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Decreased concentrations of C5a complement receptor antibodies are associated with relapse in eosinophilic granulomatosis with polyangiitis (EGPA)
Get PDFComplement activation via the alternative pathway with subsequent generation of the C5a complement fragment has an important role in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) pathophysiology .1 Binding of C5a to the G protein-coupled receptor (GPCR) C5a receptor 1 (C5aR1, CD88) boosts neutrophil activation and induces severe vessel necrosis in experimental myeloperoxidase-specific (MPO)-ANCA-induced glomerulonephritis .2 Moreover, the glucocorticoid-sparing oral C5aR antagonist avacopan improves disease control and renal recovery in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two major subgroups of AAV.3 Notably, serum concentrations of endogenous anti-GPCR antibodies targeting C3a and C5a complement receptors are decreased in GPA and MPA compared with healthy individuals. Lower concentrations of anti-C5aR antibodies, but not anti-C3aR antibodies, were associated with disease activity and relapse suggestive of C5aR as an immune checkpoint regulated by endogenous anti-C5aR antibodies in AAV .4 Similar to neutrophils, eosinophils constitutively display C5aR1 expression .5 As suggested by an earlier study showing increased C4 complement and CH50 serum concentrations, complement activation may also play a role in eosinophilic granulomatosis with polyangiitis (EGPA), the third and minor subgroup of AAV characterised by eosinophil-rich necrotising granulomatous inflammation and systemic small vessel vasculitis .6 Therefore, we were interested in examining anti-C3aR and anti-C5aR antibody concentrations and analysing their association with disease activity and relapse in EGPA
Single-Eye Porcine Retinal Pigment Epithelium Cell Cultures—A Validated and Reproducible Protocol
Get PDFBackground: Age-related macular degeneration (AMD) is the leading cause of severe vision loss in industrialized nations. AMD models based on standardized optimized cell culture models are warranted. The aim of this study is to implement a standard operation protocol for the preparation of porcine retinal pigment epithelium (RPE) from pig eyes with cells from one eye designated for one culture, generating a genetic homology within one culture and genetic heterogeneity between cultures, thereby implementing a relevant in vitro model for AMD investigations. In addition, the use of pigs’ eyes from slaughterhouse waste material is an active measure to reduce animal experimentation in ophthalmological research. Methods: Primary porcine RPE cells were prepared, and cells from one eye were seeded into one well of a twelve-well polystyrene plate. They were cultured for 7, 14, and 28 days. Different post-mortem times (2, 4, and 6 h), coatings (collagen I, IV, Poly-d-Lysine, fibronectin, and laminin), and serum content of media (1%, 5%, and 10%) were tested. The success rate for confluence and survival was determined. At the different time points, cell number (trypan blue exclusion assay), confluence and morphology (microscope imaging), VEGF content of supernatants, and gene and protein expression, as well as tight junctions (fluorescence imaging), were examined. In addition, a baseline for RPE morphometry using CellProfiler software was established. Results: A post-mortem time of 4 to 5 h is most suitable. A coating with Poly-d-Lysine is recommended due to high success rates, the fastest confluence, the highest expression of RPE65, and suitable morphologic properties. The results for confluence, protein expression, and morphology showed that a reduction of 10% to 5% FBS is acceptable. Conclusion: A basic best practice protocol for the preparation of porcine single-eye cultures with optimized parameters was established and is provided
Detection of Genomic Copy Number Variations in Ovarian Cancer in the Peripheral Blood System
Get PDFOur research aims to test the suitability of ddPCR for the detection of tumor-related genomic imbalances (CNVs) in ovarian cancer (OC) in the peripheral blood system. In principle, in an artificial CNV simulation, we can show that CNVs can be detected even in larger dilutions in diploid DNA using ddPCR. Furthermore, we identified ovarian cancer CNVs by using aCGH and used this information to produce suitable ddPCR tests. These ddPCR tests are based on the principle of two differently colored comparative DNA loci that mark both very common genome imbalances in OC and regions that hardly indicate genome imbalances in OC. We were able to generate six ddPCR tests that indicate OC by identifying cell-free tumor DNA with a sensitivity of 0.8 and a specificity of 0.
