Ethical challenges at the science-policy interface: an ethical risk assessment and proposition of an ethical infrastructure

Developing an interface between knowledge holders, stakeholders and decision makers on biodiversity issues, just as any science-policy interface, will face many challenges. In the crucial endeavour to tackle all those challenges, determining an ethical course of actions will be essential to the prestige and credibility of such an interface. The paper identifies and assesses potential ethical risks that may arise in interactions between science, society and policy and uses the Network of Knowledge (NoK) process as an example to show how an ethical infrastructure could be developed for minimizing the ethical risks and their potential consequences. Indeed, when various actors from different spheres (politics, academia, lobbyism, media, etc.) are called upon to interact within one process as complex as the NoK, the integrity and credibility of the latter are at high risk of being compromised if the ethical risks are not adequately addressed. In order to limit those risks, which science-policy interfaces such as IPCC and IPBES have already encountered, we propose to set up an ethical governance infrastructure that will guide (and regulate) interactions among internal actors of the NoK (knowledge coordination body, secretariat, expert working groups, etc.) as well as with external actors (requesters, stakeholders, etc.). A thorough evaluation of the interaction between the actors for every step of the process is carried out and potential ethical risks are identified. Suggestions as to how the risks can be handled and prevented are presented and integrated as part of an ethical infrastructure. The main objective of the paper is to address how a science-policy interface and the scientific community as a whole would benefit from implementing ethical measures and instruments to help prevent sensitive issues and undesired consequences undermining credibility and legitimacy.     

The Network of Knowledge approach: improving the science and society dialogue on biodiversity and ecosystem services in Europe

The absence of a good interface between scientific and other knowledge holders and decision-makers in the area of biodiversity and ecosystem services has been recognised for a long time. Despite recent advancements, e.g. with the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES), challenges remain, particularly concerning the timely provision of consolidated views from different knowledge domains. To address this challenge, a strong and flexible networking approach is needed across knowledge domains and institutions. Here, we report on a broad consultation process across Europe to develop a Network of Knowledge on biodiversity and ecosystem services (NoK), an approach aiming at (1) organising institutions and knowledge holders in an adaptable and responsive framework and (2) informing decision-makers with timely and accurate biodiversity knowledge. The consultation provided a critical analysis of the needs that should be addressed by a NoK and how it could complement existing European initiatives and institutions at the interface between policy and science. Among other functions, the NoK provides consolidated scientific views on contested topics, identification of research gaps to support relevant policies, and horizon scanning activities to anticipate emerging issues. The NoK includes a capacity building component on interfacing activities and contains mechanisms to ensure its credibility, relevance and legitimacy. Such a network would need to ensure credibility, relevance and legitimacy of its work by maximizing transparency and flexibility of processes, quality of outputs, the link to data and knowledge provision, the motivation of experts for getting involved and sound communication and capacity building.     

Forty research issues for the redesign of animal production systems in the 21st century

Agroecology offers a scientific and operational framework for redesigning animal production systems (APS) so that they better cope with the coming challenges. Grounded in the stimulation and valorization of natural processes to reduce inputs and pollutions in agroecosystems, it opens a challenging research agenda for the animal science community. In this paper, we identify key research issues that define this agenda. We first stress the need to assess animal robustness by measurable traits, to analyze trade-offs between production and adaptation traits at within-breed and between-breed level, and to better understand how group selection, epigenetics and animal learning shape performance. Second, we propose research on the nutritive value of alternative feed resources, including the environmental impacts of producing these resources and their associated non-provisioning services. Third, we look at how the design of APS based on agroecological principles valorizes interactions between system components and promotes biological diversity at multiple scales to increase system resilience. Addressing such challenges requires a collection of theories and models (concept–knowledge theory, viability theory, companion modeling, etc.). Acknowledging the ecology of contexts and analyzing the rationales behind traditional small-scale systems will increase our understanding of mechanisms contributing to the success or failure of agroecological practices and systems. Fourth, the large-scale development of agroecological products will require analysis of resistance to change among farmers and other actors in the food chain. Certifications and market-based incentives could be an important lever for the expansion of agroecological alternatives in APS. Finally, we question the suitability of current agriculture extension services and public funding mechanisms for scaling-up agroecological practices and systems.     

