7th Framework Programme Research Articles

Abstract A115: Cancer vaccine development for hepatocellular carcinoma – HEPAVAC

Abstract The HEPAVAC Consortium aims to develop a highly innovative, novel cancer vaccine approach for hepatocellular carcinoma (HCC). The international project consortium consists of 9 European Partners from academia and the biotech industry with complementary and substantial expertise in developing immunotherapeutic strategies to treat cancer. The project has started in September 2013 and is supported by the European Commission's 7th Framework Program (www.hepavac.eu). HCC/normal adjacent tissue matched samples have been collected for HLA immunopeptidome analysis. 17 HCC samples from HLA-A*02+ patients and 15 samples from HLA-A*24+ patients have been analysed by mass spectrometry (LC-MS/MS). RNA-expression profiles have been established for 12 HCC samples. HLA-presentation/expression of peptides and mRNA on primary HCC samples are compared to n>140 normal tissue samples from relevant organs (including heart, brain, lung, kidney, liver, nerve, skin etc.) from Immatics' database. A total of 9051 HLA-A*02-restricted different tumor-associated peptides (TUMAPs) have been identified from HLA-A*02+ samples, while a total of 3286 different HLA-A*24-restricted TUMAPs have been identified from HLA-A*24+ samples. Of these, 33 HLA-A*02+ TUMAPS and 33 HLA-A*24+ TUMAPs are currently in the process of validation, including peptide synthesis, immunogenicity testing and pharmaceutical evaluation. Most promising TUMAP candidates show selective expression only in HCC samples and no expression in normal tissues. In parallel, more than 6600 HLA-DR TUMAPs have been identified in Hep3B cells transfected with CIITA as well as an average of 1500 HLA-DR TUMAPs have been identified in HCC samples. Additional HLA-DR TUMAPs derived by distinct CIITA-transfected cell lines with different HLA-DR haplotypes are under scrutiny. The discovery phase of the HEPAVAC project is proceeding according to the proposed timelines. HCC-specific epitopes to be included in the vaccine cocktail will be selected in the coming weeks for GMP production. In parallel, preclinical studies assessing the formulation and combination of the immunological RNA-based adjuvant (RNAdjuvant®) with peptide cocktails are underway. Citation Format: Luigi Buonaguro, Sarah Kutscher, Roberto Accolla, Yuk T. Ma, Regina Heidenreich, Francesco Izzo, Alfred Koenigsrainer, Markus Loeffler, Phillip Mueller, Andrea Mayer, Hans-Georg Rammensee, Bruno Sangro, Sven Francque, Danila Valmori, Toni Weinschenk, Harpreet Singh-Jasuja. Cancer vaccine development for hepatocellular carcinoma – HEPAVAC. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A115.

The impact of new data for identification and authorship: the case of The Last Judgement, triptych from the National Museum in Gdańsk, a Northern Renaissance work, by Rogier van der Weyden and Hans Memling

The triptych The Last Judgement from the National Museum in Gdańsk is one of the most mysterious of the Flemish Renaissance works of the 15th century. Since the late 1960s, based on conservation research, art historians have known that another painting lays underneath the work. Until 2012-2014, however, identification and seeing all hidden image in detail has been impossible. There are no known historical sources making specific reference to the origin of this work. Its authorship has often been questioned. Since Hotho’s hypothesis of 1843, the painting is regularly attributed to Hans Memling. The earliest and only certain date in the history of the triptych is the 27 April 1473, the date when it was seized by pirates at sea during its transportation from the port of Bruges to Badia Fiesolana near Florence. As a Hanseatic spoil of war, the triptych passed to St. Mary’s Basilica in Gdańsk. The artwork was analysed from a number of perspectives, ranging from a humanistic enquiry to its physico-chemical properties. It was found that the triptych was painted with a multilayer tempera-oil technique on oak support. Dendrochronological work by Tomasz Ważny showed that the oak support was prepared for painting at the end of 1460. The results of these tests facilitate a fresh approach to the dating of the work and a new interpretation of its origins. A number of scientific examinations were undertaken owing to a grant from the 7th Framework Programme in 2012-2014 in collaboration with an international group of scientists in the project CHARISMA-MOLAB and ARCHLAB. The project offered an access to most advanced EU scientific instrumentations and knowledge to enhance our research, the goal of studies at ARCHLAB in the C2RMF was to confront documents and draw a comparison of the results of The Last Judgement investigations with data of other works of Rogier van der Weyden and Hans Memling.This provided a number of new results based on MNIR results concerning the several stages of the artistic process. New information confirmed the thesis of the dates 1460 – instead of 1466-1467, as expressed previously – as well as three stages in the composition and underdrawing of the work; with the priming layers probably made by Rogier van der Weyden with his collaborators. It was the norm in 15th century painting workshops, while the completion of the painting and final layers were probably the work of Hans Memling (his earliest and most important achievements in his oeuvre). The results shed light on the original proto-Renaissance pedigree of 15th century Flemish painting with its identity born in the north of Europe.

