Directorate-General for Research and Innovation

The paper outlines a vision for Responsible Innnovation

miRNAs are a class of versatile small RNAs that control gene expression post-transcriptionally, governing many facets of plant cell functions. They interact with their target mRNA at a site of sequence complementarity and modulate their expression levels. Here, we provide evidence, based on transient assays and stable transgenic lines, that the 3' UTR of the Arabidopsis SBP box gene SPL3 contains a functional miRNA-responsive element (MRE) that is complementary to miR156 and miRNA157. Seedlings of transgenic lines constitutively over-expressing an SPL3 transgene either carrying an unaltered or a disrupted MRE accumulate considerable levels of SPL3 transcripts. However, while the unaltered MRE UTR does not allow the expression of detectable levels of SPL3 protein, the altered MRE does. Translational inhibition thus provides an important mechanism for miRNA-mediated post-transcriptional repression of SPL3. As a consequence of precocious translation of the constitutively expressed SPL3 transgene, due to the absence of a functional MRE, plants exhibit very early flowering in addition to frequent morphological changes.

Understanding the surface O 3 response over a “receptor” region to emission changes over a foreign “source” region is key to evaluating the potential gains from an international approach to abate ozone (O 3 ) pollution. We apply an ensemble of 21 global and hemispheric chemical transport models to estimate the spatial average surface O 3 response over east Asia (EA), Europe (EU), North America (NA), and south Asia (SA) to 20% decreases in anthropogenic emissions of the O 3 precursors, NO x , NMVOC, and CO (individually and combined), from each of these regions. We find that the ensemble mean surface O 3 concentrations in the base case (year 2001) simulation matches available observations throughout the year over EU but overestimates them by >10 ppb during summer and early fall over the eastern United States and Japan. The sum of the O 3 responses to NO x , CO, and NMVOC decreases separately is approximately equal to that from a simultaneous reduction of all precursors. We define a continental‐scale “import sensitivity” as the ratio of the O 3 response to the 20% reductions in foreign versus “domestic” (i.e., over the source region itself) emissions. For example, the combined reduction of emissions from the three foreign regions produces an ensemble spatial mean decrease of 0.6 ppb over EU (0.4 ppb from NA), less than the 0.8 ppb from the reduction of EU emissions, leading to an import sensitivity ratio of 0.7. The ensemble mean surface O 3 response to foreign emissions is largest in spring and late fall (0.7–0.9 ppb decrease in all regions from the combined precursor reductions in the three foreign regions), with import sensitivities ranging from 0.5 to 1.1 (responses to domestic emission reductions are 0.8–1.6 ppb). High O 3 values are much more sensitive to domestic emissions than to foreign emissions, as indicated by lower import sensitivities of 0.2 to 0.3 during July in EA, EU, and NA when O 3 levels are typically highest and by the weaker relative response of annual incidences of daily maximum 8‐h average O 3 above 60 ppb to emission reductions in a foreign region (<10–20% of that to domestic) as compared to the annual mean response (up to 50% of that to domestic). Applying the ensemble annual mean results to changes in anthropogenic emissions from 1996 to 2002, we estimate a Northern Hemispheric increase in background surface O 3 of about 0.1 ppb a −1 , at the low end of the 0.1–0.5 ppb a −1 derived from observations. From an additional simulation in which global atmospheric methane was reduced, we infer that 20% reductions in anthropogenic methane emissions from a foreign source region would yield an O 3 response in a receptor region that roughly equals that produced by combined 20% reductions of anthropogenic NO x , NMVOC, and CO emissions from the foreign source region.

Support for parties opposed to European Union (EU) integration has risen rapidly, and a wave of discontent has taken over the EU. This discontent is purportedly driven by the very factors behind the surge of populism: differences in age, wealth, education, or economic and demographic trajectories. This paper maps the geography of EU discontent across more than 63,000 electoral districts in the EU-28 and assesses which factors push anti-EU voting. The results show that the anti-EU vote is mainly a consequence of local economic and industrial decline in combination with lower employment and a less educated workforce. Many of the other suggested causes of discontent, by contrast, matter less than expected, or their impact varies depending on levels of opposition to European integration.

