TY - THES A1 - Achtsnicht, Stefan T1 - Multiplex-Magnetdetektion von superparamagnetischen Beads zur Identifizierung von Trinkwasserkontaminationen N2 - Die qualitative und quantitative Detektion von Zielsubstanzen innerhalb einer wässrigen Probe ist für viele Fragestellungen von Interesse, etwa bei der Detektion von Kontaminationen in Trinkwasser in Krisensituationen. Hierbei ist es nicht nur wichtig, dass Pathogene möglichst sensitiv detektiert werden können, sondern auch, dass die Analyse schnell erfolgt, um Betroffenen im Katastrophenfall zügig sicheres Trinkwasser zu Verfügung stellen zu können. Da bei einem solchen Szenario nicht von einer in der Nähe befindlichen funktionierenden Laborinfrastruktur ausgegangen werden kann, ist es wichtig, dass die Messung direkt vor Ort erfolgen kann. Im Rahmen dieser Arbeit wurde untersucht, ob eine derartige Schnellanalytik mithilfe von superparamagnetischen Beads (MBs) und der magnetischen Frequenzmischtechnik möglich ist. Dabei werden die MBs mit Hilfe von primären Antikörpern an die Zielsubstanz gebunden und mit sekundären Antikörpern an die Poren-Oberfläche eines Polyethylen-Filters fixiert (Sandwich-Immunoassay). So kann die Quantifizierung der Zielsubstanz auf eine magnetische Messung der immobilisierten MB-Marker zurückgeführt werden. Die magnetische Frequenzmischtechnik basiert auf der Anregung der Probe mit Magnetfeldern zweier verschiedener Frequenzen. Die durch die nichtlineare Magnetisierungsform der superparamagnetischen MBs entstehenden Mischfrequenzen werden typischerweise mithilfe einer zweistufigen Lock-in-Detektion analysiert (analoge Demodulation), die in einem Magnetreader als Handheldgerät realisiert wurde. Zusätzlich zu dieser Technik wurde das Prinzip der direkten Digitalisierung des gesamten Antwortsignals mit anschließender Fourier-Analyse der erzeugten Mischfrequenzen experimentell umgesetzt, um die Amplituden und Phasen mehrerer Mischfrequenzen simultan zu erfassen. Eine Möglichkeit zur Sensitivitätssteigerung ist die magnetische Aufkonzentration, indem vor der magnetischen Analyse eine Separation der MBs aus einem größeren Probenvolumen mittels magnetischem Feldgradienten durchgeführt wird. Zur Charakterisierung verschiedener kommerzieller MBs hinsichtlich ihrer magnetischen Separierbarkeit wurde ein Aufbau zur Messung ihrer magnetophoretischen Beweglichkeiten realisiert und ihre Geschwindigkeiten im Gradientenfeld mikroskopisch gemessen.Da eine Probe oftmals nicht nur auf eine einzige Zielsubstanz, sondern simultan auf mehrere verschiedene Pathogene hin untersucht werden soll, wurden verschiedene Ansätze entwickelt und getestet, die einen solchen multiparametrischen magnetischen Immunoassay ermöglichen. Einerseits wurde eine räumliche Separation der Bindungsbereiche für verschiedene Zielsubstanzen realisiert, die sequentiell ausgewertet werden können. Andererseits wurde die Unterscheidung von verschiedenen Zielsubstanzen anhand der Charakteristika der an sie gebundenen, verschieden funktionalisierten MB-Typen untersucht. Für eine solche Unterscheidung wurde zum einen die Anregefrequenz der magnetischen Frequenzmischtechnik während einer Messung variiert. Damit konnte gezeigt werden, dass sich verschiedene MB-Sorten anhand der Phase ihrer Frequenzmischsignale voneinander unterscheiden lassen. Weiterhin wurde gezeigt, dass sich der Signalverlauf einer binären Mischung zweier verschiedener MB-Typen als gradueller Übergang der Verläufe der beiden reinen MB-Lösungen ergibt. Eine weitere Analysemethode für einen multiparametrischen Immunoassay besteht darin, ein zusätzliches einstellbares statisches magnetisches Offsetfeld zu verwenden. Hierfür wurden mehrere Aufbauten auf Basis von Permanent- und Elektromagneten simuliert, konstruiert und charakterisiert. Mithilfe von Simulationen konnte gezeigt werden, dass eine auf diesem Verfahren beruhende Unterscheidung für MBs mit unterschiedlichen magnetischen Partikelmomenten möglich ist. Als direkte Anwendung des hier entwickelten Magnetreaders in Zusammenspiel mit der digitalen Demodulation wurde ein