Efficacy of Nano and Conventional Zinc and Silicon Fertilizers for Nutrient Use Efficiency and Yield Benefits in Maize Under Saline Field Conditions
Get PDFThe increasing severity of salinity stress, exacerbated by climate change, poses significant challenges to sustainable agriculture, particularly in salt-affected regions. Soil salinity, impacting approximately 20% of irrigated lands, severely reduces crop productivity by disrupting plants' physiological and biochemical processes. This study evaluates the effectiveness of zinc (Zn) and silicon (Si) nanofertilizers in improving maize (Zea mays L.) growth, nutrient uptake, and yield under both saline and non-saline field conditions. ZnO nanoparticles (NPs) were synthesized via the co-precipitation method due to its ability to produce highly pure and uniform particles, while the sol-gel method was chosen for SiO2 NPs to ensure precise control over the particle size and enhanced surface activity. The NPs were characterized using UV-Vis spectroscopy, XRD, SEM, and TEM-EDX, confirming their crystalline nature, morphology, and nanoscale size (ZnO~12 nm, SiO2~15 nm). A split-plot field experiment was conducted to assess the effects of the nano and conventional Zn and Si fertilizers. Zn was applied at 10 ppm (22.5 kg/ha) and Si at 90 ppm (201 kg/ha). Various agronomic, chemical, and physiological parameters were then evaluated. The results demonstrated that nano Zn/Si significantly enhanced the cob length and grain yield. Nano Si led to the highest biomass increase (110%) and improved the nutrient use efficiency by 105% under saline and 110% under non-saline conditions compared to the control. Under saline stress, nano Zn/Si improved the nutrient uptake efficiency, reduced sodium accumulation, and increased the grain yield by 66% and 106%, respectively, compared to the control. A Principal Component Analysis (PCA) highlighted a strong correlation between nano Zn/Si applications with the harvest index and Si contents in shoots, along with other physiological and yield attributes
Momentum-Resolved Signatures of Carrier Screening Effects on Electron–Phonon Coupling in MoS2
Get PDFElectron-phonon coupling is central to many condensed matter phenomena. Harnessing these effects for functionality in materials always involves nonequilibrium electronic states, which in turn alter quasi-free-carrier density and screening. Thus, gaining a fundamental understanding of the interplay of carrier screening and electron-phonon coupling is essential for advancing ultrafast science. Prior work has mainly focused on the impact of carrier screening on electronic structure properties. Here, we investigate the nonequilibrium lattice dynamics of MoS2 after a photoinduced Mott transition. The experimental data are closely reproduced by ab initio ultrafast dynamics simulations. We find that the nonthermal diffuse scattering signals in the vicinity of the Bragg peaks, originating from long-wavelength phonon emission, can only be reproduced upon explicitly accounting for the screening of electron-phonon interaction introduced by the Mott transition. These results indicate that carrier screening influences electron-phonon coupling, leading to a suppression of intravalley phonon-assisted carrier relaxation. Overall, the combined experimental and computational approaches introduced here offer prospects for exploring the influence of screening of the electron-phonon interactions and relaxation pathways in driven solids
Underwater Coherent Optical Wireless Communications with Electronic Beam Steering and Turbulence Compensation Using Adaptive Optics and Aperture Averaging
