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Subject of this diploma thesis is break wheel optimalization analysis. Break wheels are used in mountain bike downhill races in extreme conditions. It is the first product of this type of an emergent company that was made by the use of intuitive approach. The reason for optimalization is improper behavior of existing solution that occurred during testing. This optimalization consists of finding and analyzing existing characteristics, deciding which factors influence this improper behavior, suggesting new solution and verification of this solution. Break wheel characteristics were detected in an experiment. For realization and evaluation of this experiment, a method named Design of experiments, was selected. This method is used for elaboration of results coming from the Regression analysis. It is possible to effectively achieve the result data by using this procedure. The experiment was oriented to gain data of temperature behavior of break wheel during real load. Mathematical model was adapted on the basis of this data and finally, the calculation was made by the use of Final element method by ANSYS WORKBENCH. Calculations were also coordinated through Design of calculation, and were oriented on temperature deformation and stress. Solution achieved by the Final element method, was evaluated by the Regression analysis and served as a proposition for a new break wheel construction.

Diplomová práce se zabývá plánováním a analýzou experimentu. Je zde zkoumán vliv počtu centrálních bodů v plánu experimentu na nalezení významných faktorů procesu. Pro určení tohoto vlivu je použita metoda Monte Carlo, pomocí které hledáme míru nalezení významných faktorů procesu. Simulace experimentu je vytvořena v programu MATLAB, kde se především využívá Statistics toolbox pro generování náhodných čísel. V závěru je zhodnoceno a graficky ukázáno, jak je určení významnosti faktoru procesu závislé na počtu uvažovaných faktorů experimentu a na počtu měření v centrálním bodě.

The main aim of the work was the investigation of the effect of operational parameters of the combustion process (combustion air excess, primary fuel ratio) and burner constructional parameters (the pitch angle of secondary nozzles, tangential orientation of secondary nozzles towards the axis of the burner) on the formation of NOx and CO, flue gas temperature, the shape, dimensions and stability of the flame, in-flame temperatures in the horizontal symmetry plane of the combustion chamber and the amount of heat extracted from the hot combustion gases in the combustion chamber’s shell. Experimental activities were carried out in the laboratory of the Institute of Process and Environmental Engineering, which is focused on burners testing. The combustion tests were performed with the experimental low-NOx type burner, namely the two-gas-staged burner. Mathematical model developed based on the experimental data describes the dependency of NOx on the operating parameters of the combustion process and burner constructional parameters. The model shows that increasing air excess and increasing angle of tangential orientation of the secondary nozzles reduce the formation of NOx. The temperature peaks in the horizontal symmetry plane of the combustion chamber decreases with increasing combustion air excess. The thermal load to the combustion chamber’s wall along the length of the flame was evaluated for selected settings. It was validated that the thermal efficiency of is reduced when higher air excess is used.

La médecine de précision (MP) est un nouveau paradigme qui révolutionne la pratique médicale actuelle et remodèle complètement la médecine de demain. La MP aspire à placer le patient au centre du parcours de soins en y intégrant les données médicales et biologiques individuelles tout en tenant compte de la grande diversité interindividuelle. La prédiction des états pathologiques chez les patients nécessite une compréhension dynamique et systémique. Les erreurs innées du métabolisme (EIM) sont des troubles génétiques résultant de défauts dans une voie biochimique donnée en raison de la déficience d'une enzyme, de son cofacteur ou d’un transporteur. Les EIM ne sont plus considérées comme des maladies monogéniques mais tendent à être plus complexes et multifactorielles. Le profil métabolomique permet le dépistage d’une pathologie, la recherche de biomarqueurs et l’exploration des voies métaboliques mises en jeu. Dans ce travail de thèse, nous avons utilisé l’approche métabolomique qui est particulièrement pertinente pour les EIM compte tenu de leur physiopathologie de base qui est étroitement liée au métabolisme. Ce travail a permis la mise en place d’une méthodologie métabolomique non ciblée basée sur une stratégie analytique multidimensionnelle comportant la spectrométrie de masse à haute résolution couplée à la chromatographie liquide ultra-haute performance et la mobilité ionique. La mise en place de la méthodologie de prétraitement, d’analyse et d’exploitation des données générées avec des outils de design expérimental et d’analyses multivariées ont été aussi établies. Enfin, cette approche a été appliquée pour l’exploration des EIM avec les mucopolysaccharidoses comme preuve de concept. Les résultats obtenus suggèrent un remodelage majeur du métabolisme des acides aminés dans la mucopolysaccharidose de type I. En résumé, la métabolomique pourrait être un outil complémentaire pertinent en appui à l’approche génomique dans l’exploration des EIM. / The new field of precision medicine is revolutionizing current medical practice and reshaping future medicine. Precision medicine intends to put the patient as the central driver of healthcare by broadening biological knowledge and acknowledging the great diversity of individuals. The prediction of physiological and pathological states in patients requires a dynamic and systemic understanding of these interactions. Inborn errors of metabolism (IEM) are genetic disorders resulting from defects in a given biochemical pathway due to the deficiency of an enzyme, its cofactor or a transporter. IEM are no longer considered to be monogenic diseases, which adds another layer of complexity to their characterization and diagnosis. To meet this need for faster screening, the metabolic profile can be a promising candidate given its ability in disease screening, biomarker discovery and metabolic pathway investigation. In this thesis, we used a metabolomic approach which is particularly relevant for IEM given their basic pathophysiology that is tightly related to metabolism. This thesis allowed the implementation of an untargeted metabolomic methodology based on a multidimensional analytical strategy including high-resolution mass spectrometry coupled with ultra-high-performance liquid chromatography and ion mobility. This work also set a methodology for preprocessing, analysis and interpretation of the generated data using experimental design and multivariate data analysis. Finally, the strategy is applied to the exploration of IEM with mucopolysaccharidoses as a proof of concept. The results suggest a major remodeling of the amino acid metabolisms in mucopolysaccharidosis type I. In summary, metabolomic is a relevant complementary tool to support the genomic approach in the functional investigations and diagnosis of IEM.

Dans certains domaines de la formulation, comme la cosmétique, les phénomènes étudiés peuvent être très chaotiques avec des zones de rupture ou de non linéarité. Dans ce cas, le formulateur doit se poser de nombreuses questions avant de proposer la stratégie expérimentale optimale qui doit être adaptée au mieux à son problème. Pour de tels phénomènes, des plans d'expériences classiques, tels que les réseaux de Scheffé ou les plans D-optimaux, se révèlent insuffisants car les points expérimentaux ne couvrent pas uniformément l'espace expérimental. En effet, il est intéressant dans ces cas d'étude d'explorer l'ensemble du domaine expérimental et de répartir uniformément les points dans l'espace. Pour cela, les plans uniformes ou Space-Filling Designs (SFD), fréquemment utilisés