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To understand effects of inhalable substances in the lung, it is reasonable to investigate these substances using biological models. Until recently, tests for this purpose had to be performed mainly in vivo. Due to ethical, political and scientific reasons, alternative in vitro test methods are of increasing importance. At the Fraunhofer Institute ITEM, a testing procedure based on air-liquid interface (ALI) culture technology was developed for this purpose (P.R.I.T.® ExpoCube®). In cooperation with the Fraunhofer Institute SCAI this in vitro testing procedure was revised by applying Computational Fluid Dynamics (CFD) for the layout of the aerosol conduction and sampling. The aim of the study was to characterize and improve the deposited amount of test aerosols on cultured human cells and to increase the amount of aerosols extracted from a sampling box. The calculations focused the construction layout of the aerosol box, the shape of inlets for cell exposure and the thermophoresis effect as a measure for improvement of particle deposition on exposed cells. For this purpose commercial CFD software was applied in which the airborne aerosols were regarded as solid particles in a Lagrangian frame of reference. Due to the partially submicronic size of the particles, Brownian motion and Cunningham correction for the drag and thermophoretic forces were considered. Results demonstrated improvements of the particle extraction from the aerosol sampling by optimization of the construction, only minor effects of the inlet shape on the particle deposition on cells and a clear improvement of the particle deposition by applying thermophoretic effects.

Cranial cruciate ligament rupture is the most frequently occurring disease of the canine stifle. After introduction of corrective osteotomies of the proximal tibia as surgical treatment option in medium, large and giant breeds, the tibial plateau leveling osteotomy (TPLO) evolved into one of the favorite procedures. In the past small breed dogs have usually been treated by extra-articular stabilization techniques. TPLO has recently become an accepted treatment method in these breeds as well as, and is nowadays used with increasing frequency. The purpose of this study was to evaluate long-term outcomes of TPLO compared to an extra-articular stabilization technique in small breed dogs.A total of 40 stifles of 30 small breed dogs weighing ≤ 15 kg were treated for cranial cruciate ligament rupture with either TPLO (n = 23) or a lateral capsular-fascial imbrication technique (CFI; n = 17). Dogs were clinically examined before and at least 6 months after surgery by treadmill analysis and radiography. Moreover a questionnaire was provided to the owners to assess postoperative function and overall satisfaction.Twenty-one of 23 operated limbs (91.3%) treated with TPLO and five of 17 (29.4%) treated with the CFI showed absolute values comparable to healthy dogs when evaluated by peak vertical force, vertical impulse and its symmetry index during objective gait analysis. Both groups showed mild, but continuous progression of osteoarthritis. TPLO led to a significantly faster recovery and a higher degree of owner satisfaction.Based on clinical examination and objective gait analysis TPLO yielded excellent long-term results and a high degree of owner satisfaction in small breed dogs ≤ 15 kg treated for cranial cruciate ligament rupture.TPLO seems to be superior to CFI treatment of small breed dogs in this study, although CFI should be considered as treatment option under certain circumstances.

The governmental decision for the 'Energiewende' has put some urgent questions on the future of the P&T research. The Bundesministerium für Wirtschaft und Energie and the Bundesministerium für Bildung und Forschung have launched a study managed by acatech in 2012 to answer these questions on a broad scientific basis. The major mandate was to evaluate scientific and technological as well as socio-economic challenges and opportunities of the P&T technology in the view of the phase out decision. The main topics were: - Starting point and boundary conditions – waste amounts and final disposal strategies - Definition and description of scenarios – possible ways for transmutation in the view of the phase out, European vs. national - Technological challenges of P&T – description of the major challenges to be solved on the way to industrial application - Current status of R&D – discussion of possible transmutation systems, current R&D status of P&T, development gaps, and future research strategy - Safety aspects – special safety aspects including all steps of the P&T cycle - International projects & competences in Germany – what is going on around the world and what can be served by the German industry The socio-scientific, the ecologic, and the economic aspects have been analyzed in parallel using expert interviews, group Delphi, and independent expert opinions on economic, legal, and environmental aspects. An overview on the results of the study in the view of the contributing Helmholtz research centers (KIT, HZDR, and FZJ) is given. Special focus is put on the political recommendations and the developed research strategy which has been proposed to the ministries. Finally the conclusions of the Helmholtz-Centres regarding their current and future activities are given.

