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Hugenroth, Kristin ; Neidlin, Michael ; Engelmann, Ulrich M. ; Kaufmann, Tim A. S. ; Steinseifer, Ulrich ; Heilmann, Torsten
The anticancer activity of titanium complexes has been known since the groundbreaking studies of Köpf and Köpf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.
Nanotubular tobacco mosaic virus (TMV) particles and RNA-free lower-order coat protein (CP) aggregates have been employed as enzyme carriers in different diagnostic layouts and compared for their influence on biosensor performance. In the following, we describe a label-free electrochemical biosensor for improved glucose detection by use of TMV adapters and the enzyme glucose oxidase (GOD). A specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CP aggregates was achieved via bioaffinity binding. Glucose sensors with adsorptively immobilized [SA]-GOD, and with [SA]-GOD cross-linked with glutardialdehyde, respectively, were tested in parallel on the same sensor chip. Comparison of these sensors revealed that TMV adapters enhanced the amperometric glucose detection remarkably, conveying highest sensitivity, an extended linear detection range and fastest response times. These results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for applications in biosensorics and biochips. Here, we describe the fabrication and use of amperometric sensor chips combining an array of circular Pt electrodes, their loading with GOD-modified TMV nanotubes (and other GOD immobilization methods), and the subsequent investigations of the sensor performance.
Bäcker, Matthias ; Koch, Claudia ; Eiben, Sabine ; Geiger, Fania ; Eber, Fabian ; Gliemann, Hartmut ; Poghossian, Arshak ; Wege, Christina ; Schöning, Michael Josef
The conjunction of (bio-)chemical recognition elements with nanoscale biological building blocks such as virus particles is considered as a very promising strategy for the creation of biohybrids opening novel opportunities for label-free biosensing. This work presents a new approach for the development of biosensors using tobacco mosaic virus (TMV) nanotubes or coat proteins (CPs) as enzyme nanocarriers. Sensor chips combining an array of Pt electrodes loaded with glucose oxidase (GOD)-modified TMV nanotubes or CP aggregates were used for amperometric detection of glucose as a model system for the first time. The presence of TMV nanotubes or CPs on the sensor surface allows binding of a high amount of precisely positioned enzymes without substantial loss of their activity, and may also ensure accessibility of their active centers for analyte molecules. Specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CPs was achieved via bioaffinity binding. These layouts were tested in parallel with glucose sensors with adsorptively immobilized [SA]-GOD, as well as [SA]-GOD crosslinked with glutardialdehyde, and came out to exhibit superior sensor performance. The achieved results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for future applications in biosensorics and biochips.
Tool supported requirements analysis for the user centered development of mobile enterprise software
(2008)
A user centered development method has proved satisfactory for the development of mobile enterprise software. To make use of this method, detailed information about the user and the place where the user interacts with his mobile device is required. This article describes how both can be modeled by a stereotypical and conceptual extended UML extension. Finally, a software tool is presented that supports the developed UML extension.
This paper describes the implementation of topographic curvature effects within the RApid Mass MovementS (RAMMS) snow avalanche simulation toolbox. RAMMS is based on a model similar to shallow water equations with a Coulomb friction relation and the velocity dependent Voellmy drag. It is used for snow avalanche risk assessment in Switzerland. The snow avalanche simulation relies on back calculation of observed avalanches. The calibration of the friction parameters depends on characteristics of the avalanche track. The topographic curvature terms are not yet included in the above mentioned classical model. Here, we fundamentally improve this model by mathematically and physically including the topographic curvature effects. By decomposing the velocity dependent friction into a topography dependent term that accounts for a curvature enhancement in the Coulomb friction, and a topography independent contribution similar to the classical Voellmy drag, we construct a general curvature dependent frictional resistance, and thus propose new extended model equations. With three site-specific examples, we compare the apparent frictional resistance of the new approach, which includes topographic curvature effects, to the classical one. Our simulation results demonstrate substantial effects of the curvature on the flow dynamics e.g., the dynamic pressure distribution along the slope. The comparison of resistance coefficients between the two models demonstrates that the physically based extension presents an improvement to the classical approach. Furthermore a practical example highlights its influence on the pressure outline in the run out zone of the avalanche. Snow avalanche dynamics modeling natural terrain curvature centrifugal force friction coefficients.