dans le cas de variables orthogonales, mais très peu dans le cas des variables de mélange, sont particulièrement intéressants. L'objectif de cette thèse est d’adapter des algorithmes de construction de plans uniformes dans le cas de plans de mélanges, de proposer des règles simples pour aider au choix de la nature et du nombre de points du plan d'expériences de mélange / In some domains of formulation, as cosmetics, the phenomena can be very chaotic with discontinuities or not linear zones. In the cosmetic field, the formulator has to propose the optimal experimental strategy which must be well adapted to the constraints imposed by the experimenters. For such phenomena, classical designs of experiments, such as Scheffé simplexes lattices or the D-optimal designs, are proving insufficient because the experimental points do not uniformly cover the experimental space. Indeed, it is essential in these studies to explore the whole experimental domain and to uniformly distribute points in the space. For that purpose, the Space-Filling Designs (SFD), frequently used in the case of orthogonal variables, but less in the case of the mixture variables, are particularly interesting. The objective of this thesis is to adapt the algorithms for construction of uniform designs in the case of mixture designs and to propose guidelines for the choice of the nature and the number of points of the experimental design

The aim of this diploma thesis was the development of a screening method for analysis of 17 benzodiazepines in urine samples using ultra high-performance liquid chromatography with tandem mass spectrometric detection. The partial task was to optimize the conditions for the enzymatic hydrolysis of benzodiazepine glucuronides present in urine using design of experiments (DOE). The optimized chromatographic system consisted of a Zorbax Eclipse Plus Phenyl-Hexyl RRHD column (100 × 2.1 mm, 1.8 μm) and mobile phase consisting of water with 0.1 % acetic acid (component A) and acetonitrile with 0.1 % acetic acid (component B) in various ratios according to the gradient program. Flow rate was 0.2 ml/min, column temperature was 40 řC, and total analysis time was 12 min. Calibration curves for all analytes were measured under optimized conditions in methanol and urine. After optimal detection conditions for oxazepam-glucuronide were found, oxazepam glucuronide was hydrolysed using β-glucuronidase from the abalone to confirm the functionality of the enzyme within the pilot experiment. Optimization of enzymatic hydrolysis conditions via 27 experiments proposed by program Minitab 16 using the Box-Behnken design will be realized later.

Den ökande efterfrågan på högre produktkvalitet inom tillverkningsindustrin kräver hög stabilitet och lång livslängd på borrverktyg under borrningbearbetningsprocessen. En metod för att öka produktkvaliteten och därmed förlänga livslängden på borrverktyg är skäreggpreparering. Skäreggpreparering används för att skapa en kantgeometri som ger borrverktyget både en bättre styrka och högre tålighet mot slitage. Det mest förekommande slitaget på borrverktyg är fasförslitning och det utvecklas snabbt under den initiala slitningsperioden under borrens livslängd. Syftet med det här examensarbetet var att genom flerfaktorförsök undersöka hur skäreggprepareringsprocessen kan förbättras för att minska fasförslitning under den initiala slitningsperioden på belagda hårdmetallborrar. Skäreggprepareringsprocessen studerades som en fallstudie på Scania Motorbearbetning. Fallstudien genomfördes efter problemlösningsmetodiken DMAIC (Define, Measure, Analyse, Improve och Control) som inkorporerade försöksplanering, vilket medförde att två ytterligare faser tillkom: Pre-analyze och Experiment. Datainsamlingen bestod av både kvalitativ och kvantitativ data. Den kvalitativa datan erhölls från intervjuer under Measure-fasen och den kvantitativa datan erhölls från det genomförda experimentet under Experiment-fasen, som sedan analyserades i Analyze-fasen. Baserat på litteraturstudien, nulägesbeskrivningen och intervjuerna bestämdes försöksfaktorerna till processtid, borrens djup i slipmedel, rotationsriktning på rotor och rotationshastighet på spindel samt responsvariablerna till skäreggradie och total fasförslitning. Försöksfaktorerna testades i ett fullständigt tvånivåers faktorförsök med 4 faktorer och 4 centrumpunkter. Analysen av resultaten från experimentet visade att korrelationen mellan responsvariablerna var försumbar under den initiala slitningsperioden. Vidare identifierades inte några signifikanta effekter baserade på