The Lead-Based VENUS-F Facility: Status of the FREYA Project

The GUINEVERE project in the 6th European Framework Program (FP6) (1) aimed to check the methods for sub-criticality monitoring. To execute the project, the water- moderated thermal VENUS facility was modified into the lead fast VENUS-F facility in the period 2007-2010. To prove the reliability of the reactivity monitoring methods, first of all a critical reference configuration was assembled and characterized by measurements of criticality, power distribution, and spectral indexes. These experiments were communicated for benchmarking at ISRD-14 (2). The Monte Carlo MCNP 5-1.60 code with the JEFF 3.1.2 data library is used to perform simulations of the VENUS-F core, in particular to obtain Calculated-to-Experimental ratios (C/E) for fission rates and spectral indices. A sensitivity study is performed focusing on the impact of global and local parameters on C/E. In most cases C/E is close to unity within the uncertainties. Only a few exceptions were found, e.g. for the F28/F25 spectral index (3). In order to investigate the discrepancies, a new measurement campaign with the same critical configuration was included in the currently ongoing FREYA project in FP7 (4). The facility status, experimental plans, and the sensitivity study are presented in this paper.

PROGRESS TOWARDS TARGETING DISEASE PROPHYLAXIS IN EUROPEAN FISH FARMING (TARGETFISH)

TargetFish is a large collaborative project funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993). The project will run for 5 years, started in November 2012 and thus is approximately halfway. TargetFish brings together a large number of leading European research groups (RTD) that are experts on fish pathology and immunology and small-to-medium enterprises (SME) as well as some larger industries from the Biotech and Veterinary sectors, which all share a common interest and experience: vaccination of fish. To achieve this challenging task, we brought together approximately 30 partners from 10 EU member states, two associated countries and one International Cooperation Partner Country (Chile). In this large multidisciplinary consortium an approximate equal number of RTD and SME partners cooperate closely while keeping an intensive communication with the vaccine and nutrition industries. The main objectives of the project are to: 1) generate knowledge by studying antigens and adjuvants for different routes of administration while analyzing the underpinning protective immune mechanisms; 2) validate this knowledge with response assays for monitoring vaccine efficacy and safety, including issues associated with DNA vaccines; 3) approach implementation of prototype vaccines shortening the route to exploitation and 4) optimize vaccination strategies in order to obtain maximum protection in different sizes of fish. At present, progress has been made in particular with regard to main objectives 1-3. The vaccine delivery systems under investigation include oral routes of administration using, for example, alginate microencapsulation and MicroMatrixTM technologies. TargetFish also focuses on investigating mucosal vaccination routes and associated immunity and in developing antigens and adjuvants specifically suited for mucosal delivery. Most fish vaccines on the market are delivered by injection, being this a labour-intensive, expensive method that provokes stress in the fish. Mucosal vaccination routes (immersion or oral) would certainly be more desirable.

