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The paper describes the on-line dynamic security assessment functions developed within the European Union, DGXII programme, CARE. These functions are based exclusively on the application of machine learning techniques. A description of the problem and the data set generation procedure for the Crete island power system are included. Comparative results regarding performances of Decision Trees, Kernel Regression Trees and Neural Networks are presented and discussed.The paper describes the on-line dynamic security assessment functions developed within the European Union, DGXII programme, CARE. These functions are based exclusively on the application of machine learning techniques. A description of the problem and the data set generation procedure for the Crete island power system are included. Comparative results regarding performances of Decision Trees, Kernel Regression Trees and Neural Networks are presented and discussed.

SIMPLE SUMMARY: Three-dimensional (3D) cell culture models have been proposed as alternatives for initial drug screening to increase drug development efficiency. In addition to their ability to reproduce key aspects of the tumor architecture and microenvironment, 3D cell culture models may help decrease the use of laboratory animals in drug testing, in accordance with the 3R principles (Replacement, Reduction, Refinement). This review aims to help researchers making a transition from two-dimensional (2D) to 3D cell culture models for drug screening, by discussing the impact of 3D models on cancer research, their advantages, limitations, and compatibility with high-throughput screenings. It also outlines the relevance of available readouts provided by such models as well as the importance of incorporating key microenvironmental cues towards improving the predictive value of drug efficacy and safety. ABSTRACT: Today, innovative three-dimensional (3D) cell culture models have been proposed as viable and biomimetic alternatives for initial drug screening, allowing the improvement of the efficiency of drug development. These models are gaining popularity, given their ability to reproduce key aspects of the tumor microenvironment, concerning the 3D tumor architecture as well as the interactions of tumor cells with the extracellular matrix and surrounding non-tumor cells. The development of accurate 3D models may become beneficial to decrease the use of laboratory animals in scientific research, in accordance with the European Union's regulation on the 3R rule (Replacement, Reduction, Refinement). This review focuses on the impact of 3D cell culture models on cancer research, discussing their advantages, limitations, and compatibility with high-throughput screenings and automated systems. An insight is also given on the adequacy of the available readouts for the interpretation of the data obtained from the 3D cell culture models. Importantly, we also emphasize the need for the incorporation of additional and ...

Mushroom extracts have been studied extensively for their potential antitumor effect in tumor cell lines and in animal models [1]. Recently, some of our collaborators have described that the methanolic extract from the medicinal mushroom Cordyceps militaris (L.) Link presented tumor cell growth inhibitory activity. In particular, this extract inhibited the growth of the nonsmall cell lung cancer (NSCLC) cell line NCI-H460, presenting a GI50 of approximately 50 μg/ml [2]. The aim of this work was to further study the effect of C. militaris methanolic extract in NCIH460 cells, regarding its mechanism of action. NCI-H460 cells were treated with C. militaris methanolic extract (at 25 and 50 μg/ml) for 48 h. Viable cell number was then assessed with the Trypan blue exclusion assay. Cellular proliferation was analyzed with the BrdU incorporation assay and cell cycle profile with flow cytometry following propidium iodide (PI) labeling. Levels of apoptotic cell death were determined with flow cytometry following Annexin V-FITC /PI labeling. Treatment of cells with the C. militaris extract caused a dose-dependent decrease in viable cell number. Moreover, a clear and strong decrease in cellular proliferation was observed. In addition, alterations in cell cycle profile were found, with a strong decrease in the S and G2/M phases of the cell cycle together with an increase in G0/G1 phase. Furthermore, treatment with the extract also induced apoptosis in this cell line. In conclusion, C. militaris methanolic extract was shown to interfere with cell proliferation, cell cycle and to induce apoptosis of NCI-H460 cells. Further studies will aim at further understanding the mechanism of action of this extract.

The cellular respiration process is a crucial subject in biochemistry learning. The use of ludic tools appears to be a good strategy in education intensifying the teach and learning process. The aim of this work was to create and introduce a game as educational tool helping the students to construct the knowledge. This work was accomplished in UFC involving three groups of 5 students of Introduction to Biochemistry discipline from Food Engineering course. It was developed a board game entitled: The dynamics OXI-REDOXI in Respiratory Chain. The game consisted in a board with the scheme of the respiratory chain, chips to complete the gaps and 12 question cards. The students had previous classes about the subject and a survey right before playing the game. The monitor explained the rules and the wrong answers of the students to question cards. During the game it was observed mistakes in the answers of the students to question cards and either regarding placing the chips representing the reactions of the respiratory chain. The monitor stimulated the discussion among them and elucidated the doubts. The students demonstrated motivation and interest during the game. The majority of the students found it easy to play and confirmed that it facilitate the learning process. The application of the same survey after the game showed that they understood the respiratory chain and the grades were at least 50% higher after the game. This game reveals itself a dynamic and constructive tool for the learning process in biochemistry.

Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human tumor cell lines. Nonetheless, the mechanism of action involved is still not known. This work aimed at further studying the effect of the methanolic extract of C. militaris regarding its antitumor mechanism of action, using the non-small cell lung cancer cell line (NCI-H460) as a model. Results showed that treatment with the extract decreased cellular proliferation, induced cell cycle arrest at G0/G1 and increased apoptosis. In addition, the extract increased the levels of p53 and p21. Moreover, an increase in p-H2A.X and 53BP1 levels, together with an increase in the number of 53BP1 foci/cell (all indicative of DNA damage), were also observed after treatment with the extract. This work suggests that this extract affected NCI-H460 cellular viability through a mechanism involving DNA damage and p53 activation. This further supports the potential of this extract as a source of bioactive compounds, which may be used in anticancer strategies. ; IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. This work is funded by FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE) and National Funds through the FCT, Foundation for Science and Technology, under the projects "PEst-C/SAU/LA0003/2013" and FCOMP-01-0124-FEDER-015752 (ref FCT PTDC/SAU-FAR/110848/2009). The authors also thank: FCT for the grant to R.T.L. (SFRH/BPD/68787/2010) and QREN for the grant of D.S. (NORTE-07-0124-FEDER-000023).

Mushroom extracts are recognized by their numerous potential medicinal properties. Recently, a methanolic extract from Cordyceps militaris (L.) Link (an edible entomopathogenic fungus widely used in traditional Chinese medicine) has been shown to inhibit cell growth of several human tumour cell lines [1,2]. However, its mechanism of action remained unknown. The aim of the present work was to study the antitumour mechanism of action of the methanolic extract of C. militaris, in the NCI-H460 cell line which is representative of non-small cell lung cancer. Results showed that the extract reduced viable cell number (observed with the trypan blue exclusion assay) by: i) decreasing cellular proliferation (analysed with the BrdU incorporation assay), ii) inducing cell cycle arrest at GO/GI phase (analysed by flow cytometry following propidium iodide-PI labelling) and iii) increasing apoptosis (analysed by flow cytometry following Annexin V-FITC and PI labelling). In addition, results also showed that treatment with the extract increased the cellular levels of p53 and p21. Moreover, this study also showed evidences of DNA damage caused by this extract, since an increase in the levels ofp-H2A.X and 53BP1 were observed, together with an increase in the number of 53BP1 foci/cell. In conclusion, this extract reduced NCI-H460 cellular viability, possibly through a mechanism which involves DNA damage and p53.

The Biochemistry study is complex and many times is restricted to memorization of theorical contents. The educational game could be an catalytic element, capable to contribute in the process of regaining the student's interest. The aim of this work was to create, apply and evaluate an educative game called "Krebs Roulette". The game contents were 1 roulette, 3 board cards, 48 question cards and complementary game chips. In an experimental tryout, five students joined the test-play in the presence of a mediator. The game duration was one hour. The students were submitted to an evaluation under Krebs Cycle before and after the game. About the game strategy, the students noticed as positive points: easy to play, didactic, making the learn easier. The evaluation of the quizzes, even with a so small experimental group, indicated a significant increase in the teach-learning process. The achieved results suggest that the game could be used as complementary tool for comprehension of the Krebs Cycle as strategy of learning-teaching in Biochemistry.

Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human tumor cell lines. Nonetheless, the mechanism of action involved is still not known. This work aimed at further studying the effect of the methanolic extract of C. militaris regarding its antitumor mechanism of action, using the non-small cell lung cancer cell line (NCI-H460) as a model. Results showed that treatment with the extract decreased cellular proliferation, induced cell cycle arrest at G0/G1 and increased apoptosis. In addition, the extract increased the levels of p53 and p21. Moreover, an increase in p-H2A.X and 53BP1 levels, together with an increase in the number of 53BP1 foci/cell (all indicative of DNA damage), were also observed after treatment with the extract. This work suggests that this extract affected NCI-H460 cellular viability through a mechanism involving DNA damage and p53 activation. This further supports the potential of this extract as a source of bioactive compounds, which may be used in anticancer strategies.

REanalysis of the TROpospheric chemical composition over thepast 40 years (RETRO)Objectives:• exploit (often under-utilised) existing data sets from ground based stations,aircraft, and satellite instruments, integrating these into common datasets,• develop tools for the analysis, interpretation and exploitation of the data,• formulate recommendations for future measurement strategies,• assess changes in trace compound emissions and their effect on troposphericchemical composition and aerosols, and the associated radiative forcing, overthe past 40 years,• provide an assessment of uncertainties caused by climate variability,• evaluate emission control strategies in Europe,• predict changes over the next 20 years in tropospheric composition, andradiative forcing through model studies using the emission scenarios definedfor the IPCC 2001 climate assessment,• analyze the magnitude of intercontinental pollutant transport.Scientific achievements:• first detailed, comprehensive and consistent data sets on global emissionsfrom fossil and biofuel combustion and from open vegetation burningcovering the time period 1960-2000; available as gridded data sets with0.5°×0.5° and monthly mean resolution,• first global long-term atmospheric chemistry integrations with several stateof-the-art models using the ERA-40 meteorological data, the RETROemissions and other constrains in a consistent and well-documented manner,• analysis of key parameters controlling the interannual and seasonalvariability and the longer-term trends in the tropospheric composition relatedto ozone and its precursors,• development of new software tools for the analysis of observational data andmodel results; standardisation of model output and data formats anddefinition of model evaluation metrics and skill scores,• development of a comprehensive data base for tropospheric compositionobservations with complete metadata definition and a user-friendly interfacefor data access,• multi-model analysis of specific scenarios related to power generation andthe ...

BACKGROUND: Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation. METHODS: 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets. RESULTS: RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses. CONCLUSION: RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent.