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Seamless Science: Lifting Experimental Mechanical Testing Lab Data to an Interoperable Semantic Representation
Get PDFThe scientific landscape is undergoing rapid transformations with the advent of the digital age which revolutionizes research methodologies. In materials science and engineering, an adoption of modern data management techniques is desirable to maximize the efficiency and accessibility of research efforts. Traditional practices in testing laboratories are usually inadequate for efficient data acquisition and utilization as they lead to local storage and difficulty in publication and correlation with other results. Electronic laboratory notebooks (ELNs) are promising prospects in this respect. Semantic concepts and ontologies enhance interoperability by standardizing experimental data representation. An in‐laboratory pipeline seamlessly integrating an ELN with transformation scripts to convert experimental into interoperable data in a machine‐actionable format is created in this study as a proof of concept. Tensile test results and the corresponding tensile test ontology are used exemplary. Linking ELN data to semantic concepts enriches the stored information while improving interpretability and reusability. Involving undergraduate students builds a bridge between theory and practice during their training and promotes their digital skills. This study underscores the potential of ELNs and knowledge representations as beneficial means toward improved data management practices that enhance collaborative research and education while ensuring compatibility with evolving standards and technologies
The Role of Trimodulin in Modulating COVID-19- and sCAP-Associated Inflammation in Endothelial and Immune Cells
Get PDFRespiratory diseases are among the leading causes of death from diseases worldwide. The latest data from the World Health Organization (WHO) indicate that respiratory diseases, particularly COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2), as well as severe community-acquired pneumonia (sCAP), have already resulted in ten million deaths worldwide. These data suggest that currently available medications are not sufficient to effectively combat these diseases. A promising option for the treatment of severe respiratory diseases is the immunoglobulin preparation trimodulin. It consists primarily of Immunoglobulin G (IgG) and additionally contains Immunoglobulins M (IgM) and A (IgA). Trimodulin has already demonstrated a significant clinical impact on the treatment of respiratory diseases in patients with sCAP and COVID-19. The effectiveness of trimodulin is based on its bifunctional molecular mechanisms. On one hand, trimodulin combats pathogens by promoting opsonization, phagocytosis, and initiating the complement system, triggering an initial defense response. On the other hand, the IgM and IgA enriched immunoglobulin preparation modulates the immune system by suppressing complement-dependent toxicity (CDC), binding to cytokines, inducing Fc receptor signaling, and reducing lymphocyte proliferation. However, previous studies primarily focused on the mode of action of trimodulin regarding bacterial endotoxins and phagocytosis in immune cells related to sCAP and COVID-19. Endothelial inflammation and dysfunction are key features of both respiratory diseases, making vascular endothelial cells crucial as they lead to excessive immune cell transmigration and tissue damage.
This doctoral thesis firstly investigated trimodulin's influence on vascular endothelial cells in a model of sCAP and COVID-19-associated endothelial inflammation, where human umbilical vein endothelial cells (HUVECs) were stimulated with lipopolysaccharide (LPS) and SARS-CoV-2 envelope protein (env). Endothelial inflammation was assessed by measuring the protein expression of ICAM-1 and VCAM-1, along with RNA expression of ICAM-1, VCAM-1, and E-selectin. Trimodulin significantly reduced LPS and SARS-CoV-2 env-induced inflammation in HUVECs by downregulating ICAM-1, VCAM-1 protein expression, as well as ICAM-1, VCAM-1 and E-selectin RNA expression. Proteomic analysis revealed that trimodulin significantly impacts TGFβ-associated proteins by reducing the abundance of TGFβ-related propeptides. An enzyme-linked immunosorbent assay (ELISA) confirmed that trimodulin activated TGFβ. Furthermore, the use of an integrin αvβ6/αvβ1 inhibitor, bexotegrast, demonstrated, that the trimodulin mediated TGFβ release was partially integrin dependent, and the inhibitory effect of trimodulin on ICAM-1 and VCAM-1 expression was linked to the activation of TGFβ. These findings underscore the positive impact of trimodulin in the treatment of sCAP and COVID-19-induced inflammation and provide a mechanistic explanation for its effect on reducing patient mortality.
In addition, this thesis provides new insights into trimodulin’s influence on COVID-19-associated inflammation in primary immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with SARS-CoV-2 env and R848, a toll-like receptor 7/8 (TLR7/8) activator. The production of the pro-inflammatory cytokines IL-6 and IL-1β was then measured at both RNA and protein levels. Trimodulin significantly reduced IL-6 and IL-1β RNA expression, as well as IL-6 protein release, in response to stimulation. These results suggest that trimodulin has immunomodulatory effects that could be beneficial in managing sCAP and COVID-19. By reducing IL-6-mediated inflammation, a marker of poor prognosis, trimodulin may prevent inflammation progression and tissue damage.