GASTONE – Development of a New Powertrain Concept Based on the Integration of Electric Generation, Energy Recovery and Storage

The new challenge in the reduction of CO2 emissions by heavy duty trucks is leading to a technological evolution in powertrain efficiency.Towards this objective, the EU has funded in the frame of the 7th framework program the project GASTONE: a collaborative project between several private and public companies and institutions: CRF, FTP, Continental, GENTHERM, MAGNA and U. Politécnica de Valencia, targeting the development of a new powertrain concept based on the integration of electric generation, energy recovery and storage with engine system and control strategies.The main features of this CNG engine concept are:•The energy recovery from the exhaust gases heat with a cascade approach thanks to the adoption of an advanced thermoelectric generator and a turbo-generator.•The integration of a smart kinetic energy recovery system to substitute the alternator with a smarter electrical machine.•The electrification of the main auxiliaries (coolant and oil pumps, auxiliary e-supercharger and air conditioning compressor).The electrification process is supported by an improvement of the performance of the CNG engine (the actual average value is about 38%): this number is expected to rise by 4% thanks to the engine control strategy improvement, by 1% due to the introduction of the water charge air cooler, by 2% from the reduction of the belt drive and gear losses, by 1% from the system strategy and management optimization and by 7% from the exhaust heat recovery (thermo-electric generator plus turbo-generator).This paper presents the details of the new powertrain concept design, the simulation tool developed to support the design and optimize the system and a cost per function tool to perform an economic analysis in the hypothesis to introduce the system in the market.The obtained benefits are expressed in terms of fuel saving for a target real driving cycle and effects related to the new devices are developed and tested.The project is in the design phase and the paper collects a first estimation of results based on the design, strategy and control improvement.

A collaborative (web-GIS) framework based on empirical data collected from three case studies in Europe for risk management of hydro-meteorological hazards

This paper presents a collaborative framework of an interactive web-GIS platform integrated with a multi-criteria evaluation tool. The platform aims to support the engagement of different stakeholders and the encouragement of a collaborative, decision-making process for flood and landslide management. The conceptual framework is based on initial data collected from field visits and stakeholder meetings carried out in the case study areas of the CHANGES33CHANGES project is a Marie Curie ITN funded by the European Community's 7th Framework Program. project: the Małopolska Voivodeship of Poland, Buzău County of Romania and the Friuli-Venezia-Giulia region of Italy. Based on the needs and issues identified in each case study, this paper also presents how such a platform could potentially assist and enhance the interactions between risk management stakeholders in formulating and selecting risk management measures. The developed prototype was presented to the local and regional stakeholders of the study areas and feedback was collected to understand the stakeholders’ perspectives in determining whether the platform is useful and applicable for their activities in risk management. Feedback from stakeholder responses indicate that stakeholders found the prototype not only useful, but innovative and supportive in potentially assisting their activities. However, feedback also highlighted several aspects of the platform that can be improved for the development of a full-scale system to apply in practice. This includes the engagement of stakeholders toward higher levels of participation and a more extensive evaluation of the platform by carrying out concrete group exercises in the study areas.

Hybrid Communication Network for the Smart Grid: Validation of a Field Test Experience

The business of distribution system operators is rapidly evolving as the distribution grid is hosting more distributed energy resources. Technology for monitoring, control, and protecting the grid is progressively pervading the lower segment of the network. These changes require a performing communication infrastructure to enable data exchange among the control centers of the grid. The 7th Framework Program European Project INTEGRIS proposes a hybrid infrastructure—based on broadband power line (BPL), Wi-Fi, and fiber optics (FO)—to enable services for grid management. This mix of technologies provides a balanced tradeoff between investments and benefits, meeting most of the requirements of the smart grid. This paper investigates the technologies that could be adopted and describes the experimental assessment performed in an operational environment in Italy. Using this installation, transfer time, time synchronization accuracy, dependability, and throughput are evaluated and analyzed over a long-term campaign. Results show that the FO is the best communication media, able to provide a two-way latency of 3 ms (95 percentile), whereas BPL has a two-way latency of 57 ms (95 percentile —4 hops). Those results confirm that a careful selection of the technologies is required to satisfy requirements of smart grid.

