Octa­deca­bromidobis(dicarbido)deca­dysprosium, [Dy10Br18(C2)2]

Single crystals of [Dy10Br18(C2)2] were obtained during the reaction of DyBr3 with dysprosium metal and graphite in a sealed tantalum container. In the crystal structure, the Dy atoms form dimers of edge-sharing octa­hedra, each encapsulating a C2 unit. The metal atoms are surrounded by Br atoms above the cluster edges and vertices, respectively. The dimers are connected to each other by Br atoms, leading to a three-dimensional network. [Dy10Br18(C2)2] is isotypic with its iodido analogue [Dy10I18(C2)2]

Holmium dodeca­iodidoiron-octa­hedro-hexa­holmium, {FeHo6}I12Ho

Single crystals of {FeHo6}I12Ho were obtained during the reaction of HoI3 with metallic holmium and iron in a sealed tantalum container. The crystal structure consists of isolated holmium clusters encapsulating a single Fe atom, {FeHo6} ( symmetry). The rare earth metal atoms are surrounded by 12 edge-capping and six terminal iodide ligands that either connect the clusters to each other directly or via HoI6 octa­hedra ( symmetry)

Sicherheit und Effektivität der größten selbst-expandierenden Transkatheter-Aortenklappe

Ziel dieser Arbeit ist die Untersuchung der Sicherheit und Effektivität der CoreValve Evolut R® 34 mm, die die CE-Kennzeichnung im Januar 2017 erhalten hat und das derzeit größte erhältliche Implantat für TAVI-Patienten mit einem Annulusdurchmesser bis 30 mm darstellt. Die Studienpopulation setzt sich zusammen aus den ersten 101 Patienten, die eine CoreValve Evolut R® 34 mm Klappe an den teilnehmenden Zentren erhalten haben. Es wurden retrospektiv Daten zum Erfolg der Prozedur, zu Sterblichkeit, Schlaganfall, Myokardinfarkt, Blutungskomplikationen, Überleitungsstörungen, Arrhythmien und Klappen(dys)funktion erhoben. Primäre Zielgrößen sind die VARC-2-Kriterien sowie echokardiographische Daten vor- und nach TAVI. Für alle Patienten galt ein Nachbeobachtungszeitraum von 30 Tagen. Auf Grund der explorativen Anlage dieser Arbeit, ohne eigene Kontrollgruppe, werden qualitative Vergleiche zu bereits publizierten Daten durchgeführt. Die Ergebnisse zeigen, dass die CoreValve Evolut R® 34 mm, als zweite Generation der SEV, eine sichere und effektive Behandlungsmethode für Patienten mit AS, und einem Annulusdurchmesser von 26 mm bis 30 mm bei Patienten mit intermediärem Risikoprofil darstellt. Es konnten im Vergleich zu anderen aktuellen Klappen-Modellen positive Ergebnisse in Hinblick auf hämodynamische Eigenschaften mit einer großen AÖF von 2,0±0,4 cm² sowie einem niedrigem MPG von 7,6±3,2 mmHg, geringen Komplikationen wie PVL, Schrittmacher-Implantationen und Blutungsereignissen gezeigt werden

Investigation of the influence of tellurite on the effectiveness of antibiotics on uropathogenic Pseudomonas aeruginosa-isolates