responsvariabeln total fasförslitning. Däremot kunde det konstateras att de försöksfaktorer som påverkade responsvariabeln skäreggradie var processtid, borrens djup i slipmedel och rotationsriktning på rotor. En optimeringsmodell togs fram i Improve-fasen för att optimera skäreggprepareringsprocessen med avseende på skäreggradie. Optimeringen utgick från att ha en stor skäreggradie under förutsättningen att den nuvarande processtiden halveras. Optimeringsmodellen kunde inte bekräftas, därför togs en rekommendation fram som beskriver stegen för att bekräfta den framtagna optimeringsmodellen. Vidare togs två ytterligare rekommendationer fram med syfte att undersöka skäreggprepareringsprocessen med avseende på andra typer av slitage samt undersöka verktygsslitage under verktygets fulla livslängd. I Control-fasen togs en kontrollplan fram som stöd för att kontrollera rekommendationerna. Avslutningsvis bidrog det här examensarbetet med nya insikter och slutsatser om utveckling av fasförslitningen under den initiala slitningsperioden under en borrs livslängd. / The increasing demand for higher product quality in the manufacturing industry requires high stability and long service life of drilling tools during the drilling process. One method of increasing product quality and thus extending the tool life for drills is cutting edge preparation. Cutting edge preparation is used to create an edge geometry that gives the drilling tool both better strength and higher resistance to wear. The most common wear on drill tools is flank wear that develops rapidly during the initial wear period of the drill's life. The purpose of this thesis was to investigate how the cutting edge preparation process can be improved by factorial design in order to reduce flank wear during the initial wear period on coated solid carbide drills. The cutting edge preparation process was studied as a case study at Scania's motor processing department. The case study followed problem-solving methodology DMAIC (Define, Measure, Analyze, Improve and Control) incorporating design of experiments. This resulted in two additional phases: Pre-Analyze and Experiment. Data collection consisted of both qualitative and quantitative data. The qualitative data were obtained from interviews during the Measure phase and the quantitative data was obtained from the experiment conducted during the Experiment phase, which was later analyzed in the Analyze phase.     Based on a literature study, current description, and interviews, the identified experimental factors were process time, depth in the grinding granulate, rotational direction of the rotor, and rotational speed of spindle. The identified response variables were cutting edge radius and total flank wear. The experimental factors were tested in a full two-level factorial design with 4 factors and 4 center points. The analysis of the results from the experiment showed that the correlation between the response variables was negligible during the initial wear period. Furthermore, no significant effects could be found based on the response variable total flank wear. However, it was found that the experimental factors that influenced the response variable cutting edge radius were process time, depth in grinding granulate, and direction of rotation of the rotor. An optimization model was developed during the Improve phase to optimize the cutting edge preparation process in regards to the cutting edge radius. The optimization was based on generating a large cutting edge radius and at the same time reducing the current process time by half. The optimization model could not be confirmed; therefore, a recommendation was developed outlining the steps to confirm the optimization model. Furthermore, two additional recommendations were made to investigate the cutting edge preparation process concerning other types of wear and to examine tool wear during the tool’s full life. A control plan was developed in the Control phase to help to control the recommendations. In conclusion, this thesis contributed new insights and conclusions on the development of flank wear during the initial wear period during the tool life.

