Agile software development methods keep increasing in popularity. Many organizations who are using traditional software development methods, such as water-fall and stagegate based methods are switching to agile software development methods. This transition can be challenging, especially for organizations using project governance models that hinder the adoption of agile practices. This study aims to provide guidance to managers on how to introduce agile software development methods in such traditional organizations. The study is a single-case study on a large governmental agency in Sweden. Eight interviews with developers, team-leads and managers were conducted. The study identifies practical tools and ideas that managers can use to introduce a shared definition of agile, adopting an agile mindset, dedicated teams, and CI&CD. Together, this guidance supports managers with the introduction of agile software development methods in organizations utilizing traditional project governance structures and traditional software development methods. / Agila systemutvecklingsmetoder fortsätter öka i popularitet. Många organisationer som använder sig av traditionella systemutvecklingsmetoder så som vattenfallsmodellen byter till agila systemutvecklingsmetoder. Denna övergång kan vara utmanande, speciellt för organisationer som använder sig av projektbaserade förvaltningsmodeller som hindrar implementeringen av agila metoder. Den här studien syftar till att ge vägledningen till chefer kring hur de kan introducera agila systemutvecklingsmetoder iden nyss nämnda typen av traditionella organisationer. Studien är en fallstudie gjort på en stor myndighet i Sverige. Åtta intervjuer med systemutvecklare, lag-ledare och chefer har utförts. Studien identifierar verktyg och idéer som chefer kan använda sig avför att introducera en delad gemensam definition av agilt, anamma ett agilt tankesätt, introducera dedikerade teams och CI&CD. Tillsammans hjälper de här verktygen med introduktionen av agila systemutvecklingsmetoder i organisationer som använder sig av traditionella systemutvecklingsmetoder och förvaltningsmodeller.

There is a great demand for fast deliveries of improved and updated software in different software development areas, like Internet of Things, web, and cloud, in today’s digitalized world. Software developers and organizations must adapt to be able to deliver according to customers’ wishes, to be able to retain them, and remain competitive with other organizations. Continuous integration and continuous delivery (CI/CD) are methods used within the software development world, allowing developers to automate parts of their work to develop and deliver software faster and with better quality. Tools used for CI/CD come with different benefits and performances making it difficult for developers to choose a tool. There are numerous tools to choose from, and there is a lack of performance comparisons of them. This thesis aims to give developers a performance comparison between the two well-known CI/CD tools, GitHub Actions and Jenkins, to facilitate their choice of a CI/CD tool. The research was qualitative, inductive, and comparative. A literature study and practical tests were conducted to study the performance differences between the two wellknown CI/CD tools, GitHub Actions and Jenkins. The literature study was conducted f irst and gave the necessary knowledge to perform the practical tests, and the practical tests gave the actual results. The practical tests were performed on two different software projects ,and two different tests per projec, per server were conducted. The results from both projects indicated apparent differences in performance between GitHub Actions and Jenkins, as Jenkins ran faster than GitHub Actions while running on a Windows server, and GitHub Actions ran faster than Jenkins while running on an Ubuntu server. These findings indicate that the two well-known CI/CD tools perform differently depending on the server the developers would use these tools. It can not be concluded that one of the tools has better performance than the other; instead, one tool has better performance depending on the operating system the tool is running on. If the developers were to use the tools on an Ubuntu server, GitHub Actions would be the preferred tool, and if they were to use the tool on a Windows server, Jenkins would be the preferred tool. / Det finns en stor efterfrågan på snabba leveranser av förbättrad och uppdaterad mjukvara i olika mjukvaruutvecklings områden så som Sakernas Internet, webb och moln i dagens digitaliserade värld. Mjukvaruutvecklare och organisationer måste anpassa sig för att kunna leverera till kundernas önskemål för att kunna behålla dom och förbli konkurrenskraftiga med andra organisationer. Kontinuerlig integration och kontinuerlig leverans (CI/CD) är metoder som används inom mjukvaruutvecklings världen, så att utvecklare kan automatisera delar av sitt arbete för att utveckla och leverera mjukvara snabbare och med bättre kvalité. Verktyg som används för CI/CD kommer med olika fördelar och prestanda som gör det svårt för utvecklare att välja ett verktyg. Det finns många verktyg att välja mellan och det finns en brist på prestandajämförelser av dem. Detta examensarbete syftar till att ge utvecklare en prestandajämförelse mellan de två välkända CI/CD-verktygen GitHub Actions och Jenkins, för att underlätta utvecklarens val av ett CI/CD-verktyg. En kvalitativ, induktiv och komparativ forskningsmetod användes för att genomföra denna studie. En litteraturstudie och praktiska tester genomfördes för att studera prestandaskillnader mellan de två välkända CI/CD-verktygen GitHub Actions och Jenkins. Litteraturstudien genomfördes först och gav författarna nödvändiga kunskap för att utföra dem praktiska testerna, dem praktiska testerna gav de faktiska resultaten. Praktiska testerna utfördes på två olika mjukvaruprojekt och två olika tester per projekt, en per server genomfördes. Resultaten från båda projekten visade på uppenbara skillnader i prestanda mellan GitHub Actions och Jenkins. Då Jenkins kördes snabbare än GitHub Actions när körningen kördes på en Windows server och GitHub Actions kördes snabbare än Jenkins när de kördes på en Ubuntu server. Dessa resultat tyder på att de två välkända CI/CD-verktygen fungerar olika beroende på vilken server utvecklarna skulle använda dessa verktyg på. Det går inte att dra slutsatsen att ett verktyg är bättre över det andra, i stället har ett verktyg bättre prestanda beroende på vilket operativ system verktyget körs på. Om utvecklarna skulle använda verktygen på en Ubuntu server skulle GitHub Actions vara det föredragna verktyget och om utvecklarna skulle använda verktyget på en Window server skulle Jenkins vara det föredragna verktyget.

B-lymphocytes are a subset of immune cells that can be distinguished mainly by carrying clonally diversified membrane-bound immunoglobulin specialized to specific antigen recognition. Together with other immunocytes B-lymphocytes play a central role in adaptive immune system which takes part in defense of the host against wide variety of pathogens. Recently the evidence has supported the emerging concept of different B-cell subpopulations to play a direct or indirect role in a pathogenesis of spectrum of disorders. However, so far the knowledge has been limited mainly in the way of how the specific differentiation stages of B-lymphocytes are involved in pathogenesis of diseases and how course of disease, stage, and eventually different treatment can affect B-cell homeostasis. That is the reason for the thesis to be focused on an analysis of B-cell population profile changes in disease, identification of any association present among specific B-cell subpopulations, as well as association between these subpopulations and clinical parameters. Using polychromatic flow cytometry we analyzed frequencies of 11 B-cell subpopulations including stages of transient B-lymphocytes through effector antibody-producing plasma cells. We examined 81 individuals including 22 healthy controls and 59 patients with...

Rituximab (IDEC C2B8) ist ein chimärer monoklonaler Antikörper, der gegen das CD20-Antigen auf B-Lymphozyten gerichtet ist. In klinischen Studien konnten Ansprechraten von 50 Prozent bei Patienten mit niedrigmalignen NHL erzielt werden [61, 62]. Bei den hochmalignen NHL waren die Ansprechraten geringer, doch auch hier konnte eine therapeutische Wirksamkeit von Rituximab nachgewiesen werden [108]. Der genaue Wirkungsmechanismus, durch welchen Rituximab seinen therapeutischen Effekt erzielt, ist weiterhin nicht vollständig geklärt. Hauptsächlich werden dabei Apoptose, Komplement-vermittelte zelluläre Zytotoxizität (CDC) und die Antikörper-vermittelte Zytotoxizität (ADCC) diskutiert. In der vorliegenden Arbeit wurde in vitro die Proliferationsinhibition und die Komplement-vermittelte zelluläre Zytotoxizität durch Rituximab an verschiedenen humanen B-Zellinien geprüft. Anschließend wurde die in vivo-Komplementaktivierung während einer Rituximab-Infusion untersucht. Es konnte gezeigt werden, dass Rituximab in vitro eine unterschiedliche Wirksamkeit bei verschiedenen Lymphomzellinien aufweist. Durch Zugabe von humanem Komplement konnte bei zwei Zellinien eine Rituximab-induzierte CDC beobachtet werden. Bei sechs von zehn Patienten mit unterschiedlichen NHL wurde in vivo ein Anstieg der C3a-desArg-Konzentration im Plasma beobachtet. Die Ergebnisse dieser Arbeit zeigen, dass das Komplementsystem ein wichtiger Mechanismus für die Wirkung von Rituximab zu sein scheint. Die klinischen Erfolge sind viel versprechend, zeigen jedoch auch, dass der therapeutische Nutzen von Rituximab als Monotherapie begrenzt ist. Derzeit laufende prospektive Studien untersuchen die Wirksamkeit von Rituximab in Kombination mit verschiedenen Chemotherapeutika [106, 107]. Erste Ergebnisse sind viel versprechend, doch es bleibt abzuwarten, ob sich diese Ergebnisse auch langfristig in einer Verbesserung der Überlebensrate widerspiegeln. / The chimeric anti-CD20 monoclonal antibody rituximab is a new therapeutic tool for treatment of relapsed B-cell lymphomas. Because rituximab mediates complement-dependent cellular cytotoxicity (CDCC) and antibody-dependent cellular cytotoxicity (ADCC) in the lymphoblastoid cell line SB, it is suggested, that these two mechanisms are responsible for the in vivo antilymphoma effect. We tested the antiproliferative effect of rituximab in 6 CD20 positive human B cell lymphoma cell lines. In the follicular lymphoma cell line, DOHH-2, 1 µg/ml rituximab induces an inhibition of proliferation of 75.5 % (n=5), and in the diffuse large cell lymphoma cell line, Daudi, an inhibition of proliferation of 27.3 % (n=5). No effect was seen in the prelymphocytic leukemia cell line, JVM-2, the hairy cell leukemia cell line, Bonna-12, or the two high-grade lymphoma cell lines, Granta-519 and Raji. To test, whether complement increases the effect of rituximab, we studied the combination of rituximab plus complement. Guinea pig complement (dilution 1:10) increases the inhibitory effect of rituximab on the proliferation of Daudi cells. The degradation product C3a(desArg) is produced during complement cascade activation and could be used as a sensitive and specific marker of complement activation in vivo. So, we measured plasma C3a(desArg) concentration in two CLL patients receiving rituximab monotherapy. In one patient, no increase of plasma C3a(desArg) concentration could be measured during infusion of rituximab. In the other patient, in two treatment cycles C3a(desArg) increases drastically after 2 h of rituximab infusion. We conclude differential in vitro and in vivo effects of rituximab on CD20 positive lymphoma cells. Rituximab inhibits in vitro the proliferation of follicular and diffuse large cell lymphoma cells, which could be amplified by complement in Daudi cells. Furthermore, rituximab mediates in vivo complement cascade activation, highly suggestive of in vivo CDCC.

Nos travaux décrivent l’identification et la caractérisation d’une cellule immunitaire : l’IKDC pour Interferon Producing killer dendritic cell. Cette population cellulaire, découverte à la faveur de la combinaison Imatinib mesilate et Interleukine 2 dans le traitement des métastases pulmonaires de mélanome B16F10 chez la souris, combine des caractéristiques de cellule dendritique (présentation antigénique) et de cellule natural killer (lyse sans apprentissage). Le phénotype des IKDC est le suivant :CD3-, CD19-, CD11c+,B220+, NK1.1+. Nous avons établi une stratégie de culture des IKDC ex vivo grâce à la trans-présentation de l’IL-15 et montré que ces cellules sont capables de présenter des antigènes aux lymphocytes T et de vacciner une souris contre une tumeur. Ce projet se poursuit par la mise en place d’un essai clinique de phase I utilisant Imatinib mesilate et l’Interleukine 2. / In this manuscript, we describe the isolation and the characterisation of a novel immune cell: the IKDC for Interferon Producing killer dendritic cell. This cell population, discovered thanks to the combination Imatinib mesilate and Interleukine 2 for the treatment of lung metastases of B16F10 murine melanoma, shares dendritic cell (antigen presentation) and natural killer cell (non specific lysis) properties. IKDC phenotype is the following: CD3-, CD19-, CD11c+, B220+, NK1.1+. We established a culture strategy for the IKDC ex vivo thanks to the trans-presentation of IL-15 and demonstrated that these cells once cultivated are able to prime lymphocytes and to protect mice from tumor development. This project has led to a phase I clinical trial testing the antitumor effect of the combination Imatinib mesilate and Interleukin 2.

