The Benefit of Probabilistic Flood Forecasting on European Scale Results of the European Flood Alert System for 2005/2006

Results of the European Flood Alert System for 2005/2006JRC.H.7-Land management and natural hazard

Summary Report of the 1st Workshop on the use of Ensemble Prediction System in Flood Forecasting (Ispra, 21-22 November 2005)

The first workshop on the use of EPS in flood forecasting was organised by the Joint Research Centre together with researchers from King's College in London (UK) and the Lancaster University (UK). The workshop was organized to address two main concerns of EFAS regarding flood forecasting based on EPS: 1. How to extract meaningful information from the meteorological EPS for medium-range flood forecasting? 2. How to communicate the uncertainty in flood forecasting to end-users? The specific objectives of the workshop were to explore together with flood forecasting experts from the Member States: 3. The usefulness of EPS information implemented in EFAS for operational flood forecasting and decision making, and the perception of uncertainty in flood forecasting. The workshop's concept was to have a small group of flood forecasters from different river basins working through a number of case-studies, each one representing a potential flood situation as forecasted by EFAS. On the first day, the participants worked in groups on each case-study. The second day was targeted mostly to plenary discussions on the use of EPS in flood forecasting.JRC.H.7-Land management and natural hazard

A selective p53 activator and anticancer agent to improve colorectal cancer therapy

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.We thank PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) through grants UIDB/50006/2020, UID/BIO/04469/2019, UIDB/04539/2020, and UIDP/04539/2020 (CIBB); BioTecNorte operation (NORTE-01-0145-FEDER000004) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S (Norte-01-0145-FEDER-000008) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte; Masaryk University (Project MUNI/A/1127/2019) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC (IG#18985, A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences, PD/00016/2012). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) via the projects UIDB/50006/2020 (LAQV/REQUIMTE), UIDB/00313/2020, and UIDP/00313/2020, co-funded by COMPETE2020-UE.info:eu-repo/semantics/publishedVersio

SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promising Activity in Hepatocellular Carcinoma.

Half of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds as mutp53 reactivators and anticancer agents was investigated in human tumor cells and xenograft mouse models. By analysis of their anti-proliferative effect on a panel of p53-null NCI-H1299 tumor cells ectopically expressing highly prevalent mutp53, the compound SLMP53-2 was selected based on its potential reactivation of multiple structural mutp53. In mutp53-Y220C-expressing hepatocellular carcinoma (HCC) cells, SLMP53-2-induced growth inhibition was mediated by cell cycle arrest, apoptosis, and endoplasmic reticulum stress response. In these cells, SLMP53-2 restored wild-type-like conformation and DNA-binding ability of mutp53-Y220C by enhancing its interaction with the heat shock protein 70 (Hsp70), leading to the reestablishment of p53 transcriptional activity. Additionally, SLMP53-2 displayed synergistic effect with sorafenib, the only approved therapy for advanced HCC. Notably, it exhibited potent antitumor activity in human HCC xenograft mouse models with a favorable toxicological profile. Collectively, SLMP53-2 is a new mutp53-targeting agent with promising antitumor activity, particularly against HCC

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Prévisions hydrologiques d'ensemble (développements pour améliorer la qualité des prévisions et estimer leur utilité)

La dernière décennie a vu l'émergence de la prévision probabiliste de débits en tant qu'approche plus adaptée pour l'anticipation des risques et la mise en vigilance pour lasécurité des personnes et des biens. Cependant, au delà du gain en sécurité, la valeur ajoutée de l'information probabiliste se traduit également en gains économiques ou en une gestion optimale de la ressource en eau disponible pour les activités économiques qui en dépendent. Dans la chaîne de prévision de débits, l'incertitude des modèles météorologiques de prévision de pluies joue un rôle important. Pour pouvoir aller au-delà des limites de prévisibilité classiques, les services météorologiques font appel aux systèmes de prévision d'ensemble,générés sur la base de variations imposées dans les conditions initiales des modèlesnumériques et de variations stochastiques de leur paramétrisation. Des scénarioséquiprobables de l'évolution de l'atmosphère pour des horizons de prévision pouvant aller jusqu'à 10-15 jours sont ainsi proposés. L'intégration des prévisions météorologiques d'ensemble dans la chaîne de prévision hydrologique se présente comme une approche séduisante pour produire des prévisions probabilistes de débits et quantifier l'incertitude prédictive totale en hydrologie.The last decade has seen the emergence of streamflow probabilistic forecasting as the most suitable approach to anticipate risks and provide warnings for public safety and property protection. However, beyond the gains in security, the added value of probabilistic information also translates into economic benefits or an optimal management of water resources for economic activities that depend on it.In streamflow forecasting, the uncertainty associated with rainfall predictions from numerical weather prediction models plays an important role. To go beyond the limits of classical predictability, meteorological services developed ensemble prediction systems, which are generated on the basis of perturbations of the initial conditions of the models and stochastic variations in their parameterization. Equally probable scenarios of the evolution of the atmosphere are proposed for forecasting horizons up to 10 15 days.The integration of weather ensemble predictions in the hydrological forecasting chain is an interesting approach to produce probabilistic streamflow forecasts and quantify the total predictive uncertainty in hydrology. Last and final summary in the thesis.PARIS-AgroParisTech Centre Paris (751052302) / SudocSudocFranceF

Cell block technique as an additional tool in the diagnosis of ameloblastoma

The objective of this study was to evaluate the cytological content of ameloblastomas of the jaw. Nine cases of ameloblastoma were punctured, and the intralesional material was processed using the cell block technique. After centrifugation, the pellet obtained from the punctured material was fixed in formaldehyde and routinely processed to inclusion in paraffin. The obtained sections were stained with haematoxylin and eosin (H&E). Immunohistochemical reactions against anti-pan-cytokeratin (AE1/AE3) were performed to measure the presence of epithelial cells. Cytological analyses of the obtained slides revealed the presence of epithelial cells (as evidenced by AE1/ AE3 labelling) and acellular amorphous eosinophilic materials. These cytological findings, in light of clinical and imaging data, can be helpful in the presumptive diagnosis of this disease entity by eliminating other possible diagnoses. Nonetheless further studies are needed in order to determine the nature of the acellular amorphous eosinophilic material and to ascertain the immunoprofile of epithelial cells