Moreover, to investigate the connection between endothelial activation and tissue damage caused by immune cell transmigration, a leukocyte adhesion assay using the U937 cell line was developed. In a model of sCAP-associated endothelial inflammation, trimodulin significantly reduced U937 adhesion to HUVECs. These findings suggest that trimodulin has substantial potential to inhibit immune cells adhesion and therefore transmigration into inflamed tissue and thereby reducing the risk of tissue damage. Altogether, this doctoral thesis offers valuable insights into the immunomodulatory effects of trimodulin, with a focus on endothelial cells as well as immune cells, and highlights its substantial therapeutic potential in preventing tissue damage. These findings confirm the potential of trimodulin as a crucial therapeutic approach in the fight against respiratory diseases and open up new possibilities to evaluate trimodulin in other diseases in which endothelial inflammation and immune cell transmigration play a role
Electronic Structure and Electrical Conduction Analysis of Na₀.₅Bi₀.₅TiO₃-6BaTiO₃ based Piezoceramics
Get PDFNa₀.₅Bi₀.₅TiO₃ (NBT-based) ceramics are considered promising candidates to replace lead-based materials for piezoelectric applications; however, the functional properties are not the focus of this study. Instead, a comprehensive investigation was conducted on the electronic structure and electrical conduction behavior of the morphotropic phase boundary composition (6%) in the solid solution of (1−x)(Na₀.₅Bi₀.₅)TiO₃–xBaTiO₃ system (NBT-BT) with different A-site stoichiometry, A-site to B-site ratios, and 1% Zn doping. The electrical conduction behavior was analyzed using a combination of direct current (dc) and alternating current (ac) conductivity measurements, conducted over a wide range of oxygen partial pressures and temperatures under various atmospheric conditions. Additionally, multiple X-ray photoelectron spectroscopy (XPS) techniques were employed, including high-temperature XPS, near-ambient pressure XPS (NAP-XPS) on bare surfaces of oxidized and reduced samples, as well as in situ XPS measurements at interfaces between NBT-6BT and 10% Sn-doped In₂O₃ under vacuum annealing and cathodic polarization, using an electrochemical cell setup.
In oxygen partial pressure-dependent conductivity measurements, assuming that the dc method reflects electronic conductivity and the ac method measures total conductivity, the ionic contribution was determined by subtraction. This approach is valid under conditions ranging 10⁵ – 10⁰ ppm. Then, two distinct electrical conduction behaviors were identified among the samples by comparing their dc and ac conductivity: Type I (p-type) behavior is observed in Na-rich and acceptor-doped compositions, which are dominated by high ionic conductivity, with total conductivity reaching up to 4 ×10⁻⁴ S/cm at 450°C, accompanied by p-type electronic conduction. In contrast, Type II (n-type) behavior is found in slightly Na-rich and Bi-rich samples, which primarily exhibit n-type electronic conductivity with significantly lower conductivity, around 10⁻⁸ S/cm at 450°C. Then a new defect model for multivalent A-site perovskite NBT-based materials is proposed to interpret these observations, accounting for the effects of A-site nonstoichiometry through the formation of NaBi and BiNa antisite defects, and the A:B ratio through the formation of A-site or B-site vacancies. This model calculates antisite defect and vacancy concentrations to predict effective doping effects by defining the Na-to-Bi ratio as X and the A-to-B ratio as Y. Represented as a two-dimensional map of effective doping concentration versus X and Y, the model predicts that: only half of the third quadrant (X1) show an effective ''donor'' effect, while the remaining regions exhibit an effective ''acceptor'' effect. When accounting for the intrinsic donor background in our samples and the acceptor background observed in the University of Sheffield samples, described in literature, the experimental results confirm the model’s predictions. In temperature-dependent conductivity measurements at 10⁵ and 10⁰ ppm, the observed behavior cannot be explained by free carriers alone—polaron conduction must also be considered. The hole polaron binding energy, attributed to the Bi³⁺/Bi⁴⁺ charge transition levels, is found to be 1.08 eV above the valence band maximum by Na₀.₅₁Bi₀.₄₉TiO₃–6BT sample. In contrast, the electron polaron binding energy, associated with the Bi³⁺/Bi⁰ charge transition level, is found to be 2.04 eV below the conduction band minimum. These hole and electron polaron levels also define the lower and upper limits of the Fermi level, respectively.
