Scientific publications of the Saarland University
Not a member yet
14321 research outputs found
Sort by
Synthesis, Crystal Structure and Optical Properties of Novel 1,10-Phenanthroline Derivatives Containing 2,6-Diisopropylphenoxy Substituents
Full text linkTwo phenanthroline derivatives, 2-(2,6-diisopropylphenoxy)-9-phenyl-1,10-phenanthroline and 2,9-bis(2,6-diisopropylphenoxy)-1,10-phenanthroline, were synthesized. The unsymmetrical derivative was obtained in high yield through a sequence combining Suzuki coupling and nucleophilic substitution. The crystal structures of both compounds were determined by single-crystal X-ray diffraction and examined by Hirshfeld surface analysis, which outlined the main intermolecular interactions responsible for the packing. The optical properties were studied by UV–Vis absorption and fluorescence spectroscopy in different solvents. The unsymmetrical compound showed stronger intramolecular charge transfer and more pronounced solvatochromism, while the symmetrical analog had a higher fluorescence quantum yield and longer excited-state lifetime. These results demonstrate the role of substitution symmetry in controlling molecular organization and photophysical properties of phenanthroline derivatives, with relevance to sensing and optoelectronic applications
Region specific microstructural complexity of the ovine meniscus root provides an organizational basis for injury susceptibility
Full text linkComprehensive information on the meniscus root microstructure is essential to exactly understand its physiological role and susceptibility to injury. We selected the ovine medial meniscus anterior root (MAR) as model to elucidate the intricate spatial arrangement of its enthesis, root ligament and transition into the medial meniscus anterior horn (MMAH), hypothesizing that its microstructure is comparable to humans. We applied different histological, type-I, -II, and -X collagen immunohistochemical, polarization and confocal analyses to investigate its structural complexity. The results reveal unique region-specific patterns. Cell morphology, proteoglycan, and type-II collagen contents differ between regions. The enthesis is avascular while the MAR ligament and red-red zone of the MMAH are well vascularized. The ovine MAR attachment constitutes an enthesis organ together with a bare area below the root ligament covered by adipose tissue. The MAR ligament comprises large longitudinal fascicles that unweave into a complex network when entering the MMAH, changing their orientation towards its white-white zone. The blood vessels that vascularize the MAR ligament enter at its peripheral-femoral side. Only axial MMAH fibers are immunopositive for type-X collagen. This region-specific microstructural complexity of the ovine MAR is largely similar to published findings in humans, providing an organizational basis for injury susceptibility. Thus, the ovine MAR may serve to study the physiopathology of and therapeutic approaches to human root tears
Kognitive Assistenzsysteme zur Steigerung der Wandlungsfähigkeit manueller Montagestationen
Full text linkKognitive Assistenzsysteme in der manuellen Montage folgen meist einem „one-size-fits-all“-Ansatz und lassen sich nicht individuell an Nutzerkompetenzen anpassen. Zudem ist die Erstellung von Montageanweisungen insbesondere im Produktänderungsfall zeit- und ressourcenintensiv. Ziel dieser Dissertation ist es, der beschriebenen Problemstellung durch die Entwicklung eines integrierten Ansatzes zur Steigerung der Wandlungsfähigkeit manueller Montagestationen zu begegnen. Hierzu wird ein Kognitives Assistenzsystem entwickelt, das eine nutzeradaptive Informationsbereitstellung mit einer teilautomatisierten Generierung von Montageanweisungen kombiniert. Die Informationsbereitstellung erfolgt in Art und Tiefe dynamisch entlang eines vierstufigen Kompetenzstufenmodells. Ergänzend wird ein Montageanweisungsgenerator eingeführt, der mit Hilfe feinabgestimmter Large Language Models Montageanweisungen auf Grundlage vorhandener Informationen standardisiert generiert. Der entwickelte Ansatz wird im Rahmen einer Probandenstudie als Bestandteil einer als Demonstrator realisierten manuellen Montagestation am Beispiel der Montage eines Brennstoffzellen-Stacks evaluiert. Die Ergebnisse zeigen eine hohe Gebrauchstauglichkeit (System Usability Scale: 87,83 ± 4,17) und Technologieakzeptanz