Daten-basierte variable-fidelity Modelle reduzierter Ordnung zur effizienten Fahrzeugform-Optimierung

Over the last decades, aerodynamics has played a more and more important role in engineering design of vehicles. Computer simulations are used to investigate the aerodynamic behavior of new geometries. In addition to scalar-valued quantities, high-dimensional field variables such as the sensitivity map, a vector-valued quantity which indicates the sensitivity of the drag coeffcient with respect to local shape variations, are of particular interest. However, the high computational effort required for high-fidelity aerodynamic flow simulations makes their use in an optimization process unfeasable. Since the design of cars is primarily driven by aesthetics, automatic optimization of the vehicle shape is also undesirable. An interactive design tool is required which enables the computation of sufficiently accurate approximations to the aerodynamic quantities via a surrogate model in real-time. This calls for the use of non-intrusive model reduction techniques, which approximate the quantity of interest based on sampled data. However, the high computational effort associated with high-fidelity flow simulations strongly limits the available sample data. In the case of scalar-valued quantities, variable-fidelity methods can be used to drastically increase the efficiency of the surrogate model. Such methods use sample data of a computationally cheaper, but also less accurate model to obtain the global trend of the quantity of interest and in this way improve the approximation of the high-fidelity model. In this thesis, a well-known variable-fidelity methodology for scalar-valued quantities is extended to the vector-valued case. It is shown that this new approach is a generalization of known variable-fidelity methods for scalar-valued qunatities and that certain properties of these approaches transfer to the new method. An error estimator is derived which can be used to adaptively improve the model. In addition, open theoretical questions associated with the Cokriging method, a well-known variable-fidelity method for scalar-valued quantities, are addressed. The applicability of the new method in industrial vehicle shape optimization is then demonstrated in two case studies on a high-resolution model of a Volkswagen Passat B6 provided by the Volkswagen AG and compared with conventional methods.In den letzten Jahrzehnten hat die Bedeutung der Aerodynamik in der Fahrzeugentwicklung immer weiter zugenommen. Zur Untersuchung des aerodynamischen Verhaltens neuer Geometrien kommen Computersimulationen zum Einsatz. Typische Zielgrößen sind dabei neben skalaren Kennwerten auch hoch-dimensionale Feldgrößen wie die Sensitivitätslandkarte, die die Sensitivität des Widerstandsbeiwertes bezüglich lokaler Formänderungen anzeigt. Allerdings macht der hohe Rechenaufwand hochgenauer aerodynamischer Strömungssimulationen ihre Verwendung in einem Optimierungsprozess unmöglich. Da das Design von Autos vor allem durch Ästhetik bestimmt wird, ist eine automatische Optimierung der Fahrzeugform zudem ungewünscht. Ferner wird ein interaktives Design-Tool benötigt, welches die Zielgröße über ein Ersatzmodell hinreichend genau in nahezu Echtzeit näherungsweise berechnet und visualisiert. Aufgrund dieser Anforderungen kommen nicht-intrusive Modellreduktions-Verfahren in Frage, welche die Zielgröße basierend auf beobachteten Stützwerten approximiert. Der hohe Rechenaufwand hochgenauer Strömungssimulationen limitiert die Anzahl der verfügbaren Stützwerte allerdings stark. Im Falle skalarer Zielgrößen kann man mithilfe von variable-fidelity Verfahren die Effizienz der Ersatzmodell-Erstellung drastisch steigern. Solche Verfahren nutzen Stützwerte eines weniger rechenintensiven, aber auch ungenaueren Modells um den globalen Trend der Zielgröße zu erfassen und so die Approximation des hochgenauen Modells zu verbessern. Im Rahmen dieser Arbeit wird eine bekannte variable-fidelity Methodik für skalare Zielgrößen auf vektorwertigen Zielgrößen erweitert. Es wird gezeigt, dass der vorgestellte neue Ansatz eine Verallgemeinerung bekannter variable-fidelity Verfahren für skalare Zielgrößen ist und sich dadurch bestimmte Eigenschaften dieser Ansätze auf die neue Methode übertragen. Ein Fehlerschätzer wird hergeleitet, der zur adaptiven Verbesserung des Modells verwendet werden kann. Außerdem werden offene theoretische Fragen zu der Cokriging-Methode, einer bekannten variable-fidelity Methode für skalare Zielgrößen, untersucht. Anschließend wird die Anwendbarkeit der neuen Methode in der industriellen Fahrzeugform-Optimierung in zwei Fallstudien am Beispiel eines hochaufgelösten Computermodells eines Volkswagen Passat B6, welches von der Volkswagen AG zur Verfügung gestellt wurde, demonstriert und mit herkömmlichen Verfahren verglichen

