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Rheological properties of suspensions with spherical particles in shear and elongational flows
The rheological behaviour of model suspensions with spherical particles was experimentally investigated in shear an elongational flows. Particular attention was focussed on the main parameters affecting the flow behaviour of suspensions such as particle size distribution, particle size, particle surface, humidity, temperature and viscosity of the matrix fluids. All variables were investigated depending on the pre-shear conditions. In this regard the validity of the time-temperature-superposition and the Trouton-ratio was verified for suspensions with spherical particles
Effects of Process Parameters on the Mechanical Properties and Microstructure of Additively Manufactured Carbon Black Particles-Reinforced Thermoplastic Polyurethane Composite Samples
Additive manufacturing (AM) techniques make fabricating complex designs, prototypes, and end-user products possible. Conductive polymer composites find applications in flexible electronics, sensor fabrication, and electrical circuits. In this study, thermoplastic polyurethane (TPU)-based conductive polymer composite samples were fabricated via fused filament fabrication (FFF). The effects of three important process parameters, including infill density (ID), layer thickness (LT), and fan speed (FS), on various mechanical properties (tensile and compressive properties) were investigated. It was observed that all the considered process parameters affect the mechanical properties, and they are significant parameters, as per the analysis of variance (ANOVA). From scanning electron microscopy (SEM) and optical microscopy, various combinations of parameters such as low ID, high LT, and high FS resulted in the formation of defects such as voids, cracks, and warping, which resulted in low mechanical properties. Finally, process parameter optimization was performed, resulting in a conductive polymer composite with the best possible combination of mechanical properties at high ID, low LT, and medium FS.This work was supported by Researchers Supporting Project Number (RSP2025R274), King Saud University, Riyadh, Saudi Arabia.King Saud Universit
Eine Trendwende in Optimalsteuerungssimulationen für das Laufen: Prädiktion und Rekonstruktion der 3D Ganzkörperbiomechanik aus optischen und inertialen Bewegungsdaten
Many sports disciplines performed for recreation or competition involve change-of-direction running, such as running on a curved path or cutting. Change-of-direction running can induce high demands on the musculoskeletal system due to rapid directional changes and fast decelerations. Thus, the execution is fundamental for injury risk but, at the same time, determines an athlete’s performance. Reconstruction of a measured motion can give detailed insights into biomechanical variables that are not measured directly, such as joint moments. Additionally, predicting human responses allows studying conditions that cannot be measured easily or could harm the participant. Optimal control enables simulations of a human model for movement reconstruction and prediction to analyze kinematics and kinetics comprehensively. However, optimal control simulations were limited to 2D models of the lower body or straight walking and running. Therefore, this thesis aims to develop and investigate novel methods to generate optimal control simulations, especially for change-of-direction running.
The foundation of this cumulative thesis comes from three publications. In the first publication, I, together with my co-authors, created efficient optimal control simulations of a 3D full-body musculoskeletal model using implicit dynamics and trajectory optimization. We demonstrated that curved running could be predicted from a random initial guess in 1 h 17 min by prescribing a curved motion path. While the predicted kinematics and kinetics matched reference data well, our work revealed that interlimb collisions should be modeled to predict change-of-direction movements robustly. In the second publication, we developed reconstructive simulations to estimate 3D kinematics and kinetics from optical motion capture for arbitrary running movements. We tracked measured marker data directly in addition to ground reaction forces in the simulations to avoid error propagation and accumulation associated with tracking estimated generalized coordinates. We showed that tracking marker positions instead of generalized coordinates reduced the marker error by around half but required longer to solve. In the third publication, my co-authors and I designed reconstructive simulations tracking linear acceleration and angular velocity from inertial motion capture to facilitate the assessment of 3D kinematics and kinetics outside the motion lab. Our evaluation with virtual inertial data proved the feasibility and potential accuracy of our proposed optimal control problem formulation, as the reconstructed simulations were able to distinguish between individual movement repetitions. Furthermore, this cumulative thesis presents an extensive literature overview and provides broader perspectives on the contributions of the included publications.