Chemical strategies for controlling protein folding and elucidating the molecular mechanisms of amyloid formation and toxicity

It has been more than a century since the first evidence linking the process of amyloid formation to the pathogenesis of Alzheimer's disease. During the last three decades in particular, increasing evidence from various sources (pathology, genetics, cell culture studies, biochemistry, and biophysics) continues to point to a central role for the pathogenesis of several incurable neurodegenerative and systemic diseases. This is in part driven by our improved understanding of the molecular mechanisms of protein misfolding and aggregation and the structural properties of the different aggregates in the amyloid pathway and the emergence of new tools and experimental approaches that permit better characterization of amyloid formation in vivo. Despite these advances, detailed mechanistic understanding of protein aggregation and amyloid formation in vitro and in vivo presents several challenges that remain to be addressed and several fundamental questions about the molecular and structural determinants of amyloid formation and toxicity and the mechanisms of amyloid-induced toxicity remain unanswered. To address this knowledge gap and technical challenges, there is a critical need for developing novel tools and experimental approaches that will not only permit the detection and monitoring of molecular events that underlie this process but also allow for the manipulation of these events in a spatial and temporal fashion both in and out of the cell. This review is primarily dedicated in highlighting recent results that illustrate how advances in chemistry and chemical biology have been and can be used to address some of the questions and technical challenges mentioned above. We believe that combining recent advances in the development of new fluorescent probes, imaging tools that enabled the visualization and tracking of molecular events with advances in organic synthesis, and novel approaches for protein synthesis and engineering provide unique opportunities to gain a molecular-level understanding of the process of amyloid formation. We hope that this review will stimulate further research in this area and catalyze increased collaboration at the interface of chemistry and biology to decipher the mechanisms and roles of protein folding, misfolding, and aggregation in health and disease.     

A conceptual framework for understanding the perspectives on the causes of the science–practice gap in ecology and conservation

Applying scientific knowledge to confront societal challenges is a difficult task, an issue known as the science–practice gap. In Ecology and Conservation, scientific evidence has been seldom used directly to support decision‐making, despite calls for an increasing role of ecological science in developing solutions for a sustainable future. To date, multiple causes of the science–practice gap and diverse approaches to link science and practice in Ecology and Conservation have been proposed. To foster a transparent debate and broaden our understanding of the difficulties of using scientific knowledge, we reviewed the perceived causes of the science–practice gap, aiming to: (i) identify the perspectives of ecologists and conservation scientists on this problem, (ii) evaluate the predominance of these perspectives over time and across journals, and (iii) assess them in light of disciplines studying the role of science in decision‐making. We based our review on 1563 sentences describing causes of the science–practice gap extracted from 122 articles and on discussions with eight scientists on how to classify these sentences. The resulting process‐based framework describes three distinct perspectives on the relevant processes, knowledge and actors in the science–practice interface. The most common perspective assumes only scientific knowledge should support practice, perceiving a one‐way knowledge flow from science to practice and recognizing flaws in knowledge generation, communication, and/or use. The second assumes that both scientists and decision‐makers should contribute to support practice, perceiving a two‐way knowledge flow between science and practice through joint knowledge‐production/integration processes, which, for several reasons, are perceived to occur infrequently. The last perspective was very rare, and assumes scientists should put their results into practice, but they rarely do. Some causes (e.g. cultural differences between scientists and decision‐makers) are shared with other disciplines, while others seem specific to Ecology and Conservation (e.g. inadequate research scales). All identified causes require one of three general types of solutions, depending on whether the causal factor can (e.g. inadequate research questions) or cannot (e.g. scientific uncertainty) be changed, or if misconceptions (e.g. undervaluing abstract knowledge) should be solved. The unchanged predominance of the one‐way perspective over time may be associated with the prestige of evidence‐based conservation and suggests that debates in Ecology and Conservation lag behind trends in other disciplines towards bidirectional views ascribing larger roles to decision‐makers. In turn, the two‐way perspective seems primarily restricted to research traditions historically isolated from mainstream conservation biology. All perspectives represented superficial views of decision‐making by not accounting for limits to human rationality, complexity of decision‐making contexts, fuzzy science–practice boundaries, ambiguity brought about by science, and different types of knowledge use. However, joint knowledge‐production processes from the two‐way perspective can potentially allow for democratic decision‐making processes, explicit discussions of values and multiple types of science use. To broaden our understanding of the interface and foster productive science–practice linkages, we argue for dialogue among different research traditions within Ecology and Conservation, joint knowledge‐production processes between scientists and decision‐makers and interdisciplinarity across Ecology, Conservation and Political Science in both research and education.     