Röhlen, Desiree ; Pilas, Johanna ; Dahmen, Markus ; Keusgen, Michael ; Selmer, Thorsten ; Schöning, Michael Josef
Monitoring of organic acids (OA) and volatile fatty acids (VFA) is crucial for the control of anaerobic digestion. In case of unstable process conditions, an accumulation of these intermediates occurs. In the present work, two different enzyme-based biosensor arrays are combined and presented for facile electrochemical determination of several process-relevant analytes. Each biosensor utilizes a platinum sensor chip (14 × 14 mm²) with five individual working electrodes. The OA biosensor enables simultaneous measurement of ethanol, formate, d- and l-lactate, based on a bi-enzymatic detection principle. The second VFA biosensor provides an amperometric platform for quantification of acetate and propionate, mediated by oxidation of hydrogen peroxide. The cross-sensitivity of both biosensors toward potential interferents, typically present in fermentation samples, was investigated. The potential for practical application in complex media was successfully demonstrated in spiked sludge samples collected from three different biogas plants. Thereby, the results obtained by both of the biosensors were in good agreement to the applied reference measurements by photometry and gas chromatography, respectively. The proposed hybrid biosensor system was also used for long-term monitoring of a lab-scale biogas reactor (0.01 m³) for a period of 2 months. In combination with typically monitored parameters, such as gas quality, pH and FOS/TAC (volatile organic acids/total anorganic carbonate), the amperometric measurements of OA and VFA concentration could enhance the understanding of ongoing fermentation processes.
Takenaga, Shoko ; Biselli, Manfred ; Schnitzler, Thomas ; Öhlschläger, Peter ; Wagner, Torsten ; Schöning, Michael Josef
The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light-addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17–200 mM) follows a Michaelis–Menten kinetics trajectory with Kₘ = 32.8 mM, and the obtained Kₘ value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV-16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS-based measurement device.
Oberländer, Jan ; Bromm, Alexander ; Wendeler, Luisa ; Iken, Heiko ; Palomar Duran, Marlena ; Greeff, Anton ; Kirchner, Patrick ; Keusgen, Michael ; Schöning, Michael Josef
Sterilisation processes are compulsory in medicine, pharmacy, and food industries to prevent infections of consumers and microbiological contaminations of products. Monitoring the sterilisation by conventional microbiological methods is time- and lab-consuming. To overcome this problem, in this work a novel biosensor has been proposed. The sensor enables a fast method to evaluate sterilisation processes. By means of thin-film technology the sensor's transducer structures in form of IDEs (interdigitated electrodes) have been fabricated on a silicon substrate. Physical characterisation of the developed sensor was done by AFM, SEM, and profilometry. Impedance analyses were conducted for the electrical characterisation. As microbiological layer spores of B. atrophaeus have been immobilised on the sensing structure; spores of this type are a well-known sterilisation test organism. Impedance measurements at a fixed frequency over time were performed to monitor the immobilisation process. A sterilisation process according to aseptic filling machines was applied to demonstrate the sensor functionality. After both, immobilisation and sterilisation, a change in impedance could successfully be detected.
This paper describes the potential for developing a digital twin of society- a dynamic model that can be used to observe, analyze, and predict the evolution of various societal aspects. Such a digital twin can help governmental agencies and policy makers in interpreting trends, understanding challenges, and making decisions regarding investments or policies necessary to support societal development and ensure future prosperity. The paper reviews related work regarding the digital twin paradigm and its applications. The paper presents a motivating case study- an analysis of opportunities and challenges faced by the German federal employment agency, Bundesagentur f¨ur Arbeit (BA), proposes solutions using digital twins, and describes initial proofs of concept for such solutions.
Molinnus, Denise ; Drinic, Aleksander ; Iken, Heiko ; Kröger, Nadja ; Zinser, Max ; Smeets, Ralf ; Köpf, Marius ; Kopp, Alexander ; Schöning, Michael Josef
Eichenbaum, Julian ; Nikolovski, Gjorgji ; Mülhens, Leon ; Reke, Michael ; Ferrein, Alexander ; Scholl, Ingrid
Autonomous agents require rich environment models for fulfilling their missions. High-definition maps are a well-established map format which allows for representing semantic information besides the usual geometric information of the environment. These are, for instance, road shapes, road markings, traffic signs or barriers. The geometric resolution of HD maps can be as precise as of centimetre level. In this paper, we report on our approach of using HD maps as a map representation for autonomous load-haul-dump vehicles in open-pit mining operations. As the mine undergoes constant change, we also need to constantly update the map. Therefore, we follow a lifelong mapping approach for updating the HD maps based on camera-based object detection and GPS data. We show our mapping algorithm based on the Lanelet 2 map format and show our integration with the navigation stack of the Robot Operating System. We present experimental results on our lifelong mapping approach from a real open-pit mine.
Multi-enzyme immobilization onto a capacitive field-effect biosensor by nano-spotting technique is presented. The nano-spotting technique allows to immobilize different enzymes simultaneously on the sensor surface with high spatial resolution without additional photolithographical patterning. The amount of applied enzymatic cocktail on the sensor surface can be tailored. Capacitive electrolyte-insulator-semiconductor (EIS) field-effect sensors with Ta2O5 as pH-sensitive transducer layer have been chosen to immobilize the three different (pL droplets) enzymes penicillinase, urease, and glucose oxidase. Nano-spotting immobilization is compared to conventional drop-coating method by defining different geometrical layouts on the sensor surface (fully, half-, and quarter-spotted). The drop diameter is varying between 84 µm and 102 µm, depending on the number of applied drops (1 to 4) per spot. For multi-analyte detection, penicillinase and urease are simultaneously nano-spotted on the EIS sensor. Sensor characterization was performed by C/V (capacitance/voltage) and ConCap (constant capacitance) measurements. Average penicillin, glucose, and urea sensitivities for the spotted enzymes were 81.7 mV/dec, 40.5 mV/dec, and 68.9 mV/dec, respectively.
Reisert, Steffen ; Geissler, Hanno ; Flörke, Rudolf ; Näther, Niko ; Wagner, Patrick ; Schöning, Michael Josef
Kirchner, Patrick ; Oberländer, Jan ; Suso, Henri-Pierre ; Rysstad, Gunnar ; Keusgen, Michael ; Schöning, Michael Josef
A wireless sensor system based on the industrial ZigBee standard for low-rate wireless networking was developed that enables real-time monitoring of gaseous H2O2 during the package sterilization in aseptic food processes. The sensor system consists of a remote unit connected to a calorimetric gas sensor, which was already established in former works, and an external base unit connected to a laptop computer. The remote unit was built up by an XBee radio frequency (RF) module for data communication and a programmable system-on-chip controller to read out the sensor signal and process the sensor data, whereas the base unit is a second XBee RF module. For the rapid H2O2 detection on various locations inside the package that has to be sterilized, a novel read-out strategy of the calorimetric gas sensor was established, wherein the sensor response is measured within the short sterilization time and correlated with the present H2O2 concentration. In an exemplary measurement application in an aseptic filling machinery, the suitability of the new, wireless sensor system was demonstrated, wherein the influence of the gas velocity on the H2O2 distribution inside a package was determined and verified with microbiological tests.
Poghossian, Arshak ; Werner, Frederik ; Buniatyan, V. V. ; Wagner, Torsten ; Miamoto, K. ; Yoshinobu, T. ; Schöning, Michael Josef
The LAPS (light-addressable potentiometric sensor) platform is one of the most attractive approaches for chemical and biological sensing with many applications ranging from pH and ion/analyte concentration measurements up to cell metabolism detection and chemical imaging. However, although it is generally accepted that LAPS measurements are spatially resolved, the light-addressability feature of LAPS devices has not been discussed in detail so far. In this work, an extended electrical equivalent-circuit model of the LAPS has been presented, which takes into account possible cross-talk effects due to the capacitive coupling of the non-illuminated region. A shunting effect of the non-illuminated area on the measured photocurrent and addressability of LAPS devices has been studied. It has been shown, that the measured photocurrent will be determined not only by the local interfacial potential in the illuminated region but also by possible interfacial potential changes in the non-illuminated region, yielding cross-talk effects. These findings were supported by the experimental investigations of a penicillin-sensitive multi-spot LAPS and a metal-insulator-semiconductor LAPS as model systems.
Molinnus, Denise ; Sorich, Maren ; Bartz, Alexander ; Siegert, Petra ; Willenberg, Holger S. ; Lisdat, Fred ; Poghossian, Arshak ; Keusgen, Michael ; Schöning, Michael Josef
An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer’s solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure.
Hülsen, Benjamin ; Mulsow, Niklas A. ; Dabrowski, Adam ; Brinkmann, Wiebke ; Gützlaff, Joel ; Spies, Leon ; Czupalla, Markus ; Kirchner, Frank
In Europe, efforts are underway to develop key technologies that can be used to explore the Moon and to exploit the resources available. This includes technologies for in-situ resource utilization (ISRU), facilitating the possibility of a future Moon Village. The Moon is the next step for humans and robots to exploit the use of available resources for longer term missions, but also for further exploration of the solar system. A challenge for effective exploration missions is to achieve a compact and lightweight robot to reduce launch costs and open up the possibility of secondary payload options. Current micro rover concepts are primarily designed to last for one day of solar illumination and show a low level of autonomy. Extending the lifetime of the system by enabling survival of the lunar night and implementing a high level of autonomy will significantly increase potential mission applications and the operational range. As a reference mission, the deployment of a micro rover in the equatorial region of the Moon is being considered. An overview of mission parameters and a detailed example mission sequence is given in this paper. The mission parameters are based on an in-depth study of current space agency roadmaps, scientific goals, and upcoming flight opportunities. Furthermore, concepts of the ongoing international micro rover developments are analyzed along with technology solutions identified for survival of lunar nights and a high system autonomy. The results provide a basis of a concise requirements set-up to allow dedicated system developments and qualification measures in the future.
Varga, Laszlo ; Davinson, Thomas ; Glorius, Jan ; Jurado, Beatrix ; Langer, Christoph ; Lederer-Woods, Claudia ; Litvinov, Yuri A. ; Reifarth, Rene ; Slavkovska, Zuzana ; Stöhlker, Thomas ; Woods, Phil J. ; Xing, Yuan Ming
Stored and cooled, highly-charged ions offer unprecedented capabilities for precision studies in the realm of atomic, nuclear structure and astrophysics[1]. After the successful investigation of the 96Ru(p,7)97Rh reaction cross section in 2009[2], the first measurement of the 124Xe(p,7)125Cs reaction cross section has been performed with decelerated, fully-ionized 124Xe ions in 2016 at the Experimental Storage Ring (ESR) of GSI[3]. Using a Double Sided Silicon Strip Detector, introduced directly into the ultra-high vacuum environment of a storage ring, the 125Cs proton-capture products have been successfully detected. The cross section has been measured at 5 different energies between 5.5AMeV and 8AMeV, on the high energy tail of the Gamow-window for hot, explosive scenarios such as supernovae and X-ray binaries. The elastic scattering on the H2 gas jet target is the major source of background to count the (p,7) events. Monte Carlo simulations show that an additional slit system in the ESR in combination with the energy information of the Si detector will enable background free measurements of the proton-capture products. The corresponding hardware is being prepared and will increase the sensitivity of the method tremendously.