In conclusion, in this thesis, I addressed the challenges of obtaining a comprehensive biomechanical analysis for change-of-direction running by researching optimal control simulations. Future work should evaluate the proposed methods in the context of applications, such as studying cutting maneuvers on the sports field before and after injury prevention training. Additionally, further technological advancements are possible when investigating other data sources, such as radar, or by combining the physics-based optimal control simulations with machine learning. By contributing to predicting human responses and reconstructing human movement, my work lays a foundation for a better understanding of change-of-direction running movements in and outside the lab.Viele Sportarten des Freizeit- und Wettkampfsports beinhalten Laufen mit Richtungswechsel, wie Kurvenlaufen oder abrupte Richtungswechsel. Das schnelle Abbremsen und Ändern der Richtung belasten den Bewegungsapparat stark. Die Ausführung beeinflusst somit das Verletzungsrisiko, aber auch die sportliche Leistung. Die Bewegungsrekonstruktion einer gemessenen Bewegung gibt detaillierte Einblicke in nicht gemessene biomechanische Variablen, etwa Gelenkmomente. Darüber hinaus ermöglicht die Bewegungsprädiktion die Untersuchung von Faktoren, die schwer messbar oder potenziell schädlich für den Teilnehmer sind. Optimalsteuerungssimulationen von Menschmodellen können eine Bewegungsrekonstruktion und -prädiktion für eine umfassende Analyse von Kinematik und Kinetik erstellen. Ziel dieser Arbeit ist daher die Entwicklung und Untersuchung neuartiger Methoden zur Erzeugung von Optimalsteuerungssimulationen, speziell für das Laufen mit Richtungswechsel.
Drei Publikationen bilden die Grundlage dieser kumulativen Dissertation. In der ersten Publikation erarbeitete ich mit meinen Koautoren effiziente Optimalsteuerungssimulationen eines 3D Ganzkörper-Muskel-Skelett-Modells anhand impliziter Dynamik und Trajektorienoptimierung. Wir demonstrierten, dass Kurvenlaufen in 1 h 17 min vorhergesagt werden konnte, ausgehend von einem zufälligen Startwert für die Optimierung und einer kreisförmigen Bewegungsbahn. Obwohl die vorhergesagte Kinematik und Kinetik gut mit den Referenzdaten übereinstimmten, erwies es sich als notwendig Überschneidungen von Körpersegmenten zu modellieren, um Richtungswechsel robust vorherzusagen. In der zweiten Publikation entwickelten wir rekonstruktive Simulationen, um die 3D Kinematik und Kinetik für beliebige Laufbewegungen von optischer Bewegungserfassung zu schätzen. Die Simulationen verfolgten neben den Bodenreaktionskräften direkt die gemessenen Markerdaten anstatt die geschätzten generalisierenden Koordinaten, damit die damit assoziierte Fehlerfortpflanzung und -akkumulation vermieden wird. Dies reduzierte den Markerfehler um etwa die Hälfte, aber benötigte länger zum Lösen. In der dritten Publikation entwarfen meine Koautoren und ich Simulationen, die lineare Beschleunigung und Winkelgeschwindigkeit von Inertialsensorik nachverfolgen und so eine kinematische und kinetische 3D Analyse außerhalb des Bewegungslabors ermöglichen. Unsere Auswertung mit virtuellen Inertialdaten bewies die Durchführbarkeit und potenzielle Genauigkeit der vorgeschlagenen Formulierung der Optimalsteuerung, da die rekonstruierten Simulationen sich zwischen einzelnen Wiederholungen unterschieden. Darüber hinaus bietet diese kumulative Dissertation einen umfassenden Literaturüberblick und diskutiert unter breitem Gesichtspunkt die Beiträge der Publikationen.
Zusammenfassend adressierte ich in dieser Arbeit durch die Erforschung von Optimalsteuerungssimulationen die Herausforderungen einer umfassenden biomechanischen Analyse von Richtungswechseln beim Laufen. Zukünftige Arbeiten sollten die vorgestellten Methoden im Anwendungskontext evaluieren, wie der Untersuchung von Richtungswechseln auf dem Spielfeld vor und nach einem Verletzungspräventionstrainings. Darüber hinaus sind mit anderen Datenquellen, wie Radar, oder der Kombination physikbasierter Simulationen mit maschinellem Lernen weitere technologische Fortschritte möglich. Indem meine Arbeit zur Bewegungsrekonstruktion und -prädiktion beiträgt, legt sie den Grundstein für ein besseres Verständnis von Laufbewegungen mit Richtungswechsel in- und außerhalb des Labors
Analyse des Chemokinrezeptors CCR3 und seiner Rolle in der Pathogenese des allergischen Asthmas
Asthma bronchiale is a chronic disease that affects a large number of people worldwide and results in a high burden of disease. Due to the contact with airborne allergens, patients suffering from allergic asthma experience acute asthma attacks, characterized by shortness of breath, chest tightness and coughing. The progression of the disease leads to chronic lung inflammation and structural remodelling of the airways causing airway obstruction. Since there is no cure for asthma yet, the current therapy aims only at treating the symptoms and reducing the inflammatory response. The underlying immune response is highly complex and involves a variety of immune cells. Chemokines are important mediators in the correct localization of these different immune players that need to be directed to the site of inflammation. They are involved in cell migration, survival and also mediation of effector functions. CCR3 has been described primarily as a driver of eosinophil chemotaxis. However, more recent studies demonstrate its importance for mast cells, macrophages, T cells and dendritic cells. Moreover, CCR3 is expressed on structural cells such as epithelial cells or airway smooth muscle cells, suggesting its great relevance for allergic diseases including asthma bronchiale.
The present study aims at analysing the role of the chemokine receptor CCR3 in the pathogenesis of allergic asthma in more detail. In a human cohort of healthy controls and asthmatic patients, the expression of CCR3 and its ligands RANTES and eotaxin was investigated in peripheral blood cells. CCR3 expression was found to be increased in asthmatic patients and associated with worse lung function and higher blood eosinophil numbers. For further analysis, a CCR3-deficient mouse strain was used in a house dust mite-induced allergic asthma model. In the absence of CCR3, mice developed severe airway hyperresponsiveness while showing reduced eosinophilic inflammation and lower IgE levels as compared to wild-type mice. When investigating other inflammatory cells in the airways, mast cells and neutrophils were found increased in CCR3-deficient mice as compared to wild-type littermates. CCR3 KO mice showed a strong TH2 polarisation but were unable to properly release TH2 cytokines due to a reduced calcium influx in the absence of CCR3 activation. Moreover, numbers of MHCI cross-presenting cDC1 and γδ T cells were increased in CCR3 KO mice resulting in induced antigen-cross presentation in vitro. In vivo, CCR3 KO mice presented reduced CD8 T cell numbers in the lung compartment. CCR3-deficient CD8 T cell subsets shifted towards a more pronounced tissue-resident phenotype and had reduced numbers of CD8 effector-memory T cells. The CCR3-deficient CD8 T cell population was characterized by an extended chemokine receptor repertoire, reduced IL-4 signalling and the expression of exhaustion markers. Additionally, their integrin expression was increased while the production of cytotoxic mediators was significantly reduced.