COMU: scope and limitations of the latest innovation in peptide acyl transfer reagents

The methodology for peptide bond formation is undergoing a continuous evolution where the main actors are being renewed. In recent years, coupling reagents based on the Oxyma scaffold, such as the uronium salt COMU, has been a groundbreaking contribution to the field. The advantages of COMU over classic benzotriazole‐based reagents (HATU, HBTU, HCTU, TBTU) were proven in terms of solubility and coupling efficiency in bulky junctions in our groups and others. However, some aspects of the use of COMU need to be revised and improved, such as the stability of commercial samples in organic solvents, which hampers the compatibility with long synthesis in automated synthesizers. In this review, an overview of the main features and suggestions to improve the use of COMU are presented, along with a discussion on the best conditions for its use in microwave‐assisted peptide robots. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Plant–environment interactions through a functional traits perspective: a review of Italian studies

Abstract

Italy is among the European countries with the greatest plant diversity due to both a great environmental heterogeneity and a long history of man–environment interactions. Trait-based approaches to ecological studies have developed greatly over recent decades worldwide, although several issues concerning the relationships between plant functional traits and the environment still lack sufficient empirical evaluation. To draw insights on the association between plant functional traits and direct and indirect human and natural pressures on the environmental drivers, this article summarizes the existing knowledge on this topic by reviewing the results of studies performed in Italy adopting a functional trait approach on vascular plants, bryophytes and lichens. Although we recorded trait measurements for 1418 taxa, our review highlighted some major gaps in plant traits knowledge: Mediterranean ecosystems are poorly represented; traits related to belowground organs are still overlooked; traits measurements for bryophytes and lichens are lacking. Finally, intraspecific variation has been little studied at community level so far. We conclude by highlighting the need for approaches evaluating trait–environment relationship at large spatial and temporal scales and the need of a more effective contribution to online databases to tie more firmly Italian researchers to international scientific networks on plant traits.     

Challenges and solutions for networking knowledge holders and better informing decision-making on biodiversity and ecosystem services

How to effectively inform decision-making on biodiversity and ecosystem services has been under continuous debate in Europe and globally since the Convention on Biological Diversity was adopted in 1992. On the global level the Intergovernmental science–policy Platform on Biodiversity and Ecosystem Services was installed in 2012 to address this need. Yet, biodiversity and ecosystem services management have to be addressed on multiple levels, across biophysical as well as administrative scales. Also, the knowledge needed to address them has to be brought together from science, management practices and other knowledge domains to become relevant and it must be delivered in ways relevant for policies beyond the environmental sector. This Special Issue brings together papers that analyse the challenges arising from this context. Most of them are based on the EU-funded project KNEU that aimed at developing a new, integrative approach to activate knowledge holders and bring them together for targeted knowledge synthesis activities. The papers address the potential functions, structures and processes of such activities in a joint framework, the Network of Knowledge. Practical aspects are addressed via a number of trial assessments carried out in the project. All in all, they showcase new ways of knowledge synthesis that have the potential to complement and strengthen existing ones across scales and sectors, thus supporting an improved management of biodiversity and ecosystem services.     