À partir des noeuds technologiques 45nm, les lignes métalliques des interconnexions des composants microélectroniques sont isolées entre elles par des matériaux diélectriques à faible permittivité (SiOCH poreux). Ces matériaux poreux sont sensibles aux procédés de fabrication et leur dégradation doit être minimisée afin de conserver de bonnes performances électriques et mécaniques. De plus, la réduction des dimensions des lignes métalliques se traduit par une augmentation de la résistivité du cuivre. Pour limiter cette dernière, des travaux sont menés sur la métallurgie et le contrôle de la rugosité des lignes de cuivre. Ce travail se focalise sur deux limites rencontrées lors de la fabrication de structures d'interconnexions : d'une part lors du transfert par gravure plasma de motifs à partir d'un masque métallique ou organique dans les matériaux SiOCH poreux, et d'autre part lors de l'intégration d'un matériau SiOCH hybride, rendu poreux soit après l'étape de gravure ou de métallisation des tranchées. En particulier, il est mis en évidence que les masques de gravure peuvent entraîner une déformation des profils au cours des procédés de gravure plasma des structures sous l'effet de la relaxation de contraintes mécaniques pour les masques métalliques ou de la modification de leur composition pour les masques organiques. Une étude préliminaire, sur le transfert de la rugosité de bord de ligne (LWR) pendant l'étape de gravure, menée à l'aide d'un CD-AFM, est présentée. L'intérêt de l'intégration du matériau SiOCH sous sa forme hybride pour répondre à la problématique de la dégradation des SiOCH poreux par les procédés impliqués lors de la fabrication des niveaux d'interconnexions est démontré.

À partir des noeuds technologiques 45nm, les lignes métalliques des interconnexions des composants microélectroniques sont isolées entre elles par des matériaux diélectriques à faible permittivité (SiOCH poreux). Ces matériaux poreux sont sensibles aux procédés de fabrication et leur dégradation doit être minimisée afin de conserver de bonnes performances électriques et mécaniques. De plus, la réduction des dimensions des lignes métalliques se traduit par une augmentation de la résistivité du cuivre. Pour limiter cette dernière, des travaux sont menés sur la métallurgie et le contrôle de la rugosité des lignes de cuivre. Ce travail se focalise sur deux limites rencontrées lors de la fabrication de structures d'interconnexions : d'une part lors du transfert par gravure plasma de motifs à partir d'un masque métallique ou organique dans les matériaux SiOCH poreux, et d'autre part lors de l'intégration d'un matériau SiOCH hybride, rendu poreux soit après l'étape de gravure ou de métallisation des tranchées. En particulier, il est mis en évidence que les masques de gravure peuvent entraîner une déformation des profils au cours des procédés de gravure plasma des structures sous l'effet de la relaxation de contraintes mécaniques pour les masques métalliques ou de la modification de leur composition pour les masques organiques. Une étude préliminaire, sur le transfert de la rugosité de bord de ligne (LWR) pendant l'étape de gravure, menée à l'aide d'un CD-AFM, est présentée. L'intérêt de l'intégration du matériau SiOCH sous sa forme hybride pour répondre à la problématique de la dégradation des SiOCH poreux par les procédés impliqués lors de la fabrication des niveaux d'interconnexions est démontré.