Towards inclusion of the freight rail system in the industrial internet of things - Wagon 4.0
(2017)
Schöning, Michael Josef ; Abouzar, Maryam H. ; Ingebrandt, Sven ; Platen, Johannes ; Offenhäusser, Andreas ; Poghossian, Arshak
Breuer, Lars ; Pilas, Johanna ; Guthmann, Eric ; Schöning, Michael Josef ; Thoelen, Ronald ; Wagner, Torsten
Welden, Melanie ; Poghossian, Arshak ; Vahidpour, Farnoosh ; Wendlandt, Tim ; Keusgen, Michael ; Wege, Christina ; Schöning, Michael Josef
Utilizing an appropriate enzyme immobilization strategy is crucial for designing enzyme-based biosensors. Plant virus-like particles represent ideal nanoscaffolds for an extremely dense and precise immobilization of enzymes, due to their regular shape, high surface-to-volume ratio and high density of surface binding sites. In the present work, tobacco mosaic virus (TMV) particles were applied for the co-immobilization of penicillinase and urease onto the gate surface of a field-effect electrolyte-insulator-semiconductor capacitor (EISCAP) with a p-Si-SiO₂-Ta₂O₅ layer structure for the sequential detection of penicillin and urea. The TMV-assisted bi-enzyme EISCAP biosensor exhibited a high urea and penicillin sensitivity of 54 and 85 mV/dec, respectively, in the concentration range of 0.1–3 mM. For comparison, the characteristics of single-enzyme EISCAP biosensors modified with TMV particles immobilized with either penicillinase or urease were also investigated. The surface morphology of the TMV-modified Ta₂O₅-gate was analyzed by scanning electron microscopy. Additionally, the bi-enzyme EISCAP was applied to mimic an XOR (Exclusive OR) enzyme logic gate.
Many biped robots deploy a form of gait that follows the zero moment point (ZMP) approach, that is, the robot is in a stable position at any point in time. This requires the robot to be fully actuated. While very stable, the draw-backs of this approach are a fairly slow gait and high energy consumption. An alternative approach is the so-called passive-dynamic walking, where the gait makes use of the inertia and dynamic stability of the robot. In this paper we describe our ongoing work of combining the principles of passive-dynamic walking on the fully-actuated biped robot Nao, which is also deployed for robotic soccer applications. We present a simple controller that allows the robot to stably rock sidewards, showing a closed limit-cycle. We discuss first results of superimposing a forward motion on the sidewards motion. Based on this we expect to endow the Nao with a fast, robust, and stable passive-dynamic walk on the fully-actuated Nao in the future.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity.
Waiczies, Helmar ; Kühne, André ; Winter, Lukas ; Frauenrath, Tobias ; Hoffmann, Werner ; Ittermann, Bernd ; Waiczies, Sonia ; Niendorf, Thoralf
We have developed a double-tuned ¹H/¹⁹F birdcage resonator dedicated for hand and wrist imaging at 7 T to locally image non-steroidal anti-inflammatory drugs (NSAID) such as 2-{[3-(Trifluoromethyl) phenyl]amino}benzoic acid. The preliminary in vivo images acquired by the double-tuned ¹H/¹⁹F birdcage resonator demonstrate the feasibility for ¹H/¹⁹F hand- and wrist-imaging at 7 T. While the diagnostic quality of the coil needs to be assessed in patients with inflammatory rheumatoid disease, first ¹⁹F images of the NSAID are encouraging, and point towards the prospect of applying ¹⁹F-MRI to visualize and quantify the concentration of therapeutically-active compound at the sites of inflammation.