation procedures. Pre-operational qualification activities focus on testing the improvements of the quality of the new system with respect to the previous version and relies on past simulation and historical data, while NRT validation activities aim at routinely and on-line providing the skill assessment of the model analysis and forecasts and relies on the NRT available observations. The focus of this work is to present the new operational modeling system and the skill assessment including comparison with independent (insitu coastal moorings) and quasi-independent (insitu vertical profiles and satellite) datasets.PublishedBergen, Norway3SR. AMBIENTE - Servizi e ricerca per la Societ

A 1/24° resolution Mediterranean physical analysis and forecasting system for the Copernicus Marine Environment Monitoring Service

This study describes a new model implementation for the Mediterranean Sea that has been achieved in the framework of the Copernicus Marine Environment Monitoring Service (CMEMS). The numerical ocean prediction system, that operationally produces analyses and forecasts of the main physical parameters for the entire Mediterranean Sea and its Atlantic Ocean adjacent areas, has been upgraded by increasing the grid resolution from 1/16o to 1/24o in the horizontal and from 72 to 141 unevenly spaced vertical levels, by increasing the number of fresh water river inputs and by updating the data assimilation scheme. The model has a non-linear explicit free surface and it is forced by surface pressure, interactive heat, momentum and water fluxes at the airsea interface. The focus of this work is to present the new modelling system which will become operational in the near future and the validation assessment including the comparison with an independent non assimilated dataset (coastal moorings) and quasi-independent (in situ vertical profiles and satellite) datasets. The results show that the higher resolution model is capable of representing most of the variability of the general circulation in the Mediterranean Sea, however some improvements need to be implemented in order to enhance the model ability in reproducing specific hydrodynamic features particularly the Sea Level Anomaly.PublishedBergen, Norway3SR. AMBIENTE - Servizi e ricerca per la Societ

Higher resolution physical numerical model of the Mediterranean Sea in the Copernicus Marine Service

INGV is responsible for the operational production of the physical component of the Mediterranean Sea Monitoring and Forecasting Centre (Med-MFC) of the Copernicus Marine Service Monitoring System (CMEMS). The system was implemented in 2000 by the INGV National Group of Operational oceanography (GNOO) and has been developed in years thanks to a number of European projects. The Med-MFC is a coupled hydrodynamic-wave model with data assimilation component with a resolution of 1/16°. The model solutions are corrected by the variational assimilation (based on a 3DVAR scheme) of Temperature and Salinity vertical profiles (from ARGO, CTD, XBT and Gliders observations) and along track satellite Sea Level Anomaly (SLA) observations. In order to meet the requirements for Copernicus Marine Service Phase I the increase of the horizontal (to 1/24°) and vertical resolution of the hydrodynamic component of Med-MFC has been planned. The major improvements expected from this development are the following: 1) to better resolve the mesoscale processes in the Mediterranean region where the Rossby radius of deformation is about 12-15 km (1/24° is about 4-5 km); 2) to resolve the tidal forcing at Gibraltar, entering from the Atlantic into the Mediterranean, known to provide about 30% amplitude of the tidal signal in the Mediterranean; 3) to better resolve vertical mixing processes.UnpublishedIstituto Nazionale di Geofisica e Vulcanologia. Sede Centrale. Roma3SR. AMBIENTE - Servizi e ricerca per la Societ

IL-12 Can Target Human Lung Adenocarcinoma Cells and Normal Bronchial Epithelial Cells Surrounding Tumor Lesions

BACKGROUND: Non small cell lung cancer (NSCLC) is a leading cause of cancer death. We have shown previously that IL-12rb2 KO mice develop spontaneously lung adenocarcinomas or bronchioalveolar carcinomas. Aim of the study was to investigate i) IL-12Rbeta2 expression in human primary lung adenocarcinomas and in their counterparts, i.e. normal bronchial epithelial cells (NBEC), ii) the direct anti-tumor activity of IL-12 on lung adenocarcinoma cells in vitro and vivo, and the mechanisms involved, and iii) IL-12 activity on NBEC. METHODOLOGY/PRINCIPAL FINDINGS: Stage I lung adenocarcinomas showed significantly (P = 0.012) higher frequency of IL-12Rbeta2 expressing samples than stage II/III tumors. IL-12 treatment of IL-12R(+) neoplastic cells isolated from primary adenocarcinoma (n = 6) inhibited angiogenesis in vitro through down-regulation of different pro-angiogenic genes (e.g. IL-6, VEGF-C, VEGF-D, and laminin-5), as assessed by chorioallantoic membrane (CAM) assay and PCR array. In order to perform in vivo studies, the Calu6 NSCLC cell line was transfected with the IL-12RB2 containing plasmid (Calu6/beta2). Similar to that observed in primary tumors, IL-12 treatment of Calu6/beta2(+) cells inhibited angiogenesis in vitro. Tumors formed by Calu6/beta2 cells in SCID/NOD mice, inoculated subcutaneously or orthotopically, were significantly smaller following IL-12 vs PBS treatment due to inhibition of angiogenesis, and of IL-6 and VEGF-C production. Explanted tumors were studied by histology, immuno-histochemistry and PCR array. NBEC cells were isolated and cultured from lung specimens of non neoplastic origin. NBEC expressed IL-12R and released constitutively tumor promoting cytokines (e.g. IL-6 and CCL2). Treatment of NBEC with IL-12 down-regulated production of these cytokines. CONCLUSIONS: This study demonstrates that IL-12 inhibits directly the growth of human lung adenocarcinoma and targets the adjacent NBEC. These novel anti-tumor activities of IL-12 add to the well known immune-modulatory properties of the cytokine and may provide a rational basis for the development of a clinical trial

