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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 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.
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.
In competition with other modes of transport, rail freight transport is looking for solutions to become more attractive. Short-term success can be achieved through the data-driven optimization of operations and maintenance as well as the application of novel strategies such as prescriptive maintenance. After introducing the concept of prescriptive maintenance, this paper aims to prove that vehicle-focused applications of this approach indeed have the potential to increase attractiveness. However, even greater advantages can be activated if data from the horizontal network of the vehicle is available. Drawing on the state of the art in research and technology in the field of cyber-physical systems (CPS) as well as digital twins and shadows, our work serves to design a system of systems for the horizontal interconnection of a rail vehicle and to conceptualize a draft for a digital twin of a locomotive.