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Human induced pluripotent stem cells (hiPSCs) have shown to be promising in disease studies and drug screenings [1]. Cardiomyocytes derived from hiPSCs have been extensively investigated using patch-clamping and optical methods to compare their electromechanical behaviour relative to fully matured adult cells. Mathematical models can be used for translating findings on hiPSCCMs to adult cells [2] or to better understand the mechanisms of various ion channels when a drug is applied [3,4]. Paci et al. (2013) [3] developed the first model of hiPSC-CMs, which they later refined based on new data [3]. The model is based on iCells® (Fujifilm Cellular Dynamics, Inc. (FCDI), Madison WI, USA) but major differences among several cell lines and even within a single cell line have been found and motivate an approach for creating sample-specific models. We have developed an optimisation algorithm that parameterises the conductances (in S/F=Siemens/Farad) of the latest Paci et al. model (2018) [5] using current-voltage data obtained in individual patch-clamp experiments derived from an automated patch clamp system (Patchliner, Nanion Technologies GmbH, Munich).
The method of fundamental solutions is applied to the approximate computation of interior transmission eigenvalues for a special class of inhomogeneous media in two dimensions. We give a short approximation analysis accompanied with numerical results that clearly prove practical convenience of our alternative approach.
Hypertension describes the pathological increase of blood pressure, which is most commonly associated with the increase of vascular wall stiffness [1]. Referring to the “Deutsche Bluthochdruck Liga” this pathology shows a growing trend in our aging society. In order to find novel pharmacological and probably personalized treatments, we want to present a functional approach to study biomechanical properties of a human aortic vascular model.
In this method review we will give an overview of recent studies which were carried out with the CellDrum technology [2] and underline the added value to already existing standard procedures known from the field of physiology.
Herein described CellDrum technology is a system to measure functional mechanical properties of cell monolayers and thin tissue constructs in-vitro. Additionally, the CellDrum enables to elucidate the mechanical response of cells to pharmacological drugs, toxins and vasoactive agents. Due to its highly flexible polymer support, cells can also be mechanically stimulated by steady and cyclic biaxial stretching.
Clearance of blood components and fluid drainage play a crucial role in subarachnoid hemorrhage (SAH) and post hemorrhagic hydrocephalus (PHH). With the involvement of interstitial fluid (ISF) and cerebrospinal fluid (CSF), two pathways for the clearance of fluid and solutes in the brain are proposed. Starting at the level of capillaries, flow of ISF follows along the basement membranes in the walls of cerebral arteries out of the parenchyma to drain into the lymphatics and CSF [1]–[3]. Conversely, it is shown that CSF enters the parenchyma between glial and pial basement membranes of penetrating arteries [4]–[6]. Nevertheless, the involved structures and the contribution of either flow pathway to fluid balance between the subarachnoid space and interstitial space remains controversial. Low frequency oscillations in vascular tone are referred to as vasomotion and corresponding vasomotion waves are modeled as the driving force for flow of ISF out of the parenchyma [7]. Retinal vessel analysis (RVA) allows non-invasive measurement of retinal vessel vasomotion with respect to diameter changes [8]. Thus, the aim of the study is to investigate vasomotion in RVA signals of SAH and PHH patients.
Kurz vor der parlamentarischen Sommerpause hat der Bundestag am 28.6.2019 das 2. Datenschutz-Anpassungs- und Umsetzungsgesetz EU (2. DSAnpUG-EU) beschlossen, der Bundesrat hat diesem Gesetz am 20.9.2019 zugestimmt. Das Artikelgesetz, welches im sog. Omnibusverfahren zahlreiche Gesetze auf Bundesebene ändert, soll zur Vereinheitlichung und Anpassung des Bundesrechts an die seit Mai 2018 geltende Datenschutz-Grundverordnung (DSGVO) beitragen.
Sensitive and rapid detection of cholera toxin subunit B using magnetic frequency mixing detection
(2019)
Cholera is a life-threatening disease caused by the cholera toxin (CT) as produced by some Vibrio cholerae serogroups. In this research we present a method which directly detects the toxin’s B subunit (CTB) in drinking water. For this purpose we performed a magnetic sandwich immunoassay inside a 3D immunofiltration column. We used two different commercially available antibodies to capture CTB and for binding to superparamagnetic beads. ELISA experiments were performed to select the antibody combination. The beads act as labels for the magnetic frequency mixing detection technique. We show that the limit of detection depends on the type of magnetic beads. A nonlinear Hill curve was fitted to the calibration measurements by means of a custom-written python software. We achieved a sensitive and rapid detection of CTB within a broad concentration range from 0.2 ng/ml to more
than 700 ng/ml.
The movement of magnetic beads due to a magnetic field gradient is of great interest in different application fields. In this report we present a technique based on a magnetic tweezers setup to measure the velocity factor of magnetically actuated individual superparamagnetic beads in a fluidic environment. Several beads can be tracked simultaneously in order to gain and improve statistics. Furthermore we show our results for different beads with hydrodynamic diameters between 200 and 1000 nm from diverse manufacturers. These measurement data can, for example, be used to determine design parameters for a magnetic separation system, like maximum flow rate and minimum separation time, or to select suitable beads for fixed experimental requirements.
Kalkulation
(2019)
In modern bioanalytical methods, it is often desired to detect several targets in one sample within one measurement. Immunological methods including those that use superparamagnetic beads are an important group of techniques for these applications. The goal of this work is to investigate the feasibility of simultaneously detecting different superparamagnetic beads acting as markers using the magnetic frequency mixing technique. The frequency of the magnetic excitation field is scanned while the lower driving frequency is kept constant. Due to the particles’ nonlinear magnetization, mixing frequencies are generated. To record their amplitude and phase information, a direct digitization of the pickup-coil’s signal with subsequent Fast Fourier Transformation is performed. By synchronizing both magnetic beads using frequency scanning in magnetic frequency mixing technique magnetic fields, a stable phase information is gained. In this research, it is shown that the amplitude of the dominant mixing component is proportional to the amount of superparamagnetic beads inside a sample. Additionally, it is shown that the phase does not show this behaviour. Excitation frequency scans of different bead types were performed, showing different phases, without correlation to their diverse amplitudes. Two commercially available beads were selected and a determination of their amount in a mixture is performed as a demonstration for multiplex measurements.
The paper deals with an asymptotic relative efficiency concept for confidence regions of multidimensional parameters that is based on the expected volumes of the confidence regions. Under standard conditions the asymptotic relative efficiencies of confidence regions are seen to be certain powers of the ratio of the limits of the expected volumes. These limits are explicitly derived for confidence regions associated with certain plugin estimators, likelihood ratio tests and Wald tests. Under regularity conditions, the asymptotic relative efficiency of each of these procedures with respect to each one of its competitors is equal to 1. The results are applied to multivariate normal distributions and multinomial distributions in a fairly general setting.
Recognition of subjects with mild cognitive impairment (MCI) by the use of retinal arterial vessels.
(2019)
Baumaschinen
(2019)
Heimat entwerfen?
(2019)
Neue Perspektiven für die Bahn in der Produktions- und Distributionslogistik durch Prozessautomation
(2019)
Deutschland braucht mehr Eisenbahn um CO2-Emissionen aus dem Verkehr zu reduzieren. Sie muss zum Rückgrat aktueller Logistikprozesse, z.B. bei Kaufmannsgütern und E-Commerce, werden. Dies geht nicht ohne neuartige betriebliche Konzepte und eine Transformation des Güterwagens von einem „dummen Stück Stahl“ zu einem modernen Werkzeug der Logistik.
Als „Güterwagen 4.0“ wird ein kommunikativer und kooperativer Güterwagen verstanden, der die Voraussetzung zur Automatisierung aller Prozesse der Zugvorbereitung bereitstellt, sich aber ansonsten vollkommen kompatibel mit heutigen Betriebsverfahren im Hauptlauf präsentiert. Durch Kommunikation zwischen Güterwagen und umgebenden intelligenten Systemen im Sinne eines „Internet der Dinge“ gelingt damit unter Anderem die Realisierung hoch effizienter Gleisanschlussverkehre, die der Güterbahn neue Märkte abseits der klassisch bahn-affinen Verkehre erschließen und letztlich den Wandel zu einer nachhaltigen Gütermobilität fördern.