P. aeruginosa ist eines der häufigsten Erreger von komplizierten Harnwegsinfektionen. Dabei wird die Behandlung von P. aeruginosa-bedingten Infektionen durch die hohe intrinsische Resistenz dieses Mikroorganismus erschwert. Die Genome der uropathogenen P. aeruginosa-Isolate MH19, MH27, MH38 und RN21 enthielten Gene, die in den Referenzgenomen nicht vorhanden waren. Dabei wurden Gene so genannte Singletons, welche mit einer Resistenz gegenüber Schwermetallen in Verbindung gebracht werden konnten, genauer analysiert. Es wurde gezeigt, dass die uropathogenen P. aeruginoa-Isolate unterschiedlich sensitiv auf die getesteten Schwermetalle reagierten. Ein Zusammenhang zwischen den Singletons und der Sensitivität konnte nicht beobachtet werden. Um Grundlagen für neue therapeutische Strategien zu schaffen, wurde die Verabreichung von Antibiotika in Kombination mit Tellurit untersucht. Dabei wurde gezeigt, dass die uropathogenen P. aeruginosa-Isolate MH19, MH27, MH38 und RN21 sowie der Laborstamm P. aeruginosa PAO1 in Anwesenheit von Tellurit sensitiver auf die Antibiotika Ceftazidim, Ciprofloxacin und Tobramycin reagierten. Dabei entspricht das Wirkprinzip von Tellurit dem von antibiotischen Adjuvantien. Die wirksamen Telluritkonzentrationen waren nicht toxisch für eukaryontische Epithelzellen ECV304. Zur genaueren Untersuchung des Antibiotika-verstärkenden Effekts von Tellurit wurden die intrazelluläre Menge an reaktiven Sauerstoffspezies, das Transkriptionsprofil und der zentrale Kohlenstoffwechsel betrachtet. In Anwesenheit von Ciprofloxacin bzw. Tobramycin und Tellurit konnte bei den uropathogenen P. aeruginosa-Isolaten und dem Laborstamm P. aeruginosa PAO1 eine erhöhte ROS-Menge nachgewiesen werden. Die Kombination aus Ciprofloxacin und Tellurit führte zur Veränderung des Transkriptionsprofils sowie zu einer veränderten Flussverteilung innerhalb des Tricarbonsäure-Zyklus und des Glyoxylat-Shunts beim Laborstamm P. aeruginosa PAO1. Die Arbeit trägt zum Verständnis des Antibiotika-verstärkenden Effekts von Tellurit bei uropathogenen P. aeruginosa-Isolaten bei und zeigt eine neue therapeutische Strategie bei P. aeruginosa-bedingten Infektionen auf.P. aeruginosa is one of the most common pathogens of complicated urinary tract infections. The treatment of P. aeruginosa caused infections is difficult due to the high intrinsic resistance of the microorganism. The genomes of the uropathogenic P. aeruginosa isolates MH19, MH27, MH38 and RN21 contained genes, which were not present in the reference genomes. Unique genes, so called singletons, which could be associated with the resistance to heavy metals, were further analyzed. It was shown, that the uropathogenic P. aeruginosa isolates reacted with varying sensitivity to the tested heavy metals. A link between the singletons and the sensitivity could not be observed. As basis for new therapeutic strategies the application of antibiotics in combination with tellurite was investigated. It was shown, that the uropathogenic P. aeruginosa isolates MH19, MH27, MH38 and RN21 as well as the laboratory strain P. aeruginosa PAO1 were more sensitive to the antibiotics ciprofloxacin, ceftazidime and tobramycin in the presence of tellurite. Thereby the active principle of tellurite corresponds to that of antibiotic adjuvants. The effective concentrations of tellurite used in the MTT assay were not toxic on eukaryotic epithelial cells ECV304. To examine the antibiotic-potentiating effect of tellurite more precisely, the intracellular amount of reactive oxygen species, the transcriptional profile and the central carbon metabolism were analyzed. In the presence of ciprofloxacin or tobramycin and tellurite increased amounts of intracellular ROS were detected in the uropathogenic P. aeruginosa isolates and the laboratory strain P. aeruginosa PAO1. The combination of ciprofloxacin and tellurite caused a change of the transcriptional profile and of the metabolic flux of the citric acid cycle and the glyoxylate shunt in the laboratory strain P. aeruginosa PAO1. In summary this thesis contributes to the understanding of the antibiotic-potentiating effect of tellurite on uropathogenic P. aeruginosa isolates and indicates a new therapeutic strategy for P. aeruginosa induced infections

Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.

Neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD) and Parkinson's Disease (PD), are a group of heterogeneous diseases that mainly affect central nervous system (CNS) functions. A subset of NDDs exhibit CNS dysfunction and muscle degeneration, as observed in Gangliosidosis 1 (GM1) and late stages of PD. Neuromuscular disorders (NMDs) are a group of diseases in which patients show primary progressive muscle weaknesses, including Duchenne Muscular Dystrophy (DMD), Pompe disease, and Spinal Muscular Atrophy (SMA). NDDs and NMDs typically have a genetic component, which affects the physiological functioning of critical cellular processes, leading to pathogenesis. Currently, there is no cure or efficient treatment for most of these diseases. More than 200 clinical trials have been completed or are currently underway in order to establish safety, tolerability, and efficacy of promising gene therapy approaches. Thus, gene therapy-based therapeutics, including viral or non-viral delivery, are very appealing for the treatment of NDDs and NMDs. In particular, adeno-associated viral vectors (AAV) are an attractive option for gene therapy for NDDs and NMDs. However, limitations have been identified after systemic delivery, including the suboptimal capacity of these therapies to traverse the blood-brain barrier (BBB), degradation of the particles during the delivery, high reactivity of the patient's immune system during the treatment, and the potential need for redosing. To circumvent these limitations, several preclinical and clinical studies have suggested intrathecal (IT) delivery to target the CNS and peripheral organs via cerebrospinal fluid (CSF). CSF administration can vastly improve the delivery of small molecules and drugs to the brain and spinal cord as compared to systemic delivery. Here, we review AAV biology and vector design elements, different therapeutic routes of administration, and highlight CSF delivery as an attractive route of administration. We discuss the different aspects of neuromuscular and neurodegenerative diseases, such as pathogenesis, the landscape of mutations, and the biological processes associated with the disease. We also describe the hallmarks of NDDs and NMDs as well as discuss current therapeutic approaches and clinical progress in viral and non-viral gene therapy and enzyme replacement strategies for those diseases

Digital twin concept for aircraft components

Digital twins are one way to develop future intelligent systems. Aviation brings along very special circumstances, since the majority of the components do not remain in the first aircraft (A/C) over the life cycle and are constantly changing as they belong to other systems. Due to the high values of these assets, many of them are subjected to a maintenance process and then mounted to another aircraft. In this paper, a digital twin concept is developed for these components. For this purpose, requirements from different areas are derived and merged to the new concept. First, the stakeholders of the aviation maintenance ecosystem are considered. Then the concept of digital twin or digital twin web is explained. In order to enable the identification of the data sets in the digital twin, unique identifiers must be introduced before the specifics of aviation components and their processes are discussed. At the end the new concept is described. The various identifiers, the distributed system and the roles of the stakeholders in the ecosystem are discussed

CT Texture Analysis of Pulmonary Neuroendocrine Tumors—Associations with Tumor Grading and Proliferation

Texture analysis derived from computed tomography (CT) might be able to provide clinically relevant imaging biomarkers and might be associated with histopathological features in tumors. The present study sought to elucidate the possible associations between texture features derived from CT images with proliferation index Ki-67 and grading in pulmonary neuroendocrine tumors. Overall, 38 patients (n = 22 females, 58%) with a mean age of 60.8 ± 15.2 years were included into this retrospective study. The texture analysis was performed using the free available Mazda software. All tumors were histopathologically confirmed. In discrimination analysis, “S(1,1)SumEntrp” was significantly different between typical and atypical carcinoids (mean 1.74 ± 0.11 versus 1.79 ± 0.14, p = 0.007). The correlation analysis revealed a moderate positive association between Ki-67 index with the first order parameter kurtosis (r = 0.66, p = 0.001). Several other texture features were associated with the Ki-67 index, the highest correlation coefficient showed “S(4,4)InvDfMom” (r = 0.59, p = 0.004). Several texture features derived from CT were associated with the proliferation index Ki-67 and might therefore be a valuable novel biomarker in pulmonary neuroendocrine tumors. “Sumentrp” might be a promising parameter to aid in the discrimination between typical and atypical carcinoids