In the EU, the mapping and assessment of ecosystems and their services, abbreviated to MAES, is seen as a key action for the advancement of biodiversity objectives, and also to inform the development and implementation of related policies on water, climate, agriculture, forest, marine and regional planning. In this study, we present the development of an analytical framework which ensures that consistent approaches are used throughout the EU. It is framed by a broad set of key policy questions and structured around a conceptual framework that links human societies and their well-being with the environment. Next, this framework is tested through four thematic pilot studies, including stakeholders and experts working at different scales and governance levels, which contributed indicators to assess the state of ecosystem services. Indicators were scored according to different criteria and assorted per ecosystem type and ecosystem services using the common international classification of ecosystem services (CICES) as typology. We concluded that there is potential to develop a first EU wide ecosystem assessment on the basis of existing data if they are combined in a creative way. However, substantial data gaps remain to be filled before a fully integrated and complete ecosystem assessment can be carried out.

Abstract. We examine the response of Arctic gas and aerosol concentrations to perturbations in pollutant emissions from Europe, East and South Asia, and North America using results from a coordinated model intercomparison. These sensitivities to regional emissions (mixing ratio change per unit emission) vary widely across models and species. Intermodel differences are systematic, however, so that the relative importance of different regions is robust. North America contributes the most to Arctic ozone pollution. For aerosols and CO, European emissions dominate at the Arctic surface but East Asian emissions become progressively more important with altitude, and are dominant in the upper troposphere. Sensitivities show strong seasonality: surface sensitivities typically maximize during boreal winter for European and during spring for East Asian and North American emissions. Mid-tropospheric sensitivities, however, nearly always maximize during spring or summer for all regions. Deposition of black carbon (BC) onto Greenland is most sensitive to North American emissions. North America and Europe each contribute ~40% of total BC deposition to Greenland, with ~20% from East Asia. Elsewhere in the Arctic, both sensitivity and total BC deposition are dominated by European emissions. Model diversity for aerosols is especially large, resulting primarily from differences in aerosol physical and chemical processing (including removal). Comparison of modeled aerosol concentrations with observations indicates problems in the models, and perhaps, interpretation of the measurements. For gas phase pollutants such as CO and O3, which are relatively well-simulated, the processes contributing most to uncertainties depend on the source region and altitude examined. Uncertainties in the Arctic surface CO response to emissions perturbations are dominated by emissions for East Asian sources, while uncertainties in transport, emissions, and oxidation are comparable for European and North American sources. At higher levels, model-to-model variations in transport and oxidation are most important. Differences in photochemistry appear to play the largest role in the intermodel variations in Arctic ozone sensitivity, though transport also contributes substantially in the mid-troposphere.

I was requested to make a contribution on “the societal need for technology assessment”. This request forced me to reflect on the same question as Armin Grunwald when he started to work on his introduction to technology assessment (Grunwald 2010), namely: whether there is some consolidated body of scientific knowledge that could adequately represent the self-understanding of the field “technology assessment”. Without such a body of knowledge, it would be very difficult to assess this heterogeneous field on its societal needs. The claims experts make in the field on (often assumed) societal needs for TA seem to vary just as much as the working methods and scientific disciplines involved. Now Armin Grunwald succeeded in turning his “introduction” into a major reference work for the field of technology assessment and thereby creating a consolidated body of knowledge, it seems to me that this would leave me merely with the task to provide some footnotes to his work, if I would choose to describe the societal needs from the perspective of the field itself.

Appraisal of reproductive strategy and fecundity is necessary to evaluate the reproductive potential of individual fish species. To estimate reproductive potential, one needs to consider a variety of attributes including onset of maturity, fecundity, atresia, duration of reproductive season, daily spawning behaviour and spawning fraction. In this contribution, we review several methods currently used to estimate fecundity of marine fishes collected in the field in relation to their reproductive strategy. The advantages and disadvantages of each method are provided. Requirements are given to appropriately sample gonadal tissue that will enable researchers to establish incidence of sexual maturity and estimate fecundity.

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In order to support the operation of ITER and the planned experimental programme an extensive set of plasma and first wall measurements will be required. The number and type of required measurements will be similar to those made on the present-day large tokamaks while the specification of the measurements-time and spatial resolutions, etc-will in some cases be more stringent. Many of the measurements will be used in the real time control of the plasma driving a requirement for very high reliability in the systems (diagnostics) that provide the measurements.The implementation of diagnostic systems on ITER is a substantial challenge. Because of the harsh environment (high levels of neutron and gamma fluxes, neutron heating, particle bombardment) diagnostic system selection and design has to cope with a range of phenomena not previously encountered in diagnostic design. Extensive design and R&D is needed to prepare the systems. In some cases the environmental difficulties are so severe that new diagnostic techniques are required.The starting point in the development of diagnostics for ITER is to define the measurement requirements and develop their justification. It is necessary to include all the plasma parameters needed to support the basic and advanced operation (including active control) of the device, machine protection and also those needed to support the physics programme. Once the requirements are defined, the appropriate (combination of) diagnostic techniques can be selected and their implementation onto the tokamak can be developed. The selected list of diagnostics is an important guideline for identifying dedicated research and development needs in the area of ITER diagnostics.This paper gives a comprehensive overview of recent progress in the field of ITER diagnostics with emphasis on the implementation issues. After a discussion of the measurement requirements for plasma parameters in ITER and their justifications, recent progress in the field of diagnostics to measure a selected set of plasma parameters is presented. The integration of the various diagnostic systems onto the ITER tokamak is described. Generic research and development in the field of irradiation effects on materials and environmental effects on first mirrors are briefly presented. The paper ends with an assessment of the measurement capability for ITER and a forward of what will be gained from operation of the various diagnostic systems on ITER in preparation for the machines that will follow ITER.

The paper reviews recent research and development activities in the field of hydropower technology. It covers emerging and advanced technologies to mitigate flow instabilities (active and passive approach) as well as emerging magneto-rheological control techniques. Recent research findings on flow instabilities are also presented, especially concerning fluid-structure interaction and transient operating conditions. As a great number of the existing large-scale hydroelectric facilities were constructed decades ago using technologies that are now considered obsolete, technologies to achieve the digitalisation of hydropower are also analysed. Advances in the electro-mechanical components and generator design are presented; their potential role to adapt hydropower to the current operating conditions is also highlighted. The text explores current efforts to advance hydropower operation, mainly in terms of European projects. It provides a detailed overview of the recent efforts to increase the operational range of hydraulic turbines in order to reach exceptional levels of flexibility, a topic of several recent research projects. Variable speed hydropower generation and its application in pumped storage power plants are presented in detail. Moreover, revolutionary concepts for hydroelectric energy storage are also presented with the analysis focusing on underwater hydro storage and hydropower's hybridisation with fast energy storage systems. Efforts to minimise hydropower's environmental footprint are also presented via the utilisation of small-scale and fish-friendly installations.

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research.

The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of "New Approach Methodologies" (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure-activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today's regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free "Next Generation Risk Assessment" (NGRA).

Eradicating hunger in all its forms, including chronic and hidden hunger, requires good understanding of the problem's magnitude, trends, and determinants. Existing studies measure “hunger” through proxies that all have shortcomings. We use a more comprehensive metric, Disability-Adjusted Life Years (DALYs), to quantify the burden of hunger and show related trends. While the burden of chronic hunger more than halved since 1990, it remains larger than the burden of hidden hunger. Cross-country regressions show that economic growth was a major determinant of reducing the hunger burden. However, growth and other country-level determinants have larger effects on the burden of chronic hunger than on the burden of hidden hunger. Complementary micro-level interventions are required to end hunger in all its forms.

