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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.
Sabbioneta: Atlas
(2019)
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
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.