In summary, this work provides a better understanding of the involvement of CCR3 in the orchestration of asthmatic lung inflammation and its impact on different immune cell subsets. The presented results suggest a functional impact of CCR3 expression and activation on eosinophils, CD8 T cells, mast cells and dendritic cells which could represent new specific targets for future immunotherapy of asthma bronchiale
Decoding plasma cell maturation dynamics with BCMA
Plasma cells provide protective antibodies following an infection or vaccination. A network of intrinsic and extrinsic factors fine-tunes the generation of a heterogenous plasma cell pool with varying metabolic requirements, transcriptional profiles and lifespans. Among these, the B cell maturation antigen (BCMA) has been implicated in the APRIL-mediated survival of long-lived plasma cells. To characterize the terminal maturation of plasma cells, we constructed a BCMA reporter mouse (BCMA:Tom) that exclusively labeled antibody-secreting cells and revealed that BCMA:Tom expression varied by IgH isotype and increased with plasma cell maturity. The BCMA reporter, used alongside the Blimp1-GFP reporter, also allowed detailed tracking of plasma cell development and highlighted the importance of the in vivo microenvironment to complete plasma cell maturation. Therefore, the BCMA:Tom reporter mouse provides a valuable tool for tracking plasma cell development and maturation with flow cytometry or advanced imaging techniques, enabling a deeper understanding of the mechanisms regulating plasma cell heterogeneity and longevity
Meet the family − the catalog of known hot subdwarf stars
In preparation for the upcoming all-sky data releases of the Gaia mission, we compiled a catalog of known hot subdwarf stars and candidates drawn from the literature and yet unpublished databases. The catalog contains 5613 unique sources and provides multi-band photometry from the ultraviolet to the far infrared, ground based proper motions, classifications based on spectroscopy and colors, published atmospheric parameters, radial velocities and light curve variability information. Using several different techniques, we removed outliers and misclassified objects. By matching this catalog with astrometric and photometric data from the Gaia mission, we will develop selection criteria to construct a homogeneous, magnitude-limited all-sky catalog of hot subdwarf stars based on Gaia data. As first application of the catalog data, we present the quantitative spectral analysis of 280 sdB and sdOB stars from the Sloan Digital Sky Survey Data Release 7. Combining our derived parameters with state-of-the-art proper motions, we performed a full kinematic analysis of our sample. This allowed us to separate the first significantly large sample of 78 sdBs and sdOBs belonging to the Galactic halo. Comparing the properties of hot subdwarfs from the disk and the halo with hot subdwarf samples from the globular clusters ! Cen and NGC 2808, we found the fraction of intermediate He-sdOBs in the field halo population to be significantly smaller than in the globular clusters
An Active Radar Interferometer Utilizing a Heterodyne Principle-Based Target Modulator
The Active Radar Interferometer (AcRaIn) represents a novel approach in secondary radar technology, aimed at environments with high reflective clutter, such as pipes and tunnels. This study introduces a compact design minimizing peripheral components and leveraging commercial semiconductor technologies operating in the 24 GHz ISM band. A heterodyne principle was adopted to enhance unambiguity and phase coherence without requiring synchronization or separate communication channels. Experimental validation involved free-space and pipe measurements, demonstrating functionality over distances up to 150 m. The radar system effectively reduced interference and achieved high precision in both straight and bent pipe scenarios, with deviations below 1.25% compared to manual measurements. By processing signals at intermediate frequencies, advantages such as improved efficiency, isolation, and system flexibility were achieved. Notably, the integration of amplitude modulation suppressed passive clutter, enabling clearer signal differentiation. Key challenges identified include optimizing signal processing and addressing logarithmic signal attenuation for better precision. These findings underscore AcRaIn’s potential for pipeline monitoring and similar applications.This research was funded by Europäischer Fonds für regionale Entwicklung grant number 84002593.Europäischer Fonds für regionale Entwicklun
Postoperatives Hörvermögen und Rezidivwahrscheinlichkeit bei Patienten mit Cholesteatom in Abhängigkeit vom EAONO/JOS Staging- Erlanger Ergebnisse
Hintergrund und Ziele
Im Laufe der Jahre wurden eine Reihe von Klassifikationssystemen für Cholesteatome entwickelt. Im Jahr 2017 veröffentlichte die EAONO/JOS (European Academy of Otology and Neurotology/ Japanese Otologic Society) ein neues System zur Definition, Klassifizierung und zum Staging von Cholesteatomen. Das Staging beruht auf der Unterteilung des Mittelohrs in fünf unterschiedliche anatomische Bereiche. Im Stadium I der Krankheit ist ein einziger Bereich betroffen, im Stadium II sind es zwei bis fünf Bereiche. Die vorliegende Studie untersucht die Signifikanz dieser Differenzierung und somit die Aussagekraft dieses Stagings. Hierzu wird in der vorliegenden Studie der Einfluss der Anzahl der betroffenen Mittelohrbereiche auf die Residual- und Rezidivrate, das Hörvermögen und auf die Komplexität der chirurgischen Intervention analysiert.
