Hematopoiesis is coordinated by a complex regulatory network of transcription factors among them PU.1 (Spi1, Sfpi1) and GATA-1 represent key molecules. GATA-1 and PU.1 bind each other on DNA to block each others transcriptional programs to prevent development of undesired lineage during hematopoietic commitment. Murine erythroleukemia (MEL) cells, transformed erythroid precursors that are blocked from completing the late stages of erythroid differentiation, co-express GATA-1 and PU.1 and as my and others data document, are able to respond to molecular removal (down-regulation) of PU.1 or addition (up-regulation) of GATA-1 by inducing terminal erythroid differentiation. We provide novel evidence that downregulation of GATA-1 or upregulation of PU.1 induces incompletely differentiation into cell cycle arrested monocytic-like cells. Furthermore, PU.1- dependent transcriptome is negatively regulated by GATA-1 in MEL cells, including CCAAT/enhancer binding protein alpha (Cebpa) and Core-binding factor, beta subunit (Cbfb) that encode additional key hematopoietic transcription factors. Chromatin immunoprecipitation and reporter assays identified PU.1 motif sequences near Cebpa and Cbfb that are co-occupied by PU.1 and GATA-1 in the leukemic blasts. Furthermore, transcriptional regulation of these loci by...

U-Pu-Zr nuclear fuels experience a redistribution of constituents and a number of phase transformations when subjected to the thermal gradient present in nuclear reactors. This redistribution and phase separation leads to several undesirable fuel performance issues. In an effort to better understand how different alloys compositions are affected by this thermal gradient, we utilize the recently introduced Hybrid Potts-phase Field Method to study the U-Pu-Zr system. The recently introduced Hybrid method couples microstructural and compositional evolutions of a system so that the two phenomena can be studied together rather than separately, as is frequently done. However, simulation of the U-Pu-Zr system required several adaptations to the modeling framework. First the model was adapted to incorporate a thermodynamic database for free energy calculations, as well as thermal diffusion (the Soret effect). These abilities were tested in the Al-Si system. Second, the modeling framework was expanded to simulate three component systems such that ternary U-Pu-Zr alloys could be studied.Simulations capture constituent redistribution and the appropriate phase transformations as compared to experimentally irradiated a U-16Pu-23Zr (at%) nuclear fuel. Additional simulations analyze constituent redistribution over the entire spectrum of U-Pu-Zr compositions. Analysis of these simulation results indicate alloys that are likely to experience minimal constituent redistribution and fewer phase boundaries, such that their fuel performance should be improved. The outcomes of the work include a coupled microstructural-compositional modeling framework for ternary alloys and suggestions of U-Pu-Zr alloys that could lead to improved fuel performance.

Stålpartier i Norr AB (SPINAB) är ett företag som tillhör gruppen små och medelstora företag. De har företagsidén att tillverka och sälja CE-märkta fönster, dörrar och skräddarsydda produkter i stål. Företaget har identifierat en för dem ny marknad i säkerhetslösningar inom handelssektorn. SPINAB har uppmärksammat att antalet smash and grab-rån har ökat de senaste åren och att de befintliga skyltfönstren inte står upp till de krav försäkringbolagen tillsammans med Svenska Stöldskyddsföreningen satt upp. SPINAB har i och med detta utvecklat ett skyltfönster för att stå emot dessa angrepp. Syftet med examensarbetet är analysera skyltfönstret med fokus på deformationszonen. Arbetet har genomförts genom ett utföra en olinjär FEM-analys av ett krasch-förlopp, där kraschförloppet motsvarar en bil som kör in i skyltfönstret. Geometrierna är modellerade i Siemens NX och FEM-analyserna är simulerade i LS-DYNA Två olika polyuretan-skum för deformationszonen har simulerats och utvärderas. Till vederbörande simuleringar har materialparametrar tagits fram genom materialtester i laboratorium. Resultatet från analyserna visar på att polyuretan-skummet BRAND tar upp