magnetischer Assay gegen die B-Untereinheit des Choleratoxins in Trinkwasser mit einem niedrigen Detektionslimit von 0,2 ng/ml demonstriert. N2 - The qualitative and quantitative detection of target substances in an aqueous sample is of interest for many questions, for example in the detection of contaminations in drinking water in crisis situations. It is not only important that pathogens can be detected with highest possible sensitivity, but also that the analysis is carried out quickly so that safe drinking water can be provided in the event of a disaster. During such a scenario one cannot rely on a functioning laboratory infrastructure nearby. Therefore it is important that the measurement can be carried out directly on site. Within the scope of this work, it was investigated whether such a quick analysis can be performed using superparamagnetic beads (MBs) and the magnetic frequency mixing technique. The MBs are bound to the target substance with the aid of primary antibodies and fixed to the pore surfaces of a polyethylene filter with secondary antibodies (sandwich immunoassay). The quantification of the target substance can thus be traced back to a magnetic measurement of the immobilized MB markers. The magnetic frequency mixing technique is based on the excitation of the sample with magnetic fields of two different frequencies. The mixing frequencies generated due to the non-linear shape of the magnetization of the superparamagnetic MBs are typically analyzed using a two-stage Lock-in detection (analog demodulation), which was implemented in a magnetic reader as a handheld device. In addition to this technique, the principle of direct digitization of the entire response signal with subsequent Fourier analysis of the generated mixing frequencies was experimentally implemented in order to simultaneously record the amplitudes and phases of several mixing frequencies. One possibility for increasing the sensitivity is magnetic concentration. In that case, the MBs are separated from a larger sample volume by means of a magnetic field gradient before the magnetic analysis. To characterize various commercial MBs with regard to their magnetic separability, a setup for measuring their magnetophoretic mobility was implemented and their velocities in the gradient field were measured with an optical microscope.Often, a sample has to be examined not only for a single target substance, but for several different pathogens simultaneously. Various approaches have been developed and tested which enable such a multiparametric magnetic immunoassay. On the one hand, a spatial separation of the binding areas for different target substances was realized, which can be evaluated sequentially. On the other hand, a distinction among different target substances based on the magnetic characteristics of their attached different MB types was examined. For this discrimination, the excitation frequency of the magnetic frequency mixing technology was varied during measurement. It is shown that different MB types can be distinguished from one another based on the phase of their frequency mixing signals. The signal curve of a binary mixture of two different MB types is obtained as a gradual transition of the curves of the two pure MB solutions. Another method of analysis for a multiparametric immunoassay is based on an additional adjustable static magnetic offset field. For this purpose, several setups based on permanent magnets and electromagnets were simulated, designed and characterized. The simulations show that a distinction based on this method is possible for MBs with different magnetic particle moments. As a direct application of the developed magnetic reader in conjunction with digital demodulation, a magnetic assay against the B subunit of cholera toxin in drinking water was demonstrated, and a low detection limit of 0.2 ng/ml was achieved. KW - Choleratoxin B KW - Trinkwassersicherheit KW - cholera toxin B KW - drinking water safety KW - magnetic frequency mixing technique Y1 - 2020 U6 - https://doi.org/10.18154/RWTH-2020-12052 N1 - Dissertation, RWTH Aachen University, 2020 ER - TY - JOUR A1 - Özsoylu, Dua A1 - Kizildag, Sefa A1 - Schöning, Michael Josef A1 - Wagner, Torsten T1 - Differential chemical imaging of extracellular acidification within microfluidic channels using a plasma-functionalized light-addressable potentiometric sensor (LAPS) JF - Physics in Medicine N2 - Extracellular acidification is a basic indicator for alterations in two vital metabolic pathways: glycolysis and cellular respiration. Measuring these alterations by monitoring extracellular acidification using cell-based biosensors such as LAPS plays an important role in studying these pathways whose disorders are associated with numerous diseases including cancer. However, the surface of the biosensors must be specially tailored to ensure high cell compatibility so that cells can represent more in vivo-like behavior, which is critical to gain more realistic in vitro results from the analyses, e.g., drug discovery experiments. In this work, O2 plasma patterning on the LAPS surface is studied to enhance surface features of the sensor chip, e.g., wettability and biofunctionality. The surface treated with O2 plasma for 30 s exhibits enhanced cytocompatibility for adherent CHO–K1 cells, which promotes cell spreading and proliferation. The plasma-modified LAPS chip is then integrated into a microfluidic system, which provides two identical channels to facilitate differential measurements of the extracellular acidification of CHO–K1 cells. To the best of our knowledge, it is the first time that extracellular acidification within microfluidic channels is quantitatively visualized as differential (bio-)chemical images. Y1 - 2020 U6 - https://doi.org/10.1016/j.phmed.2020.100030 SN - 2352-4510 VL - 10 IS - 100030 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Sildatke, Michael A1 - Karwanni, Hendrik A1 - Kraft, Bodo A1 - Schmidts, Oliver A1 - Zündorf, Albert T1 - Automated Software Quality Monitoring in Research Collaboration Projects T2 - ICSEW'20: Proceedings of the IEEE/ACM 42nd International Conference on Software Engineering Workshops N2 - In collaborative research projects, both researchers and practitioners work together solving business-critical challenges. These projects often deal with ETL processes, in which humans extract information from non-machine-readable documents by hand. AI-based machine learning models can help to solve this problem. Since machine learning approaches are not deterministic, their quality of output may decrease over time. This fact leads to an overall quality loss of the application which embeds machine learning models. Hence, the software qualities in development and production may differ. Machine learning models are black boxes. That makes practitioners skeptical and increases the inhibition threshold for early productive use of research prototypes. Continuous monitoring of software quality in production offers an early response capability on quality loss and encourages the use of machine learning approaches. Furthermore, experts have to ensure that they integrate possible new inputs into the model training as quickly as possible. In this paper, we introduce an architecture pattern with a reference implementation that extends the concept of Metrics Driven Research Collaboration with an automated software quality monitoring in productive use and a possibility to auto-generate new test data coming from processed documents in production. Through automated monitoring of the software quality and auto-generated test data, this approach ensures that the software quality meets and keeps requested thresholds in productive use, even during further continuous deployment and changing input data. Y1 - 2020 U6 - https://doi.org/10.1145/3387940.3391478 N1 - ICSE '20: 42nd International Conference on Software Engineering, Seoul, Republic of Korea, 27 June 2020 - 19 July 2020 SP - 603 EP - 610 PB - IEEE CY - New York, NY ER - TY - JOUR A1 - Martín-Vaquero, J. A1 - Kleefeld, Andreas T1 - Solving nonlinear parabolic PDEs in several dimensions: Parallelized ESERK