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Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source
Get PDFBackground/Objectives: Satoyoshi syndrome is a rare, autoimmune disorder currently diagnosed based on clinical criteria: painful muscle spasms, diarrhea, and alopecia. Two previous reports showed a specific immunoreactive band in three Satoyoshi syndrome patients using Western blot analysis, with brain homogenate as the antigen source. These findings could be the basis for a future diagnostic test. The aim of our study was to evaluate the efficacy of using SH-SY5Y cell lysate instead of brain homogenate for a potential laboratory test for Satoyoshi syndrome using the Western blot technique. Methods: Western blot analyses were conducted using brain homogenate, SH-SY5Y cell lysates, and differentiated SH-SY5Y cell lysates. Serum samples were obtained from three Satoyoshi syndrome patients, alongside control samples from thirty blood donors and six patients with other neurological conditions. Results: Sera from patients with Satoyoshi syndrome displayed a three-band pattern in the 70-100 kDa range. This pattern was reproducible across all tested antigen sources (brain homogenate, SH-SY5Y lysate, and differentiated SH-SY5Y lysate) but was not observed for the sera from the control groups. The bands were more visible when using either type of SH-SY5Y lysate compared to brain homogenate. No differences were found between the SH-SY5Y lysate and the differentiated SH-SY5Y lysate. Conclusions: Sera from our Satoyoshi syndrome patients showed a specific band pattern that could be used for a future evaluation of Satoyoshi syndrome using Western blot. The use of SH-SY5Y cell lysate vs. brain homogenate as an antigen source may improve visualization and reproducibility of the immunobands and be less costly
Advancement of Ferroelectric Al1−xScxN thin films
Get PDFFerroelectricity in wurtzite-type (w-)Al1−xScxN has enabled new opportunities for integrating ferroelectric thin films into memory and neuromorphic devices. As the first known wurtzite-type ferroelectric, AlScN is notable for its compatibility with CMOS and GaN technologies. This thesis investigates the growth and ferroelectric properties of w-Al1−xScxN thin films, emphasizing temperature stability, epitaxy, and doping. Structural properties were studied through X-ray diffraction (XRD), atomic force microscopy, and scanning transmission electron microscopy (S/TEM). In-situ XRD and permittivity measurements showed that the wurtzite phase in Al1−xScxN remains stable up to 1100 °C. Sputter deposition of w-Al1-xScxN on doped n-GaN yielded high-quality epitaxial films with significantly improved (0002) texture. Lattice-matched w-Al0.89Sc0.11N grown by sputter epitaxy achieved a rocking-curve FWHM of ~252 arcsec. High-resolution STEM confirmed the polarity of these films in the bulk. Growing w-Al0.73Sc0.27N on epi-Pt/GaN rather than n-GaN reduced hysteresis asymmetry, leakage, and coercive field values, despite some loss of texture. Further improvements on epitaxial films were achieved by reducing the electrode thickness from 100 nm to 10 nm. Apart from that, ferroelectricity was also demonstrated in ultra-thin (~5 nm) w-Al1−xScxN layers with switching voltages near 1 V, satisfying low-voltage requirements for memory devices. Unlike conventional oxide ferroelectrics, scaling w-Al0.73Sc0.27N thickness caused no clear degradation of polarization or coercive field. Additionally, oxygen doping during sputtering reduced overall leakage without compromising structural quality. Overall, this work advances w-Al1−xScxN toward device-level implementation, particularly in terms of thermal stability, epitaxy, thickness scaling, and doping
Qualitätssicherung in der stereotaktischen Strahlentherapie von Herzrhythmusstörungen
