TET-dependent DNA methylation patterns in mammalian development and disease

TET enzymes are relatively novel players in the epigenetic regulation of mammalian DNA methylation. They participate in DNA demethylation, but their precise roles in different developmental and disease scenarios are not fully understood. The aim of this work was to investigate the biological roles of TET enzymes in lineage-committed normal and cancer cells. To this end, murine primary cells with genetic deletion of TET enzymes and human cancer cells with recurrent mutations in the cofactor providing isocitrate dehydrogenases (IDH), provoking competitive inhibition of TET enzymes, were analyzed. By characterizing mouse embryonic fibroblasts adipogenic differentiation defects, inefficient activation of genes relevant to adipogenesis and widespread gene deregulation upon TET1/2-deficiency were discovered. Examination of the genome-wide DNA methylation landscape demonstrated the hypermethylation of DNA methylation canyons as a main characteristic of the TET1/2-deficient methylome. Canyons were associated with developmentally important genes and canyon collapse due to hypermethylation coincided with developmental gene deregulation, defective induction of adipogenic markers and the hypermethylation of their promoters. Together, these findings uncovered a novel epigenetic regulatory role in the maintenance of DNA methylation canyons for TET1 and TET2 that is essential for epigenetic programming during differentiation. In the second part of this thesis, published array-based DNA methylation profiles of a large acute myeloid leukemia (AML) patient cohort were used to examine mutant IDH- (mIDH) and TET-dependent DNA methylation changes. This confirmed the known association between mIDH and genome-wide hypermethylation. However, similar global methylation changes were not present in TET2 mutant patients and mIDH carrying patients lacked specific canyon hypermethylation. Intriguingly, neither overexpression of mIDH, nor treatment of a leukemia cell line with D-2-hydroxyglutarate, which is a putative TET inhibitor produced by mIDH, recapitulated the mIDH-associated hypermethylation. Instead, comparison with hematopoietic reference methylomes revealed high similarity between mIDH-associated and myeloid progenitor methylation profiles, suggesting the involvement of differentiation state rather than TET inhibition in the hypermethylation phenotype. These findings implicate a previously unnoted factor in the epigenomic changes of AML cells with mIDH, which may be critical to understand and therapeutically target mIDH-dependent pathogenesis

Interaction of the solar wind with non-magnetized bodies: hybrid simulations of Moon and Venus

In dieser Arbeit werden numerische Simulation der Sonnenwindwechselwirkung am Mond und an der Venus durchgeführt. Hierzu wird der 3D-Hybrid-Simulationscode A.I.K.E.F. verwendet. Die Simulation des Mondes basieren dabei auf dem ersten Vorbeiflug der Sonde ARTEMIS P1 hinter dem Mond. Im Rahmen einer dynamischen Echtzeit-Simulation werden die Anströmbedingungen des Sonnenwinds kontinuierlich anhand angepasster Daten aus der NASA-OMNI-Datenbank variiert und können so sehr genau die von der Sonde hinter dem Mond gemessenen Daten reproduzieren. Zudem zeigt die Betrachtung des Magnetfelds in der Ebene senkrecht zur Anströmrichtung eine Art Friedrichs-Diagramm hinter dem Mond mit den drei grundlegenden MHD-Moden Fast, Alfvénisch und Slow, die anhand ihrer jeweils charakteristischen Signatur identifiziert werden können. Die Simulationen der Venus zielen zunächst auf die Untersuchung der ionosphärischen Magnetisierungszustände ab, die Abhängigkeit der Höhe der magnetischen Aufstauung vor der Ionosphäre vom Anströmdruck des Sonnenwindes konnte in den Simulationen reproduziert werden. Weitere Untersuchungen zeigen die Effekte eines Sektordurchgangs des Sonnenwindmagnetfeldes: Fossile Felder erreichen auf der Tagseite wie auch im Tail jeweils nur Lebensdauern von wenigen Minuten, die Neuausprägung des Bereichs mit umgekehrter y-Komponente des Magnetfelds beansprucht jedoch etwa 30 Minuten, da dieser Effekt durch die langsamen planetaren Ionen verursacht wird. Die Wechselwirkung beider Körper weist viele Gemeinsamkeiten auf, obwohl der ionosphärenlose Mond und die mit starker Ionosphäre ausgestatte Venus prinzipiell in unterschiedliche Kategorien der Wechselwirkung eingeordnet werden. Beide zeigen jedoch eine direkte Abhängigkeit der Wechselwirkungsstrukturen von der Richtung des Sonnenwindmagnetfelds, außerdem jeweils eine sehr lange nachtseitige Struktur (Wake bzw. Tail), die aus den sehr schnellen Anströmbedingungen des Sonnenwindes resultiert.Numerical simulations of the solar wind interaction with Moon and Venus are performed in this work, applying the A.I.K.E.F. 3D hybrid simulation code. The Moon simulations are based on the first flyby of the ARTEMIS P1 probe behind the Moon. In a dynamic real time simulation, the solar wind upstream parameters are constantly adapted using shifted data from the NASA OMNI database, reproducing the data measured behind the Moon in very good agreement. Additionaly, a look at the magnetic field in the plane perpendicular to the upstream direction shows the formation of a structure resembling a Friedrichs diagram behind the Moon; the three basic MHD modes fast, Alfvénic and slow can be identified by their characteristic signatures. The simulations of Venus first focus on the reproduction of the ionospheric magnetization states. The dependency of the magnetic pile-up altitude on the solar wind upstream pressure is reproduced in the simulations. Further investigations show the effects of a solar wind magnetic field sector boundary crossing: while fossil fields on day- and nightside only show a lifetime of a few minutes, the reformation of the area of reversed magnetic field y-component requires about 30 minutes, as this effect is caused by the slow planetary ions. The interaction of both bodies shows many similarities, although the Moon without an ionosphere and Venus with a strong ionosphere belong to different categories of interaction. Common features for both include the direct dependency of the interaction structures from the solar wind magnetic field direction and a very extended nightside structure (wake or tail, respectively), caused by the very fast upstream conditions of the solar wind

Food and nutrition status of households with homegardens in the Nuba Mountains of Sudan

Sudan is one of the least developed countries and many people particularly in South Kordofan suffer from food insecurity. Food production from homegardens (HG) and wild collections are seen as key elements in strategies to overcome nutrient deficiencies. Food intake 24h-recalls were conducted to evaluate the status quo of households (HHs) and the contribution from four HG and wild collection during three seasons in Sama in South Kordofan, Sudan. Dietary diversity as well as nutrient intake was determined and food samples were taken. On average people consumed 16 food items belonging to eight food groups, which is adequate or higher than reported in other studies. Mean daily intake was 1438 kcal energy, 36 g protein, 182 μg vitamin A, 23 mg vitamin C, 9 mg iron and 5 mg zinc. This indicates a nutrient deficiency, especially in vitamins. Differences between traditional and commercial (marketoriented) HGs were small. Households which considered HGs to be important for their daily life had a better nutrient intake, but less diverse diet than those with a reduced importance of HGs. Thus the perceived importance of the HGs seemed to affect HH nutrition more than the level of their commercialization. In total twelve food items from HGs (mostly green leafy vegetables, high in vitamin A) and seven from the wild (mainly Ziziphus spina-christi (L.) Willd, high in vitamin C) were used within the three weeks interview period. The results show the importance of the HG to HH´s nutrition and also indicate the importance of wild collection for the dietary status of HH in the Nuba Mountains of Sudan

Szenarien verbinden

Der Titel unseres Beitrages hätte auch lauten können: Digitale Revolution – was nun? Die Digitalisierung lässt Alles überall und jederzeit stattfinden, beschleunigt Arbeitsprozesse dramatisch, intensiviert die Kommunikation („always on“), verändert Konsum- und Freizeitverhalten und verändert die ehemals linear in Einzeldisziplinen denkbare Welt in ein komplexes, nichtlineares und disruptives System mit sehr unterschiedlichen Akteuren. Die analoge Welt besteht weiterhin, Bytes liefern weder Stoff noch Energie, sondern verbrauchen Kilojoules. Wissen um Prozesse ist Macht. Antwortsysteme auf die geschilderte Anforderungsstruktur müssen ebenfalls schnell, komplex und multidisziplinär sein. Was aber ermöglicht die dafür erforderliche schnelle und verlässliche Kommunikation? Ein Teil einer Antwort ist technisch, darauf gehen wir hier nicht ein. Ein anderer Teil hat viel damit zu tun, wie wir denken und uns in Gruppen verhalten und welche Kommunikationskultur wir nutzen. Erzählungen darüber, wer wir sind, welchen Regeln wir folgen und welche Ziele wir haben stellen den wahrscheinlich wichtigsten Mechanismus unserer Entwicklung dar und sind in Form von Modellen (Stachowiak 1973) Kern jeder Disziplin. Beispielhaft sei die Hooksche Feder als Modell für linear elastisches Werkstoffverhalten genannt; das abstraktere Modell der Elastizität ist in beinahe jedem Fach vertreten. Bei der nachträglichen Auswertung mehrerer designgetriebener Forschungsvorhaben ist zu beobachten, dass Szenarien als komplexe deskriptive und präskriptive Modellsysteme die wesentliche kulturell verankerte Kommunikationsbasis zur Zusammenarbeit in multidisziplinären Teams darstellen. Warum das so ist und wie Szenarien von multi- oder transdisziplinären Teams genutzt werden können, beschreiben wir im Folgenden

Morphology, biochemistry, and management of Russian olive (Elaeagnus angustifolia L.) accessions in Gilgit-Baltistan, northern Pakistan

Russian olive (Elaeagnus angustifolia L., Elagnaceae) is a native multi-purpose medicinal shrub or tree of Asian regions and an integral component of high altitude terraced agroforestry systems of Gilgit-Baltistan, northern Pakistan. The strong increase in deforestation, urbanisation, and the loss of ethnically-based medication practices in local communities are gradually leading to depletion of its stands and knowledge of its use. In view of these circumstances, this study was undertaken to characterise Russian olive accessions as a first step towards the conservation of this important wild plant genetic resource. Ninety-three fruits (including seeds) and leaves were sampled to determine morphological variability among accessions. In addition, the phenolic composition of fruit pulp of 40 fruits was used for determination of phenolic compounds. To assess the local importance of the fruit, 42 Russian olive collectors and traders were interviewed. Data were analysed using PCA and clustering approaches. Fruit traits across groups were equally shared. Elevation had a positive effect on fruit and seed dimensions especially on length (r = 0.606 and 0.515, respectively) and weight (r = 0.618 and 0.695, respectively). Bioactive substances such as DPPH and flavonoids in the sampled fruits exceeded most values found in the literature by a factor of 100 and 30, respectively. The socio-economic household analysis highlighted that Russian olive harvest and trade is a purely additional income strategy. On average, about 90 € (ca. 16000 PKR) were earned by one household ranging from about 35 € to about 205 € per year. Data yielded a mixed picture on morphological and biochemical diversity as well as the socio-economic background, but indicated that northern regions of Pakistan might be an important centre for biodiversity of this species in Central Asia, which merits improved marketing

SAR Satellite On-Board Ship, Wind, and Sea State Detection

This paper describes a prototype implementation of ship, wind, and sea state detection algorithms for satellite on-board SAR processing designed for Maritime Situation Awareness. Existing algorithms were adapted to run on a Multi- Processor-System-On-Chip (MPSoC) combining an FPGA and an ARM CPU and further optimized for fast runtime on the system. The achieved processing times were 20 s for ship detection and 16 s for sea state detection on a 29Mpx SAR image. SAR processing is one component of a larger prototype system being developed in the frame of the H2020 project EO-ALERT, which further comprises an optical data chain, data compression/encryption, and delivery on multiple MPSoC boards. © 2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works

Sea State from High Resolution Satellite-borne Synthetic Aperture Radar Imagery

The Sea Sate Processor (SSP) was developed for fully automatic processing of high-resolution Synthetic Aperture Radar (SAR) data from TerraSAR-X (TS-X) satellites and implemented into the processing chain for Near Real Time (NRT) services in the DLR Ground Station "Neustrelitz". The NRT chain was organised and tested to provide the processed data to the German Weather Service (DWD) in order to validate the new coastal forecast model CWAM (Coastal WAve Model) in the German Bight of the North Sea with 900 m horizontal resolution. The NRT test-runs, wherein the processed TS-X data were transferred to DWD and then incorporated into forecast products reach the best performance about 10 min for delivery of processed TS-X data to DWD server after scene acquisition. To do this, a new empirical algorithm XWAVE_C (C = coastal) for estimation of significant wave height from X-band satellite-borne SAR data has been designed for coastal applications. The algorithm is based on the spectral analysis of subscenes and the empirical model function yields an estimation of integrated sea state parameters directly from SAR image spectra without transformation into wave spectra. To provide the raster coverage analysis, the SSP intends three steps of recognising and removing the influence of non-sea-state-produced signals in the Wadden Sea areas such as ships, buoys, dry sandbars as well as nonlinear SAR image distortions produced by e.g. short and breaking waves. For the validation, more than 150 TS-X StripMap scene sequences with a coverage of ~30 km × 300 km across the German Bight since 2013 were analysed and compared with in situ Buoy measurements from 6 different locations. On this basis, the SSP autonomous processing of TS-X Stripmap images has been confirmed to have a high accuracy with an error RMSE = 25 cm for the total significant wave height

Accuracy of a Phase-Correlation Technique for Fully Automated Sea Ice Motion Retrieval based on Sequential SAR Images

In order to improve ship routing in polar waters, we present a software processor to retrieve high resolution sea ice motion fields from spaceborne Synthetic Aperture Radar (SAR) image sequences fully automatically. Sea ice is almost continually in motion. Within hours, wind and ocean currents can cause significant changes within the sea ice. When the ice is pulled apart by winds or currents from opposite directions, the ice fractures, and open water leads appear. When ice is strongly pushed together by converging wind and currents, the ice sheet will break and either pile up randomly one piece over another, forming a thick, uneven surface, or be forced upwards, creating high walls called ridges. Such obstacles are difficult or impossible even for icebreakers to overcome. SAR satellites such as TerraSAR-X or Sentinel-1 are well suitable to map different structures in the sea ice. Due to their near-polar orbit, spatially and temporally near coincident acquisitions in high latitudes are possible on a daily basis. The core of the presented software processor for sea ice motion retrieval is the well-known phase correlation technique, executed within a hierarchical motion estimation framework presented in our previous work. The output of the processor is a vector field indicating the sea ice displacement, which can be converted into sea ice velocity. Now, we investigate the accuracy of the retrieved displacement. Our test deals with a series of TerraSAR-X ScanSAR mode images acquired over drift buoys that are located in arctic waters, as well as with collocated Sentinel-1 acquisitions for comparison. We monitored the buoys during July 2017 and January 2018. In the winter sequences, an ice concentration of >90 % is predominant, while the summer acquisitions capture an ice concentration of 50 % - 80 %. Altogether, the accuracy of motion vectors estimated from TerraSAR-X image pairs amounts to 30 m (1σ-error). The motion field has a resolution of 150 m x 150 m, which gives a very detailed look into the local sea ice motion, detecting small variations. The presented processor is intended to be part of the operational data processing chain at DLR Ground Station Network sites. In ongoing work, we implement parallel processing in order to reduce computing time so vessels in ice infested waters can receive information on local sea ice motion in near real-time