The investigation of oxygen partial pressure and temperature-dependent conductivity was further extended into the strongly reducing regime (10⁻¹² to 10⁻¹⁸ ppm). The results show that under strongly reducing conditions, dc conductivity includes significant ionic contributions, invalidating the assumption that it represents purely electronic conduction. The activation energies extracted from the Arrhenius plots are 0.4–0.68 eV, corresponding to the migration energy of oxygen vacancies. After temperature-dependent measurements at 10⁻¹⁸ ppm, all samples darkened from light yellow, indicating reduction. XPS on bare surfaces confirms significant Bi³⁺reduction to metallic Bi upon heating to 350°C. Despite their high ionic conductivity, the chemical instability of Type I samples under strongly reducing conditions limits their suitability for solid oxide fuel cell applications. A clear trend in surface composition emerges from high-temperature XPS measurements on oxidized samples: a higher A:B ratio corresponds to an increased Na:Bi ratio, as Bi content rises and Na content decreases with increasing A:B ratio. Lastly, the Fermi level positions show a strong correlation with electrical conductivity: p-type samples exhibit Fermi levels that are 0.25 ± 0.05 eV lower than those of n-type samples, which may account for the higher electronic conductivity observed in p-type conduction.
Finally, electron traps in NBT-6BT were identified using in situ X-ray photoelectron spectroscopy (XPS) under vacuum annealing and cathodic polarization, employing an electrochemical cell setup. This approach comfirmed Bi³⁺/Bi⁰ as a key electron trap, with its charge transition level located at 2.47 ± 0.10 eV above the valence band maximum. Including the electron polaron binding energy, the electrical band gap for NBT(-6BT)-based materials is 4.51 eV
Experimental investigation of thermo-diffusive instabilities in lean premixed hydrogen combustion
Get PDFClimate change driven by the release of greenhouse gases from increasing fossil fuel consumption presents significant global challenges. Addressing these challenges necessitates a global transition toward renewable energy sources, which offer a sustainable and low-emission alternative to fossil fuels. Among the various candidates, hydrogen produced by low-emission methods is widely considered as a promising carbon-free alternative fuel for internal combustion engines, gas turbines and industrial burners. The integration of hydrogen into combustion systems presents several technical challenges, including flashback, flame instabilities, a wide flammability range, high burning velocities, and high nitrogen oxides emissions. To overcome these barriers, advanced hydrogen combustion technologies are essential. Among these, fuel-lean hydrogen combustion has attracted considerable research interest due to its potential to simultaneously reduce nitrogen oxides emissions and enhance thermal efficiency. One key challenge for fuel-lean hydrogen combustion is that it features intrinsic thermo-diffusive instabilities, which lead to cellular burning patterns. However, details of quantitative thermo-chemical states of cellular flames, and how these thermo-diffusive behaviors evolve with turbulence remain unclear. The main objective of this research is to advance the fundamental understanding in the effects of thermo-diffusive instabilities in fuel-lean premixed hydrogen combustion under laminar and turbulent flow conditions.
To provide a comprehensive understanding of the thermo-diffusive instabilities effects, representative fuel-lean premixed hydrogen/methane/air and hydrogen/air flames with well-defined boundary conditions are studied. First, the effects of thermo-diffusive instabilities on the basic cellular structures are investigated with laminar fuel-lean premixed hydrogen/methane/air polyhedral flames (paper I and paper II). Furthermore, the effects of interactions between thermo-diffusive instabilities and turbulence on the flame structure are studied with turbulent fuel-lean premixed hydrogen/air flames over a wide range of turbulent intensities up to distributed burning regimes (paper III and paper IV).
To quantify the flame topology and thermo-chemical states of fuel-lean premixed hydrogen/methane/air and hydrogen/air flames, advanced laser-based optical diagnostics measurements are employed. Two-dimensional measurements of planar laser-induced fluorescence of hydroxyl radicals are conducted to capture the macroscopic flame structure. Two-dimensional particle image velocimetry measurements are carried out to quantify the flow structure in turbulent flames. One-dimensional spontaneous Raman/Rayleigh spectroscopy is used to quantitatively measure the temperature and concentration of the major species. Two-dimensional Rayleigh thermometry is used to visualize the flame topology along with the one-dimensional Raman/Rayleigh measurements.