No full textEine Hauptursache für den plötzlichen Herztod ist die maligne Herzrhythmusstörung in den Herzkammern, die ventrikuläre Tachykardie (VT). Um den plötzlichen Herztod zu verhindern, erhalten Patient*innen mit einem erhöhten Risiko einen Kardioverter-Defibrillator implantiert. Patient*innen mit VT erhalten, wenn deren Auftreten durch eine medikamentöse Therapie unzureichend kontrolliert ist, meist eine invasive Katheterablation als weitere Therapiemöglichkeit (Zeppenfeld 2022). Wenn eine erneute Katheterablation nicht erfolgsversprechend ist und/oder die Patient*innen medikamentös austherapiert sind, stellt die stereotaktische Strahlentherapie der Herzrhythmusstörung eine vielversprechende, alternative Therapieoption dar (Krug 2021, Zeppenfeld 2024). Hinsichtlich der seltenen Indikationsstellung (Krug 2021) haben Zentren nur wenige Patient*innen behandelt. Dies erschwert eine detaillierte Auswertung der klinischen Ergebnisse und eine Optimierung und Standardisierung der Therapie. Infolgedessen haben sich mehrere europäische Zentren zu einem gemeinsamen Projekt zusammengeschlossen, dessen Kern ein multizentrisches Datenregister darstellt: Das Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) Konsortium (EU Horizon 2020 Nr. 945119). Die Ergebnisse der Benchmark Studien und Audits innerhalb des STOPSTORM.eu Konsortiums zeigten unterschiedlichste Ist-Zustände von Qualitätsstandards der Zentren, die einen entscheidenden Einfluss auf die Behandlungsqualität haben können. Um ein Mindestmaß an Standards und QS-Methoden für teilnehmende Zentren einer klinischen Studie zu erreichen, ist die Durchführung von Benchmark-Studien und Audits unerlässlich für die Beurteilung der Ergebnisse und damit dem Erfolg einer klinischen Studie (Abbott 2024)
Optimizing Rock Bolt Support for Large Underground Structures Using 3D DFN-DEM Method
Get PDFA systematic sensitivity analysis using three-dimensional discrete element models with discrete fracture networks (DEM-DFN) was conducted to evaluate underground excavation support in jointed rock masses at the CLAB2 site in Southeastern Sweden. The site features a joint network comprising six distinct joint sets, each with unique geometrical properties. The study examined 10 DFNs and 19 rock bolt patterns, both conventional and unconventional. It covered 200 scenarios, including 10 unsupported and 190 supported cases. Technical and economic criteria for stability were assessed for each support system. The results indicated that increasing rock bolt length enhances stability up to a certain point. However, multi-length rock bolt patterns with similar consumption can yield significantly different stability outcomes. Notably, the arrangement and properties of rock bolts are crucial for stability, particularly in blocks between bolting sections. These blocks remain interlocked in unsupported areas due to the induced pressure from supported sections. Although equal-length rock bolt patterns are commonly used, the analysis revealed that triple-length rock bolts (3, 6, and 9 m) provided the most effective support across all ten DFN scenarios
Infektionsepidemiologische Analyse der meldepflichtigen Infektionskrankheiten des Jahres 2020 in Schleswig-Holstein unter der Coronavirus-Pandemie
Get PDFAus epidemiologischer Sicht war das Jahr 2020 durch das mit schwerem Atemwegssyndrom assoziierten Coronavirus Typ 2 geprägt. Dessen Ausbreitung wurde in Deutschland ab März 2020 durch die Einführung eindämmender Maßnahmen versucht einzuschränken. Diese prospektiv aufgebaute und retrospektiv ausgewertete Arbeit befasst sich mit den Auswirkungen dieser Maßnahmen auf meldepflichtige Infektionskrankheiten in Schleswig-Holstein im Jahr 2020, den Geschlechtsunterschieden bei Infektionen mit COVID-19 und weiteren häufigenmeldepflichtigen Infektionskrankheiten in Bezug auf das Alter und den Schweregrad des Krankheitsverlaufs sowie den Sterbefallzahlen in Schleswig-Holstein und Deutschland im Jahr 2020. Die Analyse basierte auf Datens.tzen der von den Gesundheits.mtern Schleswig-Holsteins bis zum 31.3.2021 übermittelten Fälle meldepflichtiger Infektionskrankheiten des Jahres 2020 sowie den von dem Statistischen Bundesamt veröffentlichten Rohdaten der Sterbefallzahlender Jahre 2016-2020
Validity of in vitro studies with fumaric acid esters for treatment situations in humans: a literature based analysis
Get PDFBesides methotrexate, ciclosporin, hydroxycarbamide and retinoids, fumaric acid esters based drugs are used since 1971 as an immunosuppressive, respectively immunomodulatory, medication in the therapy of severe psoriasis. The latter substances are currently subject of great interest as an oral treatment for several autoimmune diseases including multiple sclerosis. During the past years, several pharmaceutical products containing dimethylfumarate as main active component of all licensed drugs have been released. The exact mechanism of action of fumaric acid esters still remains an open problem. Recent studies demonstrate that dimethylfumarate have also a significant biological effect in vitro. However, the pharmacokinetics and chemistry of dimethylfumarate and other fumaric acid esters are often not fully considered in the design and interpretation of the most experiments. In this literature-based analysis the content from more than 300 articles dating from 1971 to 2022 were compared and validated. Based on this data it was discovered that monomethylfumarate has a higher biochemical impact than dimethylfumarate, because dimethylfumarate is a plasma-membrane permeable prodrug that in vivo rapidly converts to monomethylfumarate. This makes monomethylfumarate the main active compound of oral drugs and means that monomethylfumarate is the only substance to directly interact with the intracellular signaling pathways in vivo. Recent works are often concentrated on the direct effects of dimethylfumarate on cells in vitro, which, having the metabolism of dimethylfumarate in mind will never be exposed to this particular fumaric acid ester in an actual human organism. This shows that, unfortunately, most of the performed in vitro studies are not valid for treatment situations in vivo
Experiences of child abuse and prolonged grief in adulthood - results from a population-based study
Get PDFIn recent years, various risk factors for the development of prolonged grief disorder (PGD) have been discussed. While it is well established that child abuse increases the risk of various mental disorders in later life, the relationship between child abuse, including its subtypes, and PGD is barely examined.The aim of this study was to assess the impact of child abuse and distinct abuse patterns on PGD symptoms in a population-based German sample. We used self-reported data from 911 individuals (54.3 ± 17.9 years, 59.2% women) who had experienced the loss of a loved one. Participants completed demographic, loss-related and child abuse-related questions. To investigate PGD symptoms we utilized the Prolonged Grief Disorder-13+9 (PG13+9). The Childhood Trauma Questionnaire (CTQ) was employed to assess both overall child abuse severity as well as child abuse subtypes: child emotional abuse, child physical abuse, child sexual abuse. We used k-means cluster analysis to identify distinct child abuse patterns. Two hierarchical regression analyses were conducted to examine the associations between PGD symptom severity and child abuse and the identified child abuse clusters. The prevalence rate for experiencing any child abuse was 13.5%. The occurrence of the child abuse subtypes was 7.9% for emotional abuse, 7.6% for physical abuse, and 5.9% for sexual abuse. A priori, we defined an "extreme abuse" cluster from the outliers and identified three clusters "no/low abuse", "moderate [...]. Overall child abuse severity (ß=.13, p<0.001), "high abuse" cluster (ß=.12, p=0.001) and the a priori "extreme abuse" cluster (ß=.07, p=0.040) were significant predictors of PGD symptoms. Our study indicates that child abuse impacts PGD symptoms. Possible hypotheses for this connection and their implications are discussed
Zusammenhang zwischen dem Multidimensional Prognostic Index und der körperlichen Leistungsfähigkeit und Mobilität in einer stationären geriatrischen Kohorte
Get PDFIm Rahmen des demografischen Wandels gewinnt der Einsatz von Prognoseinstrumenten wie des Multidimensional Prognostic Index (MPI) an Bedeutung. Der MPI basiert auf einem umfassenden geriatrischen Assessment und dient der Einschätzung des Sterblichkeitsrisikos älterer Menschen. Körperliche Leistungsfähigkeit und Mobilität als Kern von Selbstständigkeit und Gesundheit fließen in den MPI nicht explizit als Variablen ein. Das Ziel dieser Arbeit war es zu untersuchen, ob in einer stationären, geriatrischen Kohorte ein Zusammenhang zwischen MPI und objektiv überprüfbaren Parametern der körperlichen Leistungsfähigkeit und Mobilität besteht und ob der MPI diese eventuell sogar vorhersagen kann. Die Daten wurden im Rahmen der ComOn-Studie erhoben. Als Parameter der körperlichen Leistungsfähigkeit und Mobilität wurden sensorbasierte Schrittanzahl auf einer 20m-Strecke in normaler und schnellstmöglicher Gehgeschwindigkeit, Gesamtpunktzahl der Short Physical Performance Battery (SPPB) und maximale Handgreifkraft verwendet. In multiple lineare Regressionen flossen MPI, Größe, Gewicht, Alter und Geschlecht als unabhängige und die vier o.g. Parameter der körperlichen Leistungsfähigkeit und Mobilität als abhängige Variablen ein. 107 Patient*innen (79±8 Jahre) wurden eingeschlossen. Die Gesamtmodelle für Schrittanzahl in möglichst schneller Gehgeschwindigkeit (p=0.03), SPPB-Gesamtpunktzahl (p=0.02) und maximale Handgreifkraft (p<0.001) waren signifikant. Das Gesamtmodell für Schrittanzahl in normaler Gehgeschwindigkeit war nicht signifikant. Als Regressor war der MPI für SPPB-Gesamtpunktzahl und maximale Handgreifkraft signifikant. Der MPI kann somit in einer geriatrischen Kohorte Aspekte von körperlicher Leistungsfähigkeit und Mobilität abbilden. Dies zeigt sich vor allem in der signifikanten Assoziation des MPI mit SPPB-Gesamtpunktzahl und maximaler Handgreifkraft
Topologische Spinstrukturen auf supraleitenden Oberflächen
Get PDFTopological superconductivity can lead to the formation of Majorana zeromodes, which could be harnessed for topological quantum computing. Magnet-superconductor-hybrid (MSH) systems, built with conventional superconductors, are a promising host platform as the magnetic structure can induce topological superconductivity. Also, the magnetic state itself can exhibit a non-trivial spin topology. In this thesis realistic MSH systems are investigated with regard to the magnetic structure as well as induced topological superconductivity, focusing on the connection between the spin topology and the topology of the superconductor. Ultra-thin magnetic films on the Re(0001) surface are considered as model MSH systems. Complex magnetic structures are identified via density functional theory (DFT) calculations. The stabilizing mechanisms are revealed by mapping the obtained total DFT energies of various collinear and non-collinear spin states onto an atomistic spin model. The effect of the spin structure on the electronic properties of the superconducting substrate is vinvestigated by a tight-binding model. Spin-polarized scanning tunnelingv microscopy (SP-STM) simulations allow a direct comparison between theoretically predicted magnetic ground states or edge states in superconductors and experimental observations, performed by collaborators of the University of Hamburg
The molecular participants of the defense response to the necrotrophic fungus Alternaria alternata on cultivated and wild tomato
Get PDFTomato (Solanum lycopersicum L.) is one of the world’s most valuable vegetable crops, but its production is increasingly threatened by fungal pathogens—particularly Alternaria spp., which cause early blight and brown spot disease complex (EBDC). These necrotrophic fungi kill host tissue and thrive under changing climate conditions, leading to major yield losses and widespread fungicide use. Current cultivars lack strong genetic resistance, making the development of durable, sustainable defense strategies an urgent agricultural priority. We used gene regulatory networks (GRNs) and weighted gene co-expression network analysis (WGCNA) to analyze the transcriptional landscape of resistance to EBDC. This dissertation addresses this challenge by investigating resistance to EBDC through a multi-scale lens, combining quantitative phenotyping, network biology, and wild tomato diversity. It focuses on Solanum chilense, a wild relative of the cultivated tomato. Notably, resistant genotypes exhibited strong transcriptional activity and early activation of defense modules, while susceptible genotypes showed weak, fragmented networks. Temporal network rewiring and module preservation analyses further emphasized that effective resistance relies not just on the presence of defense genes but on their dynamic regulatory coordination. We used high-throughput quantitative phenotyping to capture subtle differences in infection progression across 124 S. chilense accessions. By leveraging phenotypic diversity to resolve resistant/susceptible gene network topologies, this dissertation advances both the understanding of necrotrophic pathogen resistance and the tools available to improve it. The findings highlight S. chilense as a rich source of resistance alleles and demonstrate the potential of systems biology to breed crops with resilience to complex pathogens in the future