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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).
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.
Kyphoplasty of Osteoporotic Fractured Vertebrae: A Finite Element Analysis about Two Types of Cement
(2019)
A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions
(2019)
Production and Characterization of Porous Fibroin Scaffolds for Regenerative Medical Application
(2019)
Neuromuscular strength training of the leg extensor muscles plays an important role in the rehabilitation and prevention of age and wealth related diseases. In this paper, we focus on the design and implementation of a Cartesian admittance control scheme for isotonic training, i.e. leg extension and flexion against a predefined weight. For preliminary testing and validation of the designed algorithm an experimental research and development platform consisting of an
industrial robot and a force plate mounted at its end-effector has been used. Linear, diagonal and arbitrary two-dimensional motion trajectories with different weights for the leg extension and flexion part are applied. The proposed algorithm is easily adaptable to trajectories consisting of arbitrary six-dimensional poses and allows the implementation of individualized trajectories.
Effective training requires high muscle forces potentially leading to training-induced injuries. Thus, continuous monitoring and controlling of the loadings applied to the musculoskeletal system along the motion trajectory is required. In this paper, a norm-optimal iterative learning control algorithm for the robot-assisted training is developed. The algorithm aims at minimizing the external knee joint moment, which is commonly used to quantify the loading of the medial compartment. To estimate the external knee joint moment, a musculoskeletal lower extremity model is implemented in OpenSim and coupled with a model of an industrial robot and a force plate mounted at its end-effector. The algorithm is tested in simulation for patients with varus, normal and valgus alignment of the knee. The results show that the algorithm is able to minimize the external knee joint moment in all three cases and converges after less than seven iterations.
Postural and metabolic benefits of using a forearm support walker in older adults with impairments
(2019)
The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.
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.
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.