The governmental decision to phase out electric energy production in nuclear power plants in Germany has put some questions on the future of the P&T research. The Bundesministerium für Wirtschaft (ministry of economics) and the Bundesministerium für Bildung und Forschung (ministry of education and research) have launched a study managed by acatech (national academy of science and engineering) in 2012 to answer these questions on a broad scientific basis. The major mandate was to evaluate scientific and technological as well as socio-economic challenges and opportunities of the P&T technology in the view of the phase out decision. The scientific and technological aspects of P&T are analyzed with respect to a possible contribution to the nuclear waste management using the following structure: - Starting point and boundary conditions – waste amounts and final disposal strategies - Definition and description of scenarios – possible ways for transmutation in the view of the phase out, European vs. national - Technological challenges of P&T – description of the major challenges to be solved on the way to industrial application - Current status of R&D – discussion of possible transmutation systems, current R&D status of P&T, development gaps, and future research strategy - Safety aspects – special safety aspects including all steps of the P&T cycle - International projects & competences in Germany – what is going on around the world and what can be served by the German industry The socio-scientific, the ecologic, and the economic aspects have been analyzed in parallel using expert interviews, group Delphi, and independent expert opinions on economic, legal, and environmental aspects. An overview on the results of the study in the view of the contributing Helmholtz research centers (KIT, HZDR, and FZJ) will be given with special focus on the political recommendations and the developed research strategy which has been proposed to the ministries.

Im Fokus der wissenschaftlichen Arbeiten des ISF steht der Mensch als exponiertes Individuum mit all seinen anatomischen und physiologischen Eigenschaften unter Berücksichtigung des Strahlen-Expositionsszenarios. Dabei werden verschiedene Aspekte der Dosimetrie mit dem Ziel einer optimierten und personenbezogenen Quantifizierung der Strahlenexposition untersucht. Folgende Themen werden im ISF 2010 behandelt: Externe Dosimetrie, Modellierung und Interne Strahlenexposition.

Actually, precision cut lung slices are under extensive investigation to serve as a model for acute inhalation toxicology. Slices can be employed as an ex-vivo/in-vitro model as alternative method in the context of REACH and the 3Rs. Moreover, this in vitro model represents in vivo tissue including all naturally occurring cell types of the respiratory tract situated in their physiological environment. For the reason of these beneficial characteristics, PCLS may be an in vitro model of first choice in the future, especially with respect to studies on inflammatory changes in the lung. However, since safety control and toxicology demand studies on genotoxicity, we also started to establish a Comet assay with live lung tissue in vitro from mouse lungs to expand the experimental possibilities from investigations with PCLS on toxicity and inflammatory responses to genotoxicity. The work focused on optimization of a simple and fast cell separation method by enzymatic digestion of the lung tissue, application of the alkaline Comet assay and exposure of lung slices to culture media (negative control) and test compounds in a first series of experiments. Ethyl methanesulfonate (EMS) and formalin (FA) were tested as model substances known to induce DNA damage. These alterations can be observed in the Comet assay as, respectively, an increased rate of DNA breaks (EMS) or a reduced rate of DNA breaks by induction of cross-links (FA). Factors of concern for the reproducibility and meaningfulness of results obtained with the method established here to investigate genotoxicity induced in this in-vivo-like live complex cell system by application of the Comet assay to PCLS are discussed. These include the slice-to-slice- and individual-to-individual-reproducibility as well as the background signal and the dose-dependency of the effects induced by the model substances. In summary, the experiments showed that dose-dependent effects induced by EMS and FA could be detected in mouse PCLS, and by application of the Comet assay, effects from strand-breaking and cross-linking substances could be reproducibly discriminate.