Quality of antenatal and childbirth care in rural health facilities in Burkina Faso, Ghana and Tanzania: an intervention study

To assess the impact of an intervention consisting of a computer-assisted clinical decision support system and performance-based incentives, aiming at improving quality of antenatal and childbirth care. Intervention study in rural primary healthcare (PHC) facilities in Burkina Faso, Ghana and Tanzania. In each country, six intervention and six non-intervention PHC facilities, located in one intervention and one non-intervention rural districts, were selected. Quality was assessed in each facility by health facility surveys, direct observation of antenatal and childbirth care, exit interviews, and reviews of patient records and maternal and child health registers. Findings of pre- and post-intervention and of intervention and non-intervention health facility quality assessments were analysed and assessed for significant (P < 0.05) quality of care differences. Post-intervention quality scores do not show a clear difference to pre-intervention scores and scores at non-intervention facilities. Only a few variables had a statistically significant better post-intervention quality score and when this is the case this is mostly observed in only one study-arm, being pre-/post-intervention or intervention/non-intervention. Post-intervention care shows similar deficiencies in quality of antenatal and childbirth care and in detection, prevention, and management of obstetric complications as at baseline and non-intervention study facilities. Our intervention study did not show a significant improvement in quality of care during the study period. However, the use of new technology seems acceptable and feasible in rural PHC facilities in resource-constrained settings, creating the opportunity to use this technology to improve quality of care.

The impact of dwelling renovation on spatial quality

Purpose – Non-technical dimensions such as spatial quality are just as relevant for energy efficiency as technical and economic dimensions in the renovation of dwellings. However, the significance of non-technical dimensions is often neglected in the energy renovation of dwellings. The purpose of this paper is to demonstrate how the renovation of dwellings for energy efficiency influences spatial quality in the MS-1 building in the neighbourhood of Arlequin, Grenoble, France. The Arlequin case study is part of the ZenN project, nearly zero energy neighbourhoods, funded by the European 7th Framework Programme (Grant Agreement No. 314363). Design/methodology/approach – The impact of the renovation on spatial quality is analysed by crossing technical measures, applied in the energy renovation of dwellings with the definition of spatial quality proposed by Acre and Wyckmans (2014). The spatial quality definition results from a literature review on quality of design and urban life, wherein works of Weber (1995) and Gehl (2010, 2011) are related to the residential use in the scales of the building and block. The impact of renovation on spatial quality is further evaluated by using the spatial quality assessment developed by Acre and Wyckmans (2015). The impact on spatial quality is observed by considering all the renovation measures, instead of only considering the measures primarily related to energy performance. This emphasises the need for a cross-disciplinary approach between technical and non-technical dimensions in the energy renovation of dwellings. Findings – The results display both negative and positive impacts of the energy renovation on spatial quality in the dwellings and emphasise the potential of non-technical dimensions in promoting renovation. The impact on spatial quality is primarily negative when only measures adopted in order to improve energy efficiency are considered in the evaluation. Originality/value – This paper consists of a novel crossing of technical and non-technical dimensions in energy renovation of dwellings. The work aligns with the current European trend of nurturing energy-deep renovation to reach Europe’s 2050 energy-efficiency targets (Buildings Performance Institute Europe (BPIE) 2011).

