Today´s industry is driven into development by an increasingly difficult situation of competition that gives less room for miscalculations in the production. One of the most important factors in maintaining your competitiveness is your ability to quickly and efficiently adopt new methods of manufacturing. With the help of new manufacturing methods, the company can improve product design, add new value creating features, and get a faster and more flexible production. However, problems arose with the grading of new manufacturing methods, in order to understand their matureness and if they are ready to be taken into production. This paper aims to investigate the possibility of a rating scale for manufacturing methods and then test this scale on a case study at Volvo CE, Eskilstuna, regarding their introduction of the method Power Skiving in their gear manufacturing. Through studying secondary data regarding already applicable methods for rating of the maturity of technologies and products that are to be introduced into production. Furthermore, have articles regarding proposed methods of rating the maturity of manufacturing methods been revised in order to get an insight into the current situation of rating manufacturing methods and to see what in specific could be of usefulness in rating manufacturing technologies. Beyond secondary data interviews have been conducted with the division of production development at Volvo CE Eskilstuna and with the Director Global Manufacturing Technology at Volvo CE. With the goal of gaining information regarding what they consider crucial in rating manufacturing methods and what is of importance in order to make this rating scale useful in the everyday work. Visits have been made in the production of slewing rings at Volvo CE in order to be able to gather data for the case study regarding the possible introduction of Power Skiving in Volvo CE´s gear manufacturing. The Authors have been able to construct certain criteria that aim to support todays rating matric of introduction of new products in order for it to also work for rating the readiness of new manufacturing methods. Today rating scales for manufacturing methods aren’t widely accepted, the authors, however, assume that it will gain acceptance and there will be more research regarding this subject. Further studies regarding documentation of the ratings and how this rating could be further integrated into daily operation at a company is recommended.

A leptospirose é uma zoonose de importância global causada por leptospiras patogênicas, que colonizam os túbulos renais de animais selvagens e domésticos. Vacinas comerciais estão sendo usadas, porém promovem proteção apenas contra os sorovares presentes na preparação e falham em induzir imunidade de longa duração. A porção carboxi-terminal da proteina immunoglobulin like A (LigAC) é capaz de induzir imunoproteção contra a leptospirose. No entanto, a imunização com a LigAC não confere imunidade esterilizante. Flagelinas têm sido consideradas adjuvante promissor para o desenvolvimento de vacinas. As leptospiras possuem dois flagelos periplasmáticos que são constituídos por duas classes de proteínas (FlaA e FlaB). Somente as proteínas FlaB apresentam homologia com as regiões importantes que ativam as respostas dependentes ao receptor Toll-like 5 (TLR-5). Neste estudo, avaliou-se a capacidade de indução da atividade do TLR5 das cinco flagelinas de L. interrogans sorovar Copenhageni (FlaB1, FlaB2, FlaB3, FlaB4 e FlaB5) e o potencial vacinal destas flagelinas na imunidade protetora de LigAC contra o desafio letal em hamsters. As flagelinas recombinantes foram expressas em E. coli e purificadas por cromatografia de afinidade com níquel. Os hamsters foram imunizados por via subcutânea com as flagelinas purificadas e LigAC. Dados experimentais demonstram que todas as flagelinas foram capazes de ativar o receptor TLR5 e a secreção de citocinas em macrógafos estimulados de maneira similar. Nos ensaios de desafio, a maioria dos animais imunizados com as flagelinas e LigAC sobreviveram ao desafio letal entretanto, não foram protegidos contra a colonização renal. Os animais do grupo controle vacinados com PBS morreram com sintomas de leptospirose e hamsters imunizados com a vacina comercial sobreviveram após o desafio / Leptospirosis is a zoonosis of global importance caused by pathogenic leptospires that colonize the renal tubules of wild and domestic animals. Commercial vaccines are being used, but only to promote protection against the serovar in the preparation; they have failed to induce short-term immunity. The C-terminal portion of immunoglobulin-like protein A (LigAC) is able to induce immunoprotection against leptospirosis. However, immunization with LigAC did not confer sterilizing immunity. Flagellins have been considered a promising adjuvant for vaccine development. Leptospires have two periplasmic flagella that are formed by two classes of proteins (FlaA and FlaB); only FlaB proteins show homology with important regions that elicit TLR5-dependent responses. In the present study, we have evaluated their ability to induce the TLR5 activity and the protective activity of five L. interrogans sorovar Copenhageni flagellins (FlaB1, FlaB2, FlaB3, FlaB4 and FlaB5) in the protective immunity of LigAC against lethal challenge in hamsters. The recombinant flagellins expressed in E.coli were purified by nickel affinity chromatography. Hamsters were immunized subcutaneously with purified flagellins with LigAC. Experimental data showed that all flagellins activated both the TLR-5 receptor and the secretion of cytokines in stimulated macrofages, similarly. In challenge assays, the majority of hamsters immunized with the flagellins and LigAC survived the lethal challenge. However, they were not protected against kidney colonization. The control animals vaccinated with PBS died with symptoms of leptospirosis and hamsters vaccinated with commercial vaccine survived after challenge

Le Gallid Herpesvirus 2 (GaHV-2) est un herpesvirus responsable de lymphomes T chez le poulet. Son génome code pour 25 miARN matures regroupés en 2 clusters localisés au sein des régions répétées TRL/IRL etIRS/TRS. Mon travail a tout d’abord consisté en l’étude de la fonctionnalité des deux brins de mdv1-pré-miRM4sur deux cibles virales UL-28 et UL32. Le brin mdv1-miR-M4-5P ayant été identifié comme orthologue dumiARN cellulaire miR-155, leurs impacts ont été comparés sur six cibles cellulaires et la cible virale UL-28.Les différents miARN de GaHV-2 présentant des taux d’expression variables, nous avons identifié, dans larégion TRL/IRL, des ARNm responsables de leur transcription à partir d’exon ou d’intron. De plus, nous avonsidentifié un promoteur plutôt spécifique de la latence et responsable de la transcription de l’ensemble desmiARN de l’IRL/TRL, de l’oncogène meq et du transcrit Meq/vIL-8. / Gallid Herpesvirus 2 (GaHV-2) is a herpesvirus inducing T-lymphoma in chickens. Its genome encodes 25mature miRNAs splitted in two clusters localized in IRL/TRL and IRS/TRS repeated regions. In this work, wefirst analyzed the functionality of the two strands of mdv1-pre-miR-M4 on two viral targets named UL-28 andUL-32. As one strand of this miRNA was identified as an ortholog of cellular miRNA-155, their effects wereassessed on six cellular targets and on the UL-28 viral target. As a differential expression of miRNAs wasobserved during GaHV-2 infection, we found numerous IRL/TRL transcripts responsible for the intronic orexonic transcription of viral miRNAs. Moreover, we identified a latency promoter controlling at the same timetranscription of all IRL/TRL miRNAs, the oncogenic meq gene and the Meq/v-IL8 transcript.

A leptospirose é uma zoonose de importância global causada por leptospiras patogênicas, que colonizam os túbulos renais de animais selvagens e domésticos. Vacinas comerciais estão sendo usadas, porém promovem proteção apenas contra os sorovares presentes na preparação e falham em induzir imunidade de longa duração. A porção carboxi-terminal da proteina immunoglobulin like A (LigAC) é capaz de induzir imunoproteção contra a leptospirose. No entanto, a imunização com a LigAC não confere imunidade esterilizante. Flagelinas têm sido consideradas adjuvante promissor para o desenvolvimento de vacinas. As leptospiras possuem dois flagelos periplasmáticos que são constituídos por duas classes de proteínas (FlaA e FlaB). Somente as proteínas FlaB apresentam homologia com as regiões importantes que ativam as respostas dependentes ao receptor Toll-like 5 (TLR-5). Neste estudo, avaliou-se a capacidade de indução da atividade do TLR5 das cinco flagelinas de L. interrogans sorovar Copenhageni (FlaB1, FlaB2, FlaB3, FlaB4 e FlaB5) e o potencial vacinal destas flagelinas na imunidade protetora de LigAC contra o desafio letal em hamsters. As flagelinas recombinantes foram expressas em E. coli e purificadas por cromatografia de afinidade com níquel. Os hamsters foram imunizados por via subcutânea com as flagelinas purificadas e LigAC. Dados experimentais demonstram que todas as flagelinas foram capazes de ativar o receptor TLR5 e a secreção de citocinas em macrógafos estimulados de maneira similar. Nos ensaios de desafio, a maioria dos animais imunizados com as flagelinas e LigAC sobreviveram ao desafio letal entretanto, não foram protegidos contra a colonização renal. Os animais do grupo controle vacinados com PBS morreram com sintomas de leptospirose e hamsters imunizados com a vacina comercial sobreviveram após o desafio / Leptospirosis is a zoonosis of global importance caused by pathogenic leptospires that colonize the renal tubules of wild and domestic animals. Commercial vaccines are being used, but only to promote protection against the serovar in the preparation; they have failed to induce short-term immunity. The C-terminal portion of immunoglobulin-like protein A (LigAC) is able to induce immunoprotection against leptospirosis. However, immunization with LigAC did not confer sterilizing immunity. Flagellins have been considered a promising adjuvant for vaccine development. Leptospires have two periplasmic flagella that are formed by two classes of proteins (FlaA and FlaB); only FlaB proteins show homology with important regions that elicit TLR5-dependent responses. In the present study, we have evaluated their ability to induce the TLR5 activity and the protective activity of five L. interrogans sorovar Copenhageni flagellins (FlaB1, FlaB2, FlaB3, FlaB4 and FlaB5) in the protective immunity of LigAC against lethal challenge in hamsters. The recombinant flagellins expressed in E.coli were purified by nickel affinity chromatography. Hamsters were immunized subcutaneously with purified flagellins with LigAC. Experimental data showed that all flagellins activated both the TLR-5 receptor and the secretion of cytokines in stimulated macrofages, similarly. In challenge assays, the majority of hamsters immunized with the flagellins and LigAC survived the lethal challenge. However, they were not protected against kidney colonization. The control animals vaccinated with PBS died with symptoms of leptospirosis and hamsters vaccinated with commercial vaccine survived after challenge

Determining how loads are distributed in a structure has long been a way for engineers to ensure that the final product will work as intended. As components become more and more complicated so does this analysis. The advantages of quickly identifying critical features in a design are significant. By gaining this knowledge it is possible to explore the design space more thoroughly. This was previously done by collecting information over a long period of time and gradually build up the knowledge which can take several weeks or sometimes even months. The theory of the U* index as a numerical analysis method was formulated in 1986 by Takahashi [30] but due to the computational capabilities at the time there was no practical applications. It aims to give the same information compared to the current iterative process in a significantly faster way by calculating the relative stiffness. In its current form it can however be computationally heavy and has not yet seen any extended applications in the engineering sector. As the U* index is both an algorithm for calculating the load paths but also a broader theory of energy based identification of the stiffest route in a structure, it is referred to both as a method and a tool. In this thesis we initially set out to identify needs in the product development processfor a engineer team. Then we will investigate the capabilities of the U* index method, improve said capabilities by optimizing computation time and compatibility, establish a foundation for future development, and finally propose an integration of the tool into an advanced aero-engine development process. The main focus of this thesis is on the concept solutions phase as the needfinding indicated this phase to be in most need of improvement. Other applications of U* are mentioned but will not be examined in detail. In the concept solutions phase one would want to evaluate design features from a larger perspective to explore thedesign space. This can be done with U* by identifying which features are carrying the loads and how close the calculated path is to the optimal one. A possible application in optimization in the preliminary solution phase were also identified. In this case one can for example analyze the contour of the U* field and use U* sum to identify the relative load carrying contribution of certain regions. The initial state of the technology was determined to be at a technology readiness level (TRL) of 5 in the ModSim scale, meaning that the key elements have been demonstrated on a realistic problem. As the goal of applying the tool on real large models was achieved, the complete system level capabilities were demonstrated resulting in TRL 6 being reached at the end of the development. The more commonly used NASA version of TRL started out at TRL 3 which was reached with the proof of concept conducted by Ramesh [24]. According to these definitions the technology didn’t progress any further due to the specific definitions being primarily oriented towardshardware and the requirement for TRL 4 involved laboratory validation. As the TRL have been assessed with both versions, any potential future work has the option tochoose which method fit that particular work. The successful implementation of theinspection load method for calculating U∗ was critical in being able to compute thesolutions in reasonable time frame. There is however more room to optimize time byimplementing algorithms for better suited meshing and post processing. The tool is applicable on large components but the solutions still require a lot of time which reduces its usefulness in the early, time critical phase. The post-processing routines similarly take time and require extensive manual labor to determine the proper load path. This is also sub optimal for visualizing the load paths because it relies on assumptions. Future work should therefore aim to maximize the automation part of the post-processing. Further validation needs to be conducted on more complicated structures to ensure correlation between physical components and simulation. Furthermore, the quantifying of margins, uncertainties and sensitivities of the simulation is important to better understand the limitations of the tool.