Methoden
Die vorliegende Publikation ist eine retrospektive Auswertung der Krankendaten von Patienten, die in der Klinik für Hals-Nasen-Ohren-Heilkunde des Universitätsklinikums Erlangen wegen eines Cholesteatoms im Zeitraum 01.01.2010 bis zum 31.07.2019 primär operiert wurden. Wiederauftretende Cholesteatome wurden unterteilt in Residuum und Rezidiv, angelehnt an die EAONO/JOS Klassifikation. Das Hörvermögen wurde anhand des Mittelwertes der Schalleitungskomponente (Air Bone Gap, ABG) bei 0.5, 1, 2, 3 kHz ermittelt. Die Komplexität der Operation wurde anhand der Wullstein-Klassifikation für Tympanoplastiken sowie der angewandten Operationstechnik bewertet.
Ergebnisse und Beobachtungen
Im untersuchten Zeitraum wurden 513 Ohren (431 Patienten) aufgrund eines primären Cholesteatoms operiert. Die durchschnittliche Follow-Up- Zeit lag bei 21.6 ± 21.5 Monaten. Bei 107 (20.9%) Ohren war ein einziger Bereich, bei 130 (25.3%) zwei, bei 157 (30.6 %) drei, bei 72 (14.0%) vier und bei 47 (9.2%) fünf Bereiche betroffen. Eine steigende Anzahl betroffener Bereiche ging einher mit einer signifikant höheren Rate an Residuen (9.4 – 21.3 %, p=0.008), komplexere Operationen sowie schlechteren Hörergebnissen (präoperativ 14.1 – 25.3 dB, postoperativ 11.3 – 16.8 dB, p < 0.001).
Hierbei konnte gezeigt werden, dass ein signifikanter Unterschied sowohl bei der Differenzierung zwischen Stadium I und II, aber auch zwischen den verschiedenen Anzahlen an betroffenen Bereichen innerhalb des Stadiums II vorlag. Dies zeigt sich beispielsweise hinsichtlich der Residualrate. Ohren mit einem (9.3%) oder zwei (8.5%) betroffenen Bereichen hatten einen Residualrate von unter 10 %, während Ohren mit drei (21.0%), vier (12.5%) und fünf (21.3%) betroffenen Bereichen Residualraten von deutlich über 10 % aufwiesen.
Schlussfolgerungen und Diskussion
Die erhobenen Daten zeigen, dass die Anzahl der betroffenen Bereiche im Mittelohr die Residualrate, das Hörvermögen und die Komplexität des chirurgischen Eingriffes beeinflusst. Somit zeigen die Ergebnisse der Studie, dass die aktuelle EAONO/JOS-Klassifikation im Grunde zutrifft. Die ausgewerteten Daten zeigen allerdings, dass die Klassifikation zu wenig differenziert ist, da sich die Ergebnisse in Bezug auf die Residualrate, das Hörvermögen und den chirurgischen Eingriff je nach Anzahl der betroffenen Bereiche innerhalb des Stadiums II deutlich unterscheiden.
