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Year of publication
Institute
- Fachbereich Medizintechnik und Technomathematik (1594) (remove)
Document Type
- Article (1594) (remove)
Keywords
- Einspielen <Werkstoff> (7)
- FEM (4)
- Finite-Elemente-Methode (4)
- LAPS (4)
- CellDrum (3)
- Label-free detection (3)
- biosensors (3)
- hydrogen peroxide (3)
- impedance spectroscopy (3)
- shakedown analysis (3)
We consider a binary multivariate regression model where the conditional expectation of a binary variable given a higher-dimensional input variable belongs to a parametric family. Based on this, we introduce a model-based bootstrap (MBB) for higher-dimensional input variables. This test can be used to check whether a sequence of independent and identically distributed observations belongs to such a parametric family. The approach is based on the empirical residual process introduced by Stute (Ann Statist 25:613–641, 1997). In contrast to Stute and Zhu’s approach (2002) Stute & Zhu (Scandinavian J Statist 29:535–545, 2002), a transformation is not required. Thus, any problems associated with non-parametric regression estimation are avoided. As a result, the MBB method is much easier for users to implement. To illustrate the power of the MBB based tests, a small simulation study is performed. Compared to the approach of Stute & Zhu (Scandinavian J Statist 29:535–545, 2002), the simulations indicate a slightly improved power of the MBB based method. Finally, both methods are applied to a real data set.
Brockhaus, Moritz K. ; Behbahani, Mehdi ; Muris, Farina ; Jansen, Sebastian V. ; Schmitz- Rode, Thomas ; Steinseifer, Ulrich ; Clauser, Johanna C.
Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in-vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom-made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential.
Neumaier, Felix ; Weiss, Miriam ; Veldeman, Michael ; Kotliar, Konstantin ; Wiesmann, Martin ; Schulze-Steinen, Henna ; Höllig, Anke ; Clusmann, Hans ; Schubert, Gerrit Alexander ; Albanna, Walid
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH.
Hugenroth, Kristin ; Borchardt, Ralf ; Ritter, Philine ; Groß‑Hardt, Sascha ; Meyns, Bart ; Verbelen, Tom ; Steinseifer, Ulrich ; Kaufmann, Tim A. S. ; Engelmann, Ulrich M.
Cardiopulmonary bypass (CPB) is a standard technique for cardiac surgery, but comes with the risk of severe neurological complications (e.g. stroke) caused by embolisms and/or reduced cerebral perfusion. We report on an aortic cannula prototype design (optiCAN) with helical outflow and jet-splitting dispersion tip that could reduce the risk of embolic events and restores cerebral perfusion to 97.5% of physiological flow during CPB in vivo, whereas a commercial curved-tip cannula yields 74.6%. In further in vitro comparison, pressure loss and hemolysis parameters of optiCAN remain unaffected. Results are reproducibly confirmed in silico for an exemplary human aortic anatomy via computational fluid dynamics (CFD) simulations. Based on CFD simulations, we firstly show that optiCAN design improves aortic root washout, which reduces the risk of thromboembolism. Secondly, we identify regions of the aortic intima with increased risk of plaque release by correlating areas of enhanced plaque growth and high wall shear stresses (WSS). From this we propose another easy-to-manufacture cannula design (opti2CAN) that decreases areas burdened by high WSS, while preserving physiological cerebral flow and favorable hemodynamics. With this novel cannula design, we propose a cannulation option to reduce neurological complications and the prevalence of stroke in high-risk patients after CPB.