Les paramètres S constituent l'une des grandeurs de base de l'électricité-magnétisme dans le domaine radiofréquence. Ils sont normalisés par rapport à une valeur d'impédance dite de référence et sont mesurés à l'aide d'un analyseur de réseau vectoriel (Vector Network Analyzer (VNA)). La précision des paramètres S des composants micro-ondes avec un analyseur de réseau vectoriel (VNA) dépend de l'exactitude du calibrage utilisé pour corriger les erreurs inhérentes au système. Le calibrage consiste à mesurer des dispositifs particuliers plus ou moins bien connus, que l'on appelle étalons, afin de déterminer les erreurs systématiques du système avant la mesure du composant. Les coefficients d'erreurs calculés à partir de l'étalonnage seront utilisés pour caractériser les vrais paramètres S du dispositif. La procédure de calibrage LAR (Line-Attenuator-Reflect), intégrée dans les analyseurs de réseau modernes et qui permet une large bande de mesure avec un nombre limité d'étalons de référence sur wafer, est particulièrement attractive. Par contre, peu d'études sont réalisées pour évaluer sa traçabilité. C'est pourquoi le LNE (Laboratoire National de Métrologie et d'Essais) a décidé de mener des études afin d'évaluer la traçabilité et la précision de mesure quand la méthode de calibrage LAR est utilisée. Dans ce contexte, nos travaux de thèse se résument comme suit : 1)Réalisation d'un kit de calibrage sur Wafer pour exécuter à la fois le calibrage LAR et le calibrage Multiline TRL qui constitue le calibrage de référence pour les mesures sur wafer. 2)Proposition d'une méthode originale basée sur un calcul d'erreur pour tenir compte du fait que les impédances d'entrée et de sortie de l'atténuateur étalon sont différentes de 50 Ω. Outre sa précision, l'avantage de cette méthode est qu'elle ne nécessite pas la détermination précise de l'impédance de référence du calibrage LAR. 3)Proposition d'une méthode originale analytique pour déterminer l'impédance d'entrée et de sortie de calibrage et donc l'impédance de référence. 4)Réalisation d'un kit de calibrage large bande pour les utilisateurs, dont l'impédance de référence du calibrage LAR est peut être obtenue par trois moyens :. ● Modélisation électrique de l'atténuateur. ● Modélisation de l'impédance de référence par interpolation polynomiale. ● Mise au point d'une méthode simplifiée : la procédure LAR-L. 5)Analyse des erreurs dans le cas ou le substrat du kit de calibrage est différent du substrat du dispositif à caractériser. Pour déterminer cette capacité, une solution consiste à graver sur le wafer du dispositif sous test une ligne de transmission dont les dimensions doivent être connues, et dont on mesure les paramètres S après calibrage du VNA.

