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Einleitung: Obwohl das Risiko eines schweren Verlaufs von COVID-19 bei Kindern gering ist, kann dies beeinflusst werden durch die Grunderkrankung und/oder immunsuppressive Medikamente. Wir analysierten klinische Daten von COVID-19-Fällen bei pädiatrischen Patienten mit rheumatischen [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Im Film Amator von Krzysztof Kieślowski wird auf exemplarische Weise der Entwicklungsweg eines unpolitischen Arbeiters in die Methoden und Ziele der Opposition im sozialistischen Polen der 70er Jahre beschrieben. Die Methoden der Opposition eignet sich Filip Mosz durch das Erlernen der Techniken des Amateurfilms und die Beobachtung seiner Stadt an. Über die Identifizierung mit diesen Filmtechniken entdeckt die Hauptfigur Filip Mosz Leerstellen und nicht beanspruchte diskursive Räume im Alltag seines Betriebes und seines Umfeldes. Durch die Analyse dieser Raumnahme in den diskursiven Leerstellen in Amator soll in dieser Arbeit veranschaulicht werden, wie Kieślowski argumentative Elemente der Opposition in seinen Spielfilm integriert. Über die Untersuchung seiner frühen Dokumentarfilme wird zunächst der Einfluss oppositioneller Ideen auf seine Filme verdeutlicht. Der zentrale Teil der Arbeit widmet sich einer quantitativen Erfassung der Szenen im Film, die sich einer Raumnahme in den Leerstellen der Ideologie zuordnen lassen. Mithilfe dieser quantitativen Aufstellung wird die schrittweise Aneignung oppositioneller Ideen aufgezeigt. Diese Aneignung erfolgt trotz repressiver, ideologischer Maßnahmen seitens seines Betriebes und der politischen Führung. Kieślowski vernetzt seine Auffassung über Opposition darüber hinaus mit der filmischen, ideologiekritischen Avantgarde seiner Zeit durch die Thematisierung des Filmes Camouflage von Krzysztof Zanussi.

MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options.

Wir untersuchten 543 Nierenempfänger und deren Spender über einen Zeitraum von 16 Jahren. Es konnte keinerlei Zusammenhang zwischen dem GP IIIa PlA1/A2-Polymorphismus und dem Transplantat- und Patientenüberleben nach Nierentransplantation gefunden werden. Weder gab es signifikante Unterschiede im Hinblick auf die Anzahl akuter Abstoßungsreaktionen noch auf die chronische Transplantatnephropathie oder das Transplantatüberleben an sich zwischen den verschiedenen Genotyp-Gruppen. Nach Berücksichtigung anderer Einflussgrößen wie der HLA-Kompatibilität, der kalten Ischämiezeit, des Spenderalters oder der ursprünglichen Nierenerkrankung konnte ebenfalls kein Zusammenhang mit dem GP IIIa PlA1/A2- Polymorphismus als Risikofaktor gesehen werden. Auch bezüglich der kardiovaskulären Mortalität konnte kein Zusammenhang mit dem GP IIb/IIIa PlA1/A2- Polymorphismus als Risikofaktor aufgezeigt werden., Our data do not confirm the hypothesis that the PlA1/A2 genotype is associated neither with patient and kidney transplant survival and acute rejections nor with cardiovascular events in renal patients.

