Mechanical engineers have difficulties when attempting to convey three-dimensional product information in a two-dimensional style. Effective collaboration between various users requires capability to deliver standardized data in a digital format. By digitizing product information and making it available for users apart from designers, Model-Based Definition (MBD) provides a solution by defining to product digitally in a three-dimensional environment. The use of MBD in mechanical design processes can have a positive impact on cost, time, and quality of the final product. Although there are standards for defining digital products, they sometimes do not satisfy specific needs of a variety of product landscapes, necessitating company-specific rules. For a successful deployment of MBD the IT infrastructure must be mature, and a company-tailored guideline document is required to bridge current gaps from standards to corporate needs. Therefore, the aim of this study is to analyse software tools and verify if the IT infrastructure is ready to support transition from drawing-based engineering to model-centric practice. Changes are identified and recommendations will be given. The gained experience from creating models in CAD software along with requirements and feedback from stakeholders and users of the product and manufacturing information is input for creation of the guideline and manual for MBD data practices. This supports the company’s transition to a more efficient product definition. With release of the guideline for applying MBD, the milestone is set to sustainably rely on models instead of drawings for communicating product and manufacturing information. The applied CAD programmes provide all functions transcribing MBD according to applicable standards. The resulting data sets can be interpreted by humans and machines, bringing significant benefits when advancing to model-based enterprise where models are used in all business operations. / Maskiningenjörer och konstruktörer från av olika brancher har svårigheter när de försöker förmedla tredimensionell produktinformation på ett tvådimensionellt sätt. Ett effektivt samarbete mellan olika användare kräver kapacitet att leverera standardiserad data i digitalt format. Genom att digitalisera produktinformation och göra den tillgänglig för andra användningsområden än design ger Model-Based Definition (MBD) en lösning. Användningen av MBD i den mekaniska designprocessen kan ha en positiv inverkan på kostnaden, tiden och kvaliteten på slutprodukten. Även om det finns standarder för att definiera digitala produkter, tillfredsställer de ibland inte de specifika behoven hos en mängd olika produktlandskap, vilket kräver företagsspecifika regler. För en framgångsrik implementering av MBD måste företagets IT-infrastruktur vara mogen, och ett riktlinjedokument krävs för att överbrygga de nuvarande klyftorna från standarderna till företagets behov. Därför analyseras mjukvaruverktygen om dessa är redo att stödja övergången från ritningsbaserad teknik till modellcentrerad praktik. Förändringar identifieras och rekommendationer ges. Erfarenheten från att skapa modeller i CAD-programmen kom tillsammans med input från intressenter och användare av produktdatainmatningen för skapandet av manualen för datapraxis för digital produktdefinition. En nedströmsstudie för interoperabilitet begränsades av en grov programvara tillgänglighet. Med lanseringen av manualen för tillämpning av MBD är milstolpen satt att på ett hållbart sätt förlita sig på modeller istället för ritningar för att kommunicera produkt- och tillverkningsinformation. De tillämpade CAD-programmen tillhandahåller alla funktioner som transkriberar MBD enligt tillämpliga standarder. De resulterande datamängderna kan tolkas av människor och maskiner, vilket ger betydande fördelar när man går vidare till det modellbaserade företaget där modellen används i hela nedströmsströmmen.

