@article{GrajewskiKleefeld2023, author = {Grajewski, Matthias and Kleefeld, Andreas}, title = {Detecting and approximating decision boundaries in low-dimensional spaces}, series = {Numerical Algorithms}, volume = {93}, journal = {Numerical Algorithms}, number = {4}, publisher = {Springer Science+Business Media}, address = {Dordrecht}, issn = {1572-9265}, pages = {35 Seiten}, year = {2023}, abstract = {A method for detecting and approximating fault lines or surfaces, respectively, or decision curves in two and three dimensions with guaranteed accuracy is presented. Reformulated as a classification problem, our method starts from a set of scattered points along with the corresponding classification algorithm to construct a representation of a decision curve by points with prescribed maximal distance to the true decision curve. Hereby, our algorithm ensures that the representing point set covers the decision curve in its entire extent and features local refinement based on the geometric properties of the decision curve. We demonstrate applications of our method to problems related to the detection of faults, to multi-criteria decision aid and, in combination with Kirsch's factorization method, to solving an inverse acoustic scattering problem. In all applications we considered in this work, our method requires significantly less pointwise classifications than previously employed algorithms.}, language = {en} } @article{WendlandtKochBritzetal.2023, author = {Wendlandt, Tim and Koch, Claudia and Britz, Beate and Liedek, Anke and Schmidt, Nora and Werner, Stefan and Gleba, Yuri and Vahidpour, Farnoosh and Welden, Melanie and Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Facile Purification and Use of Tobamoviral Nanocarriers for Antibody-Mediated Display of a Two-Enzyme System}, series = {Viruses}, volume = {9}, journal = {Viruses}, number = {15}, publisher = {MDPI}, address = {Basel}, issn = {1999-4915}, doi = {doi.org/10.3390/v15091951}, pages = {Artikel 1951}, year = {2023}, abstract = {Immunosorbent turnip vein clearing virus (TVCV) particles displaying the IgG-binding domains D and E of Staphylococcus aureus protein A (PA) on every coat protein (CP) subunit (TVCVPA) were purified from plants via optimized and new protocols. The latter used polyethylene glycol (PEG) raw precipitates, from which virions were selectively re-solubilized in reverse PEG concentration gradients. This procedure improved the integrity of both TVCVPA and the wild-type subgroup 3 tobamovirus. TVCVPA could be loaded with more than 500 IgGs per virion, which mediated the immunocapture of fluorescent dyes, GFP, and active enzymes. Bi-enzyme ensembles of cooperating glucose oxidase and horseradish peroxidase were tethered together on the TVCVPA carriers via a single antibody type, with one enzyme conjugated chemically to its Fc region, and the other one bound as a target, yielding synthetic multi-enzyme complexes. In microtiter plates, the TVCVPA-displayed sugar-sensing system possessed a considerably increased reusability upon repeated testing, compared to the IgG-bound enzyme pair in the absence of the virus. A high coverage of the viral adapters was also achieved on Ta2O5 sensor chip surfaces coated with a polyelectrolyte interlayer, as a prerequisite for durable TVCVPA-assisted electrochemical biosensing via modularly IgG-assembled sensor enzymes.}, language = {en} } @article{JanusAchtsnichtTempeletal.2023, author = {Janus, Kevin Alexander and Achtsnicht, Stefan and Tempel, Laura and Drinic, Aleksaner and Kopp, Alexander and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Influence of fibroin membrane composition and curing parameters on the performance of a biodegradable enzymatic biosensor manufactured from Silicon-Free Carbon}, series = {Physica status solidi : pss. A, Applications and materials science}, volume = {220}, journal = {Physica status solidi : pss. A, Applications and materials science}, number = {22}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6300 (Print)}, doi = {10.1002/pssa.202300081}, pages = {10 Seiten}, year = {2023}, abstract = {Herein, fibroin, polylactide (PLA), and carbon are investigated for their suitability as biocompatible and biodegradable materials for amperometric biosensors. For this purpose, screen-printed carbon electrodes on the biodegradable substrates fibroin and PLA are modified with a glucose oxidase membrane and then encapsulated with the biocompatible material Ecoflex. The influence of different curing parameters of the carbon electrodes on the resulting biosensor characteristics is studied. The morphology of the electrodes is investigated by scanning electron microscopy, and the biosensor performance is examined by amperometric measurements of glucose (0.5-10 mM) in phosphate buffer solution, pH 7.4, at an applied potential of 1.2 V versus a Ag/AgCl reference electrode. Instead of Ecoflex, fibroin, PLA, and wound adhesive are tested as alternative encapsulation compounds: a series of swelling tests with different fibroin compositions, PLA, and Ecoflex has been performed before characterizing the most promising candidates by chronoamperometry. Therefore, the carbon electrodes are completely covered with the particular encapsulation material. Chronoamperometric measurements with H2O2 concentrations between 0.5 and 10 mM enable studying the leakage current behavior.}, language = {en} } @article{MoraisSumanSchoeningetal.2023, author = {Morais, Paulo V. and Suman, Pedro H. and Sch{\"o}ning, Michael Josef and Siqueira Junior, Jos{\´e} R. and Orlandi, Marcelo O.