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Bei vielen fur die hausarztliche Praxis wichtigen Erkrankungsbildern, aber auch bei seltenen Syndromen, geben ophthalmologische Begleiterkrankungen und Symptome ein wichtiges differentialdiagnostisches Werkzeug zur Hand. Mit der richtigen Blickdiagnose oder dem entsprechendem Leitbild kann der Hausarzt gezielte Fragestellungen an den Augenarzt richten, aber auch praventiv fachubergreifende Krankheitsbilder einer Therapie zufuhren.

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles.

Studies of π and σ interactions in molecular crystals of donoracceptor complexes have stimulated interest in the crystallization and structure determination of {1,3,5-trithiane…I2}, {1,5,8,12-tetrathiocyclotetradecane…I2} and {1,4,7,10,13,16-hexathiocyclooctadecane…(I2)3} in order to detect structural changes. The II bond lengths are stretched by up to 0.16 A relative to the gas-phase value and prove iodine to be the acceptor species. Additional distance data >S…I2 and II from the Cambridge Structural Database establish a nonlinear correlation. In contrast, bond lengths and bond angles of the sulphide donors remain largely unperturbed on complexation, even when considerable conformational changes are observed. For example, on addition of four iodine molecules, the rather flexible 18-thio-crown-6 with a C2-symmetric bowl-shape is flattened to a Cs-symmetric rectangle. The structural results complement those reported for stronger acceptor effects of metal cations.

In Model-Driven Engineering MDE the employed setting of languages as well as automated and manual activities has major impact on productivity. Furthermore, such settings for MDE evolve over time. However, currently only the evolution of modeling languages, tools, and transformations is studied in research. It is not clear whether these are the only relevant changes that characterize MDE evolution in practice. In this paper we address this lack of knowledge. We first discuss possible changes and then report on a first study that demonstrates that these forms of evolution can be commonly observed in practice. To investigate the complex nature of MDE evolution in more depth, we captured the evolution of three MDE settings from practice and derive eight observations concerning reasons for MDE evolution. Based on the observations we then identify open research challenge concerning MDE evolution.

Model-Driven Engineering (MDE) automates development activities by employing model transformations. Thereby, a plethora of model transformation approaches with individual capabilities have been developed. In certain cases, complex and automated MDE activities require the interaction of various, potentially heterogeneous, model transformations. This can be achieved by a loosely coupled and highly cohesive composition of model transformations implemented in different model transformation languages. However, existing approaches either do not support context composition, using other model transformations as additional context, or they violate the important black-box principle because they require adapting model transformations for context composition. In this paper, we present a dedicated model transformation composition framework (MoTCoF) that does not require the adaptation of model transformations and, thus, treats model transformations as true black-boxes. We illustrate our approach with an application example taken from an industrial case study.

Model-Driven Engineering (MDE) employs models and model transformations as first-class citizens throughout the whole software development life cycle. Support for automated traceability is necessary because models in MDE usually have inherent dependencies between each other, which must be visible. Furthermore, software evolves which implies to also maintain traceability. In this chapter, we present an efficient and scalable traceability maintenance approach. It uses formal rules to specify conditions for maintaining traceability links. We also show the constitution of our rules and how we improved them, in comparison to a previous approach. Based on this formalism, we present two maintenance strategies. We show an initial (batch) strategy that is applied in case that no change information is available. The second strategy is incremental and therefore scalable. The incremental strategy is applied when change information is available. We explain our approach and evaluate the efficiency and scalability of our approach by means of the mobile phone product line case study presented in this book.

Model-Driven Engineering (MDE) mixes up manual activities, like coding or modeling, with automated activities, such as transformation or generation steps, which can lead to constraints on the development process. Currently, we know little about such constraints. For gaining more knowledge about this it is necessary to capture and compare MDE activities from practice to identify reoccurring structures that can be associated to constraints on the software development process. However, current techniques to capture MDE activities are not sufficient for comparison. Therefore, we developed a new approach to characterize activities based on relations between consumed and produced artifacts. Further, we evaluated this approach by applying it to activities from industrial case studies. Thereby, we found that our approach is applicable to capture complex industrial activities and that the identification of reoccurring structures is possible. These results enable future research about the influence of MDE activities on software development processes.

