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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 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
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.
Heimat entwerfen?
(2019)