A review of spatial computational models for multi-cellular systems, with regard to intestinal crypts and colorectal cancer development

Colon rectal cancers (CRC) are the result of sequences of mutations which lead the intestinal tissue to develop in a carcinoma following a “progression” of observable phenotypes. The actual modeling and simulation of the key biological structures involved in this process is of interest to biologists and physicians and, at the same time, it poses significant challenges from the mathematics and computer science viewpoints. In this report we give an overview of some mathematical models for cell sorting (a basic phenomenon that underlies several dynamical processes in an organism), intestinal crypt dynamics and related problems and open questions. In particular, major attention is devoted to the survey of so-called in-lattice (or grid) models and off-lattice (off-grid) models. The current work is the groundwork for future research on semi-automated hypotheses formation and testing about the behavior of the various actors taking part in the adenoma–carcinoma progression, from regulatory processes to cell–cell signaling pathways.     

Engineering inkjet bioprinting processes toward translational therapies

Bioprinting is the assembly of three-dimensional (3D) tissue constructs by layering cell-laden biomaterials using additive manufacturing techniques, offering great potential for tissue engineering and regenerative medicine. Such a process can be performed with high resolution and control by personalized or commercially available inkjet printers. However, bioprinting's clinical translation is significantly limited due to process engineering challenges. Upstream challenges include synthesis, cellular incorporation, and functionalization of “bioinks,” and extrusion of print geometries. Downstream challenges address sterilization, culture, implantation, and degradation. In the long run, bioinks must provide a microenvironment to support cell growth, development, and maturation and must interact and integrate with the surrounding tissues after implantation. Additionally, a robust, scaleable manufacturing process must pass regulatory scrutiny from regulatory bodies such as U.S. Food and Drug Administration, European Medicines Agency, or Australian Therapeutic Goods Administration for bioprinting to have a real clinical impact. In this review, recent advances in inkjet-based 3D bioprinting will be presented, emphasizing on biomaterials available, their properties, and the process to generate bioprinted constructs with application in medicine. Current challenges and the future path of bioprinting and bioinks will be addressed, with emphasis in mass production aspects and the regulatory framework bioink-based products must comply to translate this technology from the bench to the clinic.     

New insights into the phylogenetics and biogeography of Arum (Araceae): unravelling its evolutionary history

The heat‐ and odour‐producing genus Arum (Araceae) has interested scientists for centuries. This long‐term interest has allowed a deep knowledge of some complex processes, such as the physiology and dynamics of its characteristic lure‐and‐trap pollination system, to be built up. However, mainly because of its large distributional range and high degree of morphological variation, species' limits and relationships are still under discussion. Today, the genus comprises 28 species subdivided into two subgenera, two sections and six subsections. In this study, the phylogeny of the genus is inferred on the basis of four plastid regions, and the evolution of several morphological characters is investigated. Our phylogenetic hypothesis is not in agreement with the current infrageneric classification of the genus and challenges the monophyly of several species. This demonstrates the need for a new infrageneric classification based on characters reflecting the evolution of this enigmatic genus. To investigate the biogeography of Arum deeply, further spatiotemporal analyses were performed, addressing the importance of the Mediterranean basin in the diversification of Arum. Our results suggest that its centre of origin was the European–Aegean region, and that major diversification happened during the last 10 Myr. © 2010 The Linnean Society of London, Botanical Journal of the Linnean Society, 2010, 163 , 14–32.     

Life Cycle Approach in the Procurement Process: The Case of Defence Materiel (9 pp)

