An airfoil shape optimization problem with conflicting objectives is handled using two different multi-objective approaches. These are an a priori scalarization approach where the conflicting objectives are assigned weights and summed together to form a single objective, and the Pareto-optimal multi-objective approach. The optimization formulations for both approaches contain challenging numerical characteristics which include noise, multi-modality and undefined regions. Gradient-, surrogate- and population-based single objective optimization methods are applied to the `a priori' formulations. The gradient methods are modified to improve their performance on noisy problems as well as to handle undefined regions in the design space. The modifications are successful but the modified methods are outperformed by the surrogate methods and population based methods. Population-based techniques are used for the Pareto-optimal multi-objective approach. Two established optimization algorithms and two custom algorithms are implemented. The custom algorithms use fitted unrotated hyper ellipses and linear aggregating functions to search the design space for non-dominated designs. Various multi-objective formulations are posed to investigate different aspects of the airfoil design problem. The non-dominated designs found by the Pareto-optimal multi-objective optimization algorithms are then presented. / Dissertation (MEng)--University of Pretoria, 2011. / Mechanical and Aeronautical Engineering / unrestricted

This thesis is an attempt to understand the concept of ma 間 as it appears traditionally in Japan and how it may be applied to literature as an analytical framework. Ma is most simply defined as an empty space, but has a long history of artistic connotations in various fields, such as architecture, music, and poetry, that may theoretically be applied to literature as well. First, I look at the historical and theoretical background of the concept of ma as it exists in the visual, musical, and literary arts. I consider how ma was first used when it was developed in the eighth century, how it was used prior to World War II, and how it has been used since World War II. I also look at Western theories that I believe could be used to further analyze the concept of ma – namely, the Iceberg Theory and the study of hermeneutics. I use the information in this portion to develop my thesis statement: that ma as an aesthetic term is primarily concerned with encouraging audience participation with the piece of art and that such participation with literature can be facilitated by certain writing techniques, including use of symbolism, juxtaposition, and understatement. Then, I look more closely at three works that I consider prime examples of ma in literature: Takekurabe by Higuchi Ichiyō, Yukiguni by Kawabata Yasunari, and Riaru wārudo by Kirino Natsuo. These works span a wide time range – from the late 1800s to the early 2000s – but all contain themes of disconnect, transition, and confusion, as well as specific writing techniques, that encourage reader participation through introspection. Additionally, I have included a glossary at the end for any Japanese words, with their hiragana and kanji counterparts, that a reader might be unfamiliar with.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24480号 / 医博第4922号 / 新制||医||1063(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 波多野 悦朗, 教授 山本 洋介, 教授 小林 恭 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Today, Real World Data (RWD) is a popular topic in many studies. In particular, it is anticipated to be a significant resource for addressing issues brought on by drug development costs, lengthy development times, and safety concerns. The Swedish healthcare Quality Registries (QR) are studied to contribute to the improvement of health care with individual-based clinical data. Recorded data is used for quality improvement, guidance compliance monitoring, and research. However, the workflow for such a framework that applies RWD which is patient-related data that came from various sources to the new drug development field is currently not well-defined. Thus the main aim of this project is to establish a strategy for integrating RWD with pharmaceutical modeling. To achieve this aim, QRs were examined through an ontological approach. The data and procedures necessary for modeling the development of new drugs, as well as the correspondence of the pieces offered by QR, were studied to assess the feasibility. The modeling of new drug development was studied for three applications: Adverse Drug Event (ADE), Computer-based Simulation (CBS), and drug repurposing, and the analysis of QRs was conducted on seven diseases. After in-depth analysis, although there were differences between the registries, it showed enough feasibility in terms of how much the data provided in the studies on drug repurposing and computer-based simulation satisfied the items required for new drug development. However, in the case of rare diseases, given the lack of an automated method, the ethical ambiguity, and the speed of the process, there still seems to be potential for improvement.  