codes JF - Journal of Computational Physics N2 - There is a very large number of very important situations which can be modeled with nonlinear parabolic partial differential equations (PDEs) in several dimensions. In general, these PDEs can be solved by discretizing in the spatial variables and transforming them into huge systems of ordinary differential equations (ODEs), which are very stiff. Therefore, standard explicit methods require a large number of iterations to solve stiff problems. But implicit schemes are computationally very expensive when solving huge systems of nonlinear ODEs. Several families of Extrapolated Stabilized Explicit Runge-Kutta schemes (ESERK) with different order of accuracy (3 to 6) are derived and analyzed in this work. They are explicit methods, with stability regions extended, along the negative real semi-axis, quadratically with respect to the number of stages s, hence they can be considered to solve stiff problems much faster than traditional explicit schemes. Additionally, they allow the adaptation of the step length easily with a very small cost. Two new families of ESERK schemes (ESERK3 and ESERK6) are derived, and analyzed, in this work. Each family has more than 50 new schemes, with up to 84.000 stages in the case of ESERK6. For the first time, we also parallelized all these new variable step length and variable number of stages algorithms (ESERK3, ESERK4, ESERK5, and ESERK6). These parallelized strategies allow to decrease times significantly, as it is discussed and also shown numerically in two problems. Thus, the new codes provide very good results compared to other well-known ODE solvers. Finally, a new strategy is proposed to increase the efficiency of these schemes, and it is discussed the idea of combining ESERK families in one code, because typically, stiff problems have different zones and according to them and the requested tolerance the optimum order of convergence is different. KW - Multi-dimensional partial differential equations KW - Higher-order codes KW - Nonlinear PDEs Y1 - 2020 U6 - https://doi.org/10.1016/j.jcp.2020.109771 SN - 0021-9991 IS - 423 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Gaigall, Daniel T1 - Rothman–Woodroofe symmetry test statistic revisited JF - Computational Statistics & Data Analysis N2 - The Rothman–Woodroofe symmetry test statistic is revisited on the basis of independent but not necessarily identically distributed random variables. The distribution-freeness if the underlying distributions are all symmetric and continuous is obtained. The results are applied for testing symmetry in a meta-analysis random effects model. The consistency of the procedure is discussed in this situation as well. A comparison with an alternative proposal from the literature is conducted via simulations. Real data are analyzed to demonstrate how the new approach works in practice. Y1 - 2020 U6 - https://doi.org/10.1016/j.csda.2019.106837 SN - 0167-9473 VL - 2020 IS - 142 SP - Artikel 106837 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Gaigall, Daniel T1 - Testing marginal homogeneity of a continuous bivariate distribution with possibly incomplete paired data JF - Metrika N2 - We discuss the testing problem of homogeneity of the marginal distributions of a continuous bivariate distribution based on a paired sample with possibly missing components (missing completely at random). Applying the well-known two-sample Crámer–von-Mises distance to the remaining data, we determine the limiting null distribution of our test statistic in this situation. It is seen that a new resampling approach is appropriate for the approximation of the unknown null distribution. We prove that the resulting test asymptotically reaches the significance level and is consistent. Properties of the test under local alternatives are pointed out as well. Simulations investigate the quality of the approximation and the power of the new approach in the finite sample case. As an illustration we apply the test to real data sets. KW - Marginal homogeneity test KW - Crámer–von-Mises