Tillämpningen av fiberförstärkt polymerkomposit har senaste decenniet ökat kraftigt inom flertalet högteknologiska branscher. Trots framgången är förekomsten av tillverkningsinducerade avvikelser fortfarande en utmaning. Avvikelserna försämrar materialets mekaniska egenskaper och förkortar dess livslängd, vilket orsakar kassationer, miljöbelastningar och försvårad produktetablering för industriaktörer. ABB Composites i Piteå står inför en liknande situation. Företaget producerar cylindriska isolatorer i fiberförstärkt komposit till högspänningsindustrin, och behöver utreda förekomsten av en specifik avvikelse, som under senaste tre åren medfört omfattande kvalitetsbristkostnader. Produkten tillverkas genom vakuuminjicering där en hartsblandning impregnerar en glasfiberform, för att sedan övergå från flytande till fast form genom en exoterm reaktion. Hartsblandningens reaktionsförlopp har länge misstänkts påverka avvikelsernas förekomst, men har inte bekräftats, på grund av flera svårkontrollerade egenskaper. Examensarbetets syfte har därför varit att utreda om hartsblandningens egenskaper påverkar förekomsten av tillverkningsinducerade avvikelser vid tillverkning av cylindriska isolatorer. Arbetet har bedrivits som ett Sex Sigma-projekt enligt problemlösningsmetodiken DMAIC. Ett blandningsexperiment med sex komponenter genomfördes i laborationsmiljö där en datagenererad design med 36 delförsök tillämpades, varav sex stycken egenskaper hos hartsblandningen undersöktes. Experimentet påvisade att samtliga egenskaper var möjliga att styra genom att förändra proportionerna av ingredienserna. Däremot visade sig flera av egenskaperna vara korrelerade och kan därav inte justeras oberoende av varandra. Kunskapen användes till att utveckla och testa två nya varianter av hartsblandningen vid tillverkning av cylindriska isolatorer. Resultatet bekräftade att hartsblandningens egenskaper signifikant påverkar förekomsten av tillverkningsinducerade avvikelser. En viss kombination av egenskaperna som kännetecknade ett långsamt reaktionsförlopp minskade förekomsten av avvikelser på isolatorerna med 99.3 procent i jämförelse med den ordinarie hartsblandningen. Förbättringen förväntas medföra betydelsefulla besparingar, ökad konkurrenskraft och förhöjd kvalitetsmedvetenhet för ABB Composites. Examensarbetets kunskapsbidrag anses också betydelsefullt för kompositindustrin i strävan mot fortsatt reducering av tillverkningsinducerade avvikelser. / The application of fibre-reinforced polymer composites (FRPC) have during the last decades increased in many high-tech industries. Despite the success, the existence of manufacturing-induced deviations has been a long-standing challenge. These deviations affect the lifetime and the mechanical properties of the composite, which in turn lead to scrap of products and environmental impact, obstructing market exploitation for industry stakeholders. ABB Composites in Piteå is facing a similar scenario. The company produces cylindrical insulators in fibre-reinforced composite for the high-voltage industry and need to investigate a specific deviation, which has caused extensive costs during the last three years. The product is manufactured through vacuum assisted resin transfer molding (VARTM), where a resin blend impregnates a fibreglass preform, as the resin cures and transforms from liquid to solid form through an exothermic reaction. One suspected cause for the deviation has been the curing process of the resin. However, it is dependent on several difficult-to-control characteristics and is yet to be confirmed. The purpose of this thesis has therefore been to investigate whether the characteristics of the resin blend affects the occurrence of manufacturing-induced deviations while producing cylindrical insulators. The work has been conducted as an internal Six Sigma-project following the DMAIC improvement cycle. A mixture experiment with six components was performed, using a computer-generated design with 36 runs, in which six characteristics of the resin blend were examined. The experiment proved that all characteristics could be controlled by changing the proportions of the design factors. However, many of the characteristics were correlated, implying that the characteristics cannot be independently controlled. The knowledge from the experiment were used to develop two new resin blends, which were infused to cylindrical insulators in regular production environment. The result confirmed that the characteristics of the resin blend significantly affects the quality of the insulator. One of the blends, which represented a slower curing process, reduced the deviations by 99.3 percent in relation to the original blend. The improvement is expected to generate substantial savings, increased competitiveness and enhanced quality awareness for ABB Composites. Possible contributions to the industry are related to the development of a method to experimentally investigate the resin blend with the objective of reducing manufacturing-induced deviations.

