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This chapter describes three general strategies to master uncertainty in technical systems: robustness, flexibility and resilience. It builds on the previous chapters about methods to analyse and identify uncertainty and may rely on the availability of technologies for particular systems, such as active components. Robustness aims for the design of technical systems that are insensitive to anticipated uncertainties. Flexibility increases the ability of a system to work under different situations. Resilience extends this characteristic by requiring a given minimal functional performance, even after disturbances or failure of system components, and it may incorporate recovery. The three strategies are described and discussed in turn. Moreover, they are demonstrated on specific technical systems.
The CellDrum technology (The term 'CellDrum technology' includes a couple of slightly different technological setups for measuring lateral mechanical tension in various types of cell monolayers or 3D-tissue constructs) was designed to quantify the contraction rate and mechanical tension of self-exciting cardiac myocytes. Cells were grown either within flexible, circular collagen gels or as monolayer on top of respective 1-mum thin silicone membranes. Membrane and cells were bulged outwards by air pressure. This biaxial strain distribution is rather similar the beating, blood-filled heart. The setup allowed presetting the mechanical residual stress level externally by adjusting the centre deflection, thus, mimicking hypertension in vitro. Tension was measured as oscillating differential pressure change between chamber and environment. A 0.5-mm thick collagen-cardiac myocyte tissue construct induced after 2 days of culturing (initial cell density 2 x 10(4) cells/ml), a mechanical tension of 1.62 +/- 0.17 microN/mm(2). Mechanical load is an important growth regulator in the developing heart, and the orientation and alignment of cardiomyocytes is stress sensitive. Therefore, it was necessary to develop the CellDrum technology with its biaxial stress-strain distribution and defined mechanical boundary conditions. Cells were exposed to strain in two directions, radially and circumferentially, which is similar to biaxial loading in real heart tissues. Thus, from a biomechanical point of view, the system is preferable to previous setups based on uniaxial stretching.
The anticancer activity of titanium complexes has been known since the groundbreaking studies of Köpf and Köpf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.
Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.
The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept.
To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a ‘critical period’ for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research.
Suspension depletion approach for exemption of infected Solanum jasminoides cells from pospiviroids
(2018)
Despite numerous studies, viroid elimination from infected plants remains a very challenging task. This study introduces for the first time a novel ‘suspension depletion’ approach for exemption of Solanum jasminoides plants from viroids. The proposed method implies initial establishment of suspension cultures of the infected plant cells. The suspended cells were then physically treated (mild thermotherapy, 33 °C), which presumably delayed the replication of the viroid. The viroid concentration in the treated biomass was monitored weekly using pospiviroid-specific PCR. After 10–12 weeks of continuous treatment, a sufficient decrease in viroid concentration was observed such that the infection became undetectable by PCR. The treated single cells then gave rise to microcolonies on a solid culture medium and the obtained viroid-negative clones were further promoted to regenerate into viroid-free plants. Three years of accumulated experimental data suggests feasibility, broad applicability, and good efficacy of the proposed approach.
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.
Past earthquakes demonstrated the high vulnerability of industrial facilities equipped with complex process technologies leading to serious damage of the process equipment and multiple and simultaneous release of hazardous substances in industrial facilities. Nevertheless, the design of industrial plants is inadequately described in recent codes and guidelines, as they do not consider the dynamic interaction between the structure and the installations and thus the effect of seismic response of the installations on the response of the structure and vice versa. The current code-based approach for the seismic design of industrial facilities is considered not enough for ensure proper safety conditions against exceptional event entailing loss of content and related consequences. Accordingly, SPIF project (Seismic Performance of Multi- Component Systems in Special Risk Industrial Facilities) was proposed within the framework of the European H2020 - SERA funding scheme (Seismology and Earthquake Engineering Research Infrastructure Alliance for Europe). The objective of the SPIF project is the investigation of the seismic behavior of a representative industrial structure equipped with complex process technology by means of shaking table tests. The test structure is a three-story moment resisting steel frame with vertical and horizontal vessels and cabinets, arranged on the three levels and connected by pipes. The dynamic behavior of the test structure and installations is investigated with and without base isolation. Furthermore, both firmly anchored and isolated components are taken into account to compare their dynamic behavior and interactions with each other. Artificial and synthetic ground motions are applied to study the seismic response at different PGA levels. After each test, dynamic identification measurements are carried out to characterize the system condition. The contribution presents the numerical simulations to calibrate the tests on the prototype, the experimental setup of the investigated structure and installations, selected measurement data and finally describes preliminary experimental results.
Purpose
To design and evaluate a modular transceiver coil array with 32 independent channels for cardiac MRI at 7.0T.
Methods
The modular coil array comprises eight independent building blocks, each containing four transceiver loop elements. Numerical simulations were used for B1+ field homogenization and radiofrequency (RF) safety validation. RF characteristics were examined in a phantom study. The array's suitability for accelerated high spatial resolution two-dimensional (2D) FLASH CINE imaging of the heart was examined in a volunteer study.
Results
Transmission field adjustments and RF characteristics were found to be suitable for the volunteer study. The signal-to-noise intrinsic to 7.0T together with the coil performance afforded a spatial resolution of 1.1 × 1.1 × 2.5 mm3 for 2D CINE FLASH MRI, which is by a factor of 6 superior to standardized CINE protocols used in clinical practice at 1.5T. The 32-channel transceiver array supports one-dimensional acceleration factors of up to R = 4 without impairing image quality significantly.
Conclusion
The modular 32-channel transceiver cardiac array supports accelerated and high spatial resolution cardiac MRI. The array is compatible with multichannel transmission and provides a technological basis for future clinical assessment of parallel transmission techniques at 7.0T.
The Atmospheric Remote-Sensing Infrared Exoplanet Large-survey, ARIEL, has been selected to be the next (M4) medium class space mission in the ESA Cosmic Vision programme. From launch in 2028, and during the following 4 years of operation, ARIEL will perform precise spectroscopy of the atmospheres of ~1000 known transiting exoplanets using its metre-class telescope. A three-band photometer and three spectrometers cover the 0.5 µm to 7.8 µm region of the electromagnetic spectrum. This paper gives an overview of the mission payload, including the telescope assembly, the FGS (Fine Guidance System) - which provides both pointing information to the spacecraft and scientific photometry and low-resolution spectrometer data, the ARIEL InfraRed Spectrometer (AIRS), and other payload infrastructure such as the warm electronics, structures and cryogenic cooling systems.