The ever-increasing concentration of people and economic growth in the largest cities relative to the rest of the country has slowed down or even reversed in many of the developed European countries over the last decade. This trend contradicts what the global cities, urban economics and new economic geography literature would predict. This trend can be interpreted from two points of view: (1) the trend is due to large obstacles to further large city urbanization and thus is inefficient or (2) this trend highlights alternative pathways to growth than the mega-city approach and may be as, if not more, efficient. This trend may be linked to Europe's uniquely polycentric urban structure with high number of small- and medium-sized cities. In addition, improvements in the access to services, including broadband, outside large cities may have facilitated the higher growth rates of smaller centres and rural regions and increased their appeal for residents and firms. Last but not least, negative externalities in the large cities, such as congestion costs, pollution, labour crowding and high cost of living, may increase the appeal of smaller centres and rural regions.

CRONOS is a suite of numerical codes for the predictive/interpretative simulation of a full tokamak discharge. It integrates, in a modular structure, a 1D transport solver with general 2D magnetic equilibria, several heat, particle and impurities transport models, as well as heat, particle and momentum sources. This paper gives a first comprehensive description of the CRONOS suite: overall structure of the code, main available models, details on the simulation workflow and numerical implementation. Some examples of applications to the analysis of experimental discharges and the predictions of ITER scenarios are also given.

The European Green Deal, the European Commission's new Action Plan for a Circular Economy, the new European Industrial Strategy and the Chemicals Strategy for Sustainability launched in October 2020 are ambitious plans to achieve a sustainable, fair and inclusive European Union's economy. In line with the United Nations Sustainable Development Goals 2030, these policies require that any new material or product should be not only functional and cost-effective but also safe and sustainable to ensure compliance with regulation and acceptance by consumers. Nanotechnology is one of the technologies that could enable such a green growth. This paper focuses on advanced nanomaterials that actively respond to external stimuli, also known as 'smart nanomaterials', and which are already on the market or in the research and development phase for non-medical applications such as in agriculture, food, food packaging and cosmetics. A review shows that smart nanomaterials and enabled products may present new challenges for safety and sustainability assessment due to their complexity and dynamic behaviour. Moreover, existing regulatory frameworks, in particular in the European Union, are probably not fully prepared to address them. What is missing today is a systematic and comprehensive approach that allows for considering sustainability aspects hand in hand with safety considerations very early on at the material design stage. We call on innovators, scientists and authorities to further develop and promote the 'Safe- and Sustainable-by-Design' concept in nanotechnology and propose some initiatives to go into this direction.

Comprehensive Monitoring of Wildfires in Europe: The European Forest Fire Information System (EFFIS)

The International Rare Diseases Research Consortium (IRDiRC) was founded in 2011 with the conviction that rare diseases research had reached a critical juncture. Proof of principle existed that rare diseases could be diagnosed, new treatments successfully developed and approved, and improvements in quality and quantity of life achieved. Government research funders, companies, scientists, and patient advocacy groups had all demonstrated their commitment and effectiveness in contributing to progress in rare diseases research. However, the work was largely atomized, with each organization, each country, and the champions of each disease pursuing independent, often duplicative solutions. The scale of the "rare disease problem"-thousands of rare diseases, the vast preponderance of them with no approved treatment, and decades-long diagnostic odysseys for many patients-led to the realization that the time had arrived for global cooperation and collaboration among the many stakeholders active in rare diseases research, to capitalize on these proofs of principle, and maximize the output of rare diseases research efforts around the world. IRDiRC's initial aims were to aid in the achievement of two overarching objectives: to contribute to the development of 200 new therapies and the means to diagnose most rare diseases by the year 2020. 1 For more detailed information on the history, governance, and nascent stages of the Consortium, please refer to the accompanying piece on the first 6 years of IRDiRC.

Growth before and especially after the crisis differed from large-city-led growth pattern. The crisis has led to big contractions especially in urban regions and in remote rural regions, while intermediate and rural regions close to a city displayed more resilience. In some countries, the capital metro region had much higher economic growth prior to the crisis, but this pattern was inverted by the crisis. Capital cities are now central to the problems faced by national economies in Europe, and appear to have exacerbated the adverse effects of the crisis. This implies that a development strategy primarily focused on the capital city can lead to more volatile and potentially lower growth, than a more a balanced development strategy. The article uses data from the OECD regional database to investigate the performance of rural, intermediate and urban regions and Eurostat data to investigate metro regions.