The main conclusions of this dissertation are summarized as follows. In laminar flows, classic cellular burning patterns are observed in fuel-lean premixed hydrogen/methane/air polyhedral flames. The thermo-chemical states in positively and negatively curved flame segments show significant differences due to the focusing/defocusing of highly diffusive hydrogen by positive/negative curved flame surface. Specifically, flame regions with positive curvatures have a higher hydrogen mole fraction, local equivalence ratio and temperature compared to those with negative curvatures. The hydrogen mole fraction differences between positively and negatively curved flame cells are enlarged with decreasing flow velocity, and with increasing hydrogen content and equivalence ratio.
In turbulent flows, interactions between turbulence and flame significantly modify the thermo-diffusive behaviors. At low turbulence intensities, locally intense burning characterized by elevated local equivalence ratio, high water mole fraction, and super-adiabatic flame temperature is mainly observed in post-flame regions surrounded by positively curved flame surfaces, where the highly diffusive hydrogen is locally enriched. This reveals that turbulence imposes synergistic effects with thermo-diffusive instabilities. As the turbulence intensity increases, the local burning enhancement near positively curved flame surfaces is weakened, even though the flame surface is more disturbed by turbulence, which indicates that both molecular diffusion and turbulent transport play significant roles in the combustion process. At high turbulence intensities, no intense burning regions are observed in the flame as turbulent mixing dominates over molecular mixing. However, increasing residence time leads to the occurrence of thermo-diffusive behaviors in positively curved cells formed by the fully developed initial turbulent eddies.
The comprehensive multi-scalar data presented in this dissertation not only enhance the fundamental understanding of thermo-diffusive instabilities in fuel-lean premixed hydrogen combustion, but also provide crucial quantitative data for the development and validation of simulation models
Development of human brain tumor assembloids that mimic the interaction of normal and tumorous tissue to assess the impact of ionizing radiation
Get PDFAlthough brain and other central nervous system (CNS) cancers are relatively rare, they have a high mortality rate [1] despite treatment with surgery, chemotherapy, and/or radiation therapy [2–5]. To further improve therapeutic approaches and to diminish the lethality of patients with brain and other CNS cancers, it is crucial to understand the treatment-induced cellular and molecular alterations in both normal brain and tumorous tissues, as well as their interactions. For this purpose, the main objective of this thesis was to generate a three-dimensional human cell culture model that simulates brain tumors, including early tumorigenesis, and that is suitable for investigating radiation-induced effects exerted on normal and tumorous brain tissue as well as their interaction. The brain tumor assembloid model generated in this thesis consisted of two connected parts with the same genetic background: the normal neural tissue was modeled using neural spheroids generated from human embryonic stem cells (hESCs), and the tumor-like tissue was modeled using genetically modified MYC overexpressing (MYCOE) cells, which were generated in an autologous setting from neural spheroids. Tumor initiation and promotion were simulated by overexpression of the oncogene MYC [6], which was stably integrated into the genome of single cells of the neural spheroid, and by the proliferation of these MYCOE cells within the neural spheroid thereafter. To balance the physiological cellular and morphological heterogeneity observed in vivo with the cellular and morphological similarity of replicate samples across experiments, a heterogeneous MYCOE cell population was isolated, aggregated into uniform spheres (MYCOE spheres), and fused with normal d100 neural spheroids, containing neuronal and glial cells, to simulate the tumor-like part of the generated brain tumor assembloid model. The proliferating MYCOE cells showed an immature neural phenotype, lower expression of tumor suppressor genes, as well as infiltrative and metastatic characteristics. In the assembloids, astrocytes from the neural spheroids extended their branches into the bordering MYCOE spheres and enveloped the infiltrated MYCOE cells within the neural spheroid. The assembloids are suitable for analyzing and interpreting radiation therapy effects using, for example, X-ray irradiation. Exposition of 1 or 3 Gy X-rays resulted in increased extend of MYCOE cell death, a lower number of infiltrating MYCOE cells, and shorter infiltration depth. The model bridges the gap between different model systems, is adaptable to specific tumor features, and offers a suitable possibility for human brain tumor modeling. A schematic overview of the brain tumor assembloid generation is shown in Figure 1
Der Neubau der Höheren Gewerbschule am Kapellplatz
Get PDFVor 175 Jahren, am 19. Dezember 1844, wurde der Neubau der Höheren Gewerbschule Darmstadt am Kapellplatz feierlich eingeweiht. Die Gewerbschule ist die Wiege der Technischen Universität Darmstadt. Denn im Unterschied zu anderen hessischen Universitäten wurde die damalige Technische Hochschule nicht in einem feierlichen Festakt gegründet. Vielmehr wurde sie 1877 von Großherzog Ludwig IV. zur Hochschule erhoben. Damit fand eine Entwicklung zur höheren technischen Bildung in Darmstadt ihren vorläufigen Abschluss