In Vertebraten ist das Dkk1-Gen notwendig für die Kopfinduktion durch den Spemann'schen Organisator. Dabei beruht die induzierende Eigenschaft auf der Fähigkeit von Dkk1, den Wnt/b-Catenin-Signalweg zu inhibieren. Daneben existieren in Vertebraten noch drei weitere Dickkopf-Gene, deren Funktionen aber weitestgehend unbekannt sind. Wie die Sequenzierung des Seeigelgenoms gezeigt hat, besitzt der Seeigel zwei Dickkopf-Gene (SpDkk1 und SpDkk3), über deren Funktionen aber bislang noch nichts bekannt ist. Lediglich das Expressionsmuster von SpDkk1 ist bekannt und deutet darauf hin, dass SpDkk1 an der Endomesoderm-Differenzierung sowie an der Bildung des apikalen Ektoderms beteiligt ist. In dieser Arbeit durchgeführte phylogenetische Analysen belegen, dass die beiden bei der Genomanalyse identifizierten Dickkopf-Gene tatsächlich Mitglieder der Dickkopf- Familie sind. Außerdem wurde gezeigt, dass es sich bei diesen beiden Genen um die Ursprungsgene handelt, aus denen sich durch Genomduplikationen die weiteren Mitglieder der Vertebraten- Dickkopf-Gene entwickelt haben. Des Weiteren konnte durch Überexpression und Depletion von SpDkk1 bzw. SpDkk3 sowie durch Promotoranalysen von SpDkk1 gezeigt werden, dass Dkk1 auch im Seeigel ein Inhibitor und zugleich ein Zielgen des Wnt/b-Catenin-Signalwegs ist. Aufgrund dieser Fähigkeit fungiert es als Regulator der Kernel-Gene und wirkt dadurch auf die Endomesoderm- Differenzierung des Seeigelembryos. Darüber hinaus ist Dkk1 wie auch Dkk3 an der Bildung von serotonergen Zellen beteiligt. In einem WISH Screen wurden zudem 13 weitere Gene identifiziert, die während der Embryogenese im apikalen Ektoderm exprimiert werden. Unter ihnen befinden sich drei, die spezifisch in serotonergen Zellen exprimiert sind. Durch verschiedene Perturbations- experimente und anschließende qPCR-Analysen wurde ein GRN für das apikale Ektoderm und serotonerge Zellen erstellt. Dabei zeigte sich, dass sich Dkk1 an der Spitze dieses GRN befindet und durch Regulation verschiedener Transkriptionsfaktoren erheblichen Einfluss auf die Bildung von serotonergen Zellen hat. Auch Dkk3 ist an der Regulation von serotonergen Zellen beteiligt, allerdings ist dessen Einfluss innerhalb des GRN auf eine kleinere Anzahl von Genen begrenzt. Dies zeigt, dass Dkk1 bereits im Seeigel ein wichtiges Organisator-Molekül ist, das in der Endomesoderm-Differenzierung und der Neurogenese involviert ist. Außerdem ist nicht nur seine Eigenschaft zur Inhibierung des Wnt/b-Catenin-Signalwegs evolutionär konserviert, sondern auch die Fähigkeit, anteriore Strukturen zu induzieren., In vertebrates the Dkk1 gene is necessary for head induction by the Spemann organizer. The inductive capacity is based on the ability of the Dkk1 protein to inhibit the wnt/b-catenin signaling pathway. Furthermore there are three additional dickkopf genes in vertebrates, whose functions are still unknown. As shown by genome sequencing, two different dickkopf genes exist in the sea urchin genome (SpDkk1 and SpDkk3). Neither the functions of these are known so far. Only the expression pattern of SpDkk1 is available and indicates that SpDkk1 is involved in the differentiation of the endomesoderm and the formation of the apical ectoderm. The phylogenetic analysis performed for this thesis revealed that both identified sea urchin dickkopf genes are indeed members of the dickkopf family and that they are the anchestor genes from which the different vertebrate dickkopf genes were evolved by genome duplications. Furthermore gain-of-function and loss-of-function studies of SpDkk1 and SpDkk3 as well as promotor analysis of SpDkk1 demonstrate that also sea urchin Dkk1 is an inhibitor of the wnt/b-catenin signaling pathway and a target of this pathway at the same time. Due to this ability Dkk1 acts as a regulator of the kernel genes and thereby affects the endomesoderm differentiation of the sea urchin embryo. Apart from that Dkk1 as well as Dkk3 participate in the formation of serotonergic cells. In a WISH screen 13 other genes were identified, which are expressed in the apical ectoderm during sea urchin embryogenesis. Among them are three genes, which are specifically expressed in serotonergic cells. By different genetic perturbation experiments followed by qPCR analysis a GRN for the apical ecoderm and serotonergic cells was generated. Thus it appears that Dkk1 acts at the top of the GRN for the apical ectoderm and serotonergic cells and that Dkk1 has an important influence on the formation of serotonergic cells by regulating several transcription factors. Also Dkk3 is involved in the regulation of serotonergic cells, but its influence is limited to only a few genes. Overall the results showed that already in the sea urchin Dkk1 is an important organizer molecule that participates in the differentiation of endomesoderm and neurogenesis. It is not only its ability to inhibit the wnt/b-catenin signaling pathway which is evolutionary conserved, but also its ability to induce anterior structures.