Une des caractéristiques les plus frappantes de la conception inventive est le fait qu’évaluer des solutions peut se révéler être plus difficile que de les trouver. Avoir des idées est inutile si celles-ci sont rejetées à un stade précoce. Dans de nombreuses évaluations qualitatives et méthodes sélectives, les critères d’évaluation sont généralement constitués à partir des besoins de conception qui sont fortement influencé par les préférences ou l’expérience des décideurs. Afin de tirer parti de l’inventivité d’une entreprise en octroyant des chances supplémentaires quant à des concepts possibles, cette thèse présente des approches et des outils d’aide à l’évaluation et à la sélection de concepts de solution obtenus dans le cadre de la Méthode de Conception Inventive. Les contributions de cette thèse peuvent servir comme outils d’aide à la conception et à la prise de décision. / One of the most striking characteristics of inventive design is that evaluating solutions may prove to be more difficult than finding them. Having good ideas is useless if they are rejected at an early stage. In many existing qualitative evaluation and selection methods (see design model), evaluation criteria are usually taken from the design requirement, which is strongly influenced by customer preferences or decision makers’ experience. In order to leverage inventiveness of a company through additional chances of feasible concepts. This thesis presents approaches and support tools to evaluate and select Solution Concepts obtained from Inventive Design Method (IDM) framework. The contributions in this thesis can be used as a decision-making aid and tool.

An improved Short-Open-Load-Thru (SOLT) on-wafer vector network calibration method for broad-band accuracy is proposed. Accurate measurement of on-wafer devices over a wide range of frequency, from DC to high frequencies with a minimum number of space conservative standards has always been desirable. Therefore, the work is aimed at improving the existing calibration methods and suggesting a best "practice" strategy that could be adopted to obtain greater accuracy with a simplified procedure and calibration set. Quantitative and qualitative comparisons are made to the existing calibration techniques. The advantages and drawbacks of each calibration are analyzed. Prior work done at the University of South Florida by an improved SOLT calibration is briefed. The presented work is a culmination and refinement of the prior USF work that suggested that SOLT calibration improves with more complex definitions for the calibration standards. Modeling of the load and thru standards is shown to improve accuracy as the frequency variation of the two standards can be significant. The load is modeled with modified equivalent circuit to include the high frequency parasitics. The model is physically verified on different substrates. The relation of load impedance with DC resistance is verified and its significance in SOLT calibrations is illustrated. The thru equation accounts for the losses in a transmission line reflections and phase shift including dielectric and conductor losses. The equations used are important for cases where a non-zero length of thru is assumed for the calibration. The complex definitions of the calibration standards are included in the calibration algorithm with LabView and tested on two different VNA's -- Wiltron 360B and Anritsu Lightning. The importance of including the forward and reverse switch terms error correction in the algorithm is analyzed and measurements that verify the improvement are shown. The concept using same foot size calibration standards to simplify the calibration process is highlighted with results to verify the same. The proposed technique thus provides for calibration strategy that can overcome the low frequency problems of TRL, retain TRL accuracy at high frequencies while enabling the use of a compact common footprint calibration set.

Les travaux de cette thèse traitent de l'élaboration d'une méthodologie efficace pour la modélisation des effets parasites dans une carte en large bande de fréquence. La réduction du «Time to Market» pour la conception des produits RF et hyperfréquences nécessite le développement d'une méthode efficace de caractérisation et de modélisation pour mieux prendre en compte les erreurs incluses dans la carte de test.Les principaux résultats concernent les contributions suivantes :- Mise au point des standards de calibrage innovateur pour caractériser et modéliser les effets parasites inhérent au modèle.- Élaboration d'une nouvelle approche basée sur une technique de calibrage TRL et une méthode d’élimination efficace de ces effets.- Application aux dispositifs différentiels lors de l'utilisation du calibrage TRL dans le cas de plusieurs ports.La nouvelle approche proposée pour le calibrage et le de-embedding est appliquée à un dispositif actif qui est actuellement utilisé dans l'industrie. Les résultats de mesure d’un dispositif inclus dans une carte de test ont été comparés à des mesures calibrées à l’aide d’une carte d’évaluation comportant des standards TRL.Cette étude a été prolongée avec le calibrage TRL multi-port pour être utilisé pour la bande large des dispositifs comme les dispositifs différentiels. / The work of this thesis deals with the developing of an efficient methodology for modeling parasitic effects within a broadband board. Reducing “Time to Market” for the design of RF and microwave products necessitates the development of an efficient characterization and modeling methodologies for better calibrating the errors embedded within the test board.Main results concern the following contributions:- Development of an innovative calibration standards to characterize and model the parasitic effects embedded within the model.- Elaboration of a new approach based on a TRL calibration technique and de-embedding method effective to de-embed these effects.- Application on differential devices upon using multi-port TRL calibration.The new proposed approach for calibration and de-embedding is applied to an active device which is being in use in industry nowadays. The measurement result of the device within a load board has been compared to a calibrated measurement using an evaluation board that include TRL standards.This study has been extended with multi-port TRL calibration to be used for large variety of devices like the differential ones.