Les protéines à « Methyl-CpG-binding domain » (MBD) jouent un rôle important dans l’interprétationde la méthylation de l’ADN conduisant à la répression transcriptionnelle via le recrutement decomplexes remodelant la chromatine. Dans les cancers, MBD2 jouerait un rôle essentiel dans la perted’expression des gènes hyperméthylés. Ainsi, MBD2 serait une cible potentielle pour rétablir, enpartie au moins, leur expression. Caractériser, à l’échelle du génome, la distribution de MBD2 et sesconséquences sur la répression transcriptionnelle au cours de la cancérogenèse est donc une étapeincontournable. (1) L’impact sur l’expression génique de l’inhibition de MBD2 par interférence àl’ARN, a été étudié en utilisant des puces, dans des cellules normales MRC5. La perte de MBD2n’induit pas de surexpression génique globale et la densité en CpG des promoteurs méthylés sembleêtre une composante importante dans la force de répression par MBD2. (2) Les profils de méthylationde l’ADN, de liaisons de MBD2 et de l’ARN polymérase II dans les cellules HeLa ont été analysés parChIP-on-chip avec des puces promoteurs. Ces mêmes approches couplées à l’analyse de l’acétylationdes histones H3 ont été réalisées dans un modèle cellulaire syngénique de progression tumoralemammaire humain. Dans les modèles étudiés, une forte proportion de gènes silencieux et méthylés estliée par MBD2. Les comparaisons entre cellules immortalisées et transformées ne montrent pas dechangements majeurs de la méthylation de l’ADN ou de la répression transcriptionnelle, par contreune redistribution de MBD2 parmi ces sites est observée, suggérant une redondance entre les protéinesliant l’ADN méthylé. / The Methyl-CpG-Binding Domain (MBD) proteins represent key molecules in the interpretation ofDNA methylation signals leading to gene silencing through recruitment of chromatin remodelingcomplexes. In cancer, a member of this protein family, MBD2, seems to play an important role in theloss of expression of aberrantly methylated genes. Thus, MBD2 may be a potential target toreestablish their expression. Mapping of MBD2 binding sites and the relationship between MBD2binding and transcriptional activity was, therefore, a crucial step. (1) We investigated the impact ofMBD2 inhibition by RNA interference on gene expression, using microarray analysis, in a normalhuman fibroblastic cell line, MRC-5. MBD2 depletion did not induce global gene overexpression andCpG density of the methylated promoters seems to be an important parameter in the strength of thetranscriptional repression mediated by MBD2. (2) Global profiling for different layers of epigeneticmodifications (DNA methylation, MBD2 association) and RNA polymerase II binding sites in HeLacells was analyzed by a ChIP-chip method using human promoter arrays. This approach, combinedwith an analysis of H3 histone acetylation patterns, was performed in a syngenic model of breastcancer progression. In the models analyzed MBD2 appeared to be a true methylation-dependenttranscriptional repressor. Furthermore, MBD2 binds to a high proportion of methylated silent genes.Comparisons between immortalized and transformed cells did not indicate major changes of DNAmethylation or gene silencing, while a redistribution of MBD2 among these sites was observed,suggesting a redundancy between methylated binding proteins.

Cette thèse s'inscrit dans le cadre de la mise en œuvre de l’ingénierie dirigée par les modèles (IDM) pour le développement des systèmes embarquées. Ces systèmes ayant généralement des ressources limitées (mémoire et/ou calculs), exigent que le code généré soit le plus optimisé possible. L’objectif de cette thèse est de produire à partir d’un modèle spécifié dans le langage UML, un code assembleur plus compact que le code assembleur produit par les compilateurs de code. Malgré l’évolution croissante des compilateurs optimisés, les compilateurs les plus répandus comme le GCC (Gnu Compiler Collection) sont incapables d’effectuer certains types d’optimisations qu'il est possible d'effectuer à un plus haut niveau d'abstraction dans une phase de pré-génération de code. En effet, certaines informations (liées à la sémantique d’exécution du langage UML) sont perdues lors de la génération de code. Ces informations, utiles pour les optimisations de haut niveau, sont invisibles par le compilateur de code vue qu’il prend toutes les informations liées au système modélisé à partir du code généré. Nous proposons ainsi une nouvelle approche dirigée par les modèles pour le développement des systèmes à ressources limitées, qui élimine l’étape de la génération de code en remplaçant cette étape par une compilation directe des modèles. Nous avons développé le premier compilateur de modèles UML (GUML : le front-end UML pour le compilateur GCC) qui génère directement de l’assembleur (sans passer par un langage de programmation) à partir des modèles UML. GUML permet de compiler les classes, les activités et les machines à états UML. Il permet de générer, en compilant certaines machines à états, un code assembleur plus compact que le code assembleur produit par GCC. Deux optimisations de GCC sont améliorées : l’élimination de code mort et l’élimination des expressions redondantes. / Model-Based Development (MBD) provides an additional level of abstraction, the model, which allows dealing with the increasing complexity of systems. Models let engineers focus on the business aspect of the developed system and permits automatic treatments of these models with dedicated tools like for instance synthesis of system's application by automatic code generation. Embedded Systems are often constrained by their environment and/or the resources they own in terms of memory, energy consumption or performance requirements. Hence, an important problem to deal with in embedded system development is linked to the optimization of software part of those systems according to the resources provided by their platform. Although automatic code generation and the use of optimizing compilers bring some answers to application optimization issue, this thesis shows that optimization results may be enhanced by adding a new level of optimizations at the model level before the code generation step. Actually, during the code generation, an important part of the modeling language semantics which could be useful for optimization is lost, thus, making impossible some optimizations achievement. We propose in this thesis a novel MBD approach that compiles directly UML models. The biggest challenge for this approach –tackled in this thesis- is to propose a model compiler that is as efficient as code compiler. Our model compiler (GUML: the UML front end for GCC) performs optimizations that GCC is unable to perform resulting in a more compact assembly code. Two GCC optimizations are enhanced: the dead code elimination optimization and the block merging.