Many registries have begun to support research on the development of novel medications, such as by independently recording the features of drugs. These initiatives could enable the future potential of new Real World Evidence (RWE) such as in the field of proteomics and genomics discovery. / Idag är Real World Data (RWD) ett populärt ämne i många studier. I synnerhet förväntas det vara en betydande resurs för att ta itu med problem som orsakas av kostnader för läkemedelsutveckling, långa utvecklingstider och säkerhetsproblem. Kvalitetsregistren studeras för att bidra till att förbättra hälso- och sjukvården med individbaserade kliniska data. Registrerade data används för kvalitetsförbättring, övervakning av efterlevnad av riktlinjer och forskning. Arbetsflödet för ett sådant ramverk som tillämpar RWD som är patientrelaterad data som kom från olika källor till det nya läkemedelsutvecklingsområdet är dock för närvarande inte väldefinierat. Därför är huvudsyftet med detta projekt att upprätta en strategi för att integrera RWD med läkemedelsmodellering. För att uppnå detta mål undersöktes kvalitetsregister genom ett ontologiskt tillvägagångssätt. De data och procedurer som krävs för att modellera utvecklingen av nya läkemedel, såväl som överensstämmelsen mellan de bitar som erbjuds av kvalitetsregister, studerades för att bedöma genomförbarheten. Modelleringen av utvecklingen av nya läkemedel studerades för tre tillämpningar: skadlig läkemedelseffekt, datorbaserad simulering och återanvändning av läkemedel, och analys av kvalitetsregister genomfördes på sju sjukdomar. Efter en djupgående analys, även om det fanns skillnader mellan registren, visade den tillräcklig genomförbarhet när det gäller hur mycket data som tillhandahållits i studierna om läkemedelsåteranvändning och datorbaserad simulering uppfyllde de krav som krävdes för utveckling av nya läkemedel. Men när det gäller sällsynta sjukdomar, med tanke på avsaknaden av en automatiserad metod, den etiska oklarheten och processens snabbhet, verkar det fortfarande finnas potential för förbättringar. Många register har börjat stödja forskning om utveckling av nya mediciner, till exempel genom att oberoende registrera drogens egenskaper. Dessa initiative skulle kunna möjliggöra den framtida potentialen för nya verkliga bevis, såsom inom området för proteomik och genomik.

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Introduction: The OPTIPARK study confirmed the effectiveness and safety of opicapone as adjunct therapy to levodopa in patients with Parkinson’s disease (PD) and motor fluctuations under real-world conditions. The aim of this sub-analysis was to evaluate opicapone in the German patient cohort of OPTIPARK in order to provide country-specific data. Methods: OPTIPARK was an open-label, single-arm study conducted in routine clinical practice across Germany and the UK. Patients with PD and motor fluctuations received once-daily opicapone 50 mg for 3 months in addition to levodopa. The primary endpoint was Clinicians’ Global Impression of Change (CGI-C). Secondary assessments included Patients’ Global Impressions of Change (PGI-C), Unified Parkinson’s Disease Rating Scale (UPDRS) I–IV, Parkinson’s Disease Questionnaire (PDQ-8), and Non-Motor Symptoms Scale (NMSS). This sub-analysis reports outcomes from the German patients only. Results: Overall, 363 (97.6%) of the 372 patients included in the German cohort received ≥1 dose of opicapone and 291 (80.2%) completed the study. Improvements on CGI-C and PGI-C were reported by 70.8% and 76.3% of patients, respectively. UPDRS scores improved for activities of daily living during OFF time by −3.3 ± 4.5 points and motor scores during ON time by −5.3 ± 7.9 points. PDQ-8 and NMSS scores also demonstrated improvements. Treatment emergent adverse events considered at least possibly related to opicapone occurred in 37.7% of patients, with most being of mild or moderate intensity. Conclusion: Opicapone added to levodopa in patients with PD and motor fluctuations was effective and generally well tolerated in routine clinical practice across Germany.

Thesis (MSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Socially-based networks are of particular interest amongst the variety of communication networks arising in reality. They are distinguished by having small average path length and high clustering coefficient, and so are examples of small-world networks. This thesis studies both real examples and theoretical models of small-world networks, with particular attention to average path length. Existing models of small-world networks, due to Watts and Strogatz (1998) and Newman and Watts (1999a), impose boundary conditions on a one dimensional lattice, and rewire links locally and probabilistically in the former or probabilistically adding extra links in the latter. These models are investigated and compared with real-world networks. We consider a model in which randomness is provided by the Erdos-Rényi random network models superposed on a deterministic one dimensional structured network. We reason about this model using tools and results from random graph theory. Given a disordered network C(n, p) formed by adding links randomly with probability p to a one dimensional network C(n). We improve the analytical result regarding the average path length by showing that the onset of smallworld behaviour occurs if pn is bounded away from zero. Furthermore, we show that when pn tends to zero, C(n, p) is no longer small-world. We display that the average path length in this case approaches infinity with the network order. We deduce that at least εn (where ε is a constant bigger than zero) random links should be added to a one dimensional lattice to ensure average path length of order log n. / AFRIKAANSE OPSOMMING: Sosiaal-baseerde netwerke is van besondere belang onder die verskeidenheid kommunikasie netwerke. Hulle word onderskei deur ’n klein gemiddelde skeidingsafstand en hoë samedrommingskoëffisiënt, en is voorbeelde van kleinwêreld netwerke. Hierdie verhandeling bestudeer beide werklike voorbeelde en teoretiese modelle van klein-wêreld netwerke, met besondere aandag op die gemiddelde padlengte. Bestaande modelle van klein-wêreld netwerke, te danke aan Watts en Strogatz (1998) en Newman en Watts (1999a), voeg randvoorwaardes by tot eendimensionele roosters, en herbedraad nedwerkskakels gebaseer op lokale kennis in die eerste geval en voeg willekeurig ekstra netwerkskakels in die tweede. Hierdie modelle word ondersoek en vergelyk met werklike-wêreld netwerke. Ons oorweeg ’n prosedure waarin willekeurigheid verskaf word deur die Erdös- Renyi toevalsnetwerk modelle wat op ’n een-dimensionele deterministiese gestruktureerde netwerk geimposeer word. Ons redeneer oor hierdie modelle deur gebruik te maak van gereedskap en resultate toevalsgrafieke teorie. Gegewe ’n wanordelike netwerk wat gevorm word deur skakels willekeurig met waarskynlikheid p tot ‘n een-dimensionele netwerk C(n) toe te voeg, verbeter ons die analitiese resultaat ten opsigte van die gemiddelde padlengte deur te wys dat die aanvang van klein-wêreld gedrag voorkom wanneer pn weg van nul begrens is. Verder toon ons dat, wanneer pn neig na nul, C(n, p) nie meer klein-wêreld is nie. Ons toon dat die gemiddelde padlengte in hierdie geval na oneindigheid streef saam met die netwerk groote. Ons lei af dat ten minste εn (waar εn n konstante groter as nul is) ewekansige skakels bygevoeg moet word by ’n een-dimensionele rooster om ‘n gemiddelde padlengte van orde log n te verseker.

The current thesis explores semantic and action effects on visual perception and specifically how higher-level knowledge can co-affect the process of visual perception, along with the well established effects of low level image characteristics, such as colour, image/object saliency and general gist of the scene. Recent evidence on object recognition supports perceptual grouping effects of familiar pairings of functionally interacting objects. This leads to an advantage for their perception as compared with objects positioned in a non-interacting configuration, in cases where there are attentional limitations in perception. Similar effects were previously reported in clinical cases of people diagnosed with neglect (Humphreys & Riddoch, 2001, 2007; Riddoch et al, 2003, 2006), but the fact that they are also present in normally functioning individuals (Green & Hummel, 2006) makes them a clear example of higher order effects on perception. Given the evidence about the abstract nature of the information stored in visual memory and the fact that orientation is part of the spatial information related to an object representation, our first series of experiments aimed at further exploring the nature of this perceptual grouping and whether objects separation would have an effect on it. By combining this paradigm with a paradigm used to explore linguistic factors of perceiving space (Carlson-Radvansky & Radvansky, 1996; Carlson-Radvansky, Covey & Lattanzi, 1999; Carlson-Radvansky & Tang, 2000), we additionally explored the effect of functional interactions at higher levels of post-perceptual processing. We manipulated the locations of various pairs of objects as well as the semantic and functional relationship between them to explore if spatial configurations affect the way people talk about the relationship of the objects in the same way as they affect the same objects‟ recognition. The results revealed a difference, with the same distance manipulation affecting linguistic descriptions of spatial relationships between pairs of objects but having no effect in their perceptual grouping. One of the aims of this thesis is the interpretation of such effects according to a recently growing body of evidence on the interaction between action and perception systems. These systems which were traditionally considered to be two separate disciplines seem to connect, with information from action systems feeding on perceptual systems. Through such an interaction, for example, information about the functionally related objects could lead to their perceptual grouping. A series of experiments have demonstrated effects of action affordances on object perception and their combined results seem to imply pre-attentive effects on object perception independent of the person‟s intention to act on an object (Riddoch, Humphreys, Edwards, Baker & Wilson, 2002; Tipper, Paul & Hayes, 2006; Symes, Ellis & Tucker, 2007).To further explore the role of functional relationships and action affordances in natural scene viewing, a second series of experiments was designed. These experiments also provided evidence to an old debate about the nature of visual memory and its organisation, adding further evidence for the role of semantic relationship and action affordances in the memory encoding of a scene. This series of experiments took advantage of the phenomenon of object prioritization during unexpected object onsets or feature changes while viewing real world scenes (Brockmole & Henderson, 2005a). Using a variation of classic change detection paradigms, eye-tracking data were recorded to measure at which point action affordance manipulations would have an effect and to reveal whether object functionality changes can still produce attention capture (quantified as fixation probability to the object of interest), similarly to previously tested semantic changes. Functionality manipulation was achieved by orientation changes of a critical object in the scene, but in a way which constitutes it non functional to the specific context. By comparing action affordance interference during object onsets against interference during object orientation changes we differentiated between pre-attentive and post-selection mechanisms. Our results indicate that although there is no evidence of pre-attentive modulation of object prioritization, action affordances do have an effect in post-selection mechanisms, with functionally inconsistent objects attracting attention faster and affecting the encoding of an object in the scene representation during memory guided prioritization but not during oculomotor capture. Our results also support the existence of two separate mechanisms for object prioritization. As a summary, this family of semantic relationships, action affordances and the interplay between action and perception systems has been tested during my PhD research from the very early stages of perception until post perceptual and linguistic accounts of the perceived image. Their role in attention capture and their mediating role to visual memory have also been explored using eye-tracking technology and realistic and rich in information real world scenes. Overall my thesis is oriented towards the aspects that tie all these effects together and further explores the role of action affordances in memory encoding.