Goal, Scope and Background Procurement in public and non-public organisations has the potential to influence product development towards more environmentally friendly products. This article focuses on public procurement with procurement in Swedish defence as a special case. In 2003, public procurement in Sweden was 28% of the GDP. In the Swedish defence sector the amount was 2% of the GDP. The total emissions from the sector were of the same order of magnitude as from waste treatment (2% of Sweden's emissions). According to an appropriation letter from the Ministry of Defence in 1998, the Swedish Armed Forces (SAF) and the Swedish Defence Materiel Administration (FMV) are required to take environmental issues into consideration during the entire process of acquiring defence materiel. Environmental aspects are considered today, but without a life-cycle perspective. - The aims of this article are to recommend suitable tools for taking environmental concerns into account, considering a product's life-cycle, in the procurement process for defence materiel in Sweden; to make suggestions for how these tools could be used in the acquisition process; and to evaluate these suggestions through interviews with actors in the acquisition process. The procurement process does not include aspects specific to Swedish defence, and it is therefore likely to be comparable to processes in other countries. Methods The method involved a study of current literature and interviews with various actors in the acquisition process. The life cycle methods considered were quantitative Life Cycle Assessments, a simplified LCA-method called the MECO method and Life Cycle Costing (LCC). Results and Discussion Methodology recommendations for quantitative LCA and simplified LCA are presented in the article, as well as suggestions on how to integrate LCA methods in the acquisition process. We identified four areas for use for LCA in the acquisition process: to learn about environmental aspects of the product; to fulfil requirements from customers; to set environmental requirements and to choose between alternatives. Therefore, tools such as LCAs are useful in several steps in the acquisition process. Conclusion From the interviews, it became clear that the actors in the acquisition process think that environmental aspects should be included early in the process. The actors are interested in using LCA methods, but there is a need for an initiative from one or several of them if the method is to be used regularly in the process. Environmental and acquisition issues are handled with very little interaction in the controlling and ordering organisation. An integration of environmental and acquisition parts in these organisations is probably needed in order to integrate environmental aspects in general and life-cycle thinking in particular. Other difficulties identified are costs and time constraints. Recommendation and Perspective In order to include the most significant aspects when procuring materiel, it is important to consider the whole life-cycle of the products. Our major recommendation is that the defence sector should work systematically through different product groups. For each product group, quantitative, traditional LCAs or simplified LCAs (in this case modified MECOs) should be performed for reference products within each product group. The results should be an identification of critical aspects in the life-cycles of the products. The studies will also form a database that can be used when making new LCAs. This knowledge should then be used when writing specifications of what to procure and setting criteria for procurement. The reports should be publicly available to allow reviews and discussions of results. To make the work more cost-effective, international co-operation should be sought. In addition, LCAs can also be performed as an integrated part of the acquisition process in specific cases.     

Flows of Chemical Risk Information in the Consumer Paint Product Chain

In this study the flows of chemical risk information for paint as a consumer product were investigated from a product chain perspective. The main method of research involved semi‐structured interviews with Swedish manufacturers of paint and chemicals. In addition, retailers and consumers were interviewed. The flows of chemical risk information between actors within (e.g., manufacturers, retailers, and consumers) and outside (e.g., industry associations and regulators) the paint product chain are described. Because the European chemical legislation REACH (Registration, Evaluation, Authorization and restriction of CHemicals) plays a large role in the management of chemical risk information at companies, some consequences of REACH on actors in the paint product chain are described. Examples of such consequences are that importing of chemicals from non–European Union (EU) countries may be discouraged and that some low‐volume chemicals may no longer be produced. However, manufacturers do not yet see these consequences as impediments to innovation. The results of this work show that chemical risk information is most comprehensive during the manufacturing steps of the product chain. This is due not only to tradition and industry initiatives, but also to REACH and other legislation. The results also illustrate the need for evaluation of how chemical risk information is used in different contexts and the importance of directing the right information at the right target group. Following legislative development, more specialized information is required in the safety data sheet (SDS), and because of this many manufacturers find it necessary to create simplified safety sheets that make the most pertinent safety and hazard information easily accessible to individuals that handle the chemicals in their factories. The study found that in creating the simplified safety sheets, the content and use of chemical risk information is evaluated and adjusted for presentation to this particular target group. It is evident that the Swedish Paint and Printing Ink Makers Association plays an important role in the interpretation of legal requirements and even in agreements for providing information that exceeds legal requirements.     