}, title = {Layer-by-layer film based on Sn₃O₄ nanobelts as sensing units to detect heavy metals using a capacitive field-effect sensor platform}, series = {Chemosensors}, volume = {11}, journal = {Chemosensors}, number = {8}, publisher = {MDPI}, address = {Basel}, issn = {2227-9040}, doi = {10.3390/chemosensors11080436}, pages = {Artikel 436}, year = {2023}, abstract = {Lead and nickel, as heavy metals, are still used in industrial processes, and are classified as "environmental health hazards" due to their toxicity and polluting potential. The detection of heavy metals can prevent environmental pollution at toxic levels that are critical to human health. In this sense, the electrolyte-insulator-semiconductor (EIS) field-effect sensor is an attractive sensing platform concerning the fabrication of reusable and robust sensors to detect such substances. This study is aimed to fabricate a sensing unit on an EIS device based on Sn₃O₄ nanobelts embedded in a polyelectrolyte matrix of polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) using the layer-by-layer (LbL) technique. The EIS-Sn₃O₄ sensor exhibited enhanced electrochemical performance for detecting Pb²⁺ and Ni²⁺ ions, revealing a higher affinity for Pb²⁺ ions, with sensitivities of ca. 25.8 mV/decade and 2.4 mV/decade, respectively. Such results indicate that Sn₃O₄ nanobelts can contemplate a feasible proof-of-concept capacitive field-effect sensor for heavy metal detection, envisaging other future studies focusing on environmental monitoring.}, language = {en} } @article{KarschuckSchmidtAchtsnichtetal.2023, author = {Karschuck, Tobias and Schmidt, Stefan and Achtsnicht, Stefan and Poghossian, Arshak and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Multiplexing system for automated characterization of a capacitive field-effect sensor array}, series = {Physica Status Solidi A}, volume = {220}, journal = {Physica Status Solidi A}, number = {22}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6300 (Print)}, doi = {10.1002/pssa.202300265}, pages = {7 Seiten}, year = {2023}, abstract = {In comparison to single-analyte devices, multiplexed systems for a multianalyte detection offer a reduced assay time and sample volume, low cost, and high throughput. Herein, a multiplexing platform for an automated quasi-simultaneous characterization of multiple (up to 16) capacitive field-effect sensors by the capacitive-voltage (C-V) and the constant-capacitance (ConCap) mode is presented. The sensors are mounted in a newly designed multicell arrangement with one common reference electrode and are electrically connected to the impedance analyzer via the base station. A Python script for the automated characterization of the sensors executes the user-defined measurement protocol. The developed multiplexing system is tested for pH measurements and the label-free detection of ligand-stabilized, charged gold nanoparticles.}, language = {en} } @article{LiphardtFernandezGonzaloAlbrachtetal.2023, author = {Liphardt, Anna-Maria and Fernandez-Gonzalo, Rodrigo and Albracht, Kirsten and Rittweger, J{\"o}rn and Vico, Laurence}, title = {Musculoskeletal research in human space flight - unmet needs for the success of crewed deep space exploration}, series = {npj Microgravity}, volume = {9}, journal = {npj Microgravity}, number = {Article number: 9}, publisher = {Springer Nature}, issn = {2373-8065}, doi = {10.1038/s41526-023-00258-3}, pages = {1 -- 9}, year = {2023}, abstract = {Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper "Human Physiology - Musculoskeletal system", this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight. In addition, understanding the kinetics of the different components of the musculoskeletal system in parallel with a detailed description of the molecular mechanisms driving these alterations appears to be the best approach to address potential musculoskeletal problems that future exploratory-mission crew will face. These research efforts should be accompanied by technical advances in molecular and phenotypic monitoring tools to provide in-flight real-time feedback.}, language = {en} } @article{RingersBialonskiEgeetal.2023, author = {Ringers, Christa and Bialonski, Stephan and Ege, Mert and Solovev, Anton and Hansen, Jan Niklas and Jeong, Inyoung and Friedrich, Benjamin M. and Jurisch-Yaksi, Nathalie}, title = {Novel analytical tools reveal that local synchronization of cilia coincides with tissue-scale metachronal waves in zebrafish multiciliated epithelia}, series = {eLife}, volume = {12}, journal = {eLife}, publisher = {eLife Sciences Publications}, issn = {2050-084X}, doi = {10.7554/eLife.77701}, pages = {27 Seiten}, year = {2023}, abstract = {Motile cilia are hair-like cell extensions that beat periodically to generate fluid flow along various epithelial tissues within the body. In dense multiciliated carpets, cilia were shown to exhibit a remarkable coordination of their beat in the form of traveling metachronal waves, a phenomenon which supposedly enhances fluid transport. Yet, how cilia coordinate their regular beat in multiciliated epithelia to move fluids remains insufficiently understood, particularly due to lack of rigorous quantification. We combine experiments, novel analysis tools, and theory to address this knowledge gap. To investigate collective dynamics of cilia, we studied zebrafish multiciliated epithelia in the nose and the brain. We focused mainly on the zebrafish nose, due to its conserved properties with other ciliated tissues and its superior accessibility for non-invasive imaging. We revealed that cilia are synchronized only locally and that the size of local synchronization domains increases with the viscosity of the surrounding medium. Even though synchronization is local only, we observed global patterns of traveling metachronal waves across the zebrafish multiciliated epithelium. Intriguingly, these global wave direction patterns are conserved across individual fish, but different for left and right noses, unveiling a chiral asymmetry of metachronal coordination. To understand the implications of synchronization for fluid pumping, we used a computational model of a regular array of cilia. We found that local metachronal synchronization prevents steric collisions, i.e., cilia colliding with each other, and improves fluid pumping in dense cilia carpets, but hardly affects the direction of fluid flow. In conclusion, we show that local synchronization together with tissue-scale cilia alignment coincide and generate metachronal wave patterns in multiciliated epithelia, which enhance their physiological function of fluid pumping.}, language = {en} } @article{Gaigall2023, author = {Gaigall, Daniel}, title = {On the applicability of several tests to models with not identically distributed random effects}, series = {Statistics : A Journal of Theoretical and Applied Statistics}, volume = {57}, journal = {Statistics : A Journal of Theoretical and Applied Statistics}, publisher = {Taylor \& Francis}, address = {London}, isbn = {0323-3944}, issn = {1029-4910}, doi = {10.1080/02331888.2023.2193748}, pages = {14 Seiten}, year = {2023}, abstract = {We consider Kolmogorov-Smirnov and Cram{\´e}r-von-Mises type tests for testing central symmetry, exchangeability, and independence. In the standard case, the tests are intended for the application to independent and identically distributed data with unknown distribution. The tests are available for multivariate data and bootstrap procedures are suitable to obtain critical values. We discuss the applicability of the tests to random effects models, where the random effects are independent but not necessarily identically distributed and with possibly unknown distributions. Theoretical results show the adequacy of the tests in this situation. The quality of the tests in models with random effects is investigated by simulations. Empirical results obtained confirm the theoretical findings. A real data example illustrates the application.}, language = {en} } @article{KuchlerGuenthnerRibeiroetal.2023, author = {Kuchler, Timon and G{\"u}nthner, Roman and Ribeiro, Andrea and Hausinger, Renate and Streese, Lukas and W{\"o}hnl, Anna and Kesseler, Veronika and Negele, Johanna and Assali, Tarek and Carbajo-Lozoya, Javier and Lech, Maciej and Adorjan, Kristina and Stubbe, Hans Christian and Hanssen, Henner and Kotliar, Konstantin and Haller, Berhard and Heemann, Uwe and Schmaderer, Christoph}, title = {Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation}, volume = {26}, publisher = {Springer Nature}, address = {Dordrecht}, doi = {10.1007/s10456-023-09885-6}, pages = {547 -- 563}, year = {2023}, abstract = {Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42\% ± 1.77\% vs. 4.64\% ± 2.59\%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5-190.2] vs. 189.1 [179.4-197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8-0.9] vs. 0.88 [0.8-0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = - 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.}, language = {en} } @article{BertzMolinnusSchoeningetal.2023, author = {Bertz, Morten and Molinnus, Denise and Sch{\"o}ning, Michael Josef and Homma, Takayuki}, title = {Real-time monitoring of H₂O₂ sterilization on individual bacillus atrophaeus spores by optical sensing with trapping Raman spectroscopy}, series = {Chemosensors}, volume = {8}, journal = {Chemosensors}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2227-9040}, doi = {10.3390/chemosensors11080445}, pages = {Artikel 445}, year = {2023}, abstract = {Hydrogen peroxide (H₂O₂), a strong oxidizer, is a commonly used sterilization agent employed during aseptic food processing and medical applications. To assess the sterilization efficiency with H₂O₂, bacterial spores are common microbial systems due to their remarkable robustness against a wide variety of decontamination strategies. Despite their widespread use, there is, however, only little information about the detailed time-resolved mechanism underlying the oxidative spore death by H₂O₂. In this work, we investigate chemical and morphological changes of individual Bacillus atrophaeus spores undergoing oxidative damage using optical sensing with trapping Raman microscopy in real-time. The time-resolved experiments reveal that spore death involves two distinct phases: (i) an initial phase dominated by the fast release of dipicolinic acid (DPA), a major spore biomarker, which indicates the rupture of the spore's core; and (ii) the oxidation of the remaining spore material resulting in the subsequent fragmentation of the spores' coat. Simultaneous observation of the spore morphology by optical microscopy corroborates these mechanisms. The dependence of the onset of DPA release and the time constant of spore fragmentation on H₂O₂ shows that the formation of reactive oxygen species from H₂O₂ is the rate-limiting factor of oxidative spore death.}, language = {en} }