TY - JOUR A1 - Bernau, C. R. A1 - Knödler, Matthias A1 - Emonts, Jessica A1 - Jäpel, Ronald Colin A1 - Buyel, Johannes Felix T1 - The use of predictive models to develop chromatography-based purification processes JF - Frontiers in Bioengineering and Biotechnology N2 - Chromatography is the workhorse of biopharmaceutical downstream processing because it can selectively enrich a target product while removing impurities from complex feed streams. This is achieved by exploiting differences in molecular properties, such as size, charge and hydrophobicity (alone or in different combinations). Accordingly, many parameters must be tested during process development in order to maximize product purity and recovery, including resin and ligand types, conductivity, pH, gradient profiles, and the sequence of separation operations. The number of possible experimental conditions quickly becomes unmanageable. Although the range of suitable conditions can be narrowed based on experience, the time and cost of the work remain high even when using high-throughput laboratory automation. In contrast, chromatography modeling using inexpensive, parallelized computer hardware can provide expert knowledge, predicting conditions that achieve high purity and efficient recovery. The prediction of suitable conditions in silico reduces the number of empirical tests required and provides in-depth process understanding, which is recommended by regulatory authorities. In this article, we discuss the benefits and specific challenges of chromatography modeling. We describe the experimental characterization of chromatography devices and settings prior to modeling, such as the determination of column porosity. We also consider the challenges that must be overcome when models are set up and calibrated, including the cross-validation and verification of data-driven and hybrid (combined data-driven and mechanistic) models. This review will therefore support researchers intending to establish a chromatography modeling workflow in their laboratory. KW - biopharmaceutical production process KW - Data-driven models KW - downstream processing design KW - experiment quality KW - hybrid model validation Y1 - 2022 U6 - https://doi.org/10.3389/fbioe.2022.1009102 SN - 2296-4185 (online-ressource) IS - 10 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Bandlitz, Stefan A1 - Nakhoul, Makram A1 - Kotliar, Konstantin T1 - Daily variations of corneal white-to-white diameter measured with different methods JF - Clinical and experimental optometry N2 - Purpose: A precise determination of the corneal diameter is essential for the diagnosis of various ocular diseases, cataract and refractive surgery as well as for the selection and fitting of contact lenses. The aim of this study was to investigate the agreement between two automatic and one manual method for corneal diameter determination and to evaluate possible diurnal variations in corneal diameter. Patients and Methods: Horizontal white-to-white corneal diameter of 20 volunteers was measured at three different fixed times of a day with three methods: Scheimpflug method (Pentacam HR, Oculus), placido based topography (Keratograph 5M, Oculus) and manual method using an image analysis software at a slitlamp (BQ900, Haag-Streit). Results: The two-factorial analysis of variance could not show a significant effect of the different instruments (p = 0.117), the different time points (p = 0.506) and the interaction between instrument and time point (p = 0.182). Very good repeatability (intraclass correlation coefficient ICC, quartile coefficient of dispersion QCD) was found for all three devices. However, manual slitlamp measurements showed a higher QCD than the automatic measurements with the Keratograph 5M and the Pentacam HR at all measurement times. Conclusion: The manual and automated methods used in the study to determine corneal diameter showed good agreement and repeatability. No significant diurnal variations of corneal diameter were observed during the period of time studied. Y1 - 2022 U6 - https://doi.org/10.2147/OPTO.S360651 SN - 0816-4622 IS - 14 SP - 173 EP - 181 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Uysal, Karya A1 - Firat, Ipek Serat A1 - Creutz, Till A1 - Aydin, Inci Cansu A1 - Artmann, Gerhard A1 - Teusch, Nicole A1 - Temiz Artmann, Aysegül T1 - A novel in vitro wound healing assay using free-standing, ultra-thin PDMS membranes JF - membranes N2 - Advances in polymer science have significantly increased polymer applications in life sciences. We report the use of free-standing, ultra-thin polydimethylsiloxane (PDMS) membranes, called CellDrum, as cell culture substrates for an in vitro wound model. Dermal fibroblast monolayers from 28- and 88-year-old donors were cultured on CellDrums. By using stainless steel balls, circular cell-free