This dissertation is centered around two comprehensive themes: the extraction of information embedded in equity index option prices, and how to use this information in order to be able to make optimal decisions in the equity index option markets. These problems are important for decision makers in the equity index options markets, since they are continuously faced with making decisions under uncertainty given observed market prices. The methods developed in this dissertation provide robust tools that can be used by practitioners in order to improve the quality of the decisions that they make. In order to be able to extract information embedded in option prices, the dissertation develops two different methods for estimation of stable option implied surfaces which are consistent with observed market prices. This is a difficult and ill-posed inverse problem which is complicated by the fact that observed option prices contain a large amount of noise stemming from market micro structure effects. Producing estimated surfaces that are stable over time is important since otherwise risk measurement of derivatives portfolios, pricing of exotic options and calculation of hedge parameters will be prone to include significant errors. The first method that we develop leads to an optimization problem which is formulated as a convex quadratic program with linear constraints which can be solved very efficiently. The second estimation method that we develop in the dissertation makes it possible to produce local volatility surfaces of high quality, which are consistent with market prices and stable over time. The high quality of the surfaces estimated with the second method is the crucial input to the research which has resulted in the last three papers of the dissertation. The stability of the estimated local volatility surfaces makes it possible to build a realistic dynamic model for the equity index derivatives market. This model forms the basis for the stochastic programming (SP) model for option hedging that we develop in the dissertation. We show that the SP model, which uses generated scenarios for the squared local volatility surface as input,  outperforms the traditional hedging methods that are described in the literature. Apart from having an accurate view of the variance of relevant risk factors, it is when building a dynamic model also important to have a good estimate of the expected values, and thereby risk premia, of those factors. We use a result from recently published research which lets us recover the real-world density from only a cross-section of observed option prices via a local volatility model. The recovered real-world densities are then used in order to identify and estimate liquidity premia that are embedded in option prices. We also use the recovered real-world densities in order to test how well the option market predicts the realized statistical characteristics of the underlying index. We compare the results with the performance of commonly used models for the underlying index. The results show that option prices contain a premium in the tails of the distribution. By removing the estimated premia from the tails, the resulting density predicts future realizations of the underlying index very well.

Decades of research on compression ignition engines have led to a highly efficient combustion cycle in contemporary diesel engines. Nonetheless, the combustion process is being studied perpetually to meet both current and future emission regulations. One of the most influential parameters that impacts the combustion quality, is the fuel spray evolution during injection, and subsequent fuel-air mixture formation inside the engine cylinder. The spray evolution has been investigated to a high level of detail, and the highly complex processes of mixture formation and combustion are well-documented for diesel engines. Most of these investigations are limited to studying either research-grade injectors, or brand new production injectors. Injectors in real-world diesel engines, i.e. normal passenger cars and trucks that are used on a daily basis, are however subject to deposit formation at the tip of the injector nozzle. These deposits have the potential of altering the internal nozzle flow and fuel spray pattern, which in turn degrades combustion quality and increases engine emissions. In the work presented in this thesis the spray evolution of production injectors has been studied over a wide range of injector conditions. Common rail light-duty injectors with a usage history of up to 90 000 miles were acquired from the UK commuter car parc, and several brand new injectors were studied for comparison purposes. It is shown that the spray pattern of the injected fuel changes over the lifetime of the injector. For used injectors a reduced penetration rate was observed in the transient regime of fuel injection, during needle lift. The reduced penetration rate was often accompanied by anomalous radial expansions. Although the magnitude of the effects varied from injector to injector, the highest mileage injectors tended to produce the strongest spray deviations. For several high-mileage injectors the end of injection appeared retarded with respect to new injectors. Expulsions of liquid ligaments and droplets after the end of injection were observed from all injectors, irrespective of the mileage of the injector.