Self-assembly studies with heterocyclic amino acids

This thesis describes investigations towards the self-assembly of heterocyclic amino acids to form cyclopeptides, including the natural products dendroamide A and nostacyclamide. The Introduction highlights a variety of different natural products including the lissoclinum cyclopeptides and other oxazole and thiazole based natural products. The conformation of the lissoc1inum cyclopeptides and the affect different substituents have on their conformation is explored. The ability of a variety of natural products to chelate metal ions and the evidence for metal ion chelation within the lissoclinum cyclopeptides is also discussed. The Introduction is concluded with a statement of the aims and objectives of our research. The Results and Discussion section of the thesis details the development of a novel cyc1ooligomerisation reaction of heterocyclic amino acids. This cyc1ooligomerisation is applied to the self-assembly of thiazole and oxazole amino acids to form analogues of naturally occurring cyc1opeptides. The protocol is then extended to the self-assembly of the natural products dendroamide A and nostacyclamide. Additionally the ability of metal ions to act as templates and promote the formation of particular products is illustrated throughout these studies. Detailed discussions are also presented within this section into the methods for thiazole and oxazole formation. The third part of the thesis is the Experimental section containing full details of the preparative work completed and listing spectroscopic and analytical data on all new compounds synthesised during this study

Finite-Size Scaling from the non-perturbative Renormalization Group

The phase diagram of QCD at finite temperature and density and the existence of a critical point are currently very actively researched topics. Although tremendous progress has been made, in the case of two light quark flavors even the order of the phase transition at zero density is still under discussion. Finite-size scaling is a powerful method for the analysis of phase transitions in lattice QCD simulations. From the scaling behavior, critical exponents can be tested and the order as well as the universality class of a phase transition can be established. This requires knowledge of the critical exponents and the scaling behavior. We use a non-perturbative Renormalization Group method to obtain critical exponents and the finite-size scaling functions for the O(4) universality class in three dimensions. These results are useful for a comparison to the actual scaling behavior in lattice QCD simulations with two flavors, as well as for an estimate of the size of the scaling region and the deviations from the expected scaling behavior.Comment: contribution to the proceedings of the workshop QCD@work 2007, Martina Franca (Italy), June 2007, proceedings to be published by AIP, 6 pages, 6 figures (scaled down from published version

Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future

In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2). Both the PROMID (placebo-controlled, prospective, randomized study in patients with metastatic neuroendocrine midgut tumors) and the CLARINET (controlled study of lanreotide antiproliferative response in neuroendocrine tumors) trial showed a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) upon SSA treatment, compared to placebo. Moreover, the combination of SSA with peptide receptor radionuclide therapy (PRRT) in small intestinal NETs has proven efficacy in the phase 3 neuroendocrine tumours therapy (NETTER 1) trial. PRRT is currently being tested for enteropancreatic NETs versus everolimus in the COMPETE trial, and the potential of SSTR-antagonists in PRRT is now being evaluated in early phase I/II clinical trials. This review provides a synopsis on the pharmacological development of SSAs and their use as antisecretory drugs. Moreover, this review highlights the clinical evidence of SSAs in monotherapy, and in combination with other treatment modalities, as applied to the antiproliferative management of neuroendocrine tumors with special attention to recent high-quality phase III trials

Self-assembly studies with heterocyclic amino acids

This thesis describes investigations towards the self-assembly of heterocyclic amino acids to form cyclopeptides, including the natural products dendroamide A and nostacyclamide. The Introduction highlights a variety of different natural products including the lissoclinum cyclopeptides and other oxazole and thiazole based natural products. The conformation of the lissoc1inum cyclopeptides and the affect different substituents have on their conformation is explored. The ability of a variety of natural products to chelate metal ions and the evidence for metal ion chelation within the lissoclinum cyclopeptides is also discussed. The Introduction is concluded with a statement of the aims and objectives of our research. The Results and Discussion section of the thesis details the development of a novel cyc1ooligomerisation reaction of heterocyclic amino acids. This cyc1ooligomerisation is applied to the self-assembly of thiazole and oxazole amino acids to form analogues of naturally occurring cyc1opeptides. The protocol is then extended to the self-assembly of the natural products dendroamide A and nostacyclamide. Additionally the ability of metal ions to act as templates and promote the formation of particular products is illustrated throughout these studies. Detailed discussions are also presented within this section into the methods for thiazole and oxazole formation. The third part of the thesis is the Experimental section containing full details of the preparative work completed and listing spectroscopic and analytical data on all new compounds synthesised during this study

Levels of Structural Integration Mediate the Impact of Metacognition on Functioning in Non-affective Psychosis: Adding a Psychodynamic Perspective to the Metacognitive Approach

Synthetic metacognition is defined by integrative and contextualizing processes of discrete reflexive moments. These processes are supposed to be needed to meet intrapsychic as well as interpersonal challenges and to meaningfully include psychotic experience in a personal life narrative. A substantial body of evidence has linked this phenomenon to psychosocial functioning and treatment options were developed. The concept of synthetic metacognition, measured with the Metacognition Assessment Scale-Abbreviated (MAS-A), rises hope to bridge gaps between therapeutic orientations and shares valuable parallels to modern psychodynamic constructs, especially the 'levels of structural integration' of the Operationalized Psychodynamic Diagnosis (OPD-2). As theoretical distinctions remain, aim of this study was to compare the predictive value of both constructs with regard to psychosocial functioning of patients with non-affective psychoses, measured with the International Classification of Functioning, Disability and Health (MINI-ICF-APP). It was further explored if levels of structural integration (OPD-LSIA) would mediate the impact of metacognition (MAS-A) on function (MINI-ICF-APP). Expert ratings of synthetic metacognition (MAS-A), the OPD-2 'levels of structural integration' axis (OPD-LSIA), psychosocial functioning (MINI-ICF-APP) and assessments of general cognition and symptoms were applied to 100 individuals with non-affective psychoses. Whereas both, MAS-A and OPD-LSIA, significantly predicted MINI-ICF-APP beyond cognition and symptoms, OPD-LSIA explained a higher share of variance and mediated the impact of MAS-A on MINI-ICF-APP. Levels of structural integration, including the quality of internalized object representations and unconscious interpersonal schemas, might therefore be considered as valuable predictors of social functioning and as one therapeutic focus in patients with non-affective psychoses. Structural integration might go beyond and form the base of a person's actual reflexive and metacognitive capabilities. Psychotherapeutic procedures specific for psychoses may promote and challenge a patient's metacognitive capacities, but should equally take the need for maturing structural skills into account. Modern psychodynamic approaches to psychosis are shortly presented, providing concepts and techniques for the implicit regulation of interpersonal experience and aiming at structural integration in this patient group

Evaluative judgement – a practitioner's case in chemistry research projects

Engaging students actively in assessment, using a range of formative activities, consistently over sustained periods is a common recommendation in the assessment for learning literature. Despite this, practice still lags behind. Our case study aims to bridge the widening gap between theory and practice by illustrating the application of recent theoretical concepts in practice. The literature contains many examples and research on isolated events to engage students in assessment. Cases that explore engagement in different formative practices, over extended periods of time, are scarce and challenging for practitioners to implement in the absence of examples and evidence. Consequently, whilst adoption of theory informed practices remains limited, research also remains limited. Our case study aims to bridge the widening gap between practice and theory by elaborating a case example for practitioners. The redesign of a third year laboratory module, in which students undertake research projects, is presented. Our case illustrates how practitioners can incorporate assessment for learning principles, outlined in contemporary frameworks (evaluative judgement) considering process and a learning sequence over an entire year. The learning design of a module, before and after, is fully described to exemplify how practitioners can implement theoretical principles in practice. Students’ perception of the value of the new tasks were gathered to inform reflections for practitioners in the implementation of evaluative judgement

A Serious Gaming Approach For Serious Stakeholder Participation

Serious games are a category of games which are designed for a specific purpose other than for pure entertainment. It is not a new concept but serious games using real data, coupled with real time modelling and combining model results with social and economic factors opens up a new paradigm for active stakeholder participation. DHI and UNEP-DHI Centre initiated a project called Aqua Republica where a virtual world is developed which allows participants to develop a river basin and visualise the consequences of their decisions. The aim of this project is to raise awareness of the interconnectivity of water and educate on integrated water resources management. Aqua Republica combines a game layer with a water allocation model, MIKE BASIN, to create an interactive, realistic virtual environment where players play the role of a catchment manager of an undeveloped river catchment. Their main objective is to develop the river catchment to be as prosperous as it can be. To achieve that, they will need to generate a good economy in the catchment to provide the funds needed for development, have a steady food supply for their population and enough energy and water for the catchment. Through these actions by the player, a meaningful play is established to engage players and to educate them about the complex relationships between developmental actions in a river basin and the natural environment as well as their consequences. The game layer also consists of a reward system to encourage learning. People can play and replay the game, get rewarded from performing the right principles and penalised from failures in the game. This abstract will explain the concept of the game and how it has been used in a stakeholder participation environment

Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite