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Evaluation of ground motion and optimum seismic monitoring at an inner-city deep geothermal power plant
Experience shows that even non-pressure-stimulated geothermal power plants can generate induced seismicity even in low seismic hazard settings. Due to the shallow hypocentral depth of a few kilometers, already relatively small earthquakes can lead to ground shaking, which is felt by the population. As most of the geothermal power plants are located within or close to densely inhabited areas, monitoring and estimating the maximum ground motion and its spatial distribution are of crucial importance for the authorities and the public. However, this is challenging as in most cases the monitoring network is weak, due to high noise levels and limited station numbers, and only few information about local site effects are available. Therefore, several open questions for the development of proper risk governance strategies remain: How does the shallow subsurface structure look like and is there the risk of seismic wave amplification? How large is the expected ground motion and what areas are affected? How can the seismic monitoring within urban environments be improved?
These questions are going to be answered by the example of Munich, Germany, where Eu-rope’s largest inner-city geothermal project was carried out with a total of six deep wells, which increases the risk of induced seismicity in the area.
To answer the question of local site effects a microzonation study is conducted in Munich´s inner city. The common approach of array measurements is challenging in urban environments due to the space requirements. Therefore, the recently developed approach of single-station six-component (6C) measurements is applied, combining three translational and three rotational motions. This new method is much simpler in terms of logistics and therefore allows an easier and faster estimation of the local velocity structure.
Another problem that is encountered in microzonation studies is the existing ambiguity of the inversion results. Since conventional inversion methods suffer from different limitations, a machine learning algorithm is trained, which selects the appropriate number of subsurface layers and returns a complete probability distribution of the S-wave velocity structure.
The shallow velocity structure is important, as it can amplify seismic waves. However, the maximum induced ground motion is often not recorded because the station network is sparse at most geothermal sites. A dense network is neither feasible nor required by (Bavarian) law, which impedes a spatial interpretation of the ground motion after an earthquake. Because of that, large uncertainties remain in the determination of affected areas according to the German mining laws. This is a major problem when it comes to compensating for damage claims brought forward by local population and companies. I show that 3D numerical simulations are able to close observational gaps and can be used to estimate the maximum ground motion and its spatial distribution. This way public authorities can make fast and precise decisions in case of damaging events.
Not only the sparse number of stations, but also the high noise levels pose a big problem for microseismic monitoring within urban environments, which make it difficult to reach the required magnitude threshold and location accuracy. Therefore, a network optimization method is applied, which calculates the optimum number and location of seismic stations even in environments with heterogeneous noise conditions.
The dissertation results have implications for future inner-city geothermal projects, as they will facilitate the seismic risk assessment during the planning stage, the seismic monitoring during operation and the evaluation of shaking effects after an event
Gesundheitsökonomische Bewertungen immunonkologischer Therapien am Beispiel der CAR-T-Zell-Therapie bei Patienten mit DLBCL
Der Einfluss von somatoformen Störungen, Angststörungen und Depressionen auf das Ergebnis minimal-invasiver Wirbelsäuleneingriffe
Oncogenic signaling in idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC) are two devastating pulmonary disorders, which are marked by excessive tissue production, irreversible damage to lung structure, and eventually loss of pulmonary function. The natural history of both diseases is characterized by chronic progression and represents a fatal prognosis for the affected patients. Treatments are able to slow down the diseases’ progression, but to date no approved, curative treatment option exists. IPF is frequently associated with lung cancer and both diseases’ pathogenesis share common hallmarks, such as altered cellular phenotypes, misregulated biological pathways and mediators, and similar genetic changes. We aimed to establish a link between the pathomechanisms of IPF and NSCLC by analyzing patterns of gene expression alterations and to further characterize the role of candidate genes in the pathogenesis of IPF.
NSCLC microarray datasets (GSE44077, GSE43458, GSE18842) from Gene Expression Omnibus (GEO) were analyzed and differentially expressed genes (DEGs) were extracted. Gene set enrichment analysis (GSEA) was used to determine the enrichment of DEGs from NSCLC in an IPF microarray dataset (GSE47460) and to describe the subsequent list of candidate genes. Further characterization of these genes of interest was achieved by annotation enrichment analysis, protein-protein interaction networks, BioGPS, and principal component analysis. The final candidate genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR) as well as western blot analysis in human and mouse lung tissue samples, human bronchial epithelial cells, and primary murine alveolar epithelial type II (pmATII) cells. Finally, treatment of bronchial epithelial cells with pro-fibrotic transforming growth factor beta 1 (TGF-beta) was performed and the expression of the candidate genes was analyzed.
IPF and NSCLC showed a significant pattern of shared gene expression alterations in the GSEA. Further analysis revealed a common set of 92 equally misregulated genes in IPF and NSCLC (log2 fold change > 1; adjusted p-value < 0.05), which demonstrated an IPF-specific signature in the principal component analysis. Annotation enrichment analysis of this gene set highlighted common themes, such as P53 regulation, extracellular matrix (ECM) organization, cell cycle, and proliferation. Western blot and qRT-PCR validated a significantly increased expression of the two candidate genes G protein-coupled receptor 87 (GPR87) and phosphoserine aminotransferase 1 (PSAT1) in NSCLC, IPF, and bleomycin-induced lung fibrosis in mice. TGF-beta treatment of bronchial epithelial cells resulted in a significant upregulation of GPR87 in vitro.
In summary, we demonstrated a pathogenic link between IPF and NSCLC, which resulted in a subset of potential novel therapeutic targets. Further analysis of GPR87 and the other candidate genes might improve our understanding of IPF and enable novel therapeutic strategies
Einflussfaktoren auf die Zusammensetzung von ovinen und caprinen Urolithen und auf das Überleben nach obstruktiver Urolithiasis
Urolithiasis ist eine häufige Erkrankung männlicher Schafe und Ziegen. Struvit wird oft als häufigste Harnsteinart vermutet. Umfangreiche Analysen, vor allem im europäischen Raum, fehlen jedoch. Prognostische Faktoren zum kurz- und langfristigen Überleben nach der Behandlung sind nur in einzelnen Studien untersucht. Neunzig Harnsteine von kleinen Wiederkäuern, die als Patienten in eine Überweisungsklinik eingeliefert wurden, wurden mittels Infrarotspektroskopie untersucht. Faktoren mit einem möglichen Einfluss auf die Harnsteinart sowie die Überlebenschance von 148 Schafen und Ziegen mit obstruktiver Urolithiasis wurden statistisch analysiert. Hier wurde ein besonderer Fokus auf potenzielle Einflussfaktoren für eine erfolgreiche Zystostomie mit Foley-Katheter (n=89) und auf das langfristige Überleben gelegt. Calciumcarbonat war die häufigste Harnsteinart, gefolgt von Silikat und Calciumphosphat. Tierart, Alter, Nutzung, Haltung, Kastrationsstatus, Übergewicht und Fütterung waren signifikant mit der Harnsteinart assoziiert. Ziegen, Hobbytiere, ältere Tiere, Weidehaltung, kastrierte Tiere und Übergewicht waren signifikant mit der Bildung von kalziumbasierten Harnsteinen assoziiert, während Schafe, jüngere Tiere, ganzjährige Stallhaltung, intakte Tiere, normalgewichtige Tiere und kraftfutterreiche Fütterung mit der Bildung von phosphathaltigen Harnsteinen assoziiert waren. Nach temporärer Zystostomie mit Foley-Katheter konnten 36 von 89 operierten Tieren (40,4 %) aus der Klinik entlassen werden. Zeitnahe Einlieferung in die Klinik, erfolgreiche orthograde Spülung der Urethra während der Operation sowie ein unbeeinträchtigtes Allgemeinbefinden nach der Operation waren positive Einflussfaktoren auf das kurzfristige Überleben. Die Rezidivrate nach erfolgreicher initialer Therapie war jedoch hoch (41,3 %), und es konnten keine signifikanten Einflussfaktoren auf das langfristige Überleben identifiziert werden. Übereinstimmend mit den Ergebnissen früherer Studien zeigen die vorliegenden Daten, dass die Prognose bei obstruktiver Urolithiasis vorsichtig ist.Obstructive urolithiasis is common in male small ruminants. Struvite is often assumed the most frequent urolith type, but urolith analyses are rarely published, especially in Europe. Prognostic factors for short- and long-term outcomes following treatment are also rarely studied. Ninety urolith samples from small ruminants presented to a veterinary hospital were examined by infrared spectroscopy, and factors potentially associated with urolith type were statistically analysed. Treatment outcomes for 148 sheep and goats with obstructive urolithiasis were additionally assessed with particular focus on potential predictors for successful tube cystostomy (n=89) and long-term outcomes. Calcium carbonate was the most frequent urolith type, followed by silica and calcium phosphate. Species, age, animal purpose, husbandry, castration status, body condition and nutrition were significantly associated with urolith type. Goats, older animals, pets, access to pasture, castration and obesity were significantly associated with the development of calcium-based uroliths, while sheep, young age, year-round housing, intact animals, non-obese body condition and high concentrate diet were associated with the development of phosphatic calculi. Of the 89 animals receiving tube cystostomy, 36 (40.4%) could be discharged from the hospital. Positive predictors for a successful short-term outcome were timely presentation for treatment, successful orthograde urethral flushing and uncompromised general condition following surgery. The recurrence rate following initially successful treatment was however high (41.3%), and statistical analyses did not identify any significant predictors for a successful long-term outcome. In accordance with previous studies, our data indicate that obstructive urolithiasis remains a disease with a guarded prognosis