Inom militär flygindustri är produktdatahantering i produktlivscykeln och utveckling av logistikstöd centrala områden för att hantera krav och kostnader. Senaste strategin för dessa utmaningar grundar sig i modellbaserat konstruktionsunderlag – model-based definition (MBD). I detta perspektiv står disciplinen teknikinformation inför förändringsarbetet att utnyttja möjligheterna med MBD. Förbättringar i presentationsmetod för illustrationer och effektivare arbetsmetoder för produktion förväntas. Detta förändringsarbete undersöktes genom en fallstudie av Saabs konceptutveckling för teknikinformation till stridsflygplanet Gripen NG. Studien fokuserade på publikationstypen reservdelskatalog och användningen av den. Arbetet bidrar med en modell som beskriver fyra nivåer för design av informationssystem, varav nivån presentation är i fokus. Därtill undersöks jämförbara arbetsmetoderför hantering av MBD-data inom fallet. Studien fann att teknikinformationsavdelningen står inför en övergång från dokumentbaserad förvaltning till utveckling av informationssystem. Därefter diskuteras tre förslag för nästa generations reservdelskatalog. Det mynnar ut i två slutsatser: dels att en bristfällig bild av reservdelskatalogens användning gör det svårt att bedöma nya presentationsmetoders lämplighet, och dels att förbättringarna gjorda i arbetsmetod och presentationsmetod vid MBD-införande på andra områden i produktlivscykeln inte är direkt överförbara på reservdelskatalogen. Till följd av detta presenteras förslag på framtida forskning och arbete. / In the military aerospace industry, product data management in the product lifecycle, and development of logistics support are key areas that affect management of requirements and costs. The most recent strategy for these challenges is model-based definition (MBD). The discipline of technical communication has yet to explore and exploit the potential of MBD. Expected benefits include better ways of presenting illustrations and more efficient methodologies for production. This problem was investigated through a case study of the concept development of technical communication for Saab's fighter aircraft Gripen NG. The study focused on the illustrated parts catalog and its use. This work contributes with a model that describes four design levels for information systems, where presentation is the one in focus. In addition, comparable practices for management of MBD data were investigated in the case. The study found that the technical communication department is facing a transition from document-based management to development of information systems. Furthermore, three proposals for the next generation of parts catalogs are discussed. Two conclusions were reached. First, a lack of knowledge regarding the use of the parts catalog makes it difficult to assess new ways of presentation. And second, the improvements made in methodology and presentation in other MBD applications of the product life cycle are not immediately transferable to the parts catalog. Hence, suggestions for future research and work are presented.

Submitted diploma thesis deals about operational deformations in the cylinder unit of turbocharged diesel engine used in commercial vehicles. Introductory part analyses combustion engines computational modelling based on finite element method. The next step is the creation of computational models for thermal-structural analyses of the piston and engine block. In order to determine material characteristics of the head gasket, experiment is performed on the OEM gasket to determine its real behaviour under compressive load. The results shows strong nonlinear behaviour which justifies the decision of making such an experiment in the first place. The results of computational models are radial deformations of the piston and cylinder liners during load conditions. The last chapter deals with the application of these results to an advanced computational piston assembly dynamics model.

Diplomová práce popisuje vývojovou techniku Model Based Design a její použití pro návrh a testování algoritmů. Popis této techniky je proveden na příkladu praktického využití v praxi při vývoji modulu monitorování stavu motoru ve spolupráci se společností UNIS,a.s. Vývoj v oblasti současné letecké techniky klade velký důraz na monitorování životnosti zařízení. Podle výstupů algoritmu se dají naplánovat preventivní opravy s ohledem na aktuální podmínky opotřebení a provozování. Implementace algoritmů je provedena v prostředí Matlab/Simulink s následným testováním na platformě dSpace

The United States is the world's largest oil consumer demanding about twenty five percent of the total world oil production. Whenever there are difficulties to supply the increasing quantities of oil demanded by the market, the price of oil escalates leading to what is known as oil price spikes or oil price shocks. The last oil price shock which was the longest sustained oil price run up in history, began its course in year 2004, and ended in 2008. This last oil price shock initiated recognizable changes in transportation dynamics: transit operators realized that commuters switched to transit as a way to save gasoline costs, consumers began to search the market for more efficient vehicles leading car manufactures to close 'gas guzzlers' plants, and the government enacted a new law entitled the Energy Independence Act of 2007, which called for the progressive improvement of the fuel efficiency indicator of the light vehicle fleet up to 35 miles per gallon in year 2020. The past trend of gasoline consumption will probably change; so in the context of the problem a gasoline consumption model was developed in this thesis to ascertain how some of the changes will impact future gasoline demand. Gasoline demand was expressed in oil equivalent million barrels per day, in a two steps Ordinary Least Square (OLS) explanatory variable model. In the first step, vehicle miles traveled expressed in trillion vehicle miles was regressed on the independent variables: vehicles expressed in million vehicles, and price of oil expressed in dollars per barrel. In the second step, the fuel consumption in million barrels per day was regressed on vehicle miles traveled, and on the fuel efficiency indicator expressed in miles per gallon. The explanatory model was run in EVIEWS that allows checking for normality, heteroskedasticty, and serial correlation. Serial correlation was addressed by inclusion of autoregressive or moving average error correction terms. Multicollinearity was solved by first differencing. The 36 year sample series set (1970-2006) was divided into a 30 years sub-period for calibration and a 6 year "hold-out" sub-period for validation. The Root Mean Square Error or RMSE criterion was adopted to select the "best model" among other possible choices, although other criteria were also recorded. Three scenarios for the size of the light vehicle fleet in a forecasting period up to 2020 were created. These scenarios were equivalent to growth rates of 2.1, 1.28, and about 1 per cent per year. The last or more optimistic vehicle growth scenario, from the gasoline consumption perspective, appeared consistent with the theory of vehicle saturation. One scenario for the average miles per gallon indicator was created for each one of the size of fleet indicators by distributing the fleet every year assuming a 7 percent replacement rate. Three scenarios for the price of oil were also created: the first one used the average price of oil in the sample since 1970, the second was obtained by extending the price trend by exponential smoothing, and the third one used a longtime forecast supplied by the Energy Information Administration. The three scenarios created for the price of oil covered a range between a low of about 42 dollars per barrel to highs in the low 100's. The 1970-2006 gasoline consumption trend was extended to year 2020 by ARIMA Box-Jenkins time series analysis, leading to a gasoline consumption value of about 10 millions barrels per day in year 2020. This trend line was taken as the reference or baseline of gasoline consumption. The savings that resulted by application of the explanatory variable OLS model were measured against such a baseline of gasoline consumption. Even on the most pessimistic scenario the savings obtained by the progressive improvement of the fuel efficiency indicator seem enough to offset the increase in consumption that otherwise would have occurred by extension of the trend, leaving consumption at the 2006 levels or about 9 million barrels per day. The most optimistic scenario led to savings up to about 2 million barrels per day below the 2006 level or about 3 millions barrels per day below the baseline in 2020. The "expected" or average consumption in 2020 is about 8 million barrels per day, 2 million barrels below the baseline or 1 million below the 2006 consumption level. More savings are possible if technologies such as plug-in hybrids that have been already implemented in other countries take over soon, are efficiently promoted, or are given incentives or subsidies such as tax credits. The savings in gasoline consumption may in the future contribute to stabilize the price of oil as worldwide demand is tamed by oil saving policy changes implemented in the United States.

This master thesis aims to examine how the transfer of product related information is carried out in the manufacturing industry. The study was supposed to give suggestions for improving the CAD courses provided at Linköping University. This thesis is the concluding step for the authors’ master’s degree in mechanical engineering.In the beginning of the project a study of relevant literature was made. The literature was aimed to gain more knowledge of the subject at hand and finding relevant methods for collecting and analyzing data. To examine how the industry deals with product related data a multiple case study was conducted, investigating seven different companies that are working with both product development and production. As data collection method, semi-structured interviews of employees on the different companies were conducted.An adaptation of the “affinity diagram technique” was used when analyzing the collected data. The method divided the answers to questions provided by the different companies into different categories, in the form of statements. These where compared between the companies by the use of tables, showing the results in a clear manner. To give better insight in each company´s methods, a descriptive summary was written for each of the studied companies.To be able to give propositions of improvement for the courses at the University, some of the courses given where analyzed by reviewing the course description and goals, and through informal interviews of the course administrator. This led to better insight in what is included in the courses and what they are supposed to teach the students. The knowledge of what is included in the courses at this time and the results of the study of the companies, were the foundation when determining what could be changed in the courses.The case study showed that it varies greatly how much the companies are adapting new approaches for generating and spreading product related data. This made it difficult to find tangible evidence supporting changes to the courses, however, a few conclusions could be drawn from the results. It was found that 2D-drawings are still used to a great extent for carrying product related information. Only one of the studied companies have transitioned to using the 3D-model as an information carrier. Although it was mentioned on some of the other companies that such an approach seemed interesting.The study also showed that less handling of physical papers seems to be something most companies are interested in, and are also trying to achieve. It was also noted that all the companies studied had implemented some form of digital platform for handling product related documents.A few things that were deemed worth implementing in the mandatory courses were the introduction to PDM/PLM, introduction of 3D-annotations for dimensions and tolerances and increased use of the 3D-model for manufacturing operations. / Detta examensarbete ämnar undersöka hur informationsöverföringen av produktrelaterad data sker i industrin för att kunna ge förbättringsförslag för Linköpings Universitets CAD- och ritteknikskurser. Detta för att kurserna bättre ska spegla industrins nuvarande och även framtida behov. Examensarbetet utfördes på avdelningen maskinkonstruktion vid Linköpings Universitet och är det avslutande momentet på författarnas civilingenjörsutbildning i maskinteknik.Till att börja med utfördes en litteraturstudie. Detta för att ge kunskap inom det aktuella området och vilka metoder som kan användas för datainsamling och analys. För att undersöka hur industrins arbetssätt ser ut utfördes en flerfallstudie på sju olika företag som bedriver produktutveckling tillsammans med egen produktion. Som datainsamlingsmetod valdes semistrukturerade intervjuer med anställda på de olika företagen.Analysen utfördes med hjälp av en adaption av ”affinity diagram technique” vilket delade upp företagens svar i kategorier i form av påståenden. Dessa jämfördes mellan företagen med hjälp av tabeller eftersom det var tydligt sätt att representera resultatet. För att ge en inblick i hur varje enskilt företag arbetar utarbetades även en deskriptiv sammanfattning av varje företag.För att kunna ge förbättringsförslag till universitetets CAD- och ritteknikskurser granskades några av de nuvarande kursernas kursplaner. Detta tillsammans med en informell intervju av de kursansvariga ledde till bättre insikt om hur kurserna är uppbyggda och vad målen med dem är. Insikten om vad kurserna innehåller i dagsläget tillsammans med analysen av de studerade företagens arbetssätt bidrog till att ett antal förbättringsförslag kunde föreslås.Det visade sig att graden av användande av modernare arbetssätt varierar kraftigt bland företagen. Detta gjorde det svårt att komma fram till ett enhetligt resultat som gällde för alla de studerade företagen. Däremot kunde ett antal slutsatser dras. Bland annat används fortfarande 2D-ritningar flitigt som ett informationsbärande dokument. En övergång till att enbart använda 3D-modellen som informationsbärare noterades endast på ett utav företagen men nämndes på ett par andra.Papperslöst arbete verkar vara på frammarsch trots att vissa specifika moment fortfarande utförs på papper. Det noterades även att digitala system används för lagring och hantering av produktrelaterad information hos alla de studerade företagen.Det som ansetts värt att implementera i universitets obligatoriska kurser efter genomförd studie är främst ökad användning av PDM/PLM-system, introduktion av 3D-måttsättning samt utnyttjande av 3D-modellen vid tillverkning.