des Systems. Die Evaluierung des Montageanweisungsgenerators belegt eine deutliche Beschleunigung der Erstellung von Montageanweisungen, bei gleichzeitig hoher Qualität der generierten Anweisungen.Cognitive assistance systems in manual assembly often follow a static “one-size-fits-all” approach and lack adaptability to individual worker competencies or changing production conditions. Additionally, authoring assembly instructions – especially in the case of product modifications – is time- and resource-intensive. The objective of this dissertation is to develop an integrated approach that enhances the adaptability of manual assembly stations by combining user-adaptive information delivery with the semi-automated generation of assembly instructions. A cognitive assistance system is developed that dynamically adjusts the level of instructional detail based on a four-stage competency model. In addition, an assembly instruction generator powered by fine-tuned Large Language Models is introduced to produce standardized instruction texts from existing process data. The proposed approach is implemented in a test bed environment and evaluated through a user study involving the manual assembly of a fuel cell stack. The results indicate high usability (System Usability Scale: 87,83 ± 4,17) and technological acceptance of the system. In addition, the evaluation of the assembly instruction generator demonstrates a substantial acceleration in the generation of assembly instructions, while maintaining a high standard of instruction quality
Cooperative Systems Based on Arrays of Dielectric Elastomer Actuators
Full text linkThis work introduces two cooperative dielectric elastomer actuator (DEA) array designs,
enabling comparison between a fully soft, wearable-oriented system and a rigid, high performance platform. The soft silicone-based array achieves strokes up to 1.9 mm and
maintains 44% displacement under strong bending, demonstrating suitability for haptic
feedback in wearable applications. The rigid prototype, based on thermoformed buck ling beams, provides strokes up to 2.8 mm, reduced hysteresis, improved stability, and
reproducible fabrication, while allowing fine-tuning of preload conditions. Experiments
revealed frequency-dependent coupling, enabling stimulation of defective actuators via
neighboring elements and amplification of single-element strokes through cooperative exci tation. Furthermore, self-sensing effects were exploited for error detection. These results
underline the potential of DEA arrays for decentralized control, fault-tolerant actuation,
and future applications in soft robotics and wearable systems
Die Blockade des Erythropoietin-producing hepatoma receptor B4 (EphB4) - Signalwegs hemmt die Vaskularisierung und das Wachstum von Endometrioseherden
Full text linkDie Endometriose ist mit einer Prävalenz von ca. 10% eine häufig vorkommende, benigne Erkrankung in der Gynäkologie, unter der insbesondere Frauen im gebärfähigen Alter leiden. Histopathologisch ist die Erkrankung durch das Auftreten von funktionalem, Endometrium-ähnlichem Gewebe außerhalb der Gebärmutterhöhle definiert. Nach der Implantationstheorie von Sampson werden während der Menstruation Endometriumfragmente retrograd über die Eileiter in die Bauchhöhle verschleppt, wo sie dann adhärieren und proliferieren. Dieser Pro-zess ist in hohem Maße von der Ausbildung neuer Blutgefäße abhängig, welche die heran-wachsenden Endometrioseherde mit Sauerstoff und Nährstoffen versorgen. Die Etablierung eines funktionsfähigen Gefäßnetzwerks in den Endometrioseherden wird durch verschiedene pro- und anti-angiogene Signalwege gesteuert. Einer dieser Signalwege wird durch die membranständige Tyrosinkinase Erythropoietin-producing hepatoma receptor B4 (EphB4) und ihren Liganden Erythropoietin-producing hepatoma interactor B2 (EprinB2) vermittelt. Interessanterweise wurde eine erhöhte Expression von EphB4 auch in ektopem Endometri-umgewebe nachgewiesen.
In der vorliegenden Arbeit wurde erstmalig untersucht, ob die Hemmung des EphB4-Signalwegs durch den Kinase-Inhibitor 4-Methyl-3-[[1-methyl-6-(3-pyridinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino]-N-[3-(trifluoromethyl)phenyl]-benzamide (NVP-BHG712) zu einer Unterdrückung der angiogenen Aktivität von Endothelzellen in vitro und der Vaskularisierung sowie des Größenwachstums von Endometrioseherden in vivo führt.
Anhand von verschiedenen Angiogenese-Assays konnte gezeigt werden, dass die Migration, die Tube Formation und die Sprouting-Aktivität sowohl von humanen Endothelzellen als auch von kultivierten Maus-Aortenringen durch NVP-BHG712 gehemmt wird.
Zur Untersuchung der Effekte von NVP-BHG712 auf die Entwicklung von neuen mikrovaskulären Netzwerken in Endometrioseherden unter in vivo Bedingungen wurden zwei etablierte Mausmodelle eingesetzt. Im ersten Modell wurden Endometriumfragmente auf die quergestreifte Muskulatur in der Rückenhautkammer von weiblichen BALB/c Mäusen transplantiert. Dieses Modell wurde zur Analyse der Gefäßmorphologie und Mikrohämodynamik der heranwachsenden Endometrioseherde mittels intravitaler Fluoreszenzmikroskopie gewählt. In Übereinstimmung mit den Ergebnissen aus den in vitro Analysen konnte eine signifikant reduzierte funktionelle Kapillardichte mit individuell dilatierten Mikrogefäßen unter der NVP-BHG712-Behandlung im Vergleich zur Vehikel-behandelten Kontrollgruppe über einen 14-tägigen Beobachtungszeitraum nachgewiesen werden. Dieser anti-angiogene Effekt wurde am Ende der in vivo Versuche immunhistochemisch mit einer Fluoreszenzfärbung gegen CD31 zur Markierung der Mikrogefäße in den Endometrioseherden bestätigt.
Durch die syngene Transplantation von Uterusgewebe in die Bauchhöhle von BALB/c Mäu-sen konnte im zweiten Modell die Wirkung von NVP-BHG712 auf das Wachstum von Endo-metrioseherden mittels repetitiver, hochauflösender Ultraschallbildgebung über 28 Tage un-tersucht werden. Die Behandlung mit NVP-BHG712 führte zu einer Reduktion des Stromagewebes und zu einer verringerten Gesamtgröße der Endometrioseherde im Ver-gleich zur Kontrollgruppe. Zusätzliche immunhistochemische Analysen an Tag 28 zeigten jedoch keine signifikanten Unterschiede in der mikrovaskulären Dichte und der Stromapro-liferationsrate zwischen NVP-BHG712- und Vehikel-behandelten Endometrioseherden. Dies ist dadurch zu erklären, dass zu diesem späten Zeitpunkt der Herdentwicklung hauptsächlich ein Umbau der vorhandenen Gefäße und keine Angiogenese mehr stattfindet. Daher wurden in einem weiteren Experiment intraperitoneal induzierte Endometrioseherde bereits nach 7 Tagen histologisch analysiert. Zu diesem frühen Zeitpunkt konnte eine signifikant reduzierte mikrovaskuläre Dichte und Proliferationsrate des Stromagewebes unter der Behandlung mit NVP-BHG712 nachgewiesen werden.
In weiteren Analysen wurde mit Hilfe einer quantitativen Echtzeit-Polymerase-Kettenreaktion (qRT-PCR) eine tendenziell geringere messenger ribonucleic acid (mRNA)-Expression von EphB4 in NVP-BHG712 behandelten, intraperitonealen Endometrioseherden nach 28 Tagen gemessen. Dieses Ergebnis lässt darauf schließen, dass NVP-BHG712 nicht nur einen inhi-bitorischen Effekt auf die Kinase-Aktivität von EphB4 haben könnte, sondern auch auf die Genexpression.
Zusammenfassend konnte in der vorliegenden Arbeit erstmalig gezeigt werden, dass die Blockade des EphB4-Signalwegs die Vaskularisierung und das Wachstum von Endometrio-seherden hemmt. Daher könnte EphB4 ein vielversprechendes pharmakologisches Target für die zukünftige Behandlung von Endometriose-Patientinnen darstellen.Endometriosis is a frequent gynecological disorder affecting approximately 10% of women especially during the reproductive age. Histopathologically the disease is defined by the presence of functional endometrium-like tissue outside the uterine cavity. According to Sampson´s implantation theory, endometrial fragments are shed retrogradely through the fallopian tubes to the peritoneal cavity during menstruation, where they adhere and proliferate. This process is highly dependent on the formation of new blood vessels, which supply the growing endometriotic lesions with oxygen and nutrients. The establishment of a functional vascular network in endometriotic lesions is regulated by various pro- and anti-angiogenic signaling pathways. One of these signaling pathways is mediated by the membrane-based tyrosine kinase erythropoietin-producing hepatoma receptor B4 (EphB4) and its ligand erythropoietin-producing hepatoma interactor B2 (EprinB2). Interestingly, an increased expression of EphB4 has also been detected in ectopic endometrial tissue.