Karl Otmar Freiherr von Aretin - bedeutender Historiker des 20. Jahrhunderts
Get PDFVor hundert Jahren, am 2. Juli 1923, wurde Karl Otmar von Aretin in München geboren. Bekannt wurde er als Professor für Zeitgeschichte und aufgrund seiner prägenden Stellung an der TH Darmstadt
Additive manufacturing by means of parametric robot programming
Get PDF3D printing or additive manufacturing (AM) is now becoming a common technology in industry. The research activities in this area are constantly increasing, because with the high level of automation and the possibility to produce individual and complex structures, the advantages of additive manufacturing are promising. Most materials used in the construction industry can be used for additive manufacturing, for example steel and concrete. The print head (for example, a welding torch in the AM of steel) is mainly led by industrial robots, whose movements must be transferred from the 3D geometry files to be manufactured. In contrast to all-in-one systems, where hardware, software and printed material are coordinated, most robot-based AM systems are made of components from different manufacturers and branches. The objects to be manufactured are complex and the manufacturing parameters, which significantly influence the geometry and quality of the manufactured part, are manifold. This makes the workflow from the 3D model to the finished object difficult, especially because it is almost impossible to predict the exact manufactured structure geometry or layer height (which would be indispensable for accurate slicing). During the manufacturing process, deviations between the target and actual geometry can occur. In this paper, parametric robot programming (PRP) is presented, which allows flexible motion programming, and a quick and easy reaction to deviations between target and actual geometry during the manufacturing process. Complex geometries are divided into iso-curves whose mathematical functions are determined by means of polynomial regression. The robot can calculate the coordinates to be approached from these functions itself. This allows a simple adjustment of the manufacturing coordinates during the process as soon as target–actual deviations occur. The workflow from the file to the manufactured object is explained. The principle of PRP is transferable and applicable to all robot manufacturers and all conceivable printing processes. In the following article, it will be presented using wire + arc additive manufacturing, in which welding robots or portals can be used to produce steel structures with high deposition rates. Furthermore, the project “AM Bridge 2019” is presented, in which a steel bridge was manufactured in situ over a little creek and the presented PRP was applied
Cheating Automatic Short Answer Grading with the Adversarial Usage of Adjectives and Adverbs
No full textAutomatic grading models are valued for the time and effort saved during the instruction of large student bodies. Especially with the increasing digitization of education and interest in large-scale standardized testing, the popularity of automatic grading has risen to the point where commercial solutions are widely available and used. However, for short answer formats, automatic grading is challenging due to natural language ambiguity and versatility. While automatic short answer grading models are beginning to compare to human performance on some datasets, their robustness, especially to adversarially manipulated data, is questionable. Exploitable vulnerabilities in grading models can have far-reaching consequences ranging from cheating students receiving undeserved credit to undermining automatic grading altogether—even when most predictions are valid. In this paper, we devise a black-box adversarial attack tailored to the educational short answer grading scenario to investigate the grading models’ robustness. In our attack, we insert adjectives and adverbs into natural places of incorrect student answers, fooling the model into predicting them as correct. We observed a loss of prediction accuracy between 10 and 22 percentage points using the state-of-the-art models BERT and T5. While our attack made answers appear less natural to humans in our experiments, it did not significantly increase the graders’ suspicions of cheating. Based on our experiments, we provide recommendations for utilizing automatic grading systems more safely in practice
Fillafer, Franz Leander: Aufklärung habsburgisch. Staatsbildung, Wissenskultur und Geschichtspolitik in Zentraleuropa. 1750–1850, 632 S., Wallstein, Göttingen 2020.
No full text„Aufklärung habsburgisch“ ist ein beeindruckend gelehrtes Buch über die intellektuelle Landschaft des Habsburgerreiches von der Mitte des 18. bis zur Mitte des 19. Jahrhunderts. Franz Leander Fillafer verbindet mit seinem gut 600 Seiten starken Werk den Anspruch, den Epochenbruch um 1800 weniger scharf zu zeichnen als vielfach vormals geschehen. Insbesondere auf dem Gebiet der „Staatbildung, Wissenskultur und Geschichtspolitik in Zentraleuropa“ – so der Untertitel der Studie – möchte er aufzeigen, wie sich die Gedankenwelt der Zeitgenossen kontinuierlich fortentwickelte. Starke Brüche, wie sie bereits von den Zeitgenossen durch die Kanonisierung gewisser Werke der josephinischen Zeit (S. 122) konstruiert wurden, sieht Fillafer als überzeichnet an