Fibroblast growth factor-23 (FGF23) was initially identified as the causative factor of autosomal dominant hypophosphatemic rickets. Further studies confirmed that FGF23 is predominantly expressed in the osteocytes and osteoblasts of bone and that circulating FGF23 acts on the kidney to inhibit renal phosphate reabsorption and 1,25(OH)2D3 hydroxylation. With the progression of chronic kidney disease (CKD), the kidneys become insufficient to maintain a normal systemic mineral homeostasis, resulting in various abnormalities of bone and mineral metabolism, generally referred to as Chronic Kidney Disease – Mineral and Bone Disorders (CKD-MBD). FGF23 increases early in the course of CKD in order to maintain normal serum phosphate levels; long before a significant increase in serum phosphate can be detected. Recent studies suggest that increased FGF23 levels are associated with progression of CKD, mortality, and the development of refractory secondary hyperparathyroidism. Because FGF23 is the very earliest marker of CKD-MBD, it is of particular interest to evaluate the relation between FGF23 and CKD-MBD abnormalities, in the setting of early CKD and also in individuals with normal renal function. In the present work, we show that FGF23 is linked to several dynamic measurements of vascular function, including endothelial dysfunction, arterial stiffness, and atherosclerosis. FGF23 is also positively associated with left ventricular mass index and an increased risk of having left ventricular hypertrophy. All associations were independent of serum phosphate and were strengthened in subjects with diminished renal function. Furthermore, we found significant evidence for an association between higher FGF23 and increased fat mass and dyslipidemia, which could represent a novel pathway linking FGF23 to cardiovascular disease. Finally, we show that FGF23 is a significant predictor of future fracture risk. Although these associations could be reflecting the increased risk associated with hyperphosphatemia and calcitriol deficiency, current evidence points towards FGF23 being more than an innocent bystander. At the very least, FGF23 holds promise of being a bio-marker of cardiovascular status and phosphate-related toxicity both in CKD and in the general population, and might be a therapeutic target that could improve the fatal prognosis in CKD patients.

The area of powertrain dynamics has received considerable attention over a number of years. The recent introduction of more stringent emission requirements together with economic pressure has led to a particular focus on increasing powertrain efficiency. This has seen the incorporation of on-board, real-time measurements to predict system behaviour and engine condition. In this domain, accurate models for all powertrain components are important. One strategy to improve accuracy is to evaluate the assumptions made when deriving each model and then to address the simplifications that may introduce large errors. To this end, the aim of the work presented in this dissertation was to investigate the consequences of some of the more common assumptions and simplifications made in low frequency torsional powertrain models, and to propose improved models where appropriate. In particular, the effects of piston-tocylinder friction, crank/gudgeon pin offset, and the torsional behaviour of tyres were studied. Frequency and time domain models were used to investigate system behaviour and model predictions were compared with measurements on a small single cylinder engine. All time domain engine and powertrain models also include a variable inertia function for each reciprocating mechanism. It was found that piston-to-cylinder friction can increase the apparent inertia variation of a single reciprocating engine mechanism. This has implications for the nonlinear behaviour of engines and the drivetrains they are connected to. The effect of crank/gudgeon pin offset also modified the nonlinear behaviour of the mechanism. Though, for typical (small) gudgeon offset values these effects are small. However, for large offset values, achievable practically with crank offset, the modification to the nonlinear behaviour should not be ignored. The low frequency torsional damping properties of a small pneumatic tyre were found to be more accurately represented as hysteretic rather than viscous. Time domain modelling was then used to extend the results to a multi-cylinder engine powertrain and was achieved using the Time Domain Receptance (TDR) method. Various powertrain component TDRs were developed using Laplacians. Powertrain simulations showed that piston-to-cylinder friction can provide additional excitation to the system.