In the present thesis, it was analyzed for the first time whether the inhibition of the EphB4-pathway by the kinase inhibitor 4-methyl-3-[[1-methyl-6-(3-pyridinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino]-N-[3-(trifluoromethyl)phenyl]-benzamide (NVP-BHG712) suppresses the angiogenic action of endothelial cells in vitro and the vascularization as well as the growth of endometriotic lesions in vivo.
By means of various angiogenesis assays, it could be demonstrated that the migration, tube formation and sprouting activity of both human endothelial cells and of cultivated mouse aor-tic rings is inhibited by NVP-BHG712.
To analyze the effects of NVP-BHG712 on newly developing microvascular networks in en-dometriotic lesions in vivo, two different, well-established murine models were chosen. In a first experimental setting, endometrial fragments were transplanted onto the striated muscle within the dorsal skinfold chamber of female BALB/c mice. This model was selected for the analysis of the vascular morphology and microhemodynamics within the growing endometri-otic lesions by means of intravital fluorescence microscopy. In line with the results of the in vitro analysis, a significantly reduced functional capillary density with individually dilated mi-crovessels was found under NVP-BHG712 treatment when compared to vehicle-treated con-trols during an observation period of 14 days. This anti-angiogenic effect was confirmed im-munohistochemically at the end of the in vivo experiments by fluorescence staining against CD31 to label the microvessels within the endometriotic lesions.
In a second set of experiments, the syngeneic transplantation of uterine tissue into the peri-toneal cavity of BALB/c mice allowed studying the effect of NVP-BHG712 on the growth of endometriotic lesions over 28 days by means of repeated high-resolution ultrasound imaging. Treatment with NVP-BHG712 caused a regression of the stromal tissue and a decrease of the overall lesion size when compared to controls. However, in immunohistochemical anal-yses on day 28 no significant differences in the microvascular density and the stromal prolif-eration rate were detected between NVP-BHG712- and vehicle-treated endometriotic lesions. This can be explained by the fact that in this late phase of lesion development a remodeling of the existent vessels occurs rather than angiogenesis. Therefore, intraperitoneally induced endometriotic lesions were analyzed after only 7 days in an additional approach. At this early time point, a significantly reduced microvessel density and stromal proliferation rate could be detected under the treatment with NVP-BHG712.
Additional analyses by means of real-time quantitative polymerase chain reaction (qRT-PCR) demonstrated a tendency towards lower messenger ribonucleic acid (mRNA) expression levels of EphB4 in NVP-BHG712-treated intraperitoneal endometriotic lesions after 28 days. Hence, it may be speculated that NVP-BHG712 not only suppresses the kinase activity of EphB4 but also its gene expression.
In summary, in this thesis it could be demonstrated for the first time that interrupting EphB4 signaling suppresses the vascularization and growth of endometriotic lesions. Hence, EphB4 may represent a promising pharmacological target for the future treatment of endometriosis patients
Personality Characteristics as Predictors of Temporary Labor Migration Intentions and The Moderating Role of Family Influence: A Case of Prospective Ugandan Female Migrant Domestic Workers to Saudi Arabia
Full text linkWith the rising number of temporary migrant workers, there is growing scholarly interest in understanding the factors shaping labor migration intention. This study examined the role of personality characteristics in predicting labor migration intention as housemaids among prospective female migrant domestic workers from Uganda to the Middle East. Personality characteristics included the Big Five factor model, which categorizes personality into five broad dimensions; and core self-evaluation, which reflects the fundamental assessments people make of themselves. Data was obtained from female Ugandan university students (N = 365). According to our regression analyses, among Big Five traits, Extraversion, Conscientiousness, and (tentatively) Neuroticism positively predicted labor migration intention, whereas Openness and Agreeableness did not. Core self-evaluation negatively predicted labor migration intention and explained additional variances beyond Big Five factor traits. Furthermore, family influence moderated the link between Extraversion and labor migration intention as well as Openness and labor migration intention. These findings pave way for more empirical studies aimed at understanding the influence of psychological characteristics on temporary labor migration, especially in Global South contexts. They also contribute to literature through extending personality studies to lower-level jobs and affirming the role of family influence in labor migration decisions in collectivistic cultures like Uganda
Early Synapse-Specific Alterations of Photoreceptor Mitochondria in the EAE Mouse Model of Multiple Sclerosis
Full text linkMultiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) linked to many neurological disabilities. The visual system is frequently
impaired in MS. In previous studies, we observed early malfunctions of rod photoreceptor
ribbon synapses in the EAE mouse model of MS that included alterations in synaptic
vesicle cycling and disturbances of presynaptic Ca2+ homeostasis. Since these presynaptic
events are highly energy-demanding, we analyzed whether synaptic mitochondria, which
play a major role in synaptic energy metabolism, might be involved at that early stage.