Apoptosis plays a crucial role in multicellular organisms by preserving tissue homeostasis and removing harmful cells. The anti-apoptotic B-cell CLL/lymphoma 2 (Bcl-2) and the pro-apoptotic Bcl-2-associated X protein (Bax) act as major regulators of the mitochondrial apoptotic pathway. Activation of Bax via stress signals causes its translocation to the mitochondrial outer membrane (MOM). There, Bax forms homo-oligomeric pores, leading to the release of apoptogenic factors, caspase activation and ultimately cell death. However, the underlying mechanism for the recruitment and pore forming activity of Bax is still not elucidated. Nevertheless, the mitochondrial membrane system seems to play an active and crucial role, presumably being directly involved in the onset of the mitochondrial apoptosis. Since the formation of reactive oxygen species (ROS) is a common stress signal and one of the hallmarks of the mitochondrial apoptosis, direct damage can occur to these membranes by the generation of oxidized phospholipids (OxPls), whose presence can crucially influence the pro-apoptotic action of Bax there. To better understand the impact of OxPls on membranes as well as their potential role in the mitochondrial apoptotic process, defined OxPl species were incorporated into phospholipid vesicles and studied with various biophysical techniques. Differential scanning calorimetry (DSC) and solid state nuclear magnetic resonance (NMR) spectroscopy were used to gain insight into changes in membrane properties in the presence of OxPls. In addition to circular dichroism (CD) spectroscopy, DSC and solid state NMR were furthermore performed to elucidate the impact of OxPls on Bax-membrane interactions. The occurrence of OxPls gave rise to dramatic changes in membrane organization and dynamics, manifested as lateral phase separation into OxPl-rich and -poor domains and modified hydration at the membrane interface. The presence of OxPls also had a great impact on the interaction between Bax and mitochondria-mimicking vesicles, strongly promoting the association of the protein with the membrane. At the MOM, Bax is believed to be inhibited by Bcl-2. How this inhibition occurs is still a mystery due to the lack of biophysical information on Bcl-2, in particular on the full-length protein variant. Since Bcl-2 is also one of the main culprits in the progression of various forms of cancer, knowledge of the structural and mechanistic properties of the full-length protein is essential for a fundamental understanding of its function at a molecular level. To this end, a method for the production of full-length Bcl-2 was developed. By performing cell-free protein synthesis, preparative amounts of the protein were obtained, which enabled a biophysical characterization of the putative interaction between Bax and Bcl-2 using CD and fluorescence spectroscopy. A protocol for the reconstitution of Bcl-2 into proteoliposomes was also developed, promising for future studies of the full-length protein in its native membrane environment; a prerequisite to fully understand its pro-survival functions as well as providing crucial information for the design of novel anti-cancer drugs.

Background: Adherent-invasive Escherichia coli (AIEC) is a pathogen isolated from the ileum of patients with CD. IFNγ is a key mediator of immunity, which regulates inflammatory responses to microbial infections. Previously, we showed enterohemorrhagic E. coli prevents STAT1 activation. Aims: To determine; 1) whether activation of STAT1 by IFNγ was prevented following AIEC infection, and 2) define the mechanisms used. Methods: Human epithelial cells were infected with AIEC strains or other pathogenic and commensal E. coli strains. Following infection, cells were stimulated with IFNγ. Activation of STAT1, was monitored by immunoblotting. Results: AIEC strains prevented STAT1 phosphorylation in response to IFNγ. Effect required live bacteria with active protein synthesis. A bacterial product was responsible for blocking STAT1 signalling and interfered with downstream signalling cascades. Conclusion: Suppression of epithelial cell STAT1 signal transduction by AIEC strains represents a novel mechanism by which the pathogen evades host immune responses to the infection.

Background: Adherent-invasive Escherichia coli (AIEC) is a pathogen isolated from the ileum of patients with CD. IFNγ is a key mediator of immunity, which regulates inflammatory responses to microbial infections. Previously, we showed enterohemorrhagic E. coli prevents STAT1 activation. Aims: To determine; 1) whether activation of STAT1 by IFNγ was prevented following AIEC infection, and 2) define the mechanisms used. Methods: Human epithelial cells were infected with AIEC strains or other pathogenic and commensal E. coli strains. Following infection, cells were stimulated with IFNγ. Activation of STAT1, was monitored by immunoblotting. Results: AIEC strains prevented STAT1 phosphorylation in response to IFNγ. Effect required live bacteria with active protein synthesis. A bacterial product was responsible for blocking STAT1 signalling and interfered with downstream signalling cascades. Conclusion: Suppression of epithelial cell STAT1 signal transduction by AIEC strains represents a novel mechanism by which the pathogen evades host immune responses to the infection.