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Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

We propose an interactive video browsing tool for supporting content management and selection in postproduction. The approach is based on a process model for multimedia content abstraction. A software framework based on this process model and desktop and Web-based client applications are presented. For evaluation, we apply two TRECVID style fact finding approaches (retrieval and question answering tasks) and a user survey to the evaluation of the video browsing tool. We analyze the correlation between the results of the different methods, whether different aspects can be evaluated independently with the survey, and if a learning effect can be measured with the different methods, and we also compare the full-featured desktop and the limited Web-based user interface. The results show that the retrieval task correlates better with the user experience according to the survey. The survey rather measures the general user experience while different aspects of the usability cannot be analyzed independently.

To the extent in which demographic change and selected resulting problems are considered in public, the specialist terms of demography are also losing their isolation. One such term is “carrying capacity”. Problematic are the multiple connotations with which the respective underlying problem is considered, often depending on the respective viewpoint. Like other terms it is moreover used in several disciplines and to top it all in colloquial language. This contribution understands itself as an attempt to explain carrying capacity from the perspective of regional demography, to establish linkages and also to follow a historical line. Remarkable is the variety of aspects of the term that can hardly be reconstructed but also its change in terms of content when it is occupied by political language following strategic objectives.

Funding provided under theAufbau Ost («Rebuilding the East») programme and other forms of financial transfer to theLänder (federal states) of eastern Germany have up to now been at their least effective in the area to the east of the River Elbe. Indeed, many of the instruments of both regional structure policy and economic development policy which have repeatedly proved their worth in the rural areas of the former West Germany have failed in the north-east. This area seems to be something of a bottomless pit. From a regional-demographic perspective, this region has to be clearly distinguished from more “ordinary” rural space, and assigned to a distinct new category to be termed “most rural space”.

Abstract Current approaches to project spatial biodiversity responses to climate change mainly focus on the direct effects of climate on species while regarding land use and land cover as constant or prescribed by global land‐use scenarios. However, local land‐use decisions are often affected by climate change and biodiversity on top of socioeconomic and policy drivers. To realistically understand and predict climate impacts on biodiversity, it is, therefore, necessary to integrate both direct and indirect effects (via climate‐driven land‐use change) of climate change on biodiversity. In this perspective paper, we outline how biodiversity models could be better integrated with regional, climate‐driven land‐use models. We initially provide a short, non‐exhaustive review of empirical and modelling approaches to land‐use and land‐cover change (LU) and biodiversity (BD) change at regional scales, which forms the base for our perspective about improved integration of LU and BD models. We consider a diversity of approaches, with a special emphasis on mechanistic models. We also look at current levels of integration and at model properties, such as scales, inputs and outputs, to further identify integration challenges and opportunities. We find that LU integration in BD models is more frequent than the other way around and has been achieved at different levels: from overlapping predictions to simultaneously coupled simulations (i.e. bidirectional effects). Of the integrated LU‐BD socio‐ecological models, some studies included climate change effects on LU, but the relative contribution of direct vs. indirect effects of climate change on BD remains a key research challenge. Important research avenues include concerted efforts in harmonizing spatial and temporal resolution, disentangling direct and indirect effects of climate change on biodiversity, explicitly accounting for bidirectional feedbacks, and ultimately feeding socio‐ecological systems back into climate predictions. These avenues can be navigated by matching models, plugins for format and resolution conversion, and increasing the land‐use forecast horizon with adequate uncertainty. Recent developments of coupled models show that such integration is achievable and can lead to novel insights into climate–land use–biodiversity relations. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Only a few decades ago, colorful, small‐scale, heterogeneous, and species‐rich hay meadows or extensive pastures were common, but have often been replaced by species‐poor, uniform, large‐scale multicut meadows. Technological advancements and improved efficiency in grassland management have come at the cost of biodiversity. Methods In Germany, 150 grassland plots have been investigated since 2006. Using these extensive data, we propose a new compound index for estimating the site‐specific mowing intensity in order to facilitate assessment of the impact of mowing intensity on biodiversity and ecosystem processes. Our index integrates the various qualitative components of mowing machine type, mowing height and use of a conditioner, with the annual number of cuts. Results The newly proposed index achieves a much finer gradation of mowing intensity compared to the previous quantification based on the number of cuts only. Furthermore, a decrease in plant and arthropod species was observed at higher mowing intensity. Conclusions The proposed mowing intensity index offers enhanced precision in calculations and can easily be integrated into assessments of land‐use intensity in grasslands. Further, it could serve as a basis for providing subsidies to farmers, who adopt low‐impact mowing practices.

Abstract Background Seed endophytic bacteria are beneficial to plants. They improve seedling growth by enhancing plant nutrient uptake, modulating stress-related phytohormone production, and targeting pests and pathogens with antibiotics. Seed endophyte composition can be influenced by pollination, plant cultivar, and soil physicochemical conditions. However, the effects of plant community richness on seed endophytes are unknown. To investigate the effects of increasing plant species richness on the diversity and composition of the seed microbiome, we made use of a well-established long-term biodiversity experiment in Germany (The Jena Experiment). We sampled seeds from different Plantago lanceolata blossoms in a plant diversity gradient ranging from monoculture to 16 species mixtures. The seeds were surface sterilized to remove seed surface-associated bacteria and subjected to a metabarcoding approach to assess bacterial community structure. Results Our data indicate a very stable core microbiome, which accounted for more than 90% of the reads and was present in all seeds independent of the plant richness level the seeds originated from. It consisted mainly of reads linked to Pseudomonas rhizosphaerae, Sphingomonas faeni and Pirellulla spp. 9% of the obtained reads were not part of the core microbiome and were only present in plots of specific diversity levels. The number of unique ASVs was positively correlated with plant richness. Interestingly, most reads described as non-core members belonged to the same genera described as the core microbiome, indicating the presence of different strains or species with possibly different functional properties important for seed performance. Conclusion Our data indicate that Plantago lanceolata maintains a large seeds core microbiome across the plant richness gradient. However, the number of unique ASVs increases alongside the plant community richness, indicating that ecosystem biodiversity also mitigates diversity loss in seed endophytes.

Abstract There is no doubt about the insect decline currently taking place in ecosystems with large anthropogenic impacts. Thus, there is a need for practices that avoid insect decline and or help to recover insect communities that have already suffered. Plant diversity has been shown to be positively related to insect abundance and diversity and to ecosystem functions provided by insects. However, it remains open if increased plant diversity can help to recover decreased populations. Here, we tested over one decade the effects of plant diversity on the carabid community in a large grassland biodiversity experiment and how plant diversity fostered the establishment of a natural grassland community after conversion of an arable field. There was a dramatic decline in carabid abundance from 2003, the first year after establishing the diversity experiment, to 2005. However, subsequently, the abundance increased constantly. One year after the land use change most individuals and species were those commonly found in agricultural fields. In subsequent years the community was dominated by grassland species. While plant diversity did not affect the abundance and richness of the carabid community, the turnover to a more native grassland community was accelerated by plant diversity in the first years after the land use change. In contrast, in later years plant diversity stabilized the community assemblage. Our study shows that high plant diversity can contribute to a faster transition of insect populations towards naturally occurring community assemblages and at later stages to more stabilized assemblages.

Most European forests are used for timber production. Given the limited extent of unmanaged (and especially primary) forests, it is essential to include commercial forests in the conservation of forest biodiversity. In order to develop ecologically sustainable forest management practices, it is important to understand the management impacts on forest-dwelling organisms. Experiments allow testing the effects of alternative management strategies, and monitoring of multiple taxa informs us on the response range across forest-dwelling organisms. To provide a representative picture of the currently available information, metadata on 28 multi-taxa forest management experiments were collected from 14 European countries. We demonstrate the potential of compiling these experiments in a single network to upscale results from the local to continental level and indicate directions for future research. Among the different forest types, temperate deciduous beech and oak-dominated forests are the best represented in the multi-taxa management experiments. Of all the experimental treatments, innovative ways of traditional management techniques (e.g., gap cutting and thinning) and conservation-oriented interventions (e.g., microhabitat enrichment) provide the best opportunity for large-scale analyses. Regarding the organism groups, woody regeneration, herbs, fungi, beetles, bryophytes, birds and lichens offer the largest potential for addressing management–biodiversity relationships at the European level. We identified knowledge gaps regarding boreal, hemiboreal and broadleaved evergreen forests, the treatments of large herbivore exclusion, prescribed burning and forest floor or water manipulations, and the monitoring of soil-dwelling organisms and some vertebrate classes, e.g., amphibians, reptiles and mammals. To improve multi-site comparisons, design of future experiments should be fitted to the set-up of the ongoing projects and standardised biodiversity sampling is suggested. However, the network described here opens the way to learn lessons on the impact on forest biodiversity of different management techniques at the continental level, and thus, supports biodiversity conservation in managed forests.

This research investigates the potential of additive manufacturing and digital planning tools for the creation of location-specific façade redesigns that can host cavity-dependent animal species and develops methods for their realization. The proposed approach is explored based on a case study of a student dormitory in need of renovation in the urban area of Munich. Based on theoretical knowledge and design experimentations that link the fields of architecture, climate-responsive design, terrestrial ecology, and digital fabrication, a set of design principles for the additive manufacturing of inhabitable ceramic tiles is conceived and transferred into a computational design tool. The conception of single tiles and the overall façade design are developed in terms of their positive climatic impact on both the animal species and humans, their nesting opportunities, their structural feasibility, and their integrability with standard ceramic façade systems. To verify the fabricability of the proposed design, a façade fragment was additively manufactured as a prototype in 1:1 scale. The initial findings presented in this paper provide a glimpse of how emerging digital technologies could provide new ways to expand current habitual architectural planning and fabrication tools, to enable the creation of site-specific solutions, and to bring together human and animal needs.