mer energi än ÅRET RUNT. Polyuretan-skum BRAND sänker hastigheten med 21,5 % innan genomslag i förhållande till ÅRET RUNT. Deformationszonen ger i detta skyltfönster en möjlighet att forma den kraftpåkänning som skyltfönstrets balkar samt fastighetens fasad och grund upplever. Således kan man med materialvalet i deformationszonen konstruera och optimera en lastkurva för att motverka att bakomliggande konstruktion går sönder på grund utav den uppkomna chocklasten. / Stålpartier I Norr AB (SPINAB) is a company belonging to the group of small and medium-sized companies. They have the business idea to manufacture and sell CE-marked windows, doors and tailor-made steel products. The company has identified one for them new market in security solutions in the commerce sector. They have noted that the number of smash and grab robberies has increased in recent years and the existing storefront windows do not meet the requirements of the insurance companies and the Swedish Anti-Theft Association. With this, SPINAB has developed a storefront window to resist these attacks. The purpose of the thesis work is to analyze the storefront window with focus on the deformation zone. The work has been carried out by performing a nonlinear FEM analysis of a crash process, where the crash process corresponds to a car that crash into the storefront window. The geometries are modeled in Siemens NX and the FEM analyzes are simulated in LS-DYNA. Two different polyurethane foams for the deformation zone have been simulated and evaluated. For the relevant simulations, material parameters have been gathered by laboratory tests. The results from the analyzes show that the polyurethane foam BRAND absorbs more energy than ÅRET RUNT. Polyurethane foam BRAND reduces speed by 21.5% before impact relative to ÅRET RUNT. The deformation zone in this window gives an opportunity to shape the stress of the storefront window, as well as the facade and foundation of the property. Thus, with the material selection in the deformation zone, one can design and optimize a stress curve to prevent the underlying structure from breaking due to the resulting shock load.

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The first chapter of this thesis examines the textual transmission of Pu Songling's collection of tales, Liaozhai zhiyi, and through a study of extant manuscripts and editions concludes that in its original format the work consisted of eight volumes. After a review of evidence for dating the composition of the collection, the two volumes of earliest and latest date are identified and their contents analysed. There is traced a pattern of development from relatively simple supernatural and romantic stories in Pu's early work to more complex character configurations in the later stories, where social criticism also plays a more conspicuous role. The second chapter focuses on the life and times of Pu Songling and discusses the process by which the social realities of Shandong in the early Qing period - famine, military campaigns, bandit raids - and particular aspects of the author's personal experience - examination failure, observation of administrative abuses, professional activities, and family and personal relations - intrude persistently into his stories. Special attention is paid to Pu's examination career and the institutional factors which impeded his progress; his criticisms of the selection system are shown to be qualified by passive acquiescence. The third chapter questions conventional definitions of Liaozhai zhiyi's place in literary tradition. After a survey of the Classical tale from l500 to l700, it is demonstrated that Pu's work can be distinguished from the early-Ming story, and should be regarded as a development of existing trends in late-Ming and early-Qing fiction. In its romantic orientation, realistic detail, and prose style, Liaozhai zhiyi has a kinship with its immediate literary forebears. What links it has to vernacular fiction concern thematic and descriptive emphases rather than the occasional use of colloquialisms. Methods of determining the derivation of plots and motifs in Pu's tales are critically examined, and a distinction is drawn between analogues and written sources.