Linking ecological and social systems in cities: urban planning in Finland as a case

The loss of urban green space as a result of urbanization threatens the overall biodiversity of urban areas, and prompts us to consider the importance of existing urban nature more carefully. Because urban ecological systems are in intense interaction with human-social systems, it is fruitful to create an interdisciplinary research and planning framework to ensure the maintenance of biodiversity in urban areas. For this purpose, we adapted a suitable theoretical and conceptual scheme for the setting of Finnish urban development, which provides an example of a situation where a lot of nature has so far remained inside and around urban area. The adapted scheme focuses on the land use change as a result of urban land use planning and development, and may provide a way to address the important variables and feedback mechanisms between information flowing from ecological systems and drivers from the social system. Furthermore, we outlined a more specific framework around the Finnish urban detailed planning process in order to study the interactions between these systems further. After addressing ecology-oriented questions of quantity, quality and needs of urban nature, and human-oriented drivers, such as flow and incorporation of information, knowledge, values and institutions, we identified several challenges in integrating the components of ecological and social systems. Creating common conceptual ground for different actors and disciplines, improving communication in the process, matching contradictory values and perceptions, and improving stakeholder participation would be in the best interest of nature and people of urban areas.     

The Human Specialized DNA Polymerases and Non-B DNA: Vital Relationships to Preserve Genome Integrity

In addition to the canonical right-handed double helix, DNA molecule can adopt several other non-B DNA structures. Readily formed in the genome at specific DNA repetitive sequences, these secondary conformations present a distinctive challenge for progression of DNA replication forks. Impeding normal DNA synthesis, cruciforms, hairpins, H DNA, Z DNA and G4 DNA considerably impact the genome stability and in some instances play a causal role in disease development. Along with previously discovered dedicated DNA helicases, the specialized DNA polymerases emerge as major actors performing DNA synthesis through these distorted impediments. In their new role, they are facilitating DNA synthesis on replication stalling sites formed by non-B DNA structures and thereby helping the completion of DNA replication, a process otherwise crucial for preserving genome integrity and concluding normal cell division. This review summarizes the evidence gathered describing the function of specialized DNA polymerases in replicating DNA through non-B DNA structures.     

The Dynamic Consequences of Cooperation and Competition in Small-World Networks

We present a study of the social dynamics among cooperative and competitive actors interacting on a complex network that has a small-world topology. In this model, the state of each actor depends on its previous state in time, its inertia to change, and the influence of its neighboring actors. Using numerical simulations, we determine how the distribution of final states of the actors and measures of the distances between the values of the actors at local and global levels, depend on the number of cooperative to competitive actors and the connectivity of the actors in the network. We find that similar numbers of cooperative and competitive actors yield the lowest values for the local and global measures of the distances between the values of the actors. On the other hand, when the number of either cooperative or competitive actors dominate the system, then the divergence is largest between the values of the actors. Our findings make new testable predictions on how the dynamics of a conflict depends on the strategies chosen by groups of actors and also have implications for the evolution of behaviors.     

Paths to last in mixed crop–livestock farming: lessons from an assessment of farm trajectories of change

Mixed crop–livestock systems, combining livestock and cash crops at farm level, are considered to be suitable for sustainable intensification of agriculture. Ensuring the survival of mixed crop–livestock systems is a challenge for European agriculture: the number of European mixed crop–livestock farms has been decreasing since 1970. Analysis of farming system dynamics may elucidate past changes and the forces driving this decline. The objectives of this study were (i) to identify the diversity of paths that allowed the survival of mixed crop–livestock farming and (ii) to elucidate the driving forces behind such survival. We analysed the variety of farm trajectories from 1950 to 2005. We studied the entire farm population of a case study site, located in the ‘Coteaux de Gascogne’ region. In this less favoured area of south-western France, farmers have limited specialisation. Currently, half of the farms use mixed crop–livestock systems. The data set of 20 variables for 50 farms on the basis of six 10-year time steps was collected through retrospective surveys. We used a two-step analysis including (i) a visual assessment of the whole population of individual farm trajectories and (ii) a computer-based typology of farm trajectories on the basis of a series of multivariate analyses followed by automatic clustering. The European Common Agricultural Policy, market globalisation and decreasing workforce availability were identified as drivers of change that favoured the specialisation process. Nevertheless, farmers’ choices and values have opposed against these driving forces, ensuring the survival of some mixed crop–livestock farming systems. The trajectories were clustered into five types, four of which were compatible with mixed crop–livestock systems. The first type was the maximisation of autonomy by combining crops and livestock. The second type was diversification of production to exploit economies of scope and protect the farm against market fluctuations. The other two types involved enlargement and progressive adaptation of the farm to the familial workforce. The survival of mixed crop–livestock systems in these two types is largely dependent on workforce availability. Only one type of trajectory, on the basis of enlargement and economies of scale, did not lead to mixed crop–livestock systems. In view of the current evolution of the driving forces, maximising autonomy and diversification appear to be suitable paths to deal with current challenges and maintain mixed crop–livestock systems in Europe.     