areas were created in the cell layer (wounding). Sinusoidal strain of 1 Hz, 5% strain, was applied to membranes for 30 min in 4 sessions. The gap circumference and closure rate of un-stretched samples (controls) and stretched samples were monitored over 4 days to investigate the effects of donor age and mechanical strain on wound closure. A significant decrease in gap circumference and an increase in gap closure rate were observed in trained samples from younger donors and control samples from older donors. In contrast, a significant decrease in gap closure rate and an increase in wound circumference were observed in the trained samples from older donors. Through these results, we propose the model of a cell monolayer on stretchable CellDrums as a practical tool for wound healing research. The combination of biomechanical cell loading in conjunction with analyses such as gene/protein expression seems promising beyond the scope published here. Y1 - 2022 U6 - https://doi.org/10.3390/membranes13010022 N1 - This article belongs to the Special Issue "Latest Scientific Discoveries in Polymer Membranes" VL - 2023 IS - 13(1) PB - MDPI CY - Basel ER - TY - JOUR A1 - Harris, Isaac A1 - Kleefeld, Andreas T1 - Analysis and computation of the transmission eigenvalues with a conductive boundary condition JF - Applicable Analysis N2 - We provide a new analytical and computational study of the transmission eigenvalues with a conductive boundary condition. These eigenvalues are derived from the scalar inverse scattering problem for an inhomogeneous material with a conductive boundary condition. The goal is to study how these eigenvalues depend on the material parameters in order to estimate the refractive index. The analytical questions we study are: deriving Faber–Krahn type lower bounds, the discreteness and limiting behavior of the transmission eigenvalues as the conductivity tends to infinity for a sign changing contrast. We also provide a numerical study of a new boundary integral equation for computing the eigenvalues. Lastly, using the limiting behavior we will numerically estimate the refractive index from the eigenvalues provided the conductivity is sufficiently large but unknown. KW - Boundary integral equations KW - Inverse spectral problem KW - Conductive boundary condition KW - Transmission eigenvalues Y1 - 2020 U6 - https://doi.org/10.1080/00036811.2020.1789598 SN - 1563-504X VL - 101 IS - 6 SP - 1880 EP - 1895 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Gaigall, Daniel A1 - Gerstenberg, Julian A1 - Trinh, Thi Thu Ha T1 - Empirical process of concomitants for partly categorial data and applications in statistics JF - Bernoulli N2 - On the basis of independent and identically distributed bivariate random vectors, where the components are categorial and continuous variables, respectively, the related concomitants, also called induced order statistic, are considered. The main theoretical result is a functional central limit theorem for the empirical process of the concomitants in a triangular array setting. A natural application is hypothesis testing. An independence test and a two-sample test are investigated in detail. The fairly general setting enables limit results under local alternatives and bootstrap samples. For the comparison with existing tests from the literature simulation studies are conducted. The empirical results obtained confirm the theoretical findings. KW - bootstrap KW - Categorial variable KW - Concomitant KW - Empirical process KW - Independence test Y1 - 2022 U6 - https://doi.org/10.3150/21-BEJ1367 SN - 1573-9759 VL - 28 IS - 2 SP - 803 EP - 829 PB - International Statistical Institute CY - Den Haag, NL ER - TY - JOUR A1 - Timme, Michael T1 - Beweislast beim gutgläubigen Erwerb eines Kraftfahrzeugs ohne Erhalt der Zulassungsbescheinigung Teil II — Zugleich eine Besprechung von BGH, Urt. v. 23.9.2022 – V ZR 148/21, MDR 2022, 1542 JF - Monatsschrift für Deutsches Recht N2 - Im Handel mit Kraftfahrzeugen gehören Aspekte des gutgläubigen Erwerbs zu den beinahe alltäglichen Standardproblemen. Der BGH fügt in seiner Entscheidung v. 23.9.2022–VZR148/21, MDR 2022, 1541 diesem im Detail breit gefächerten Themenfeld einen weiteren Mosaikstein hinzu: Der Erwerber erhielt das verkaufte Kfz ohne Übergabe einer Zulassungsbescheinigung Teil II, behauptet aber, diese Bescheinigung sei dem vom ihm eingeschalteten Vermittler bei Erwerb (als Fälschung) vorgelegt worden. Tatsächlich befand sich das Original durchgängig beim wahren Eigentümer, der nunmehr Herausgabe des Fahrzeugs verlangt. Der BGH schützt in dieser Gestaltung im Ergebnis den Erwerber. Die Entscheidung ist in mehrfacher Hinsicht bemerkenswert. Y1 - 2022 U6 - https://doi.org/doi.org/10.9785/mdtr-2023-770102 SN - 0340-1812 VL - 77 IS - 1 SP - r5 EP - r7 PB - Verlag Dr. Otto Schmidt CY - Köln ER -