This diploma thesis focuses on the influence of carbon nanotubes (CNTs) on the mechanical properties of a composite material with polyurethane (PU) matrix. The material was supplied in the form of thin films with thickness from 0.2 mm to 1.2 mm. The theoretical part of this thesis describes the production technology, properties and applications of composite materials PU/CNTs, and also deals with preparation technology and properties of both components of this composite material separately. The theoretical part also describes the principle of tensile testing of polymer materials. The experimental part of the thesis was primarily focused on comparing the tensile properties of a composite material PU/CNTs with tensile properties of pure PU. At first, tensile properties of pure PU were investigated, while the influence of various factors like strain rate, specimen thickness, heat treatment and aging was examined. In adition, stress relaxation tests and tests with strain rate jumps were performed on pure PU specimens. Then composite PU/CNTs was tested in tension and the results were compared with the results of tensile tests of pure PU. Composite material PU/CNTs was prepared with various concentrations, so it was possible to determine the effect of CNTs content on the tensile properties of the composite. The last part of this thesis deals with tensile tests of PU composite material with functionalized carbon nanotubes (PU/FCNTs), where the influence of surface modification (functionalization) of CNTs on the tensile properties composites was investigated. It was shown that the effect of both CNT and FCNT on mechanical properties of the composite is not significant. This conclusion was discussed on basis of the works of other authors, which do not unambiguously proved the positive effect of CNT or FCNT on mechanical properties of composites with polymer matrix.

Veränderungen in der lokalen Chromatinstruktur beeinflussen die dynamische Regulation von Genen, welche für die Differenzierung notwendig sind. PU.1 ist ein Master-Transkriptionsfaktor in der Hämatopoese und wird streng reguliert, um ein zelllinienspezifisches Expressionsmuster zu erzielen. Hohe Konzentrationen von PU.1 sind für myeloische Differenzierung erforderlich. In B-Zellen wird PU.1 mittelstark exprimiert und muss aktiv runterreguliert werden, um eine Ausdifferenzierung der multipotenten Vorläuferzellen zu T-Zellen zu ermöglichen. Derzeit ist wenig über die Regulierung von PU.1 in T-Zellen bekannt. Darüber hinaus wurde eine abnormale Expression von PU.1 in verschiedenen Leukämieerkrankungen beobachtet. Mittels eines genome-wide Chromatin-Interaktions-Screens konnten wir einen cis-Repressor mit insulierender Kapazität identifizieren, welcher mittels eines Chromatinloops die Promotoraktivität von PU.1 in T-Zellen, jedoch nicht in myeloischen oder B-Zellen blockiert. Sowie Looping als auch Insulation erfordern die Bindung des Chromatin-Regulatorprotein CTCF. Im Gegensatz zu normalen myeloischen Zellen finden wir, dass Krebszellen aus myeloischen Leukämie Patienten diese T-Zell-spezifische repressive Chromatinstruktur aufweisen, was einen räumlichen Kontakt des Insulator mit dem PU.1 Promotor ermöglicht. Die Ergebnisse dieser Arbeit beschrieben das CTCF gesteuerte „long distance looping“ als ein neuer molekularer epigenetischer Mechanismus, um Transkriptionsfaktor PU.1 in T-Zellen runterzuregulieren, und zeigen zum ersten mal, dass Krebszellen die Chromatinstruktur anderer Zelllinien imitieren können, um die Expression von Differenzierungsgenen zu blockieren. / Alterations in the local chromatin structure orchestrate the dynamic regulation of differentiation promoting genes. PU.1 is a master transcription factor in hematopoiesis. PU.1 gene must be tightly regulated to achieve lineage specific expression pattern. High levels of PU.1 are required for myeloid commitment: it is expressed at intermediate level in B-cells and must be actively silenced to permit T cell development from early multipotent progenitors. However, little is known of how PU.1 is regulated in T-cells. Moreover, aberrant PU.1 expressions have been observed in multiple leukemias. Using a genome-wide chromatin interaction screen we identified a cis-repressor with insulating capacity that undergoes long-distant chromatin looping to block PU.1 promoter activity in T cells but not myeloid or B cells. Looping and repression requires binding of the chromatin regulator protein CTCF. In contrast to normal myeloid cells, we found that cancer cells from myeloid leukemia patients adopt the T cell specific repressive chromatin structure bringing the insulator into spatial contact with the PU.1 promoter. These results identify CTCF controlled long-distant insulator looping as a novel mechanism to silence lineage-opposing transcription factor expression, and reveal that cancer cells can mimic the chromatin confirmation of another lineage to block expression of differentiation driving genes.