Pressgjutna Al-Si komponenter förekommer mer och mer i förbränningsmotorer med syfte att reducera vikt och förbättra hållbarhet. Ett problem vid pressgjutning, en process kännetecknad av kostnadseffektivitet vid massproduktion, är porositetsbildning vilket kan resultera i läckage, strukturell svaghet och försämrad hållbarhet och livslängd för tillverkade komponenter. Då porer oftast bildas internt försvåras dessutom identifiering av potentiellt trasiga komponenter. Det är därför av vikt att finna parameterinställningar i pressgjutningsprocessen vilka konsekvent minimerar porositetsbildning. Ett företag som drabbas av återkommande porositets-relaterade defekter är Husqvarna Group. De använder vakuumassisterad pressgjutning för att, bland annat, producera motorcylindrar av Al-Si. Kassationsgraden, specifikt hänförbar till porositet, för en cylindermodell har under de senaste tre åren fördubblats vilket har resulterat i slöseri av produktionstid och kvalitetsbristkostnader. Vakuumassisterad pressgjutning kan beskrivas stegvis: (1) smält metall hälls i en cylindrisk fyllkammare, (2) en skottkolv trycker smältan mot ett mindre inlopp i låg hastighet för att undvika turbulens, samtidigt som vakuum ansätts i fyllkammare och gjutverktyg, (3) skottkolvshastigheten ökar markant vid en förinställd omslagspunkt, vilket spray-fyller gjutverktyget, och (4) högt tryck ansätts för att eftermata smälta till gjutverktyget när solidifiering sker. Syftet med detta examensarbete har varit att undersöka om och hur diverse parametrar, hänförbara till de nämnda processtegen, påverkar porositetsbildning i en industriell produkt. Därefter applicerades den erhållna processförståelsen för att identifera parametrar kritiska för porositetsbildning och slutligen rekommendera parameterinställningar som konsekvent minimerar porositetsgraden. Det experimentella upplägget bestod av två steg varav det första ämnade undersöka, via simulering, vilka av 6 parametrar som påverkade porositetsgraden utifrån en reducerad tvånivåers försöksdesign. Det andra steget var ett verkligt experiment i produktionsmiljö där de tre identiferade parametrarna från screening-experimentet varierades enligt en central-composite design. Analysen av experimenten resulterade i parameterinställningar som förväntas reducera porositetsgraden med över 70%. En lägre porositetsgrad kommer troligen reducera kassationsgraden av den undersökta cylindermodellen, vilket hade resulterat i finansiell besparing och effektivare produktion. I ett industriellt kontext bidrar detta exjobb huvudsakligen med en systematisk kvalitetsförbättrande metod för pressgjutna komponenter baserad i såväl simulerad som verklig miljö. / Pressure die casted Al-Si components are increasingly found inside internal combustion engines, resulting in weight reduction and increased durability. Characteristic to die casting, commonly associated with cost-effective mass production, is the formation of pores which, if unnoticed, can cause leakage, structural deficiencies, and thus reduced durability and life-length of components. Pores commonly appear internally, making identification of faulty components difficult. Therefore, finding parameter settings in the die casting process that consistently minimizes the formation of pores is of importance. A company struggling with porosity-related defects is Husqvarna Group, currently using vacuum-assisted die casting to produce engine cylinders of Al-Si. Scrap-rate, specifically related to porosity, of a particular cylinder model has doubled in the last three years, causing waste of both precious production time and higher quality deficiency costs. A vacuum-assisted die casting process consists of several steps: (1) liquid Al-Si is poured into a cylindrical shot sleeve, (2) a plunger is moved towards a small gate, leading to the die cavity, at low velocity as to not cause turbulence, whilst vacuum is applied throughout the cavity and shot sleeve, (3) plunger velocity is increased substantially at a predetermined switch point, resulting in a spray-filling of the die cavity, and (4) high pressure is applied to continue the feed of molten metal into the cavity as solidification occurs. The purpose of the thesis has been to investigate if and how various parameters, related to the aforementioned four steps of the die casting process, impact the porosity amount in an industrial product. The acquired process knowledge was then applied to identify parameters affecting porosity and recommend settings that consistently minimize the porosity amount. The experimental procedure consisted of two steps: firstly, a screening experiment of six process parameters was made by simulating the die casting process according to a fractional factorial design. Secondly, a real-world experiment was conducted following a central-composite design by varying the three most impactful parameters from the screening experiment.   Analysis of the experiments resulted in a selection of parameter settings, anticipated to reduce porosity by over 70%. A lower porosity amount will most likely reduce the scrap rate of the cylinder model, resulting in substantial savings and higher production efficiency. For practitioners, the main contribution of this thesis is a method of systematic quality-improvement to die-casted components by a combination of simulation experiments and real-world tests.