Biologically sensitive field-effect devices (BioFEDs) advantageously combine the electronic field-effect functionality with the (bio)chemical receptor’s recognition ability for (bio)chemical sensing. In this review, basic and widely applied device concepts of silicon-based BioFEDs (ion-sensitive field-effect transistor, silicon nanowire transistor, electrolyte-insulator-semiconductor capacitor, light-addressable potentiometric sensor) are presented and recent progress (from 2019 to early 2021) is discussed. One of the main advantages of BioFEDs is the label-free sensing principle enabling to detect a large variety of biomolecules and bioparticles by their intrinsic charge. The review encompasses applications of BioFEDs for the label-free electrical detection of clinically relevant protein biomarkers, deoxyribonucleic acid molecules and viruses, enzyme-substrate reactions as well as recording of the cell acidification rate (as an indicator of cellular metabolism) and the extracellular potential.
Reliable automation of the labor-intensive manual task of scoring animal sleep can facilitate the analysis of long-term sleep studies. In recent years, deep-learning-based systems, which learn optimal features from the data, increased scoring accuracies for the classical sleep stages of Wake, REM, and Non-REM. Meanwhile, it has been recognized that the statistics of transitional stages such as pre-REM, found between Non-REM and REM, may hold additional insight into the physiology of sleep and are now under vivid investigation. We propose a classification system based on a simple neural network architecture that scores the classical stages as well as pre-REM sleep in mice. When restricted to the classical stages, the optimized network showed state-of-the-art classification performance with an out-of-sample F1 score of 0.95 in male C57BL/6J mice. When unrestricted, the network showed lower F1 scores on pre-REM (0.5) compared to the classical stages. The result is comparable to previous attempts to score transitional stages in other species such as transition sleep in rats or N1 sleep in humans. Nevertheless, we observed that the sequence of predictions including pre-REM typically transitioned from Non-REM to REM reflecting sleep dynamics observed by human scorers. Our findings provide further evidence for the difficulty of scoring transitional sleep stages, likely because such stages of sleep are under-represented in typical data sets or show large inter-scorer variability. We further provide our source code and an online platform to run predictions with our trained network.
Engelmann, Ulrich M. ; Shalaby, Ahmed ; Shasha, Carolyn ; Krishnan, Kannan M. ; Krause, Hans-Joachim
Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90% of the frequency mixing magnetic response signal is generated by the largest 10% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory.
Neumaier, Felix ; Kotliar, Konstantin ; Haeren, Roel Hubert Louis ; Temel, Yasin ; Lüke, Jan Niklas ; Seyam, Osama ; Lindauer, Ute ; Clusmann, Hans ; Hescheler, Jürgen ; Schubert, Gerrit Alexander ; Schneider, Toni ; Albanna, Walid
Hackl, Michael ; Nacov, Julia ; Kammerlohr, Sandra ; Staat, Manfred ; Buess, Eduard ; Leschinger, Tim ; Müller, Lars P. ; Wegmann, Kilian
Hugenroth, Kristin ; Neidlin, Michael ; Engelmann, Ulrich M. ; Kaufmann, Tim A. S. ; Steinseifer, Ulrich ; Heilmann, Torsten
Waldvogel, Janice ; Ritzmann, Ramona ; Freyler, Kathrin ; Helm, Michael ; Monti, Elena ; Albracht, Kirsten ; Stäudle, Benjamin ; Gollhofer, Albert ; Narici, Marco
Stretch-shortening type actions are characterized by lengthening of the pre-activated muscle-tendon unit (MTU) in the eccentric phase immediately followed by muscle shortening. Under 1 g, pre-activity before and muscle activity after ground contact, scale muscle stiffness, which is crucial for the recoil properties of the MTU in the subsequent push-off. This study aimed to examine the neuro-mechanical coupling of the stretch-shortening cycle in response to gravity levels ranging from 0.1 to 2 g. During parabolic flights, 17 subjects performed drop jumps while electromyography (EMG) of the lower limb muscles was combined with ultrasound images of the gastrocnemius medialis, 2D kinematics and kinetics to depict changes in energy management and performance. Neuro-mechanical coupling in 1 g was characterized by high magnitudes of pre-activity and eccentric muscle activity allowing an isometric muscle behavior during ground contact. EMG during pre-activity and the concentric phase systematically increased from 0.1 to 1 g. Below 1 g the EMG in the eccentric phase was diminished, leading to muscle lengthening and reduced MTU stretches. Kinetic energy at take-off and performance were decreased compared to 1 g. Above 1 g, reduced EMG in the eccentric phase was accompanied by large MTU and muscle stretch, increased joint flexion amplitudes, energy loss and reduced performance. The energy outcome function established by linear mixed model reveals that the central nervous system regulates the extensor muscles phase- and load-specifically. In conclusion, neuro-mechanical coupling appears to be optimized in 1 g. Below 1 g, the energy outcome is compromised by reduced muscle stiffness. Above 1 g, loading progressively induces muscle lengthening, thus facilitating energy dissipation.