The Implementing Geological Disposal Technology Platform – addressing the needs of new Member States

AbstractThe Implementing Geological Disposal of Radioactive Waste Technology Platform (IGD-TP) was launched in November 2009 to facilitate international cooperation in common areas of research, development and demonstration (RD&amp;D) with a view to advancing the implementation of geological disposal facilities for spent fuel, high-level and other long-lived waste in Europe.The IGD-TP's Vision is that “by 2025, the first geological disposal facilities for spent fuel, high-level waste and other long-lived radioactive waste will be operating safely in Europe”. Aside from most European waste management organisations, the IGD-TP currently has 124 members covering most of the RD&amp;D actors in the field of implementing geological disposal of radioactive waste in Europe.Five years after its inception, the IGD-TP has been shown to play a leading role in coordinating joint actions for RD&amp;D in radioactive waste geological disposal programmes. The work of the platform takes into account differences between the timing and challenges for the respective waste management programmes. Following implementation of Posiva's geological disposal facility in Finland it is expected that within the next 5 years the construction of the Swedish and French geological disposal facilities will commence. Within IGD-TP, the SecIGD2 project whose remit is “Coordination and Support Action under the 7th Framework programme” aims at supporting, at the European level, the networking and structuring of RD&amp;D programmes and competences in countries with less advanced geological disposal programmes, including those in the new European Union Member States. Furthermore, the SecIGD2 supports the development and coordination of the necessary competences to meet the Vision 2025 as a part of the platform's Competence Maintenance, Education and Training (CMET) working group.

Assessment of Environmental Determinants of Physical Activity: a Study of Built Environment Indicators in Brno, Czech Republic.

Research on physical activity in relation to obesity gradually becomes more focused on environmental determinants, which can potentially influence people's health choices. The present article addresses the topic of physical activity from a wider sociological perspective. Our pilot study was designed with the objective of testing the applicability of a method included in the EC 6th Framework Programme EURO-PREVOB, in the Czech context. The method examines specific determinants of the built environment that can have an impact on physical activity at the population level. In addition, the study aims to analyze possible differences in built environment indicators and their relation to the physical activity of people living in neighbourhoods with areas of varying socioeconomic status. The field study was carried out in the city of Brno, Czech Republic, in 5 neighbourhood quintiles, i.e. areas divided according to the socioeconomic status of local residents. In each quintile, we evaluated the quality of the built environment according to the quality, aesthetics and safety of segregated cycle facilities, playgrounds/playing areas, public open spaces, marked road crossings and pavements as well as signs of incivilities and devastation. Between the five quintiles, significant differences were found in the quality of parks and playgrounds/playing areas, pavements, marking of pedestrian crossings, and in general aesthetics, i.e. signs of incivilities and devastation of the built environment. No differences were found in the quality and use of cycle facilities. The method we used for the evaluation of the built environment proved highly applicable in Czech populated areas. Monitoring of built environment indicators in the Czech Republic should provide a basis for health maps, showing potential associations between the prevalence of high-incidence, non-infectious diseases and various social determinants of physical activity. This information might help in achieving an improvement in these determinants at a community level and promoting an increase in physical activity at the population level.

Book Review: Socio-Economic Impacts of Bioenergy Production

Book Review: Socio-Economic Impacts of Bioenergy Production

Job Loss, Unemployment and the Incidence of Hazardous Drinking during the Late 2000s Recession in Europe among Adults Aged 50-64 Years.

BackgroundTo estimate the incidence of hazardous drinking in middle-aged people during an economic recession and ascertain whether individual job loss and contextual changes in unemployment influence the incidence rate in that period.MethodsLongitudinal study based on two waves of the SHARE project (Survey of Health, Ageing and Retirement in Europe). Individuals aged 50–64 years from 11 European countries, who were not hazardous drinkers at baseline (n = 7,615), were selected for this study. We estimated the cumulative incidence of hazardous drinking (≥40g and ≥20g of pure alcohol on average in men and women, respectively) between 2006 and 2012. Furthermore, in the statistical analysis, multilevel Poisson regression models with robust variance were fitted and obtained Risk Ratios (RR) and their 95% Confidence Intervals (95%CI).ResultsOver a 6-year period, 505 subjects became hazardous drinkers, with cumulative incidence of 6.6 per 100 persons between 2006 and 2012 (95%CI:6.1–7.2). Age [RR = 1.02 (95%CI:1.00–1.04)] and becoming unemployed [RR = 1.55 (95%CI:1.08–2.23)] were independently associated with higher risk of becoming a hazardous drinker. Conversely, having poorer self-perceived health was associated with lower risk of becoming a hazardous drinker [RR = 0.75 (95%CI:0.60–0.95)]. At country-level, an increase in the unemployment rate during the study period [RR = 1.32 (95%CI:1.17–1.50)] and greater increases in the household disposable income [RR = 0.97 (95%CI:0.95–0.99)] were associated with risk of becoming a hazardous drinker.ConclusionsJob loss among middle-aged individuals during the economic recession was positively associated with becoming a hazardous drinker. Changes in country-level variables were also related to this drinking pattern.

Connectivity, contest and the ties of self-management support for type 2diabetes: a meta-synthesis of qualitative literature.

This paper presents a meta-synthesis of the literature on community-based self-management to support experiences of people diagnosed with type 2 diabetes. The aim was to synthesise findings on both formal and informal self-management support with particular reference to the relevance and influence of the social context operating at different levels. The review forms part of EU-WISE, a project financed through EU's 7th Framework Programme. The review was performed by systematically searching MEDLINE, PubMed, EMBASE, CINAHL, PsycINFO and Web of Science for English language publications between 2005 and 2014 presenting research conducted in Europe on the experiences and perspectives of self-management concerns of patients diagnosed with type 2 diabetes. The search yielded 587 abstracts, which were reduced through search strategy refinement and eligibility and quality criteria to 29 papers that were included in the review. This review highlights the relevance of contextual factors operating at micro- and macro-levels. The synthesis yielded six second-order thematic constructs relating to self-management: sense of agency and identity, the significance and meaning of social networks, minimal disruption of everyday life, economic hardship, the problem of assigning patients' responsibility and structural influences of primary care. Using a line of argument synthesis, these themes were revisited, and a third-order construct, connectivity emerged which refers to how links in daily life are interwoven with peoples' social networks, local communities, economic and ideological conditions in society in a way which support self-management activities. This meta-synthesis indicates a need to heed the notion of connectivity as a means of mobilising and supporting the self-management strategies of people with type 2 diabetes in everyday life.

Innovative Strategies and Machines for Physical Weed Control in Organic and Integrated Vegetable Crops

Weed control is one of the most serious problems in vegetable crops, limiting cultivated plants correct development, yields, product quality and farmers income. Therefore, the aim of this work was to set up and improve innovative strategies and machines for physical (mechanical and thermal) weed control in organic or “integrated” vegetables production in many important areas of Northern, Central and Southern Italy. Therefore, on-farm experiments were carried out since 1999 on fresh marketable spinach, processing and fresh market tomato, cauliflower, savoy cabbage, greenhouse cultivated leaf beet, garlic, chicory, fennel and carrot. These research activities started are still ongoing. The traditional farm weed management system was always compared to one or more innovative strategies that were defined according to the characteristics of the environment (i.e. soil type and conditions, water availability, etc.), typology of cultivation, crop rotation, expected technical and economical results. The innovative strategies were the combination among preventive methods (false or stale seed-bed technique), cultural methods (i.e. crop spatial arrangement that was often adjusted in order to improve operative machines effectiveness) and direct control methods (flaming, precision hoeing, etc.). Different kinds of specific implement such as flex tine and rolling harrows (patented by the University of Pisa, patent n. PI/2004/A/000071), and flamers (designed and realized by the University of Pisa) were used to perform false or stale seed-bed technique. Precision hoes equipped with rigid tools and hoeconformed rolling harrows, equipped with elastic tines for selective intra-row weed control, were used to perform post emergence interventions. The use of the innovative weed management systems always resulted in significant weed abundance reductions (from 70 to 100 %), relevant yield increases, high contractions of manpower requirement (from 20 to 80 %) and consequent relevant reductions of costs and increases of farmers gross incomes (from 15 to 75 %) in comparison with those obtained performing the standard systems. The results of these on-farm experiments emphasise that physical weed control can be effectively performed using the innovative machines designed and built at the University of Pisa. These machines can also be easily adjusted in order to be used in other crops and agricultural contexts. Moreover, the present versions of the machines, realized as “low-tech” implement in order to be available on the market at low costs, were recently modified within the RHEA Project, a 7th Framework Programme EU funded research project, in which an automatic and robotized hoeing-flaming machine able to perform VRA cross flaming was designed, fully realized and tested obtaining very promising results.