Model–data synthesis in terrestrial carbon observation: methods, data requirements and data uncertainty specifications

Systematic, operational, long‐term observations of the terrestrial carbon cycle (including its interactions with water, energy and nutrient cycles and ecosystem dynamics) are important for the prediction and management of climate, water resources, food resources, biodiversity and desertification. To contribute to these goals, a terrestrial carbon observing system requires the synthesis of several kinds of observation into terrestrial biosphere models encompassing the coupled cycles of carbon, water, energy and nutrients. Relevant observations include atmospheric composition (concentrations of CO₂ and other gases); remote sensing; flux and process measurements from intensive study sites; in situ vegetation and soil monitoring; weather, climate and hydrological data; and contemporary and historical data on land use, land use change and disturbance (grazing, harvest, clearing, fire). A review of model–data synthesis tools for terrestrial carbon observation identifies ‘nonsequential’ and ‘sequential’ approaches as major categories, differing according to whether data are treated all at once or sequentially. The structure underlying both approaches is reviewed, highlighting several basic commonalities in formalism and data requirements. An essential commonality is that for all model–data synthesis problems, both nonsequential and sequential, data uncertainties are as important as data values themselves and have a comparable role in determining the outcome. Given the importance of data uncertainties, there is an urgent need for soundly based uncertainty characterizations for the main kinds of data used in terrestrial carbon observation. The first requirement is a specification of the main properties of the error covariance matrix. As a step towards this goal, semi‐quantitative estimates are made of the main properties of the error covariance matrix for four kinds of data essential for terrestrial carbon observation: remote sensing of land surface properties, atmospheric composition measurements, direct flux measurements, and measurements of carbon stores.     

Expansion processes for cell-based therapies

Living cells are emerging as therapeutic entities for the treatment of patients affected with severe and chronic diseases where no conventional drug can provide a definitive cure. At the same time, the promise of cell-based therapies comes with several biological, regulatory, economic, logistical, safety and engineering challenges that need to be addressed before translating into clinical practice. Among the complex operations required for their manufacturing, cell expansion occupies a significant part of the entire process and largely determines the number, the phenotype and several other critical quality attributes of the final cell therapy products (CTPs). This review aims at characterizing the main culture systems and expansion processes used for CTP production, highlighting the need to implement scalable, cost-efficient technologies together with process optimization strategies to bridge the gap between basic scientific research and commercially available therapies.     

New data on the distribution of Mus spicilegus Petenyi, 1882 (Rodentia, Muridae) and a distinct mtDNA lineage in the southern Balkans

Despite extensive zoogeographical and taxonomical studies in the subgenus Mus, several issues still remain unresolved. In this context, the distribution area of the mound-building mouse, Mus spicilegus, remains undetermined at the southernmost parts of the species’ range, possibly due to low population densities and seasonal character of mound building. The new records from Greece, presented here, significantly expand the knowledge on Mus spicilegus distribution but also reveal eastern Greek populations which are genetically differentiated from all the other Greek and European ones. These results support an additional colonization route to eastern Greece as part of the migration and expansion process of the mound building mouse in Europe.