distance KW - Paired sample KW - Incomplete data KW - Resampling test Y1 - 2019 U6 - https://doi.org/10.1007/s00184-019-00742-5 SN - 1435-926X VL - 2020 IS - 83 SP - 437 EP - 465 PB - Springer ER - TY - GEN A1 - Burgeth, Bernhard A1 - Kleefeld, Andreas A1 - Naegel, Benoît A1 - Perret, Benjamin T1 - Editorial — Special Issue: ISMM 2019 T2 - Mathematical Morphology - Theory and Applications N2 - This editorial presents the Special Issue dedicated to the conference ISMM 2019 and summarizes the articles published in this Special Issue. Y1 - 2020 U6 - https://doi.org/10.1515/mathm-2020-0200 SN - 2353-3390 VL - 4 IS - 1 SP - 159 EP - 161 PB - De Gruyter CY - Warschau ER - TY - CHAP A1 - Laack, Walter van T1 - Twee Kanten van één Medaille T2 - Het Geheim van Elysion : 45 Jaar Studies naar Nabij-de-Dood-Ervaringen over Bewustzijn in Liefde zonder Waarheen Y1 - 2020 SN - 978-94-93175-44-0 SP - 97 EP - 105 PB - Van Warven CY - Kampen ER - TY - JOUR A1 - Kleefeld, Andreas A1 - Pieronek, J. T1 - Elastic transmission eigenvalues and their computation via the method of fundamental solutions JF - Applicable Analysis N2 - A stabilized version of the fundamental solution method to catch ill-conditioning effects is investigated with focus on the computation of complex-valued elastic interior transmission eigenvalues in two dimensions for homogeneous and isotropic media. Its algorithm can be implemented very shortly and adopts to many similar partial differential equation-based eigenproblems as long as the underlying fundamental solution function can be easily generated. We develop a corroborative approximation analysis which also implicates new basic results for transmission eigenfunctions and present some numerical examples which together prove successful feasibility of our eigenvalue recovery approach. KW - elastic scattering KW - method of fundamental solutions KW - Interior transmission eigenvalues Y1 - 2020 U6 - https://doi.org/10.1080/00036811.2020.1721473 SN - 1563-504X VL - 100 IS - 16 SP - 3445 EP - 3462 PB - Taylore & Francis CY - London ER - TY - JOUR A1 - Breuß, Michael A1 - Kleefeld, Andreas T1 - Implicit monotone difference methods for scalar conservation laws with source terms JF - Acta Mathematica Vietnamica N2 - 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. KW - Entropy solution KW - Source term KW - Monotone methods KW - Implicit methods KW - Finite difference methods KW - Conservation laws Y1 - 2020 U6 - https://doi.org/10.1007/s40306-019-00354-1 SN - 2315-4144 N1 - Corresponding author: Andreas Kleefeld VL - 45 SP - 709 EP - 738 PB - Springer Singapore CY - Singapore ER - TY - JOUR A1 - Gaigall, Daniel T1 - Hoeffding-Blum-Kiefer-Rosenblatt independence test statistic on partly not identically distributed data JF - Communications in Statistics - Theory and Methods N2 - 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. KW - Brownian Pillow KW - Hoeffding-Blum-Kiefer-Rosenblatt independence test KW - not identically distributed KW - random effects meta-regression model Y1 - 2020 U6 - https://doi.org/10.1080/03610926.2020.1805767 SN - 1532-415X VL - 51 IS - 12 SP - 4006 EP - 4028 PB - Taylor & Francis CY - London ER - TY - CHAP A1 - Kleefeld, Andreas ED - Constanda, Christian T1 - Numerical calculation of interior transmission eigenvalues with mixed boundary conditions T2 - Computational and Analytic Methods in Science and Engineering N2 - Interior transmission eigenvalue problems for the Helmholtz equation play an important role in inverse wave scattering. Some distribution properties of those eigenvalues in the complex plane are reviewed. Further, a new scattering model for the interior transmission eigenvalue problem with mixed boundary conditions is described and an efficient algorithm for computing the interior transmission eigenvalues is proposed. Finally, extensive numerical results for a variety of two-dimensional scatterers are presented to show the validity of the proposed scheme. Y1 - 2020 SN - 978-3-030-48185-8 (Hardcover) U6 - https://doi.org/10.1007/978-3-030-48186-5_9 SP - 173 EP - 195 PB - Birkhäuser CY - Cham ER - TY - CHAP A1 - Abele, Daniel A1 - Kleefeld, Andreas ED - Constanda, Christian T1 - New Numerical Results for the Optimization of Neumann Eigenvalues T2 - Computational and Analytic Methods in Science and Engineering N2 - We present new numerical results for shape optimization problems of interior Neumann eigenvalues. This field is not well understood from a theoretical standpoint. The existence of shape maximizers is not proven beyond the first two eigenvalues, so we study the problem numerically. We describe a method to compute the eigenvalues for a given shape that combines the boundary element method with an algorithm for nonlinear eigenvalues. As numerical optimization requires many such evaluations, we put a focus on the efficiency of the method and the implemented routine. The method is well suited for parallelization. Using the resulting fast routines and a specialized parametrization of the shapes, we found improved maxima for several eigenvalues. Y1 - 2020 SN - 978-3-030-48185-8 (Print) SN - 978-3-030-48186-5 (Online) U6 - https://doi.org/10.1007/978-3-030-48186-5_1 SP - 1 EP - 20 PB - Birkhäuser CY - Cham ER - TY - JOUR A1 - Iken, Heiko A1 - Bronder, Thomas A1 - Goretzki, Alexander A1 - Kriesel, Jana A1 - Ahlborn, Kristina A1 - Gerlach, Frank A1 - Vonau, Winfried A1 - Zander, Willi A1 - Schubert, Jürgen A1 - Schöning, Michael Josef T1 - Development of a Combined pH- and Redox-Sensitive Bi-Electrode Glass Thin-Film Sensor JF - physica status solidi a : applications and materials sciences Y1 - 2019 U6 - https://doi.org/10.1002/pssa.201900114 SN - 1862-6319 VL - 216 IS - 12 SP - 1 EP - 8 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Staat, Manfred T1 - A computational study of organ relocation after laparoscopic pectopexy to repair posthysterectomy vaginal vault prolapse JF - Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization Y1 - 2019 U6 - https://doi.org/10.1080/21681163.2019.1670095 SN - 2168-1171 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Sagymbay, Altynay A1 - G.E., Nusupbaeva A1 - N.Zh, Tleumbetova A1 - A.S., Mutalieva A1 - Nurpeisova, Ainur A1 - D.B., Jussupova A1 - Digel, Ilya T1 - Molecular genetics features of the epidemic season 2017-2018 on the influenza in Kazakhstan JF - Eurasian Journal of Ecology Y1 - 2019 SN - 2617-7358 VL - 58 IS - 1 SP - 50 EP - 60 ER - TY - JOUR A1 - Savitskaya, I.S. A1 - Kistaubayeva, A.S. A1 - Ignatova, L.V. A1 - Digel, Ilya T1 - Antimicrobial and wound healing properties of a bacterial cellulose based material containing B. subtilis cells JF - Heliyon Y1 - 2019 U6 - https://doi.org/10.1016/j.heliyon.2019.e02592 SN - 2405-8440 VL - 5 IS - 10 SP - Artikelnummer e02592 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Meyer, Carolin A1 - Gaalen, Kerstin van A1 - Leschinger, Tim A1 - Scheyerer, Max J. A1 - Neiss, Wolfram F. A1 - Staat, Manfred A1 - Müller, Lars P. A1 - Wegmann, Kilian T1 - Kyphoplasty of Osteoporotic Fractured Vertebrae: A Finite Element Analysis about Two Types of Cement JF - BioMed Research International Y1 - 2019 U6 - https://doi.org/10.1155/2019/9232813 SP - Article ID 9232813 ER - TY - CHAP A1 - Schmidts, Oliver A1 - Kraft, Bodo A1 - Siebigteroth, Ines A1 - Zündorf, Albert T1 - Schema Matching with Frequent Changes on Semi-Structured Input Files: A Machine Learning Approach on Biological Product Data T2 - Proceedings of the 21st International Conference on Enterprise Information Systems - Volume 1: ICEIS Y1 - 2019 SN - 978-989-758-372-8 U6 - https://doi.org/10.5220/0007723602080215 SP - 208 EP - 215 ER - TY - JOUR A1 - Morais, Paulo V. A1 - Silva, Anielle C. A. A1 - Dantas, Noelio O. A1 - Schöning, Michael Josef A1 - Siqueira, José R., Jr. T1 - Hybrid Layer‐by‐Layer Film of Polyelectrolytes‐Embedded Catalytic CoFe2O4 Nanocrystals as Sensing Units in Capacitive Electrolyte‐Insulator‐Semiconductor Devices JF - physica status solidi a : applications and materials sciences Y1 - 2019 U6 - https://doi.org/10.1002/pssa.201900044 VL - 216 IS - 1900044 SP - 1 EP - 9 PB - Wiley CY - Weinheim ER -