Glucose oxidase (GOx) is an enzyme frequently used in glucose biosensors. As increased temperatures can enhance the performance of electrochemical sensors, we investigated the impact of temperature pulses on GOx that was drop-coated on flattened Pt microwires. The wires were heated by an alternating current. The sensitivity towards glucose and the temperature stability of GOx was investigated by amperometry. An up to 22-fold increase of sensitivity was observed. Spatially resolved enzyme activity changes were investigated via scanning electrochemical microscopy. The application of short (<100 ms) heat pulses was associated with less thermal inactivation of the immobilized GOx than long-term heating.
Molinnus, Denise ; Drinic, Aleksander ; Iken, Heiko ; Kröger, Nadja ; Zinser, Max ; Smeets, Ralf ; Köpf, Marius ; Kopp, Alexander ; Schöning, Michael Josef
The treatment method to deactivate viable microorganisms from objects or products is termed sterilization. There are multiple forms of sterilization, each intended to be applied for a specific target, which depends on—but not limited to—the thermal, physical, and chemical stability of that target. Herein, an overview on the currently used sterilization processes in the global market is provided. Different sterilization techniques are grouped under a category that describes the method of treatment: radiation (gamma, electron beam, X-ray, and ultraviolet), thermal (dry and moist heat), and chemical (ethylene oxide, ozone, chlorine dioxide, and hydrogen peroxide). For each sterilization process, the typical process parameters as defined by regulations and the mode of antimicrobial activity are summarized. Finally, the recommended microorganisms that are used as biological indicators to validate sterilization processes in accordance with the rules that are established by various regulatory agencies are summarized.
This paper presents a novel numerical procedure for computing limit and shakedown loads of structures using a node-based smoothed FEM in combination with a primal–dual algorithm. An associated primal–dual form based on the von Mises yield criterion is adopted. The primal-dual algorithm together with a Newton-like iteration are then used to solve this associated primal–dual form to determine simultaneously both approximate upper and quasi-lower bounds of the plastic collapse limit and the shakedown limit. The present formulation uses only linear approximations and its implementation into finite element programs is quite simple. Several numerical examples are given to show the reliability, accuracy, and generality of the present formulation compared with other available methods.
Jablonski, Melanie ; Münstermann, Felix ; Nork, Jasmina ; Molinnus, Denise ; Muschallik, Lukas ; Bongaerts, Johannes ; Wagner, Torsten ; Keusgen, Michael ; Siegert, Petra ; Schöning, Michael Josef
An acetoin biosensor based on a capacitive electrolyte–insulator–semiconductor (EIS) structure modified with the enzyme acetoin reductase, also known as butane-2,3-diol dehydrogenase (Bacillus clausii DSM 8716ᵀ), is applied for acetoin detection in beer, red wine, and fermentation broth samples for the first time. The EIS sensor consists of an Al/p-Si/SiO₂/Ta₂O₅ layer structure with immobilized acetoin reductase on top of the Ta₂O₅ transducer layer by means of crosslinking via glutaraldehyde. The unmodified and enzyme-modified sensors are electrochemically characterized by means of leakage current, capacitance–voltage, and constant capacitance methods, respectively.