222 research outputs found
Atmospheric singular vectors and teleconnections
Bekanntlich sind atmosphärische Rossbywellezüge (RWTs) Lösungen der Singular Vector Analyse eines gedämpften, barotropen Modells mit Nordwinter Grundströmen. In den SV Basen der verwendeten 40 DJF Grundströme konnten nur wenige wachsende den Rossbywellenzügen ähnliche (RWT Moden) Singulären Vektoren (SVen) gefunden werden. Die RWT Moden kommen nur in wenigen Gebieten der Erde vor. Die instabilste Mode entwickelt sich in der Region des Nordpazifiks (NPACs) innerhalb von 4 Tagen in jedem der verwendeten beobachteten DJF Grundströme. Alle anderen RWT Moden kommen nur bei Verwendung einiger der Grundströme vor. Ihre Entwicklungspfade sind eindeutig für Entwicklungszeiten bis zu 96 h und streuen für längere Zeiten. Die NPAC Mode erklärt zum Optimierungszeitpunkt 96 h bis zu 60 % der atmosphärischen kinetischen Energie (KE) auf der 300 hPa Fläche in der NPAC Region. Es konnte auch gezeigt werden, daß die Zeitreihe des beobachteten Wachstums der NPAC Mode mit dem berechneten Wachstum (den Eigenwerten) konsistent ist. Interessanterweise zeigt die NPAC-KE zum Optimierungszeitpunkt 96 h auch eine schwach signifikante Korrelation mit dem PNA-Index, die für die Optimierungszeit 144 h nicht mehr existiert. Die Ergebnisse legen die Vermutung nahe, daß die verwendeten Grundströme die Entwicklung der RWT Moden bis zu einer Entwicklungszeit von 4 Tagen dominieren und daß die finite Instabilität maßgeblich zur Entwicklung der beobachteten NPAC Rossbywellenzüge in der Atmosphäre beiträgt. Die Ergebnisse geben Hinweise darauf, daß die NPAC mode auch einen Beitrag zur Entwicklung der PNA leistet
Intermedin Stabilized Endothelial Barrier Function and Attenuated Ventilator-induced Lung Injury in Mice
Background: Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILIassociated lung permeability in vivo. Methodology/Principal Findings: Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1–3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxi
Integration of CT urography improves diagnostic confidence of 68Ga-PSMA-11 PET/CT in prostate cancer patients
Background: To prove the feasibility of integrating CT urography (CTU) into 68Ga-PSMA-11 PET/CT and to analyze the impact of CTU on assigning focal tracer accumulation in the ureteric space to either ureteric excretion or metastatic disease concerning topographic attribution and diagnostic confidence.
Methods: Ten prostate cancer patients who underwent 68Ga-PSMA-11 PET/CT including CTU because of biochemical relapse or known metastatic disease were retrospectively analyzed. CTU consisted of an excretory phase 10 min after injection of 80 mL iodinated contrast material. Ureter opacification at CTU was evaluated using the following score: 0, 0% opacification; 1, < 50%; 2, 50–99%; 3, 100%. Topographic attribution and confidence of topographic attribution of focal tracer accumulation in the ureteric space were separately assessed for 68Ga-PSMA-11 PET/CT without and with CTU. Diagnostic confidence was evaluated using the following score: 0, < 25% confidence; 1, 26–50%; 2, 51–75%; 3, 76–100%.
Results: At CTU, mean ureter opacification score was 2.6 ± 0.7. At 68Ga-PSMA-11 PET/CT without CTU, mean confidence of topographic attribution of focal tracer accumulation was 2.5 ± 0.7 in total and 2.6 ± 0.7 for metastatic disease. At 68Ga-PSMA-11 PET/CT with CTU, mean confidence of topographic attribution of focal areas of tracer accumulation was significantly higher with 2.9 ± 0.2 in total and 2.7 ± 0.9 for metastatic disease (p < 0.001). In 4 of 34 findings (12%) attribution to either ureteric excretion or metastatic disease was discrepant between 68Ga-PSMA-11 PET/CT without and with CTU (n.s).
Conclusions: Integration of CTU into 68Ga-PSMA-11 PET/CT is feasible and increases diagnostic confidence of assigning focal areas of tracer accumulation in the ureteric space to either metastatic disease or ureteric excretion
protection by adrenomedullin
Ventilator-induced lung injury (VILI) contributes to morbidity and mortality
in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs
are susceptible to VILI despite protective ventilation. In a previous study,
the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI.
We hypothesized that mechanical ventilation (MV) contributes to lung injury
and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ
failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice
the impact of MV in established pneumonia on lung injury, inflammation,
bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed
the therapeutic potential of AM by starting treatment at intubation. In
pneumococcal pneumonia, MV increased lung permeability, and worsened lung
mechanics and oxygenation failure. MV dramatically increased lung and blood
cytokines but not lung leukocyte counts in pneumonia. MV induced systemic
leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung
and blood bacterial burden was not affected by MV pneumonia and MV increased
lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3
expression was increased in pneumonia and reduced by MV. Infusion of AM
protected against MV-induced lung injury (66% reduction of pulmonary
permeability p<0.01; prevention of pulmonary restriction) and against VILI-
induced liver and gut injury in pneumonia (91% reduction of AST levels p<0.05,
96% reduction of alanine aminotransaminase (ALT) levels p<0.05, abrogation of
histopathological changes and parenchymal apoptosis in liver and gut). MV
paved the way for the progression of pneumonia towards ARDS and sepsis by
aggravating lung injury and systemic hyperinflammation leading to liver,
kidney and gut injury. AM may be a promising therapeutic option to protect
against development of lung injury, sepsis and extrapulmonary organ injury in
mechanically ventilated individuals with severe pneumonia
Tomographisches Messverfahren fĂĽr die Gasverteilung in einer Axialpumpe bei Zweiphasenbetrieb
Bei einer Vielzahl von natürlichen und technischen Strömungsvorgängen besteht das strömende Medium aus mehreren Phasen. Bei der Förderung derartiger Medien mit Kreiselpumpen führen bislang nicht genügend bekannte Vorgänge bei bestimmten Betriebsbedingungen zu einer starken Verringerung der Förderleistung und einem Anstieg des Leistungsbedarfs. Bei der Förderung von gasbeladenen Flüssigkeiten kann ein zu hoher Gasanteil zum vollständigen Zusammenbruch der Förderung führen. Zusätzlich führt die erosive Wirkung von Kavitation zu einer starken Minderung der Lebensdauer der Pumpe. Diese Arbeit beschreibt ein neuartiges Verfahren, das es erstmals gestattet, die Methode der Gamma-Tomographie zur Bestimmung der örtlichen Phasenverteilung innerhalb von rotierenden Pumpenläufern und ähnlichen Bauteilen anzuwenden. Dabei wird eine Zeitauflösung von ca. 100 µs erreicht, mit der die Gasverteilung wesentlich genauer als bisher erfaßt werden kann. Mit dem Tomographen wurden die Vorgänge innerhalb des Läufers einer Axialpumpe bei Förderung eines Luft-Wasser-Gemischs visualisiert. Es wird gezeigt, wie sich die Änderung äußerer Strömungsparameter und die Variation des Arbeitspunktes auf die räumliche Phasenverteilung innerhalb des Läufers auswirkt
Phase 2 Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes
Open Surgical versus Minimal Invasive Necrosectomy of the Pancreas-A Retrospective Multicenter Analysis of the German Pancreatitis Study Group
Background Necrotising pancreatitis, and particularly infected necrosis, are still associated with high morbidity and mortality. Since 2011, a step-up approach with lower morbidity rates compared to initial open necrosectomy has been established. However, mortality and complication rates of this complex treatment are hardly studied thereafter. Methods The German Pancreatitis Study Group performed a multicenter, retrospective study including 220 patients with necrotising pancreatitis requiring intervention, treated at 10 hospitals in Germany between January 2008 and June 2014. Data were analysed for the primary endpoints "severe complications" and "mortality" as well as secondary endpoints including "length of hospital stay", "follow up", and predisposing or prognostic factors. Results Of all patients 13.6% were treated primarily with surgery and 86.4% underwent a step-up approach. More men (71.8%) required intervention for necrotising pancreatitis. The most frequent etiology was biliary (41.4%) followed by alcohol (29.1%). Compared to open necrosectomy, the step-up approach was associated with a lower number of severe complications (primary composite endpoint including sepsis, persistent multiorgan dysfunction syndrome (MODS) and erosion bleeding: 44.7% vs. 73.3%), lower mortality (10.5% vs. 33.3%) and lower rates of diabetes mellitus type 3c (4.7% vs. 33.3%). Low hematocrit and low blood urea nitrogen at admission as well as a history of acute pancreatitis were prognostic for less complications in necrotising pancreatitis. A combination of drainage with endoscopic necrosectomy resulted in the lowest rate of severe complications. Conclusion A step-up approach starting with minimal invasive drainage techniques and endoscopic necrosectomy results in a significant reduction of morbidity and mortality in necrotising pancreatitis compared to a primarily surgical intervention
The RNA workbench: Best practices for RNA and high-throughput sequencing bioinformatics in Galaxy
RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis
Fenobam: A Clinically Validated Nonbenzodiazepine Anxiolytic Is a Potent, Selective, and Noncompetitive mGlu5 Receptor Antagonist with Inverse Agonist Activity
Integration of CT urography improves diagnostic confidence of 68Ga-PSMA-11 PET/CT in prostate cancer patients
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