Rod photoreceptor presynaptic terminals contain a single large mitochondrion next to the
synaptic ribbon. In the present study, we analyzed the expression of functionally relevant
mitochondrial proteins (MIC60, ATP5B, COX1, PINK1, DRP1) by high-resolution qualitative and quantitative immunofluorescence microscopy, immunogold electron microscopy
and quantitative Western blot experiments. We observed a decreased expression of many
functionally relevant proteins in the synaptic mitochondria of EAE photoreceptors at an
early stage, suggesting that early mitochondrial dysfunctions play an important role in
the early synapse pathology. Interestingly, mitochondria in presynaptic photoreceptor
terminals were strongly compromised in early EAE, whereas extra-synaptic mitochondria in photoreceptor inner segments remained unchanged, demonstrating a functional
heterogeneity of photoreceptor mitochondria
Lutembacher syndrome with congenital atrial septal defect in an 18-year-old female: a rare case report
Full text linkIntroduction: Lutembacher syndrome (LS) is a rare condition with congenital atrial septal defect (ASD) and mitral stenosis (MS), often post-rheumatic illness. Diagnosis uses Doppler echocardiography, and treatment may involve surgery or percutaneous options. Case presentation: An 18-year-old female presented with worsening dyspnea, orthopnea, and potential undiagnosed rheumatic fever. Chest X-ray showed cardiomegaly. An echocardiogram revealed left atrial dilation and mitral stenosis with regurgitation, aortic valve showed thickening without stenosis, and the right ventricle was mildly dilated; an interatrial shunt was present. Mitral stenosis worsened left-to-right shunt. Discussion: LS results from the balance of ASD and MS. Factors influencing prognosis include pulmonary resistance, ASD size, and mitral stenosis severity. Echocardiography is essential for diagnosis, which revealed left atrial dilation, normal left ventricular function, severe mitral stenosis, and pulmonary valve changes. ECG indicated right ventricular hypertrophy. CXR showed left atrial enlargement and right ventricle enlargement. Treatment included an open heart surgery which replaced the mitral valve and closed the ASD. Conclusion: Lutembacher syndrome, a rare condition combining ASD and mitral stenosis, can cause cardiac failure and pulmonary hypertension if untreated. Given the patient’s stable condition in the early stages of the disease, early surgical or percutaneous intervention is advisable
Expanding the immune-related targetome of miR-155-5p by integrating time-resolved RNA patterns into miRNA target prediction
Full text linkThe lack of a sufficient number of validated miRNA targets severely hampers the understanding of their
biological function. Even for the well-studied miR-155-5p, there are only 239 experimentally validated
targets out of 42,554 predicted targets. For a more complete assessment of the immune-related miR-155
targetome, we used an inverse correlation of time-resolved mRNA profiles and miR-155-5p expression of
early CD4+ T cell activation to predict immune-related target genes. Using a high-throughput miRNA
interaction reporter (HiTmIR) assay we examined 90 target genes and confirmed 80 genes as direct
targets of miR-155-5p. Our study increases the current number of verified miR-155-5p targets approximately threefold and exemplifies a method for verifying miRNA targetomes as a prerequisite for the
analysis of miRNA-regulated cellular networks