In model-driven software development a multitude of interrelated models are used to systematically realize a software system. This results in a complex development process since the models and the relations between the models have to be managed. Similar problems appear when following a model-driven approach for managing software systems at runtime. A multitude of interrelated runtime models are employed simultaneously, and thus they have to be maintained at runtime. While for the development case megamodels have emerged to address the problem of managing models and relations, the problem is rather neglected for the case of runtime models by applying ad-hoc solutions. Therefore, we propose to utilize megamodel concepts for the case of multiple runtime models. Based on the current state of research, we present a categorization of runtime models and conceivable relations between them. The categorization describes the role of interrelated models at runtime and demonstrates that several approaches already employ multiple runtime models and relations. Then, we show how megamodel concepts help in organizing and utilizing runtime models and relations in a model-driven manner while supporting a high level of automation. Finally, the role of interrelated models and megamodels at runtime is discussed for self-adaptive software systems and exemplified by a case study.

Design thinking is at its best if tangible prototypes can be used to capture and validate end user needs and envision new products and services. However, today such tangible prototypes are not feasible in a cost-effective manner for complex software systems with multiple users and their complex behavior. To overcome this problem, we developed a scenario-based prototyping approach for complex multi-user software systems that uses executable software engineering models including structural as well as behavioral aspects. Simulation turns these models into tangible virtual prototypes for end users that visualize the complex behavior and capture feedback interactively. In this chapter, we elaborate our concept for cost-effective scenario-based prototyping, report on a first prototypical implementation of the approach for the validation of multi-user processes with end users, and discuss our initial findings and learnings that we gained from first experiments with the implementation.

In this tool demonstration we present an implementation for interactively validating requirements for multi-user software systems and the processes they support with end users. The tool combines the advantages of requirements animation and scenario synthesis to gather stakeholder feedback and create a common understanding amongst stakeholders. Additionally, the users' behavior during the simulation is captured and used to automatically derive new behavioral specifications.

The next generation of advanced mechatronic systems is expected to enhance their functionality and improve their performance by context-dependent behavior. Therefore, these systems require to represent information about the complex environment and changing sets of collaboration partners internally. This requirement is in contrast to the usually assumed static structures for embedded systems. In this paper, we present a model-driven approach which overcomes this situation by supporting dynamic data structures while still guaranteeing that valid worst-case execution times can be derived. It supports a flexible resource management which avoids to operate with the prohibitive coarse worst-case boundaries but instead supports to run applications in different profiles which guarantee different resource requirements and put unused resources in a profile at other applications' disposal. By supporting the proper estimation of worst case execution time (WCET) and worst case number of iteration (WCNI) at runtime, we can further support to create new profiles, add or remove them at runtime in order to minimize the over-approximation of the resource consumption resulting from the dynamic data structures required for the outlined class of advanced systems.

In the world of model-driven engineering (MDE) support for traceability and maintenance of traceability information is essential. On the one hand, classical traceability approaches for MDE address this need by supporting automated creation of traceability information on the model element level. On the other hand, global model management approaches manually capture traceability information on the model level. However, there is currently no approach that supports comprehensive traceability, comprising traceability information on both levels, and efficient maintenance of traceability information, which requires a high-degree of automation and scalability. In this article, we present a comprehensive traceability approach that combines classical traceability approaches for MDE and global model management in form of dynamic hierarchical mega models. We further integrate efficient maintenance of traceability information based on top of dynamic hierarchical mega models. The proposed approach is further outlined by using an industrial case study and by presenting an implementation of the concepts in form of a prototype.

The different perspectives stakeholders and requirements engineers have on a problem are a major hindrance to de- rive useful requirements. While formal requirements mod- els are well suited for excluding inconsistent requirements, prototypes presented to stakeholders are very effective to ensure valid requirements. In this position paper we report about our vision to combine both approaches in form of scenario-based prototyping, which enables the interactive visualization for elicitation and validation of requirements for systems with multiple users in the business domain.

Based on a well-defined component architecture the tool supports the synthesis of so-called real-time statecharts from timed sequence diagrams. The two step synthesis process addresses the existing scalability problems by a proper decomposition and allows the user to define particular restrictions on the resulting statecharts.

The title compound, 2C6H7ClN+·I−·I3−, crystallizes with undulating layers of chains containing alternate iodide and triiodide anions formed from iodine and the heterocyclic iodide salt.