Abschlussbericht für das Anwendungsprojekt 16 - „Küstenschutz und Geothermie"

Das RADOST-Anwendungsprojekt 16 sollte aufzeigen, wie die thermische Nutzung von in der Saturationszone des Küstenbereichs vorhandenem "Strandwasser" (einem Gemisch aus Grund- und Meerwasser) oder die direkte thermische Nutzung des Meerwassers planerisch in Küstenschutzmaßnahmen integriert werden kann. Der Bericht beschreibt die Planung ausgewählter geothermischer Quellenanlagen im Bereich von Küstenschutzanlagen unter Berücksichtigung von im Projekt gewonnenen Messdaten. Abschließend erfolgen eine Wirtschaftlichkeitsbetrachtung und die Ableitung von Empfehlungen zur Umsetzung einer thermischen Nutzung des Untergrundes bzw. des Meerwassers

Effect of ABCG2, OCT1, and ABCB1(MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial

Introduction Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. Materials and Methods RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated. Results The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (‰) was retained as the only significant variable (P = .02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P = .04). Patients with an ABCG2/GUSB transcript level >4.5‰ (n = 93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (≤4.5‰; n = 39) had a 12-month TFR rate of 72% (95% CI, 55%-82%). Conclusion In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation

Transient Depletion of Foxp3 Regulatory T Cells Selectively Promotes Aggressive β Cell Autoimmunity in Genetically Susceptible DEREG Mice.

Type 1 diabetes (T1D) represents a hallmark of the fatal multiorgan autoimmune syndrome affecting humans with abrogated Foxp3+ regulatory T (Treg) cell function due to Foxp3 gene mutations, but whether the loss of Foxp3+ Treg cell activity is indeed sufficient to promote β cell autoimmunity requires further scrutiny. As opposed to human Treg cell deficiency, β cell autoimmunity has not been observed in non-autoimmune-prone mice with constitutive Foxp3 deficiency or after diphtheria toxin receptor (DTR)-mediated ablation of Foxp3+ Treg cells. In the spontaneous nonobese diabetic (NOD) mouse model of T1D, constitutive Foxp3 deficiency did not result in invasive insulitis and hyperglycemia, and previous studies on Foxp3+ Treg cell ablation focused on Foxp3DTR NOD mice, in which expression of a transgenic BDC2.5 T cell receptor (TCR) restricted the CD4+ TCR repertoire to a single diabetogenic specificity. Here we revisited the effect of acute Foxp3+ Treg cell ablation on β cell autoimmunity in NOD mice in the context of a polyclonal TCR repertoire. For this, we took advantage of the well-established DTR/GFP transgene of DEREG mice, which allows for specific ablation of Foxp3+ Treg cells without promoting catastrophic autoimmune diseases. We show that the transient loss of Foxp3+ Treg cells in prediabetic NOD.DEREG mice is sufficient to precipitate severe insulitis and persistent hyperglycemia within 5 days after DT administration. Importantly, DT-treated NOD.DEREG mice preserved many clinical features of spontaneous diabetes progression in the NOD model, including a prominent role of diabetogenic CD8+ T cells in terminal β cell destruction. Despite the severity of destructive β cell autoimmunity, anti-CD3 mAb therapy of DT-treated mice interfered with the progression to overt diabetes, indicating that the novel NOD.DEREG model can be exploited for preclinical studies on T1D under experimental conditions of synchronized, advanced β cell autoimmunity. Overall, our studies highlight the continuous requirement of Foxp3+ Treg cell activity for the control of genetically pre-installed autoimmune diabetes

Ionisierende Strahlung in der Medizin (Auszug aus: PTB-Mitteilungen 2013, Band 123, Heft 2. ISSN 0030-834X)

PTB-Mitteilungen. Band 123 (2013), Heft 2, Seite 1 - 81. ISSN 0030-834X1.: Janßen, Herbert: Vorwort 2.: Ankerhold, Ulrike: Ionisierende Strahlung in Diagnostik und Therapie 3.: Büermann, Ludwig: Metrologische Aspekte der Dosimetrie in der Röntgendiagnostik 4.: Kossert, Karsten: Aktivitätsbestimmung von Radionukliden für Diagnostik und Therapie 5.: Ankerhold, Ulrike und Thorsten Schneider: Dosimetrie für die Brachytherapie 6.: Krauss, Achim: Kalorimetrische Bestimmung der Wasser-Energiedosis 7.: Kapsch, Ralf-Peter: Dosimetrie mit Ionisationskammern in der externen Strahlentherapie 8.: Anton, Mathias: Dosimetrie für die externe Strahlentherapie: Dosimetrie mit Alanin 9.: Ambrosi, Peter: Strahlenschutz in der Medizin 10.: Hupe, Oliver: Messgeräte und Herausforderungen in der Strahlenschutzmesstechnik 11.: Ambrosi,Peter, Oliver Hupe und H.-M. Kramer: Messgrößen im Strahlenschutz 12.: Hupe, Oliver: Amtliche Personendosimetrie für Medizin-Personal 13.: Hupe, Oliver: Dosis für helfende Personen in der Human-, Zahn- und Tiermedizin 14: Behrens, Rolf: Teilkörperdosimetrie für Photonen und Betastrahlung 15.: Hupe, Oliver, Hayo Zutz und Peter Ambrosi: Elektronische Dosimeter für gepulste Strahlung 16.: Zutz, Hayo: Messung der Strahlung im Beschleuniger-Therapieraum 17.: Hans Rabus: Strahlenwirkung 18.: Arndt, Alexander und Woon Yong Baek: Strahlenwirkung auf Biomoleküle 19.: Bug, Marion und Heidi Nettelbeck: Simulation der Strahlenwirkung auf biologische Objekte 20.: Hilgers, Gerhard: Messung der Spurstruktur ionisierender Strahlung 21.: Giesen, Ulrich: Strahlenwirkung auf zellulärer Eben

Exome sequencing and optical genome mapping in molecularly unsolved cases of duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that mainly affects boys due to $\it X$-linked recessive inheritance. In most affected individuals, MLPA or sequencing-based techniques detect deletions, duplications, or point mutations in the dystrophin-encoding $\it DMD$ gene. However, in a small subset of patients clinically diagnosed with DMD, the molecular cause is not identified with these routine methods. Evaluation of the 60 DMD patients in our center revealed three cases without a known genetic cause. DNA samples of these patients were analyzed using whole-exome sequencing (WES) and, if unconclusive, optical genome mapping (OGM). WES led to a diagnosis in two cases: one patient was found to carry a splice mutation in the $\it DMD$ gene that had not been identified during previous Sanger sequencing. In the second patient, we detected two variants in the fukutin gene $\it (FKTN)$ that were presumed to be disease-causing. In the third patient, WES was unremarkable, but OGM identified an inversion disrupting the $\it DMD$ gene (~1.28 Mb) that was subsequently confirmed with long-read sequencing. These results highlight the importance of reanalyzing unsolved cases using WES and demonstrate that OGM is a useful method for identifying large structural variants in cases with unremarkable exome sequencing

A complete digitization of german herbaria is possible, sensible and should be started now

Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool