@article{GossmannFrotscherLinderetal.2016, author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Bayer, Robin and Epple, U. and Staat, Manfred and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}, series = {Cellular physiology and biochemistry}, volume = {38}, journal = {Cellular physiology and biochemistry}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {1421-9778 (Online)}, doi = {10.1159/000443124}, pages = {1182 -- 1198}, year = {2016}, abstract = {Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.}, 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} } @article{ThiebesKleinZingsheimetal.2022, author = {Thiebes, Anja Lena and Klein, Sarah and Zingsheim, Jonas and M{\"o}ller, Georg H. and G{\"u}rzing, Stefanie and Reddemann, Manuel A. and Behbahani, Mehdi and Cornelissen, Christian G.}, title = {Effervescent atomizer as novel cell spray technology to decrease the gas-to-liquid ratio}, series = {pharmaceutics}, volume = {14}, journal = {pharmaceutics}, number = {11}, publisher = {MDPI}, address = {Basel}, doi = {10.3390/pharmaceutics14112421}, pages = {Artikel 2421}, year = {2022}, abstract = {Cell spraying has become a feasible application method for cell therapy and tissue engineering approaches. Different devices have been used with varying success. Often, twin-fluid atomizers are used, which require a high gas velocity for optimal aerosolization characteristics. To decrease the amount and velocity of required air, a custom-made atomizer was designed based on the effervescent principle. Different designs were evaluated regarding spray characteristics and their influence on human adipose-derived mesenchymal stromal cells. The arithmetic mean diameters of the droplets were 15.4-33.5 µm with decreasing diameters for increasing gas-to-liquid ratios. The survival rate was >90\% of the control for the lowest gas-to-liquid ratio. For higher ratios, cell survival decreased to approximately 50\%. Further experiments were performed with the design, which had shown the highest survival rates. After seven days, no significant differences in metabolic activity were observed. The apoptosis rates were not influenced by aerosolization, while high gas-to-liquid ratios caused increased necrosis levels. Tri-lineage differentiation potential into adipocytes, chondrocytes, and osteoblasts was not negatively influenced by aerosolization. Thus, the effervescent aerosolization principle was proven suitable for cell applications requiring reduced amounts of supplied air. This is the first time an effervescent atomizer was used for cell processing.}, language = {en} } @article{BreussKleefeld2020, author = {Breuß, Michael and Kleefeld, Andreas}, title = {Implicit monotone difference methods for scalar conservation laws with source terms}, series = {Acta Mathematica Vietnamica}, volume = {45}, journal = {Acta Mathematica Vietnamica}, publisher = {Springer Singapore}, address = {Singapore}, issn = {2315-4144}, doi = {10.1007/s40306-019-00354-1}, pages = {709 -- 738}, year = {2020}, abstract = {In this article, a concept of implicit methods for scalar conservation laws in one or more spatial dimensions allowing also for source terms of various types is presented. This material is a significant extension of previous work of the first author (Breuß SIAM J. Numer. Anal. 43(3), 970-986 2005). Implicit notions are developed that are centered around a monotonicity criterion. We demonstrate a connection between a numerical scheme and a discrete entropy inequality, which is based on a classical approach by Crandall and Majda. Additionally, three implicit methods are investigated using the developed notions. Next, we conduct a convergence proof which is not based on a classical compactness argument. Finally, the theoretical results are confirmed by various numerical tests.}, language = {en} } @article{Gaigall2020, author = {Gaigall, Daniel}, title = {Hoeffding-Blum-Kiefer-Rosenblatt independence test statistic on partly not identically distributed data}, series = {Communications in Statistics - Theory and Methods}, volume = {51}, journal = {Communications in Statistics - Theory and Methods}, number = {12}, publisher = {Taylor \& Francis}, address = {London}, issn = {1532-415X}, doi = {10.1080/03610926.2020.1805767}, pages = {4006 -- 4028}, year = {2020}, abstract = {The established Hoeffding-Blum-Kiefer-Rosenblatt independence test statistic is investigated for partly not identically distributed data. Surprisingly, it turns out that the statistic has the well-known distribution-free limiting null distribution of the classical criterion under standard regularity conditions. An application is testing goodness-of-fit for the regression function in a non parametric random effects meta-regression model, where the consistency is obtained as well. Simulations investigate size and power of the approach for small and moderate sample sizes. A real data example based on clinical trials illustrates how the test can be used in applications.}, language = {en} } @article{BaaderBoxbergChenetal.2023, author = {Baader, Fabian and Boxberg, Marc S. and Chen, Qian and F{\"o}rstner, Roger and Kowalski, Julia and Dachwald, Bernd}, title = {Field-test performance of an ice-melting probe in a terrestrial analogue environment}, series = {Icarus}, journal = {Icarus}, number = {409}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.icarus.2023.115852}, pages = {Artikel 115852}, year = {2023}, abstract = {Melting probes are a proven tool for the exploration of thick ice layers and clean sampling of subglacial water on Earth. Their compact size and ease of operation also make them a key technology for the future exploration of icy moons in our Solar System, most prominently Europa and Enceladus. For both mission planning and hardware engineering, metrics such as efficiency and expected performance in terms of achievable speed, power requirements, and necessary heating power have to be known. Theoretical studies aim at describing thermal losses on the one hand, while laboratory experiments and field tests allow an empirical investigation of the true performance on the other hand. To investigate the practical value of a performance model for the operational performance in extraterrestrial environments, we first contrast measured data from terrestrial field tests on temperate and polythermal glaciers with results from basic heat loss models and a melt trajectory model. For this purpose, we propose conventions for the determination of two different efficiencies that can be applied to both measured data and models. One definition of efficiency is related to the melting head only, while the other definition considers the melting probe as a whole. We also present methods to combine several sources of heat loss for probes with a circular cross-section, and to translate the geometry of probes with a non-circular cross-section to analyse them in the same way. The models were selected in a way that minimizes the need to make assumptions about unknown parameters of the probe or the ice environment. The results indicate that currently used models do not yet reliably reproduce the performance of a probe under realistic conditions. Melting velocities and efficiencies are constantly overestimated by 15 to 50 \% in the models, but qualitatively agree with the field test data. Hence, losses are observed, that are not yet covered and quantified by the available loss models. We find that the deviation increases with decreasing ice temperature. We suspect that this mismatch is mainly due to the too restrictive idealization of the probe model and the fact that the probe was not operated in an efficiency-optimized manner during the field tests. With respect to space mission engineering, we find that performance and efficiency models must be used with caution in unknown ice environments, as various ice parameters have a significant effect on the melting process. Some of these are difficult to estimate from afar.}, language = {en} } @article{WilsonWilsonScheeretal.2017, author = {Wilson, Ian D. and Wilson, Claire E. and Scheer, Nico and Dickie, A.P. and Schreiter, K. and Wilson, E. M. and Riley, R. J. and Wehr, R. and Bial, J.}, title = {The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice}, series = {Biochemical pharmacology}, volume = {Volume 135}, journal = {Biochemical pharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2968}, doi = {10.1016/j.bcp.2017.03.015}, pages = {139 -- 150}, year = {2017}, language = {en} } @article{HoughNalwalkDingetal.2015, author = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico}, title = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {9}, issn = {1521-009x}, doi = {10.1124/dmd.115.065490}, pages = {1326 -- 1330}, year = {2015}, language = {en} } @article{HaegerProbstJaegeretal.2023, author = {Haeger, Gerrit and Probst, Johanna and Jaeger, Karl-Erich and Bongaerts, Johannes and Siegert, Petra}, title = {Novel aminoacylases from Streptomyces griseus DSM 40236 and their recombinant production in Streptomyces lividans}, series = {FEBS Open Bio}, volume = {13}, journal = {FEBS Open Bio}, number = {12}, publisher = {Wiley}, address = {Hoboken, NJ}, issn = {2211-5463}, doi = {10.1002/2211-5463.13723}, pages = {2224 -- 2238}, year = {2023}, abstract = {Amino acid-based surfactants are valuable compounds for cosmetic formulations. The chemical synthesis of acyl-amino acids is conventionally performed by the Schotten-Baumann reaction using fatty acyl chlorides, but aminoacylases have also been investigated for use in biocatalytic synthesis with free fatty acids. Aminoacylases and their properties are diverse; they belong to different peptidase families and show differences in substrate specificity and biocatalytic potential. Bacterial aminoacylases capable of synthesis have been isolated from Burkholderia, Mycolicibacterium, and Streptomyces. Although several proteases and peptidases from S. griseus have been described, no aminoacylases from this species have been identified yet. In this study, we investigated two novel enzymes produced by S. griseus DSM 40236ᵀ . We identified and cloned the respective genes and recombinantly expressed an α-aminoacylase (EC 3.5.1.14), designated SgAA, and an ε-lysine acylase (EC 3.5.1.17), designated SgELA, in S. lividans TK23. The purified aminoacylase SgAA was biochemically characterized, focusing on its hydrolytic activity to determine temperature- and pH optima and stabilities. The aminoacylase could hydrolyze various acetyl-amino acids at the Nα -position with a broad specificity regarding the sidechain. Substrates with longer acyl chains, like lauroyl-amino acids, were hydrolyzed to a lesser extent. Purified aminoacylase SgELA specific for the hydrolysis of Nε -acetyl-L-lysine was unstable and lost its enzymatic activity upon storage for a longer period but could initially be characterized. The pH optimum of SgELA was pH 8.0. While synthesis of acyl-amino acids was not observed with SgELA, SgAA catalyzed the synthesis of lauroyl-methionine.}, language = {en} } @article{RuppSchulzeKuperjans2018, author = {Rupp, Matthias and Schulze, Sven and Kuperjans, Isabel}, title = {Comparative life cycle analysis of conventional and hybrid heavy-duty trucks}, series = {World electric vehicle journal}, volume = {9}, journal = {World electric vehicle journal}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2032-6653}, doi = {10.3390/wevj9020033}, pages = {Article No. 33}, year = {2018}, abstract = {Heavy-duty trucks are one of the main contributors to greenhouse gas emissions in German traffic. Drivetrain electrification is an option to reduce tailpipe emissions by increasing energy conversion efficiency. To evaluate the vehicle's environmental impacts, it is necessary to consider the entire life cycle. In addition to the daily use, it is also necessary to include the impact of production and disposal. This study presents the comparative life cycle analysis of a parallel hybrid and a conventional heavy-duty truck in long-haul operation. Assuming a uniform vehicle glider, only the differing parts of both drivetrains are taken into account to calculate the environmental burdens of the production. The use phase is modeled by a backward simulation in MATLAB/Simulink considering a characteristic driving cycle. A break-even analysis is conducted to show at what mileage the larger CO2eq emissions due to the production of the electric drivetrain are compensated. The effect of parameter variation on the break-even mileage is investigated by a sensitivity analysis. The results of this analysis show the difference in CO2eq/t km is negative, indicating that the hybrid vehicle releases 4.34 g CO2eq/t km over a lifetime fewer emissions compared to the diesel truck. The break-even analysis also emphasizes the advantages of the electrified drivetrain, compensating the larger emissions generated during production after already a distance of 15,800 km (approx. 1.5 months of operation time). The intersection coordinates, distance, and CO2eq, strongly depend on fuel, emissions for battery production and the driving profile, which lead to nearly all parameter variations showing an increase in break-even distance.}, language = {en} }