In many instances, freight vehicles exchange load or information with plants that are or will soon be Industry4.0 plants. The Wagon4.0 concept, as developed in close cooperation with e.g. port or mine operations, offers a maximum in railway operational efficiency while providing strong business cases already in the respective plant interaction. The Wagon4.0 consists of main components, a power supply, data network, sensors, actuators and an operating system, the so called WagonOS. The Wagon OS is implemented in a granular, self-sufficient manner, to allow basic features such as WiFi-Mesh and train christening in remote areas without network connection. Furthermore, the granularity of the operating system allows to extend the familiar app concept to freight rail rolling stock, making it possible to use specialised actuators for certain applications, e.g. an electrical parking brake or an auxiliary drive. In order to facilitate migration to the Wagon4.0 for existing fleets, a migration concept featuring five levels of technical adaptation was developed. The present paper investigates the benefits of Wagon4.0-implementations for the particular challenges of heavy haul operations by focusing on train christening, ep-assisted braking, autonomous last mile and traction boost operation as well as improved maintenance schedules
MedicVR : Acceleration and Enhancement Techniques for Direct Volume Rendering in Virtual Reality
(2019)
Purpose: Impaired paravascular drainage of β-Amyloid (Aβ) has been proposed as a contributing cause for sporadic Alzheimer’s disease (AD), as decreased cerebral blood vessel pulsatility and subsequently reduced propulsion in this pathway could lead to the accumulation and deposition of Aβ in the brain. Therefore, we hypothesized that there is an increased impairment in pulsatility across AD spectrum.
Patients and Methods: Using transcranial color-coded duplex sonography (TCCS) the resistance and pulsatility index (RI; PI) of the middle cerebral artery (MCA) in healthy controls (HC, n=14) and patients with AD dementia (ADD, n=12) were measured. In a second step, we extended the sample by adding patients with mild cognitive impairment (MCI) stratified by the presence (MCI-AD, n=8) or absence of biomarkers (MCI-nonAD, n=8) indicative for underlying AD pathology, and compared RI and PI across the groups. To control for atherosclerosis as a confounder, we measured the arteriolar-venular-ratio of retinal vessels.
Results: Left and right RI (p=0.020; p=0.027) and left PI (p=0.034) differed between HC and ADD controlled for atherosclerosis with AUCs of 0.776, 0.763, and 0.718, respectively. The RI and PI of MCI-AD tended towards ADD, of MCI-nonAD towards HC, respectively. RIs and PIs were associated with disease severity (p=0.010, p=0.023).
Conclusion: Our results strengthen the hypothesis that impaired pulsatility could cause impaired amyloid clearance from the brain and thereby might contribute to the development of AD. However, further studies considering other factors possibly influencing amyloid clearance as well as larger sample sizes are needed.
Transgenic plants have the potential to produce recombinant proteins on an agricultural scale, with yields of several tons per year. The cost-effectiveness of transgenic plants increases if simple cultivation facilities such as greenhouses can be used for production. In such a setting, we expressed a novel affinity ligand based on the fluorescent protein DsRed, which we used as a carrier for the linear epitope ELDKWA from the HIV-neutralizing antibody 2F5. The DsRed-2F5-epitope (DFE) fusion protein was produced in 12 consecutive batches of transgenic tobacco (Nicotiana tabacum) plants over the course of 2 years and was purified using a combination of blanching and immobilized metal-ion affinity chromatography (IMAC). The average purity after IMAC was 57 ± 26% (n = 24) in terms of total soluble protein, but the average yield of pure DFE (12 mg kg−1) showed substantial variation (± 97 mg kg−1, n = 24) which correlated with seasonal changes. Specifically, we found that temperature peaks (>28°C) and intense illuminance (>45 klx h−1) were associated with lower DFE yields after purification, reflecting the loss of the epitope-containing C-terminus in up to 90% of the product. Whereas the weather factors were of limited use to predict product yields of individual harvests conducted for each batch (spaced by 1 week), the average batch yields were well approximated by simple linear regression models using two independent variables for prediction (illuminance and plant age). Interestingly, accumulation levels determined by fluorescence analysis were not affected by weather conditions but positively correlated with plant age, suggesting that the product was still expressed at high levels, but the extreme conditions affected its stability, albeit still preserving the fluorophore function. The efficient production of intact recombinant proteins in plants may therefore require adequate climate control and shading in greenhouses or even cultivation in fully controlled indoor farms.