The EZ is an approximately 20km long and 2–3km wide coherent unit of the Tauern Window in the Eastern Alps. It is sandwiched between the Venedigerand the Glockner Nappe. While rocks in the EZ experienced HP metamorphic conditions (24 kbar/650°C), rocks from the underlying Venediger Nappe and the overlying Glockner Nappe only record lower alpine metamorphic conditions with peak pressures not exceeding 10 and 8 kbar, respectively. While metamorphism in the EZ is well dated with an average age of 31.5±0.7Ma (Glodny et al. 2005) the final emplacement of these different nappes is still under debate. Our Rb-Sr-data indicate that top-N thrusting at the base and large-scale folding of the EZ was coeval with sinistral strike-slip faulting at its upper boundary and eclogite-facies metamorphism in the EZ. The data also indicate that today’s nappe architecture must have been established in less than 2Ma after the eclogite facies metamorphism in the EZ. Very fast exhumation of the EZ was accomplished in a transpressional setting, which might explain why the exposed EZ is such a small unit., conference

In the Lindæs Nappe, Bergen Arcs Western Norway, Precambrian granulites facies anorthosites (P, conference

Process mineralogy is increasingly becoming an important part of quality control in mining operations, and chemical assays are not sufficient for predicting metallurgical performance of complex ore deposits. Knowledge of mineralogical and textural ore properties that affect the mineral processing, may lead to better utilisation of the deposit, and the prediction of recovery becomes more solid. The Storforshei iron formation (IF) is located in the Dunderlandsdalen valley c. 30 km northeast of Mo i Rana, Nordland county, Norway. The IF consists of highly metamorphosed and deformed hematite-magnetite ore deposits and belongs to the Uppermost Allochthon (UmA) in the Norwegian Caledonides. Rana Gruber (RG) mines deposits in the Storforshei IF, where the main products are hematite concentrates for pellets and sinter production, with magnetite concentrates for pigment production and water purification as a by-product. The main production today is from the Kvannevann deposit, but several other deposits have been in production previously. The deposits in the Storforshei IF show mineralogical and textural differences, and in order to investigate the effects of these differences on the metallurgical performance, a pilot circuit was constructed based on the hematite production line in the fullscale mineral processing plant. The pilot circuit consisted of autogenous milling, wet low intensity magnetic separation (LIMS), and wet high intensity magnetic separation (WHIMS). Three deposits were sampled for testing in the pilot circuit, Kvannevann, Stensundtjern, and Stortjønna. The aim of the pilot circuit was not to fully replicate the full-scale mineral processing plant, but rather to discover differences in the metallurgical performance of the deposits. Six ore types were defined based on geological mapping and drill core logging from these three deposits, and their surface hardness were measured using Schmidt hammer and Equotip. The ore types are: Granular-Hematite, Specular-Hematite, Hematite-Magnetite, Magnetite-Ore, Mylonitic-Hematite, and Massive-Hematite. Granular-Hematite and Specular-Hematite have relatively coarse-grained hematite with straight grain boundaries, and low surface hardness. The Kvannevann deposit, dominated by these ore types, had high grindability in the AG mill tests, and the mill circuit product had high hematite liberation. As the Kvannevann deposit samples were collected from drift development blasts in the underground mine, they had higher specific charge (Zang, 2016) compared to the Stensundtjern and Stortjønna which were collected from surface and open pit blasts. This and the low surface hardness in the ore types dominating in the Kvannevann deposit led to a larger amount of microcracks, and a higher grindability as a consequence. The Stensundtjern deposit is also dominated by these ore types, however, has substantial amounts of Hematite-Magnetite and Magnetite-Ore. These ore types have coarse-grained equant-irregular shaped magnetite with irregular grain boundaries, and higher surface hardness than the Granular-Hematite and Specular-Hematite. This together with a lower specific charge during blasting led to less microcracks in the Stensundtjern deposit sample, and likely caused the lower grindability observed for the Stensundtjern deposit sample compared to the Kvannevann deposit sample. The mill circuit product from the Stensundtjern deposit sample had slightly lower hematite liberation than the Kvannevann