(FRENCH)Ce travail de thèse basé sur le système visuel chez les sujets sains et chez les patients schizophrènes, s'articule autour de trois articles scientifiques publiés ou en cours de publication. Ces articles traitent des sujets suivants : le premier article présente une nouvelle méthode de traitement des composantes physiques des stimuli (luminance et fréquence spatiale). Le second article montre, à l'aide d'analyses de données EEG, un déficit de la voie magnocellulaire dans le traitement visuel des illusions chez les patients schizophrènes. Ceci est démontré par l'absence de modulation de la composante PI chez les patients schizophrènes contrairement aux sujets sains. Cette absence est induite par des stimuli de type illusion Kanizsa de différentes excentricités. Finalement, le troisième article, également à l'aide de méthodes de neuroimagerie électrique (EEG), montre que le traitement des contours illusoires se trouve dans le complexe latéro-occipital (LOC), à l'aide d'illusion « misaligned gratings ». De plus il révèle que les activités démontrées précédemment dans les aires visuelles primaires sont dues à des inférences « top- down ».Afin de permettre la compréhension de ces trois articles, l'introduction de ce manuscrit présente les concepts essentiels. De plus des méthodes d'analyses de temps-fréquence sont présentées. L'introduction est divisée en quatre parties : la première présente le système visuel depuis les cellules retino-corticales aux deux voix du traitement de l'information en passant par les régions composant le système visuel. La deuxième partie présente la schizophrénie par son diagnostic, ces déficits de bas niveau de traitement des stimuli visuel et ces déficits cognitifs. La troisième partie présente le traitement des contours illusoires et les trois modèles utilisés dans le dernier article. Finalement, les méthodes de traitement des données EEG seront explicitées, y compris les méthodes de temps-fréquences.Les résultats des trois articles sont présentés dans le chapitre éponyme (du même nom). De plus ce chapitre comprendra les résultats obtenus à l'aide des méthodes de temps-fréquenceFinalement, la discussion sera orientée selon trois axes : les méthodes de temps-fréquence ainsi qu'une proposition de traitement de ces données par une méthode statistique indépendante de la référence. La discussion du premier article en montrera la qualité du traitement de ces stimuli. La discussion des deux articles neurophysiologiques, proposera de nouvelles d'expériences afin d'affiner les résultats actuels sur les déficits des schizophrènes. Ceci pourrait permettre d'établir un marqueur biologique fiable de la schizophrénie.ABSTRACT (ENGLISH)This thesis focuses on the visual system in healthy subjects and schizophrenic patients. To address this research, advanced methods of analysis of electroencephalographic (EEG) data were used and developed. This manuscript is comprised of three scientific articles. The first article showed a novel method to control the physical features of visual stimuli (luminance and spatial frequencies). The second article showed, using electrical neuroimaging of EEG, a deficit in spatial processing associated with the dorsal pathway in chronic schizophrenic patients. This deficit was elicited by an absent modulation of the PI component in terms of response strength and topography as well as source estimations. This deficit was orthogonal to the preserved ability to process Kanizsa-type illusory contours. Finally, the third article resolved ongoing debates concerning the neural mechanism mediating illusory contour sensitivity by using electrical neuroimaging to show that the first differentiation of illusory contour presence vs. absence is localized within the lateral occipital complex. This effect was subsequent to modulations due to the orientation of misaligned grating stimuli. Collectively, these results support a model where effects in V1/V2 are mediated by "top-down" modulation from the LOC.To understand these three articles, the Introduction of this thesis presents the major concepts used in these articles. Additionally, a section is devoted to time-frequency analysis methods not presented in the articles themselves. The introduction is divided in four parts. The first part presents three aspects of the visual system: cellular, regional, and its functional interactions. The second part presents an overview of schizophrenia and its sensoiy-cognitive deficits. The third part presents an overview of illusory contour processing and the three models examined in the third article. Finally, advanced analysis methods for EEG are presented, including time- frequency methodology.The Introduction is followed by a synopsis of the main results in the articles as well as those obtained from the time-frequency analyses.Finally, the Discussion chapter is divided along three axes. The first axis discusses the time frequency analysis and proposes a novel statistical approach that is independent of the reference. The second axis contextualizes the first article and discusses the quality of the stimulus control and direction for further improvements. Finally, both neurophysiologic articles are contextualized by proposing future experiments and hypotheses that may serve to improve our understanding of schizophrenia on the one hand and visual functions more generally.

Im Fokus der wissenschaftlichen Arbeiten des ISF steht der Mensch als exponiertes Individuum mit all seinen anatomischen und physiologischen Eigenschaften unter Berücksichtigung des Strahlen-Expositionsszenarios. Dabei werden verschiedene Aspekte der Dosimetrie mit dem Ziel einer optimierten und personenbezogenen Quantifizierung der Strahlenexposition untersucht. Folgende Themen werden im ISF 2009 behandelt: Externe Dosimetrie, Modellierung und Interne Strahlenexposition.

SUMMARY: A programmable CSF shunt valve was assessed for magnetic field interactions, heating (transmit-receive body radio-frequency coil; whole-body averaged specific absorption rate, 2.1 W/kg), functional alterations, and artifacts at 3T. The programmable valve showed minor magnetic field interactions and heating was not excessive (+0.8°C). The function of the programmable valve was not altered by multiple exposures to the 3T scanner or from exposure to various MR imaging conditions. Therefore, this implant is safe for a patient undergoing MR imaging at 3T or less when the radiologist follows specific safety guidelines. Artifacts for the programmable valve were relatively large in relation to the size and shape of the valve; this finding may impact the diagnostic use of MR imaging if the area of interest is in proximity to this implant.

The goals of the MEGAPIE initiative are to design, build and operate a 1MW heavy liquid metal target. The first step towards the realization of the MEGAPIE target was the feasibility studies, which outlined the entire project. Contextually to the feasibility studies the conceptual design phase started with the establishment of R&D working groups assisting the design and validation of both the target and its ancillary systems. In this framework the EU project MEGAPIE-TEST has been structured in three work packages with tasks concerning the finalization of the engineering design, the components and subsystem testing, the integral test and the first irradiation period. The MEGAPIE-TEST consortium is composed by the 14 partners: FZK, PSI, CEA, ENEA, SCK-CEN, CNRS /IDFE, IN2P3, LMPGM, EMN, ISMRA, UNIV-NANTES, U-PSUDXI, USTL. Currently the engineering design of the target has been finalized, its manufacturing has been launched and the design activities on the ancillary systems were almost completed. R&D activities in the fields of materials, thermal – hydraulics, structural mechanics, neutronic and nuclear assessment and liquid metal technologies were performed in order to assist specific design issues. Some Subsystem and component tests were also performed and the preparation of the integral test is an ongoing activity.

During the last decades the Ultrasound Doppler Velocimetry (UDV) became a very powerful tool to measure the velocity structure of liquid flows. Because of the ability to work in opaque fluids and to deliver complete velocity profiles in real time it becomes very attractive for liquid metal applications. But, in case of hot metallic melts the user is confronted with a number of specific problems: First of all, the application of the ultrasonic transducers is usually restricted to maximum temperatures of 150°C. The transmission of a sufficient amount of ultrasonic energy from the transducer to the fluid has to be guaranteed. Here, the acoustic coupling and the wetting conditions have to be considered as important issues. Moreover, the flow has to be seeded with reflecting particles to obtain Doppler signals from the fluid. The feasibility of velocity profile measurements by UDV has already been demonstrated for low temperature liquid metals as mercury [1] and gallium [2]. Now, first successful measurements in liquid sodium at 150°C are published [3]. We will present mean profiles of a sodium flow in a rectangular duct exposed to an external, transverse magnetic field. To demonstrate the capability of UDV the transformation of a well-known turbulent, piston-like profile to a M-shaped velocity profile with growing magnetic field strength was observed. The significance of artefacts such as caused by the existence of reflecting interfaces in the measuring domain will be discussed. An integrated ultrasonic sensor with acoustic wave guide has been developed to overcome the limitation of ultrasonic transducers to temperatures lower than 200°C. This sensor can presently be applied at maximum temperatures up to 400°C, but an extension up to 800°C can reasonably be expected. In this presentation we show some experimental results obtained in PbBi bubbly flows at temperatures up to 350°C. Ar bubbles were injected through a single orifice in a cylindrical container filled with stagnant PbBi. Velocity profiles were measured in the bubble plume. Mean values of the liquid as well as the bubble velocity were extracted from the data and will be presented as function of the gas flow rate. Velocity profiles of a single-phase PbBi flow in a tube were successfully obtained at the KALLA laboratory of FZK. By means of the integrated sensor stable velocity signals could be received over a period of about 72 hours at temperatures between 180°C and 350°C. [1] Y. Takeda: Measurement of velocity profile of mercury flow by ultrasound Doppler shift method. Nucl. Techn. 79 (1987), 120-124 [2] D. Brito, H.-C. Nataf, P. Cardin, J. Aubert, J.-P. Masson: Ultrasonic Doppler velocimetry in liquid gallium. Exp. Fluids 31 (2001) 6, 653-663 [3] S. Eckert, G.Gerbeth: Velocity measurements in liquid sodium by means of Ultrasound Doppler Velocimetry. accepted for publication in Exp. Fluids (2002)

Die folgenden 5 Beiträge dokumentieren die Ergebnisse der Sektionen "Thermo- und Fluiddynamik" (Sektion 2), "Brennelemente und Kernbauteile" (Sektion 5), "Forschungsreaktoren" (Sektion 9), "Fortschrittliche Reaktorkonzepte, Energiesysteme - Energiewirtschaft" (Sektion 10) und "Werkstoffe, Herstellung und Betriebsverhalten" (Sektion 12).