ce rapport résume les développements réalisés en électronique pour lire le calorimètre à Argon Liquide (LAr) d'ATLAS au LHC puis le R&D effectué dans CALICE pour lire ceux de l'ILC en passant par les circuits développés pour lire les photomultiplicateurs multi-anode (MaPMT) pour OPERA ou pour la luminosité d'ATLAS et qui ont aussi des applications en imagerie médicale. Commencée au début des années 90, le R&D pour la calorimétrie d'ATLAS était extrêmement challenging en termes de vitesse de lecture, tenue aux radiations et précision de mesure. La vitesse élevée a nécessité une nouvelle approche de préamplificateurs de courant plutôt que de charge et la définition du bruit en ENI. Les préamplificateurs ont été développés a Orsay ainsi que les shapers monolithiques, ils sont détaillés dans le chapitre 1 ainsi que les considérations sur le filtrage numérique, qui constituait une nouveauté pour la communauté et qui ne donnait pas les résultas escomptés au début. Le chapitre 2 est consacré au système de calibration, développé et produit par Orsay et dont la performance poussée a nécessité des études approfondies. Le chapitre 3 clôt les études pour ATLAS avec un résumé des mesures qui ont dû être faites sur les 200 000 voies du détecteur pour le comprendre et le modéliser afin d'atteindre partout la précision et l'uniformité meilleures que le pourcent. Ces travaux pour ATLAS se sont achevés en 2004, même si des développements ont été réalisés pour les calorimètres de NA48 et D0 durant cette même période et sur des sujets connexes qui ne sont pas détaillés ici. La prochaine génération de collisionneurs après le LHC nécessitera une nouvelle génération de calorimètres, beaucoup plus granulaires (on parle d' « imaging calorimetry », avec des centaines de millions de canaux) et d'électronique de lecture intégrée dans le détecteur. Les ASICs développés pour cette application dans le cadre de la collaboration « CALICE » sont décrits au chapitre 4. Ils intègrent toutes les fonctions d'amplification, digitisation et lecture intégrée qui ont font de véritables « Systems On Chip » (SoC). Une famille de 3 circuits permet de lire le calorimètre électromagnétique Silicium-Tungstène, les RPCs du calorimètre hadronique digital ou les SiPM du calorimètre hadronique analogique ; très performants et versatiles, ils trouvent de nombreuses applications extérieures Ces circuits ont repris de précédents blocs de chips mis au point dans les années 2000 pour lire les photomultiplicateurs multi-anodes du Target Tracker de l'expérience OPERA puis du luminomètre de l'expérience ATLAS et qui sont décrits au chapitre 5 Ces circuits trouvent une continuation actuelle dans les photodétecteurs intégrés de grandes dimensions, développés pour de futures expériences Neutrino.

<p>In the assembly process of airframe structures there are many drilled holes and on some parts the holes are mainly drilled manually with pneumatic handheld drilling machines. During conventional drilling in metal, burrs appear. To remove these burrs the parts of the structure must be separated and deburred before they can be put together for fastening. This is a time consuming measure and therefore expensive. To facilitate this process and lower production costs some parts of the process needs to be automated.</p><p>A part of this thesis was a project in co-operation with Saab, Novator, Specma Automation and the University of Linköping. The purpose of this project was to investigate the ability of an industrial robot to drill holes in aeroplane structures using orbital drilling.</p><p>How the project tests were carried out and the results of these tests are presented in the first part of this thesis. The tests showed that slip-stick appeared when a force was applied on the working object by the robot. Because of the movement of the pressure foot the drilled hole will be in the wrong position and if the movement appears during drilling the quality of the hole is being poor.</p><p>Several different tests were performed using different amounts of forces and different pressure feet trying to prevent slip-stick from appearing. Finally tests were performed with good results concerning the quality of the holes.</p><p>In the second part of this thesis the proceeding tests that were carried out are presented. The purpose of these tests was to find out how the robot acts when a static pressure is applied on a work object by the robot and try to find out what the cause of the slip-stick was. Several tests were done where the robot applied a force on several different points on the fixture and the slip-stick was measured.</p><p>The tests that were carried out during this thesis showed that an industrial robot can be used to drill holes in aeroplane structures. To make sure that the quality of the drilled holes is sufficient for the high demands of the aeroplane industry the working area of the robot is limited to a small area in front of the robot. The slip-stick that appears when the robot is extended into a position on the far side of the robot is too large for the robot to drill the hole in an accurate position.</p> / <p>Vid flygplansmontering borras det många olika hål och på vissa delar borras större delen av dessa hål manuellt med pneumatiska handborrmaskiner. Vid konventionell borrning i metall bildas oönskade grader. Strukturen plockas därför isär så att graderna kan tas bort innan strukturens delar kan passas samman igen för att sammanfogas. Detta är en tidskrävande åtgärd och därmed dyr och i ett steg att förenkla denna process och få en billigare produktion vill man automatisera vissa steg i denna process.</p><p>En del av detta examensarbete var ett projekt i samarbete med Saab, Novator, Specma Automation och Linköpings Universitet vars syfte var att klargöra en robots förmåga att borra hål i flygplansmaterial med orbitalborrningsteknik.</p><p>I första delen av detta examensarbete redovisas genomförande och resultat av projektets tester. Testerna visade att tryckfoten gled på testmaterialets yta när roboten lade en tryckkraft på testplåten, så kallad slip-stick uppkom. Denna glidning gör att det borrade hålet inte hamnar på rätt position och sker glidningen under borroperationen så försämras hålets kvalité. Flera olika tester gjordes med varierad tryckkraft och med olika tryckfötter för att försöka förhindra att slip-stick uppkom. Tester genomfördes där hål borrades med bra kvalité.</p><p>I den andra delen av denna rapport redovisas fortsättningen på examensarbetet som var en vidareundersökning av de tidigare genomförda testerna. Syftet med denna del var att undersöka hur en industrirobot beter sig när den används för att lägga på en tryckkraft mot ett material samt att försöka ta reda på vad som är orsaken till slip-sticken. Fler tester gjordes där roboten tryckte på olika punkter på en fixtur och de uppkomna slip-sticken mättes upp.</p><p>Testerna under detta examensarbete har visat att det går att använda en industrirobot till att borra hål i flyglansmaterial. För att kvaliteten på de borrade hålen ska klara de höga krav som ställs inom flygplansindustrin är robotens arbetsområde begränsat till ett litet fönster mitt framför roboten. De glidningar som uppkommer när robotarmen är utsträckt långt åt sidan om roboten är alldeles för stora för de positioneringskrav som är på hålens placering på flygplansstrukturen.</p>

<p>Most software is now developed by professional programmers, and the millions of users of “shrink-wrapped” applications never meet the developers. The skills of professional programmers are obviously required in many software development projects. However, there are also reasons, ranging from practical and economical to philosophical and educational, why people without this background may want to develop their own applications or tailor applications to their own use.</p><p>The general purpose programming languages and development tools used by professional programmers are not suitable for people outside this profession. Instead, people outside this profession need more high-level tools that allow them to express solutions using domain and task specific terms. Despite the accumulated experience from such environments within the end-user programming community, creating a new application development environment for a domain or task remains a large development task, and can be too time-consuming and costly to be found worthwhile.</p><p>This thesis presents an approach to reducing the effort needed in developing extensible application composition environments for end users. We use the term “end user” in the same way as the end-user programming community, to denote a person who wants to develop an application or tailor an application to a specific use, without needing professional programming skills. The work in the thesis was initiated based on experience from development of proof-of-concept implementations of such environments in two European research projects. With this background, a set of user and developer roles are identified and organised into a value chain for development of such environments. Further, the approach combines the research areas of component-based software engineering and end-user programming to propose an overall architecture, component frameworks and tools suitable to support development of such environments. The validity of the results is established through partial prototyping of the frameworks and tools, combined with qualitative analyses of how these can be fully implemented and of their suitability for their intended purpose.</p><p>The main contributions of this thesis are:</p><p>• a value chain for development of application composition environments, with identification and description of tasks of each of the identified developer roles;</p><p>• an overall architecture for developing extensible application composition environments based on component frameworks;</p><p>• architecture of two component frameworks defining mechanisms and rules of behaviour for components ensuring extensibility at runtime and edit time;</p><p>• definition and description of a set of UML stereotypes for modelling domain frameworks based on the component frameworks, and a mapping to Java/JavaBeans allowing a code generator tool to produce part of the implementation;</p><p>• definition and description of tools which use the model of a domain framework as input and partially transform the work of creating composition environments and editors for domain objects from a programming task to a configuration task.</p>

The temporal behavior in applications involving visual data can be critical for the correctness of some programs. Forms/3 allows the user to specify temporal behaviors in an independent way, without introducing extraneous code in the original spreadsheet, whereas some other languages define new language devices specific to time. In this thesis, we present the implementation of a new user interface for temporal programming in Forms/3 and the results of two empirical studies. The results of the first study show that one of the models for temporal programing in Forms/3 is more suitable for end users than a traditional stream-based approach representative of the approach used by many other languages. The results of our second experiment show that the explicit information provided by the approach can help the users to judge the correctness of their spreadsheets. / Graduation date: 2002

As technology advances, health care decisions have become increasingly complex. American hospitals, based on accreditation standards, are required to have a system and process to address ethics, patient rights, and responsibilities. These practices vary widely, and there is very little consistency and few standards across the country. Key court cases have provided minor structure, and the federal government has been silent in the formulation of these structures but not necessarily in this arena. Most often, these accreditation standards related to clinical ethics are managed by Healthcare Ethics Committees (HEC). Bioethics has become a growing field, the level of integration between this discipline and healthcare practice varies widely. Using qualitative methods based on Grounded Theory, this analysis presents six key thematic findings, as well as interpretations to identify current challenges and opportunities to make recommendations for improvement by enhancing clarity and reducing ambiguity.

The nucleotide sequence at the 5´ end of genes can be specified as the sequence of a promoter associated 5´ untranslated region (UTR) together with the initial coding sequence of a gene. Because this genetic region has been implicated in the control of translation, messenger RNA (mRNA) stability and even transcription, it can be looked at as one of the central control points in gene expression. Both the 5´-UTR and the coding sequence have often been included in optimization strategies targeted to simulate recombinant protein production in E. coli and numerous reports describe various sequence-dependent structural features that can positively influence the overall expression process. Nevertheless, the actual mechanisms by which the regulation of gene expression is exerted at the 5´ end remain obscure. The work reported in this thesis has involved various types of analyses of the functionality of the 5´ end, by using mutations as a major tool. The work can be seen as mainly a detailed empirical analysis of the relation between the specific nucleotide sequences at the 5’ end of genes and the final outcome at the protein production level. The results also indicate that optimizations based on empirical laboratory protocols are currently unlikely to be exceeded by predictions based on bioinformatics software. Sequence mutagenesis of elements in the XylS/Pm - positive regulator/promoter system coupled to high-throughput screening had been previously proven to be a powerful method for increasing the expression of recombinant genes from this expression cassette. At the beginning of this thesis work the effect of introducing random mutations in the DNA sequence of the Pm promoter associated 5´-UTR and two 5´ fusion partners, whose sequences correspond either to a consensus translocation signal peptide or the first 23 codons of a well-expressed celB gene (encoding a cytoplasmic phosphoglucomutase) was investigated. The core of the experimental work was construction of large combinatorial libraries of the different DNA sequences and subsequent selection for improved expression of a reporter gene (either ampicillin or apramycin resistance gene), that was indicated by an increase in antibiotic tolerance of the corresponding E. coli host cells. A shared result of the three individual studies was the establishment of a collection of optimized sequences that generally improved protein production properties of both reporter and industrially relevant heterologous genes. In addition to random mutagenesis, also synonymous mutations were introduced in the DNA sequence of the consensus signal peptide (CSP) and the consequent expression effects were evaluated. As a conclusion, the DNA changes that did not alter the amino acid sequence led to a lesser stimulation of expression of the bla reporter (ampicillin resistance) than when complete sequence randomization was applied. Moreover, similar results were obtained when synonymous codon usage of the first 9 codons of the medically important ifn-α2b gene was optimized by a bioinformatic method, followed by experimental determination of expression levels of several rationally selected ifn-α2b synonymous variants. These results indicated that optimization of the codon usage of the 5´ coding sequence has limited effects, probably due to the sequence intrinsic characteristics. However, the use of optimized 5´ fusion partners or 5´-UTR variants can often overcome such limitations. Besides evaluating the expression at the protein level, the work also addressed how the changes of the 5´ end of a gene influence expression at the level of transcript accumulation and mRNA stability. For that purpose, a non-invasive method for accessing recombinant mRNA stability in bacteria was developed. The procedure was based on the removal of diffusible transcriptional inducers followed by qRT-PCR determination of mRNA levels at consecutive time-points. Among the principal findings was that a 5´ fusion partner (specifically: translocation signals pelB and ompA, together with the celB-based 5´ fusion) contributes to the stimulation of recombinant gene expression by enhancing the stability of the corresponding fusion mRNA. The stimulation of expression caused by specific mutations in the 5´-UTR and adjacent coding sequence (synonymous changes), on the other hand, surprisingly appeared to result from improved rate of mRNA synthesis. Three selected promoter systems (Pm, Ptac and the T7 based) were used in these studies, and part of the work also evaluated how fast each system responds to addition and removal of its inducer, respectively. The expression systems were found to affect both transcript accumulation and decay in a specific way that correlated with the type of transcription regulation each system is subjected to. Finally, a study comparing five bacterial expression systems (XylS/Pm, XylS/Pm ML1-17 (a Pm variant), the bacteriophage T7 RNA polymerase/promoter system, LacI/Ptrc and AraC/PBAD) with respect to their production capacity of five different recombinant proteins was carried out. The comparison revealed many expression system and model gene specific features and that none of the systems was superior in all evaluated aspects; which included system´s adaptability, maximum protein yield, basal expression in the absence of inducer, use of cellular resources and homogeneity of expression. However, particularly because of a large associated collection of optimized genetic elements (such as sequence variants of the Pm promoter, the XylS regulator, 5´-UTR and various translocation signals) and the possibility of simple genetic adjustments that can lead to both higher and lower expression levels, the XylS/Pm system appeared as a good starting point for optimization of various kinds of protein production processes. / A Combinatorial Mutagenesis Approach to Improve Microbial Expression Systems

Most software is now developed by professional programmers, and the millions of users of “shrink-wrapped” applications never meet the developers. The skills of professional programmers are obviously required in many software development projects. However, there are also reasons, ranging from practical and economical to philosophical and educational, why people without this background may want to develop their own applications or tailor applications to their own use. The general purpose programming languages and development tools used by professional programmers are not suitable for people outside this profession. Instead, people outside this profession need more high-level tools that allow them to express solutions using domain and task specific terms. Despite the accumulated experience from such environments within the end-user programming community, creating a new application development environment for a domain or task remains a large development task, and can be too time-consuming and costly to be found worthwhile. This thesis presents an approach to reducing the effort needed in developing extensible application composition environments for end users. We use the term “end user” in the same way as the end-user programming community, to denote a person who wants to develop an application or tailor an application to a specific use, without needing professional programming skills. The work in the thesis was initiated based on experience from development of proof-of-concept implementations of such environments in two European research projects. With this background, a set of user and developer roles are identified and organised into a value chain for development of such environments. Further, the approach combines the research areas of component-based software engineering and end-user programming to propose an overall architecture, component frameworks and tools suitable to support development of such environments. The validity of the results is established through partial prototyping of the frameworks and tools, combined with qualitative analyses of how these can be fully implemented and of their suitability for their intended purpose. The main contributions of this thesis are: • a value chain for development of application composition environments, with identification and description of tasks of each of the identified developer roles; • an overall architecture for developing extensible application composition environments based on component frameworks; • architecture of two component frameworks defining mechanisms and rules of behaviour for components ensuring extensibility at runtime and edit time; • definition and description of a set of UML stereotypes for modelling domain frameworks based on the component frameworks, and a mapping to Java/JavaBeans allowing a code generator tool to produce part of the implementation; • definition and description of tools which use the model of a domain framework as input and partially transform the work of creating composition environments and editors for domain objects from a programming task to a configuration task.

‘Internationalisation of higher education’ is considered a significant issue in many countries.One effective way to achieve internationalisation is by having an exchange study program. Thisis something which has been promoted by universities all around the globe. It has been foundthat the experience of studying abroad is beneficial to the students. There has been a trend ofincreasing number of students going to study abroad. In Sweden, Jönköping InternationalBusiness School (JIBS) is one of the most internationalised business schools that promoteexchange studies extensively. To promote study abroad it is important to know what motivatesand influences the students to go on exchange. There has been previous research oninternationalisation and push-pull factors of student mobility which acted as a guideline for thisthesis. Thus it was appealing to study the reasons behind the phenomenon of students goingabroad for exchange studies.The purpose of this paper is to explore the push-pull factors influencing student’s destinationchoice for exchange study abroad. JIBS is the institution where the case study was conducted.The empirical data have been gathered by using a qualitative approach combining face-to-faceinterviews and focus groups with international exchange students and Swedish students. Toanalyse the findings, theories relating to marketing communications in service and productattribution were used.The results derived from the empirical findings show the push-pull factors which motivatestudents to go on exchange. The initial push factor is the promotion and encouragement tostudents for studying abroad by the university. Exchange studies helps to enhance students’personal development with intercultural communication, practicing language skills andtravelling. These skills and experiences add value to their CV.On the other hand the pull factors which the students take into consideration for deciding ontheir host countries and institutions are geographic location, weather, culture, and the economicand social position of the country. Living cost and the education system which includeslanguage used, courses offered, perceived image, communication and cooperation andrecommendations are factors influencing the choices of a student’s decision on the destinationfor studying abroad. The authors in this thesis summarised their findings in a model of pushpullfactors which is specialised only for exchange students. The process of considering thesefactors leads to the outcome of choosing the destination for studying abroad. The authorsbelieve the results of this study can be applied on other universities for further research andmay be appropriate for its own case to focus on areas where it needs to improve.ii

Studien syftar till att leda till en bättre förståelse för utsattas erfarenheter av mobbning och att öka kunskapen om vad som kan göras för att motverka mobbning samt hur de utsatta kan hjälpas och stöttas. I studien har fyra kvinnor och fyra män deltagit, som alla har upplevt mobbning under skolgången, men som inte längre är utsatta. Metoden som använts är en innehålls analys. Resultatet av intervjuerna tyder på att det upplevda stödet från skola och hem inte var tillräckligt. Att mobbningen pågick under en längre period utan ingripande från vuxna i omgivningen. Samtliga deltagare upplevde mobbningen som jobbig då den pågick men är i efterhand tacksamma för den erfarenhet det har givit. I studien har vi dragit slutsatsen att skolans åtgärder fungerat i praktiken, men satts in försent. Det är viktigt att öka medvetenheten hos både skola och familjer för olika tecken på mobbning samt hantering av den.

The application of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA)-salt, to unilaterally nephrectomised rats induces severe hypertension due to volume-overload, and mimics human primary aldosteronism. Importantly, DOCA-salt hypertension is characterized by severe cardiac and renal lesions triggered by nuclear factor kappa B (NF-kappaB), activating protein (AP-1), and transforming growth factor beta1 (TGF-beta1) leading to end-stage organ damage. Although DOCA-salt hypertension is a low renin model, local production of angiotensin-II and aldosterone in cardiac and renal tissues stimulate TGF-beta1, fibronectin and collagen-1 causing fibrosis and hypertrophy. Since TGF-beta1 gene promoter contains binding sites for NF-kappaB and AP-1, cross-talk between TGF-beta1, NF-kappaBnand AP-1 can be envisaged. Accordingly, the activation of TGF-beta1, fibronectin, collagen, NF-kappaB and AP-1 may constitute a potent destructive force in hypertension.<p> Emerging evidence indicates that upregulation of the heme oxygenase (HO) system is cytoprotective with antioxidant, antihypertensive and antihypertrophic effects. Interestingly, the promoter region of HO-1 gene harbors consensus-binding sites for NF-kappaB and AP-1; therefore, the HO system may regulate these transcription factors to counteract tissue insults. However, the multifaceted interactions between the HO system, NF-kappaB, AP-1, TGF-beta1, fibronectin and collagen in mineralocorticoid-induced end-stage-organ damage have not been fully characterized. Similarly, the effect of the HO system on tissue angiotensin-II and aldosterone levels in mineralocorticoid-induced hypertension remains unclear. Therefore, the present study was designed to investigate the antihypertrophic effect of the HO system in cardiac and renal tissue of DOCA-salt hypertensive rats. In this study, the HO inducer, hemin, lowered blood pressure and attenuated cardiac/renal hypertrophy, whereas the HO inhibitor, chromium mesoporphyrin (CrMP), nullified the effects of hemin and exacerbated cardiac/renal injury the DOCA-salt hypertensive rats. The protective effect of hemin was associated with increased HO-1, HO activity, cyclic guanosine monophosphate (cGMP), superoxide dismutase activity, ferritin and the total antioxidant capacity in the cardiac and renal tissue. In contrast, angiotensin-II, aldosterone, 8-isoprostane, NF-kappaB and AP-1 were significantly downregulated. Furthermore, hemin therapy attenuated TGF-beta1 and extracellular matrix (ECM) proteins such as fibronectin and collagen, with corresponding reduction of cardiac histopathological lesions, including longitudinal/cross-sectional muscle fiber thickness, scarring, muscular hypertrophy, coronary arteriolar thickening and collagen deposition. Similarly, hemin attenuated structural lesions in the kidney such as glomerular hypertrophy, glomerular sclerosis, mononuclear cell infiltration, tubular cast formation, tubular dilation and renal arteriolar thickening with concomitant improvement of kidney function as evidenced by reduction of plasma creatinine, proteinuria, but enhanced creatinine clearance.<p> Collectively, these results suggest that the HO system suppressed hypertension, cardiac and renal fibrosis, and hypertrophy in the DOCA-salt hypertensive rat by downregulating transcription factors such as NF-kappaB and AP-1, reducing ECM proteins such as fibronectin and collagen, decreasing local tissue production of angiotensin-II and aldosterone, and improved renal functional capacity.