mill circuit product, which further indicates that there are differences in the ore type distribution between these two deposits. The Kvannevann deposit sample performed well in the magnetic separation, yielding high Fetot* grades in the hematite concentrates, and with little loss of hematite to middlings and tailings, and with high hematite liberation in these outputs, further separation on these should recover this hematite. The content of non-economic or gangue minerals are low in the final hematite concentrates. The Stensundtjern deposit sample preformed similar to the Kvannevann deposit sample in the magnetic separation, however, it had slightly higher content of composite particles. Thus, the loss of hematite to the middlings and tailings also were higher. The higher number of composite particles with hematite is also apparent from the lower hematite liberation in the tailings. The Mylonitic-Hematite and Massive-Hematite ore types are very fine-grained, where the hematite occurs either disseminated in a matrix of gangue minerals with irregular-to-no visible grain boundaries, or as massive hematite without visible grain boundaries with irregularly folded layers or veins of gangue minerals. These ore types had the highest surface hardness values of all the ore types. The Stortjønna deposit sample had low grindability in the AG milling, and the specific energy consumption was much higher than in Kvannevann and Stensundtjern. This was attributed to the textures and surface hardness values in Mylonitic-Hematite and Massive-Hematite, as breakage of fine-grained rock without grain boundaries requires more energy (Xu et al., 2013), and because the amount of microcracks were, as a consequence of the higher surface hardness and lower specific charge in blasting, lower in the Stortjønna deposit sample compared to the Kvannevann and Stensundtjern deposit samples. The hematite liberation in the Stortjønna mill circuit product was lower than the corresponding outputs from Stensundtjern and Kvannevann, and the amount of composite particles with hematite was substantial. The particle textures in the Stortjønna mill circuit product corresponds to the textures observed in the Mylonitic-Hematite and Massive-Hematite. The particle distribution in the mill circuit product was broad and there was a notable amount of fines (< 38 μm). This caused challenges in the magnetic separation, as the separation efficiency decreases for fine particles in the WHIMS. Together with the presence of substantial amount of composite particles this led to high loss of hematite to the Stortjønna middlings and tailings. The hematite liberation in these outputs were low, thus, further separation will not improve the hematite recovery as much as it would for the ore types dominating in the Kvannevann- and Stensundtjern deposits. Minerals containing Fe or Mn, like epidote, biotite/phlogopite, and hornblende, and dolomite were found in middlings and tailings from all the deposits, and as these are returned in the fullscale processing plant, an accumulation of these minerals in the WHIMS circuit might occur, which could lead to them eventually ending up in the final hematite concentrate. Given that RG produces hematite and magnetite concentrates, the Fe recovery calculations should be based on Fe residing in these minerals, which is equal to the hematite or magnetite recovery, and not the Fetot* which provides no information of Fehem, Femag, and Fesil. The relationship between Fetot*, Fehem, Femag, and Fesil was investigated on samples from the fullscale mineral processing plant. The mill circuit products and tailings contain more Fesil than the hematite concentrates, thus, calculating the recovery based on Fehem or Femag rather than on the Fetot* content led to an increase in recovery for all the hematite concentrates analysed. The importance in these investigations lies in the determination of the amount of Fehem, Femag, and Fesil in the feed ore, as it provides a more solid prediction of the iron oxide recovery, and a prediction of how much Fe bearing non-economic minerals might end up in the hematite concentrates bringing undesirable elements like Mn, S, and alkalis with them. By incorporating Equotip measurements in drill core logging, and geological mapping with focus on the ore types defined in this research, RG can easily improve the daily production quality control. However, analyses of modal mineralogy are also recommended, which together with mineral chemistry can be used to determine recoverable Fe located in iron oxides (Fehem and Femag) and the amount of Fe located in non-economic minerals (Fesil), hence, calculate real iron oxide recovery.