Land use intensification is a major driver of biodiversity change. Here the authors measure diversity across multiple trophic levels in agricultural grassland landscapes of varying management, finding decoupled responses of above- and belowground taxa to local factors and a strong impact of landscape-level land use.

An extraordinarily high intraspecific chemical diversity, i.e. chemodiversity, has been found in several plant species, of which some are of major ecological or economic relevance. Moreover, even within an individual plant there is substantial chemodiversity among tissues and across seasons. This chemodiversity likely has pronounced ecological effects on plant mutualists and antagonists, associated foodwebs and, ultimately, biodiversity. Surprisingly, studies on interactions between plants and their herbivores or pollinators often neglect plant chemistry as a level of diversity and phenotypic variation. The main aim of this Research Unit (RU) is to understand the emergence and maintenance of intraspecific chemodiversity in plants. We address the following central questions:1) How does plant chemodiversity vary across levels, i.e., within individuals, among individuals within populations, and among populations?2) What are the ecological consequences of intraspecific plant chemodiversity?3) How is plant chemodiversity genetically determined and maintained?By combining field and laboratory studies with metabolomics, transcriptomics, genetic tools, statistical data analysis and modelling, we aim to understand causes and consequences of plant chemodiversity and elucidate its impacts on the interactions of plants with their biotic environment. Furthermore, we want to identify general principles, which hold across different species, and develop meaningful measures to describe the fascinating diversity of defence chemicals in plants. These tasks require integrated scientific collaboration of experts in experimental and theoretical ecology, including chemical and molecular ecology, (bio)chemistry and evolution.

The functioning and service provisioning of ecosystems in the face of anthropogenic environmental and biodiversity change is a cornerstone of ecological research. The last three decades of biodiversity–ecosystem functioning (BEF) research have provided compelling evidence for the significant positive role of biodiversity in the functioning of many ecosystems. Despite broad consensus of this relationship, the underlying ecological and evolutionary mechanisms have not been well understood. This complicates the transition from a description of patterns to a predictive science. The proposed Research Unit aims at filling this gap of knowledge by applying novel experimental and analytical approaches in one of the longest-running biodiversity experiments in the world: the Jena Experiment. The central aim of the Research Unit is to uncover the mechanisms that determine BEF relationships in the short- and in the long-term. Increasing BEF relationships with time in long-term experiments do not only call for a paradigm shift in the appreciation of the relevance of biodiversity change, they likely are key to understanding the mechanisms of BEF relationships in general. The subprojects of the proposed Research Unit fall into two tightly linked main categories with two research areas each that aim at exploring variation in community assembly processes and resulting differences in biotic interactions as determinants of the long-term BEF relationship. Subprojects under “Microbial community assembly” and “Assembly and functions of animal communities” mostly focus on plant diversity effects on the assembly of communities and their feedback effects on biotic interactions and ecosystem functions. Subprojects under “Mediators of plant-biotic interactions” and “Intraspecific diversity and micro-evolutionary changes” mostly focus on plant diversity effects on plant trait expression and micro-evolutionary adaptation, and subsequent feedback effects on biotic interactions and ecosystem functions. This unification of evolutionary and ecosystem processes requires collaboration across the proposed subprojects in targeted plant and soil history experiments using cutting-edge technology and will produce significant synergies and novel mechanistic insights into BEF relationships. The Research Unit of the Jena Experiment is uniquely positioned in this context by taking an interdisciplinary and integrative approach to capture whole-ecosystem responses to changes in biodiversity and to advance a vibrant research field.

Here, Schuldt et al. collate data from two long-term grassland and forest biodiversity experiments to ask how plant diversity facets affect the diversity of higher trophic levels. The results show that positive effects of plant diversity on consumer diversity are mediated by plant structural and functional diversity, and vary across ecosystems and trophic levels.

Bent-core mesogens have gained considerable importance due to their ability to form new mesophases with unusual properties. Relationships between the chemical structure of bent-core molecules and the type and physical properties of the formed mesophases are relatively unknown in detail and differ strongly from those known for calamitic liquid crystals. In this paper symmetric and nonsymmetric five-ring salicylideneaniline-based bent-core mesogens are presented, and the effect of lateral substituents attached at the outer phenyl rings (F, Cl, Br) or the central phenyl ring (CH3) on the liquid-crystalline behaviour and on the physical properties is studied. Corresponding benzylideneaniline-based compounds were additionally prepared in order to study the influence of the intramolecular hydrogen bond. The occurring mesophases were investigated by differential scanning calorimetry, polarising microscopy, X-ray diffraction and dielectric and electro-optical measurements. The paper reports on new findings with respect to the structure–property relationships of bent-core mesogens. On one hand, the disruptive effect of laterally substituted halogen atoms, F, Cl and Br, on the mesophase behaviour of three isomeric series was much lower than expected. On the other hand, an increase of the clearing temperature by 34 K was observed, caused by small lateral substituents. The electro-optical behaviour, especially the type of polar switching and corresponding molecular movements, is sensitive to variations in the molecular structure.