Structure-activity relationships of novel substituted naphthalene diimides as anticancer agents

Novel 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) derivatives were synthesized and evaluated for their antiproliferative activity on a wide number of different tumor cell lines. The prototypes of the present series were derivatives 1 and 2 characterized by interesting biological profiles as anticancer agents. The present investigation expands on the study of structure-activity relationships of prototypes 1 and 2, namely, the influence of the different substituents of the phenyl rings on the biological activity. Derivatives 3-22, characterized by a different substituent on the aromatic rings and/or a different chain length varying from two to three carbon units, were synthesized and evaluated for their cytostatic and cytotoxic activities. The most interesting compound was 20, characterized by a linker of three methylene units and a 2,3,4-trimethoxy substituent on the two aromatic rings. It displayed antiproliferative activity in the submicromolar range, especially against some different cell lines, the ability to inhibit Taq polymerase and telomerase, to trigger caspase activation by a possible oxidative mechanism, to downregulate ERK 2 protein and to inhibit ERKs phosphorylation, without acting directly on microtubules and tubuline. Its theoretical recognition against duplex and quadruplex DNA structures have been compared to experimental thermodynamic measurements and by molecular modeling investigation leading to putative binding modes. Taken together these findings contribute to define this compound as potential Multitarget-Directed Ligands interacting simultaneously with different biological targets. \ua9 2012 Elsevier Masson SAS. All rights reserved

Mediterranean monitoring and forecasting operational system for Copernicus Marine Service

The MEDiterranean Monitoring and Forecasting Center (Med-MFC) is part of the Copernicus Marine Environment Monitoring Service (CMEMS, http://marine.copernicus.eu/), provided on an operational mode by Mercator Ocean in agreement with the European Commission. Specifically, Med MFC system provides regular and systematic information about the physical state of the ocean and marine ecosystems for the Mediterranean Sea. The Med-MFC service started in May 2015 from the pre-operational system developed during the MyOcean projects, consolidating the understanding of regional Mediterranean Sea dynamics, from currents to biogeochemistry to waves, interfacing with local data collection networks and guaranteeing an efficient link with other Centers in Copernicus network. The Med-MFC products include analyses, 10 days forecasts and reanalysis, describing currents, temperature, salinity, sea level and pelagic biogeochemistry. Waves products will be available in MED-MFC version in 2017. The consortium, composed of INGV (Italy), HCMR (Greece) and OGS (Italy) and coordinated by the Euro-Mediterranean Centre on Climate Change (CMCC, Italy), performs advanced R&D activities and manages the service delivery. The Med-MFC infrastructure consists of 3 Production Units (PU), for Physics, Biogechemistry and Waves, a unique Dissemination Unit (DU) and Archiving Unit (AU) and Backup Units (BU) for all principal components, guaranteeing a resilient configuration of the service and providing and efficient and robust solution for the maintenance of the service and delivery. The Med-MFC includes also an evolution plan, both in terms of research and operational activities, oriented to increase the spatial resolution of products, to start wave products dissemination, to increase temporal extent of the reanalysis products and improving ocean physical modeling for delivering new products. The scientific activities carried out in 2015 concerned some improvements in the physical, biogeochemical and wave components of the system. Regarding the currents, new grid-point EOFs have been implemented in the Med-MFC assimilation system; the climatological CMAP precipitation was replaced by the ECMWF daily precipitation; reanalysis time-series have been increased by one year. Regarding the biogeochemistry, the main scientific achievement is related to the implementation of the carbon system in the Med-MFC biogeochemistry model system already available. The new model is able to reproduce the principal spatial patterns of the carbonate system variables in the Mediterranean Sea. Further, a key result consists of the calibration of the new variables (DIC and alkalinity), which serves to the estimation of the accuracy of the new products to be released in the next version of the system (i.e. pH and pCO2 at surface). Regarding the waves, the system has been validated against in-situ and satellite observations. For example, a very good agreement between model output and in-situ observations has been obtained at offshore and/or well-exposed wave buoys in the Mediterranean Sea.PublishedVienna3SR. AMBIENTE - Servizi e ricerca per la Societ

The Mediterranean ocean Forecasting System

The Mediterranean Forecasting System (MFS) is operationally working since year 2000 and it is continuously improved in the frame of international projects. The system is part of the Mediterranean Operational Oceanography Network-MOON and MFS is coordinated and operated by the Italian Group of Operational Oceanography (GNOO). The latest upgrades and integration to MFS has been undertaken in the EU-MERSEA and BOSS4GMES Projects. Since October 2005 ten days forecasts are produced daily as well as 15 days of analyses once a week. The daily forecast and weekly analysis data are available in real time to the users through a dedicated ftp service and every day a web bulletin is published on the web site (http://gnoo.bo.ingv.it/mfs). A continuous evaluation in near real time of the forecasts and analyses produced by MFS has been developed in order to continuously verify the system and to provide useful information to the users. The R&D is focused on different aspects of the system. A new basin scale ocean model nested with operational MERCATOR global model has been developed and run in real time operationally for a test period together with a new assimilation scheme based on the 3DVAR. This system is now under evaluation. Important activities have been carried out to: implement and test a Bayesian methodologies of Ensemble and Super-Ensemble for the Mediterranean sea; produce 20 years of re-analysis; re-formulate the air-sea fluxes bulk formulae; develop dedicated products to support particular request of end users such as: indicators, real time oil spill forecasting, search & rescue.EUROGOOS and European CommissionPublishedExeter, UK4.6. Oceanografia operativa per la valutazione dei rischi in aree marineope