Get PDFA novel approach to underwater optical wireless coherent communications using liquid crystal spatial light modulators (LC-SLMs) and an aperture averaging lens, in combination with optical phased-array (OPA) antennas, is presented. A comprehensive channel model that includes a wide range of underwater properties, including absorption, scattering, and turbulence effects, is employed to simulate the underwater optical wireless communication (UOWC) system in a realistic manner. The proposed system concept utilizes aperture averaging and adaptive optics techniques to mitigate the degrading effects of turbulence. Additionally, OPA antennas are integrated into the system to provide electronic beam steering capabilities, facilitating precise pointing, acquisition, and tracking (PAT) between mobile underwater vehicles. This integration enables high-speed and reliable communication links by maintaining optimal alignment. The numerical results show that under strong turbulence, our combined turbulence-compensation approach (LC-SLM plus aperture averaging) can extend the communication range by approximately threefold compared to a baseline system without compensation. For instance, at a soft-decision FEC threshold of 1.25×10−2, the maximum achievable link distance increases from around 10m to over 30m. Moreover, the scintillation index is reduced by more than 90%, and the bit error rate (BER) improves
Langzeitergebnisse nach Ballonvalvuloplastie der Aortenklappe im Neugeborenen- und Kindesalter
No full textDie kongenitale Aortenklappenstenose gehört zu nicht zyanotischen Herzfehlern, Anteil 3 – 6 % bei angeborenen Herzfehler.Aktuell zwei gängige Behandlungsansätze: Ballonvalvuloplastie oder chirurgische Klappenrekonstruktion oder -ersatz. Es wurden Behandlungsergebnisse von 160 Patienten in 3 Gruppen (Neugeborene, Säuglinge und Kinder > Jahr) von 1989 bis 2021 retrospektiv analysiert. Bei 73% der Patienten wurde ein gutes Interventionsergebnis erzielt. Mit fast 50% fand sich eine signifikant höhere Anzahl an nicht optimalen Interventionsergebnissen bei Patienten > einem Jahr. Eine mehr als leichte postinterventionelle Klappeninsuffizienz war in mit höheren Ballon-Annulus-Ratio assoziiert. Der kombinierte Endpunkt aus Tod, Versagen der biventrikulären Strategie und Re-Intervention wurde bei knapp der Hälfte der Patienten erreicht, die mediane ereignisfreie Überlebenszeit betrug 14 Jahre. Eine höhere Ereignisrate zeigte sich bei Neugeborenen. Risikofaktoren der Neugeborenen waren eine dysplastische Aortenklappe, eine hypoplastische Klappe mit Z-Score < -2 und eine duktusabhängige Systemperfusion. Das Vorliegen einer dysplastischen Aortenklappe und einer mehr als leichten postinterventionellen Aortenklappeninsuffizienz waren unabhängige Risikofaktoren für die Notwendigkeit einer Aortenklappenchirurgie. Bei 60% der Patienten war am Ende im Median mehr als 10 Jahre langen Beobachtungszeit kein chirurgischer Eingriff an der Aortenklappe erforderlich. Es konnte gezeigt werden, dass Ballonvalvuloplastie eine effektive akute Therapie ist. Langfristig sind Re-Interventionen und teilweise eine Aortenklappenrekonstruktion oder -ersatz erforderlich. Neugeborene weisen schlechtere Behandlungsergebnisse auf. Bei guter Patientenselektion lässt sich jedoch auch in dieser Patientengruppe eine Aortenklappenoperation lange verzögern
Freisetzung eines löslichen CD109-Fragments durch Meprin β und dessen funktionelle Charakterisierung
Get PDFDie frühe Diagnostik und Therapie von Tumorerkrankungen bleiben eine Herausforderung der heutigen Zeit. Die vermehrte Expression von Cluster of Differentiation 109 (CD109) Protein wurde bei Tumorerkrankungen wie Glioblastom und Lungenepithelkarzinom nachgewiesen und mit erhöhter Mortalität korreliert. CD109 ist ein GPI-verlinktes Glykoprotein auf der Zelloberfläche, dessen Funktion ungeklärt ist. Proteasen auf Zelloberflächen beeinflussen die Extrazellulärmatrices und Signaltransduktion. Meprin β ist eine Zink-Metalloprotease, die gehäuft im Endothel von Darm und Niere sowie in Fibroblasten auftritt, aber auch bei Tumorerkrankungen eine zunehmende Rolle spielen könnte. Proben aus Zelllysaten und extrazellulären Vesikeln wurden aufbereitet und die Interaktion zwischen CD109 und Meprin β wurde mittels biochemischer, molekularbiologischer und analytischer Methoden untersucht. CD109 wurde als Meprin β Substrat identifiziert und bestätigt. CD109-Fragmente wurden mittels Western Blot Analyse detektiert. EV wurden aus CD109-überexprimierenden Zellen mit aktivem Meprin β und inaktiver E153A Variante gewonnen. Die EV zeigten keine morphologischen Unterschiede. Die Western Blot Analyse ergab verringerte CD109 Verfügbarkeit auf EV bei Meprin β im Vergleich zur E153A. Dies könnte Auswirkungen auf die Zell-Zell Kommunikation im Tumorgeschehen haben und eine Therapieoption darstellen. Diese Arbeit zeigte, dass CD109 durch Meprin β in Fragmente prozessiert wird und weniger CD109 in voller Länge auf EV sortiert wird
Ausströmbedingungen für die kompressiblen Boussinesq-Gleichungen
Get PDFIn dieser Arbeit wird die Finite-Elemente-Diskretisierung der Boussinesq-Gleichungen untersucht, welche temperaturabhängige Strömungen inkompressibler Fluide beschreiben. Der Schwerpunkt der Arbeit liegt auf der Untersuchung künstlicher Strömungsbedingungen. Diese müssen definiert werden, wenn das Strömungsgebiet für numerische Untersuchungen künstlich verkleinert werden soll. Solche Randbedingungen können nie exakt sein, da ein möglicherweise wichtiger Teil vernachlässigt wird. Wir untersuchen den Einfluss verschiedener Randbedingungen auf die Stabilität und Genauigkeit numerischer Simulationen. Nach den Grundlagen analysieren wir im zweiten Teil der Arbeit das stationäre Problem und im dritten Teil erweitern wir die Untersuchungen auf die instationären Boussinesq-Gleichungen. Hier kommt als zusätzliche Schwierigkeit die Lösung der numerischen Probleme hinzu. Wenn sehr viele Zeitschritte berechnet werden müssen, benötigt man extrem schnelle Lösungsverfahren. In beiden Teilen werden umfangreiche numerische Testrechnungen durchgeführt. Dabei wird sowohl die Genauigkeit der Finite-Elemente-Diskretisierung als auch die Stabilität der numerischen Verfahren untersucht. Insbesondere untersuchen wir den Einfluss verschiedener Strömungsbedingungen für Geschwindigkeit und Temperatur auf die Lösung
Lithospheric Structure of the West and Central African Rift Zone
Get PDFThe West and Central African Rift System (WCARS) is a geologically complex region offering insights into continental rifting, magmatism, and lithospheric evolution. This thesis integrates geophysical, petrological, and thermal data to examine lithospheric structure, crustal composition, and thermal regime, addressing four key questions: WCARS’s structural framework, the origins of the Cameroon Volcanic Line (CVL) and Bangui Magnetic Anomaly (BMA), and the link between surface heat flow, crustal composition, and magmatism. A 3D lithospheric model using gravity, seismic, and petrological data confirms WCARS’s passive origin and heterogeneity. Crustal thickness varies from 25 km in rift zones to 50 km in cratons, while lithospheric thickness ranges from 70 km in the Benue Trough to 250 km beneath cratons, highlighting tectonic inheritance in rift evolution. The CVL likely formed due to edge-driven convection from WCARS’s V-shaped opening, creating magma chambers along pre-existing weaknesses. The BMA, analyzed via gravity and magnetic data, likely results from felsic and plutonic intrusions with strong remnant magnetization during Mesozoic rifting. Heat flow variations show high heat flow in rift zones due to magmatism and radiogenic heat production, while low heat flow in cratonic regions reflects thick, insulating lithosphere. This study enhances understanding of WCARS’s lithospheric structure, geophysical anomalies, and thermal evolution, emphasizing the value of integrated geophysical and petrological analysis for studying rift systems and lithospheric modification