In künftigen Analysen sollte eine Weiterentwicklung der Klassifikation angestrebt werden. Hierfür sollten multizentrische, prospektive randomisierte Studien durchgeführt werden, um einen möglichst großen internationalen Konsens zu erzielen
Presence of brain metastasis differentially impacts long-term survival after first-line therapy in melanoma depending on BRAF mutation status
Background Modern therapeutic strategies have significantly improved the prognosis of advanced melanoma patients. Predictive factors of therapy response include serum LDH; however, predictive markers for long-term survival are currently largely lacking. Patients and methods Patients diagnosed with stage IV melanoma (AJCCv8) of cutaneous origin or unknown primary were identified from the prospective multicenter German Dermatologic Cooperative Oncology Group (DeCOG) skin cancer registry ADOREG. Baseline characteristics were compared between patient groups with short-term versus long-term survival. Statistical analysis included ROC analysis and multinomial regression analysis. Results Of 3066 stage IV melanoma patients entered into the ADOREG between 05/2014 and 06/2021, 395 were identified for this study, of whom 301 (76.2%) survived ≤1 year, and 94 (23.8%) survived ≥5 years after stage IV diagnosis. The median follow-up time was 6 months (range 0-129 months). Regarding the baseline characteristics, only elevated serum LDH (P <0.001) was found to be independently predicting survival ≤1 year. Type of first-line therapy, immune checkpoint inhibition (ICI) versus BRAF/MEK targeted therapy (TT), was not predictive of long-term survival ≥5 years. For survival ≤1 year, the presence of brain metastases at treatment start was an independent predictor in BRAF-mutated patients regardless if they received TT (N=113; P=0<0.001) or ICI (N=69; P=0.015), but not in BRAF-wildtype patients who received ICI (N=161; P=0.47). Conclusions Low serum LDH independently predicts long-term survival of stage IV melanoma patients in every subgroup of treatment type and BRAF status. Brain metastasis has a negative impact on long-term survival in BRAF-mutated, but not in BRAF-wildtype patients. Investigation of molecular features of brain metastases in BRAF-mutated vs. BRAF-wildtype melanomas may lead to new insights in tumor biology and may yield new therapeutic approaches
Evaluating smartphone-based 3D imaging techniques for clinical application in oral and maxillofacial surgery: A comparative study with the vectra M5
Purpose This study aimed to clarify the applicability of smartphone-based three-dimensional (3D) surface imaging for clinical use in oral and maxillofacial surgery, comparing two smartphone-based approaches to the gold standard. Methods Facial surface models (SMs) were generated for 30 volunteers (15 men, 15 women) using the Vectra M5 ( Canfield Scientific, USA ), the TrueDepth camera of the iPhone 14 Pro ( Apple Inc., USA ), and the iPhone 14 Pro with photogrammetry. Smartphone-based SMs were superimposed onto Vectra-based SMs. Linear measurements and volumetric evaluations were performed to evaluate surface-to-surface deviation. To assess inter-observer reliability, all measurements were performed independently by a second observer. Statistical analyses included Bland–Altman analyses, the Wilcoxon signed-rank test for paired samples, and Intraclass correlation coefficients. Results Photogrammetry-based SMs exhibited an overall landmark-to-landmark deviation of M = 0.8 mm (SD = ± 0.58 mm, n = 450), while TrueDepth-based SMs displayed a deviation of M = 1.1 mm (SD = ± 0.72 mm, n = 450). The mean volumetric difference for photogrammetry-based SMs was M = 1.8 cc (SD = ± 2.12 cc, n = 90), and M = 3.1 cc (SD = ± 2.64 cc, n = 90) for TrueDepth-based SMs. When comparing the two approaches, most landmark-to-landmark measurements demonstrated 95% Bland–Altman limits of agreement (LoA) of ≤ 2 mm. Volumetric measurements revealed LoA > 2 cc. Photogrammetry-based measurements demonstrated higher inter-observer reliability for overall landmark-to-landmark deviation. Conclusion Both approaches for smartphone-based 3D surface imaging exhibit potential in capturing the face. Photogrammetry-based SMs demonstrated superior alignment and volumetric accuracy with Vectra-based SMs than TrueDepth-based SMs.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Regensburg (8921