In parallel to the evolution of the Planetary Defense Conference, the exploration of small solar system bodies has advanced from fast fly-bys on the sidelines of missions to the planets to the implementation of dedicated sample-return and in-situ analysis missions. Spacecraft of all sizes have landed, touch-and-go sampled, been gently beached, or impacted at hypervelocity on asteroid and comet surfaces. More have flown by close enough to image their surfaces in detail or sample their immediate environment, often as part of an extended or re-purposed mission. And finally, full-scale planetary defense experiment missions are in the making. Highly efficient low-thrust propulsion is increasingly applied beyond commercial use also in mainstream and flagship science missions, in combination with gravity assist propulsion. Another development in the same years is the growth of small spacecraft solutions, not in size but in numbers and individual capabilities. The on-going NASA OSIRIS-REx and JAXA HAYABUSA2 missions exemplify the trend as well as the upcoming NEA SCOUT mission or the landers MINERVA-II and MASCOT recently deployed on Ryugu. We outline likely as well as possible and efficient routes of continuation of all these developments towards a propellant-less and highly efficient class of spacecraft for small solar system body exploration: small spacecraft solar sails designed for carefree handling and equipped with carried landers and application modules, for all asteroid user communities –planetary science, planetary defence, and in-situ resource utilization. This projection builds on the experience gained in the development of deployable membrane structures leading up to the successful ground deployment test of a (20 m)² solar sail at DLR Cologne and in the 20 years since. It draws on the background of extensive trajectory optimization studies, the qualified technology of the DLR GOSSAMER-1 deployment demonstrator, and the MASCOT asteroid lander. These enable ‘now-term’ as well as near-term hardware solutions, and thus responsive fast-paced development. Mission types directly applicable to planetary defense include: single and Multiple NEA Rendezvous ((M)NR) for mitigation precursor, target monitoring and deflection follow-up tasks; sail-propelled head-on retrograde kinetic impactors (RKI) for mitigation; and deployable membrane based methods to modify the asteroid’s properties or interact with it. The DLR-ESTEC GOSSAMER Roadmap initiated studies of missions uniquely feasible with solar sails such as Displaced L1 (DL1) space weather advance warning and monitoring and Solar Polar Orbiter (SPO) delivery which demonstrate the capability of near-term solar sails to achieve NEA rendezvous in any kind of orbit, from Earth-coorbital to extremely inclined and even retrograde orbits. For those mission types using separable payloads, such as SPO, (M)NR and RKI, design concepts can be derived from the separable Boom Sail Deployment Units characteristic of DLR GOSSAMER solar sail technology, nanolanders like MASCOT, or microlanders like the JAXA-DLR Jupiter Trojan Asteroid Lander for the OKEANOS mission which can shuttle from the sail to the asteroids visited and enable multiple NEA sample-return missions. These are an ideal match for solar sails in micro-spacecraft format whose launch configurations are compatible with ESPA and ASAP secondary payload platforms.
20 years after the successful ground deployment test of a (20 m) 2 solar sail at DLR Cologne, and in the light of the upcoming U.S. NEAscout mission, we provide an overview of the progress made since in our mission and hardware design studies as well as the hardware built in the course of our solar sail technology development. We outline the most likely and most efficient routes to develop solar sails for useful missions in science and applications, based on our developed `now-term' and near-term hardware as well as the many practical and managerial lessons learned from the DLR-ESTEC Gossamer Roadmap. Mission types directly applicable to planetary defense include single and Multiple NEA Rendezvous ((M)NR) for precursor, monitoring and follow-up scenarios as well as sail-propelled head-on retrograde kinetic impactors (RKI) for mitigation. Other mission types such as the Displaced L1 (DL1) space weather advance warning and monitoring or Solar Polar Orbiter (SPO) types demonstrate the capability of near-term solar sails to achieve asteroid rendezvous in any kind of orbit, from Earth-coorbital to extremely inclined and even retrograde orbits. Some of these mission types such as SPO, (M)NR and RKI include separable payloads. For one-way access to the asteroid surface, nanolanders like MASCOT are an ideal match for solar sails in micro-spacecraft format, i.e. in launch configurations compatible with ESPA and ASAP secondary payload platforms. Larger landers similar to the JAXA-DLR study of a Jupiter Trojan asteroid lander for the OKEANOS mission can shuttle from the sail to the asteroids visited and enable multiple NEA sample-return missions. The high impact velocities and re-try capability achieved by the RKI mission type on a final orbit identical to the target asteroid's but retrograde to its motion enables small spacecraft size impactors to carry sufficient kinetic energy for deflection.
Asteroid mining has the potential to greatly reduce the cost of in-space manufacturing, production of propellant for space transportation and consumables for crewed spacecraft, compared to launching the required resources from Earth’s deep gravity well. This paper discusses the top-level mission architecture and trajectory design for these resource-return missions, comparing high-thrust trajectories with continuous low-thrust solar-sail trajectories. This work focuses on maximizing the economic Net Present Value, which takes the time-cost of finance into account and therefore balances the returned resource mass and mission duration. The different propulsion methods will then be compared in terms of maximum economic return, sets of attainable target asteroids, and mission flexibility. This paper provides one more step towards making commercial asteroid mining an economically viable reality by integrating trajectory design, propulsion technology and economic modelling.