Als Schlüsselfaktor des hämatopoietischen Systems spielt PU.1 eine ent-scheidende Rolle in der Entwicklung der meisten hämatopoietischen Li-nien. Das PU.1 Expressionslevel bestimmt das Differenzierungspotential hämatopoietischer Stammzellen und Vorläufer. In den unterschiedlichen Zelltypen werden verschiedene Expressionsstärken etabliert. Wie diese zelltypischen Expressionslevel vonPU.1 generiert werden, ist bisher weit-gehend unbekannt. In der vorliegenden Doktorarbeit wurde mit Hilfe eines transgenen Maus-modells die cis-regulatorische Einheit von PU.1 definiert, um mit nachfol-genden molekularbiologischen und genomweiten Ansätzen Mechanismen der zellspezifischen Regulation von PU.1 zu aufzuzeigen. Die Definition der cis-regulatorischen Einheit von PU.1 erfolgte mit Hilfe eines transgenen Mausmodells, welches ein humanes PU.1 BAC Kons-trukt trägt. Es konnte gezeigt werden, dass humanes und murines PU.1 substituierbar sind und den gleichen Regulationsmechanismen unterlie-gen. Mit Hilfe genomweite DNaseI hypersensitivity Analysen, Methylie-rungs- und Bindungsstudien konnte ein neuer Regulationsmechanismus beschrieben werden, der eine spezifische kombinatorische Interaktion verschiedener cis-regulatorischer Elemente erfordert. Durch Reportergenassays in verschiedenen Zelltypen war es möglich, einen myeloischen Enhancer zu identifizieren. Es konnte gezeigt werden, dass PU.1 mit zelltyp-spezifischen Transkriptionsfaktoren interagiert, um unterschiedliche Bindungsmuster an seinen regulatorischen Elementen zu etablieren. Dadurch kommt es zu den spezifischen Expressionstärken von PU.1 / The transcription factor PU.1 occupies a central role in controlling myeloid and early B cell development and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis-element (URE) whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the URE alone is insufficient to confer physiological PU.1 expression, but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross-talk between different cis-elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell-type specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements.

Lors d’un accident grave dans un réacteur nucléaire à eau pressurisée, le combustible nucléaire va réagir avec le gaines en Zircaloy, les absorbants neutroniques et les structures métalliques environnantes pour former un mélange partiellement ou complètement fondu. Ce cœur fondu peut ensuite interagir avec la cuve en acier du réacteur pour former un mélange appelé corium en cuve. Par la suite, le corium peut percer la cuve et venir se déverser sur le radier en béton en-dessous du réacteur. En fonction du scénario considéré, le corium qui va réagir avec le béton peut être constitué soit d’une seule phase liquide oxyde ou de deux liquides, métallique et oxyde. L’objectif de la thèse est l’étude de la thermodynamique du corium en cuve, prototypique U-Pu-Zr-Fe-O. L’approche utilisée est basée sur la méthode CALPHAD, qui permet de développer un modèle thermodynamique sur ce système complexe à partir de données expérimentales thermodynamiques et de diagramme de phases. Des traitements thermiques sur le système O-U-Zr ont permis de mesurer deux conodes dans la lacune de miscibilité à l’état liquide à 2567 K. De plus, des températures de liquidus ont été mesurées sur trois échantillons riches en Zr, en utilisant le montage de chauffage laser de l’ITU. Par la même méthode, des températures de solidus ont été obtenues sur le système UO2-PuO2-ZrO2. L’influence de l’atmosphère réductrice ou oxydante sur le comportement à la fusion de ce système a été étudiée pour la première fois. Les résultats montrent que la stœchiométrie en oxygène de ces oxydes dépend fortement du potentiel d’oxygène et de la composition en métal des échantillons. La lacune de miscibilité à l’état liquide a également été mise en évidence dans un échantillon U-O-Zr-Fe. L’ensemble de ces nouvelles données expérimentales avec celles de la littérature a permis de développer le modèle sur le système U-Pu-Zr-Fe-O. Pour tous les échantillons, des calculs de chemin de solidification avec ce modèle ont servi à interpréter les microstructures de solidification observées. Un bon accord est obtenu entre les calculs et les résultats expérimentaux. Des traitements thermiques sur deux échantillons de corium hors cuve ont permis de montrer l’influence de la composition du béton sur la nature des phases liquides formées à haute température. Les microstructures de solidification ont été interprétées à l’aide de calculs avec la base de données TAF-ID. En parallèle, un nouveau montage expérimental appelé ATTILHA, utilisant la lévitation aérodynamique et le chauffage laser, a été conçu et développé pour mesurer des données de diagramme de phase à haute température. Ce montage a été validé avec des systèmes oxydes bien connus. De plus, cette méthode a permis d’observer in-situ à l’aide de la caméra infra-rouge la formation de la lacune de miscibilité à l’état liquide dans le système O-Fe-Zr lors de l’oxydation d’une bille d’alliage Fe-Zr. La prochaine étape du développement est la nucléarisation du montage pour effectuer des mesures sur des échantillons contenant de l’uranium. La mise en place d’une caméra ultra rapide (5000 Hz) pour l’étude de propriétés thermo-physiques de mélanges de corium en cuve et hors cuve est également envisagée. La synergie entre le développement de ces outils expérimentaux et de calcul devrait permettre d’améliorer la description thermodynamique du corium et des codes de calcul sur les accidents graves utilisant ces données thermodynamiques. / During a severe accident in a pressurised water reactor, the nuclear fuel can interact with the Zircaloy cladding, the neutronic absorber and the surrounding metallic structure forming a partially or completely molten mixture. The molten core can then interact with the reactor steel vessel forming a mixture called in-vessel corium. In the worst case, this mixture can pierce the vessel and pour onto the concrete underneath the reactor, leading the formation of the ex-vessel corium. Furthermore, depending on the considered scenario, the corium can be formed by a liquid phase or by two liquids, one metallic the other oxide. The objective of this thesis is the investigation of the thermodynamics of the prototypic in-vessel corium U-Pu-Zr-Fe-O. The approach used during the thesis is based on the CALPHAD method, which allows to obtain a thermodynamic model for this complex system starting from phase diagram and thermodynamic data. Heat treatments performed on the O-U-Zr system allowed to measure two tie-lines in the miscibility gap in the liquid phase at 2567 K. Furthermore, the liquidus temperatures of three Zr-enriched samples have been obtained by laser heating in collaboration with ITU. With the same laser heating technique, solidus temperatures have been obtained on the UO2-PuO2-ZrO2 system. The influence of the reducing or oxidising on the melting behaviour of this system has been studied for the first time. The results show that the oxygen stoichiometry of these oxides strongly depends on the oxygen potential and on the metal composition of the samples. The miscibility gap in the liquid phase of the U-Zr-Fe-O system has been also observed. The whole set of experimental results with the literature data allowed to develop the thermodynamic model of the U-Pu-Zr-Fe-O system. Solidification path calculations have been performed for all the investigated samples to interpret the microstructures of the solidified samples. A good accordance has been obtained between calculation and experimental results. Heat treatments on two ex-vessel corium samples showed the influence of the concrete composition on the nature of the liquid phases formed at high temperature. The observed microstructures have been interpreted by means of calculation performed with the TAF-ID database. In parallel, a novel experimental setup named ATTILHA based on aerodynamic levitation and laser heating has been conceived and developed to obtain high temperature phase diagram data. This setup has been validated on well-known oxide systems. Furthermore, this technique allowed to observe in-situ, by using an infrared camera, the formation of a miscibility gap in the liquid phase of the O-Fe-Zr system by oxidation of a Fe-Zr sample. The next step of the development will be the nuclearization of the apparatus to investigate U-containing samples. The implementation of a very fast visible camera (5000 Hz) to investigate the thermo-physical properties of in-vessel and ex-vessel corium mixtures is also underway. The synergy between the development of experimental and calculation tools will allow to improve the thermodynamic description of the corium and the severe accident code using thermodynamic input data.