La caractérisation des composants hyperfréquences après leur fabrication, est généralement réalisée par la mesure de paramètres S à l’aide d’un analyseur vectoriel de réseau (VNA). La précision de mesure dépend étroitement de la qualité du calibrage de l’analyseur vectoriel, qui permet de corriger les erreurs inhérentes au système de mesure. Des composants particuliers, dits étalons ou standards, dont les paramètres sont complètement ou partiellement connus, sont mesurés lors de la procédure de calibrage afin de déterminer les erreurs systématiques du système. La réalisation d’un circulateur coplanaire (les trois ports sont à 120 degrés les uns des autres) travaillant autour de 40 GHz est l’un des axes de recherche du laboratoire depuis plusieurs années et la caractérisation des prototypes a toujours été un souci important. Le calibrage est réalisé avec un kit commercial, avec les pointes positionnées en face à face. La mesure des dispositifs CPW à accès orthogonaux ou obliques après un calibrage avec un ensemble de standards conventionnels (droits) peut engendrer des erreurs supplémentaires. L’objectif de notre travail est donc de concevoir un ensemble de standards à accès inclinés à 120 degrés permettant de calibrer l’analyseur vectoriel « 2-ports » en positionnant directement les pointes à 120 degrés. La méthode de calibrage TRL (THRU – REFLECT - LINE) a été choisie. Le travail à accomplir se résume comme suit : - faire une étude de simulation du nouveau kit de calibrage à concevoir ; - mettre en évidence l’effet des accès coudés sur les lignes de transmission des standards ; - proposer une méthode de calcul qui tient compte de ces effets lors de la procédure de calibrage ; - mesurer quelques échantillons réalisés afin de vérifier la validité de la procédure de calibrage proposée. Les résultats obtenus au cours de ce travail ont pu être validés expérimentalement et offrent de nouvelles perspectives pour la mesure des composants planaires à accès non conventionnels / Microwave components characterization after the fabrication steps is usually performed by measuring S parameters using a Vector Network Analyzer (VNA). The measurement accuracy is highly dependent on the quality of the VNA calibration, which corrects the inherent errors in the measurement system. Specific components, called standards and whose parameters are completely or partially known, are measured during the calibration procedure to determine systematic errors of the system. Fabricating a coplanar circulator (the three ports are at 120 degrees position) functioning around 40 GHz is one of the laboratory’s research areas for several years and characterization of prototypes has always been a major concern. Usually, the calibration is made with a commercial kit ; probes are in face-to-face position. Measurements of CPW devices with orthogonal or bended accesses (120 degrees in our case) after VNA calibration with conventional (straight) set of standards may generate additional errors. The aim of our work is to design a set of standards with 120_ bended accesses allowing the calibration of the “2-ports” network analyzer. Therefore, probes are directly set at 120_ position. TRL (THRU - REFLECT -LINE) calibration procedure is chosen for the standards design. The work to be done is as follows : - to make a simulation study of the new calibration kit to design ; - to determine the bended accesses effects on the standards transmission lines ; - to propose a calculation method that takes account of these effects during the calibration procedure ; - to measure some fabricated samples to verify the validity of the proposed calibration procedure. The results of this research work have been experimentally validated and offer new perspectives for measuring planar components with unconventional accesses