Preliminary Evaluation of Recriticality Potential for ESFR Core and Conditions for Its Elimination

In the case of a severe accident in a core resulting from unprotected loss of flow (ULOF) or unprotected transient overpower, damage can propagate from subassembly to subassembly and produce a whole-core–scale molten pool. Because the core is not in its most reactive configuration, a massive collapse of the molten material could result in a rapid supercritical condition with release of a large amount of energy. However, timely and sufficient fuel relocation outside the core by dedicated means could prevent any risk of recriticality and accident escalation. Based on a reference 1500-MW(electric) sodium-cooled fast reactor design, this paper describes the main results obtained in evaluating the recriticality potential of the European Sodium Fast Reactor (ESFR) core and conditions for its elimination during a ULOF-type transient. This study has been carried out in the frame of the Collaborative Project on European Sodium Fast Reactor of the 7th Framework Programme Euratom. The numerical analyses carried out in the present work allow one to estimate the amount of fuel mass that has to be removed from the core in order to maintain it in subcritical conditions, preventing the formation of a critical pool. Requirements for successful application of this approach, in terms of the negative reactivity insertion rate by fuel relocation and timing of discharge from the core, are derived.

TEACHER TRAINING AT CHEMISTRY FACULTIES – MUTUAL BENEFITS? A CASE STUDY BASED ON THE EXAMPLE OF THE IRRESISTIBLE PROJECT

The training of teachers at educational science faculties prepares them better to deal with class management, individualization of teaching, evaluating, problems with motivation, etc. Teachers educated at chemistry faculties have a profound and well-established knowledge in the field of chemistry, but they demonstrate limited pedagogical skills. Recently, the collaboration between chemists, researchers in chemistry education and chemistry teachers has become more intense. In 2013, the Jagiellonian University joined the 7th Framework Programme project – IRRESISTIBLE (http://www.irresistible-project.eu). The goal of the project IRRESISTIBLE is to design activities that foster the involvement of students and the public in the process of Responsible Research and Innovation (RRI). A case study based on the example of the IRRESISTIBLE project is presented. Some interesting results are discussed. Key words: educational science, science education, teacher education.

Thermal conductivity and emissivity measurements of uranium carbides

Thermal conductivity and emissivity measurements on different types of uranium carbide are presented, in the context of the ActiLab Work Package in ENSAR, a project within the 7th Framework Program of the European Commission. Two specific techniques were used to carry out the measurements, both taking place in a laboratory dedicated to the research and development of materials for the SPES (Selective Production of Exotic Species) target. In the case of thermal conductivity, estimation of the dependence of this property on temperature was obtained using the inverse parameter estimation method, taking as a reference temperature and emissivity measurements. Emissivity at different temperatures was obtained for several types of uranium carbide using a dual frequency infrared pyrometer. Differences between the analyzed materials are discussed according to their compositional and microstructural properties. The obtainment of this type of information can help to carefully design materials to be capable of working under extreme conditions in next-generation ISOL (Isotope Separation On-Line) facilities for the generation of radioactive ion beams.

Abstract 3080: Definition of the Ewing sarcoma specific oncomir-1 targetome

Abstract MicroRNAs (miRNA) serve to fine-tune gene expression and thus play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a given tissue still poses a significant problem, since the presence of a seed sequence in the 3´UTR of an mRNA and its expression modulation upon forced ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. Here, we used a combination of AGO2 pull-down experiments by PAR-CLIP - to enrich and sequence RISC-associated RNAs - and of RNAseq upon miRNA depletion by ectopic sponge expression, to identify the targetome of miR17-92 in Ewing sarcoma (ES) cells. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in ES. As an aberrant ETS transcription factor it directly deregulates a multitude of genes related to proliferation control and differentiation. Recently, we reported on the EWS-FLI1 microRNA (miRNA) signature based on knockdown experiments in ES cell lines and on differential expression in primary tumors versus mesenchymal stem cells. Comparison of both datasets revealed miR20a-3p to be the top EWS-FLI1 activated miRNA. MiR-20a belongs to the miR17-92 cluster, also known as oncomir-1, which is one of the most potent oncogenic miRNAs. The whole cluster is among the small number of miRNAs down-regulated upon knockdown of EWS-FLI1 in multiple ES cell lines. Since feedback loops exists between the E2F transcription factor family and miR-17-92 and between EWS-FLI1 and E2F3, we sought to investigate the role of this miRNA cluster in ES. We found a significant enrichment of PAR-CLIP hits for members of the miR-17-92 cluster, in the 3´UTRs of genes up-regulated in response to mir-17-92 specific sponge expression. Among them we consistently identified known (i.e. CTGF, MXD1, CYLD1) and a multitude of so far unknown targets of the oncomir-1 cluster in ES in three PAR-CLIP experiments. Preliminary experiments using 3′UTRs of select novel candidate genes in gene reporter assays showed up-regulation of luciferase activity upon transfection of a sponge specific to miR-17-92 and 20a, but not to unrelated miR-9 and 10b. Site directed mutagenesis of seed sequences in the 3′UTR of these candidate genes will be used for further validation. This study provides an example for the comprehensive definition of the targetome for a defined group of miRNAs under physiological conditions. This study was supported by the 7th framework program of the European Commission (FP7-259348, “ASSET”) and the Austrian Science Fund FWF (24708-B21) Citation Format: Raphaela Schwentner, David Herrero-Martin, Maximilian Kauer, Heinrich Kovar. Definition of the Ewing sarcoma specific oncomir-1 targetome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3080. doi:10.1158/1538-7445.AM2015-3080

Abstract 2104: Evidence for E2F/EWS-FLI1 oncoprotein synergism using systems biology

Abstract Cell cycle deregulation and enhanced proliferation of cells is one of the hallmarks of oncogenesis. In Ewing Sarcoma, a highly aggressive pediatric cancer, the chimeric transcription factor EWS-FLI1 deregulates cell cycle by targeting several cell cycle regulators including the E2F family of transcription factors. ChIP-seq studies showed a significant overlap of EWS-FLI1 and E2F3/4 binding in Ewing sarcoma cells. We show that EWS-FLI1 is able to directly activate E2F3, followed by the combinatorial binding of EWS-FLI1 and E2F3 on their target genes synergistically activating their transcription. Furthermore we propose a model where EWS-FLI1 directly exchanges repressive E2F4/p130 by E2F3/pRB thereby driving cells into enhanced cell proliferation. However, so far we were unable to experimentally demonstrate a physical interaction of EWS-FLI1 with any E2F or pocket protein. As an alternative approach to the study of functional synergy between EWS-FLI1 and E2F3, we used time resolved RNA and protein expression data as a basis for mathematical modeling of EWS-FLI1 dependent E2F target gene regulation. By Bayesian model selection, we were able to postulate the formation of a complex between EWS-FLI1 and E2F3 as the most likely explanation for the observed ETS/E2F synergy. This study therefore provides an example of how computational systems approaches can complement experimental data in the discovery of disease mechanisms. This study was supported in part by the Austrian Science Fund (FWF), [grant 22328-B09], and by the 7th framework program of the European Commission, [grant 259348] (‘ASSET’). Citation Format: Raphaela Schwentner, Theodore Papamarkou, Maximilian Kauer, Vassilios Stathopoulos, Fan Yang, Sven Bilke, Paul S. Meltzer, Mark Girolami, Heinrich Kovar. Evidence for E2F/EWS-FLI1 oncoprotein synergism using systems biology. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2104. doi:10.1158/1538-7445.AM2015-2104