Dark-field computed tomography reaches the human scale

X-ray computed tomography (CT) is one of the most commonly used three-dimensional medical imaging modalities today. It has been refined over several decades, with the most recent innovations including dual-energy and spectral photon-counting technologies. Nevertheless, it has been discovered that wave-optical contrast mechanisms—beyond the presently used X-ray attenuation—offer the potential of complementary information, particularly on otherwise unresolved tissue microstructure. One such approach is dark-field imaging, which has recently been introduced and already demonstrated significantly improved radiological benefit in small-animal models, especially for lung diseases. Until now, however, dark-field CT could not yet be translated to the human scale and has been restricted to benchtop and small-animal systems, with scan durations of several minutes or more. This is mainly because the adaption and upscaling to the mechanical complexity, speed, and size of a human CT scanner so far remained an unsolved challenge. Here, we now report the successful integration of a Talbot–Lau interferometer into a clinical CT gantry and present dark-field CT results of a human-sized anthropomorphic body phantom, reconstructed from a single rotation scan performed in 1 s. Moreover, we present our key hardware and software solutions to the previously unsolved roadblocks, which so far have kept dark-field CT from being translated from the optical bench into a rapidly rotating CT gantry, with all its associated challenges like vibrations, continuous rotation, and large field of view. This development enables clinical dark-field CT studies with human patients in the near future

HotCity—A Gamified Token System for Reporting Waste Heat Sources

Urban planning needs to discover and incorporate new energy sources to meet climate protection targets in the future. Waste heat from industrial and urban infrastructure has proven to be a viable solution, but its proper identification can be challenging, especially for smaller and unconventional sources. Our project relies on the principles of gamification enhanced by a blockchain based token system and crowdsourcing as methods to collect and utilise spatial data such as the location and the size of previously unused heat sources. The mobile platform-neutral HotCity App en ables users to collectively patrol the city in search of waste heat sources and to gain tokens that can be exchanged for rewards. The blockchain platform Ardor was used for cheat proofing and to enable transparency for the reward system. The field test conducted in winter 2020/2021 showed high usability scores as well as high acceptance ratings of our approach opening up new use case scenarios in the context of spatial energy planning.©2022 Elsevier. This manuscript version is made available under the Creative Commons Attribution–NonCommercial–NoDerivatives 4.0 International (CC BY–NC–ND 4.0) license, https://creativecommons.org/licenses/by-nc-nd/4.0/fi=vertaisarvioitu|en=peerReviewed

Long-term monitoring (1953–2019) of geomorphologically active sections of Little Ice Age lateral moraines in the context of changing meteorological conditions

We show a long-term erosion monitoring of several geomorphologically active gully systems on Little Ice Age lateral moraines in the European Central–Eastern Alps, covering a total time period from 1953 to 2019 and including several survey periods in order to identify corresponding morphodynamic trends. For the implementation, DEM (digital elevation model) of Differences (DoDs) were calculated, based on multitemporal high-resolution digital elevation models from historical aerial images (generated by structure from motion photogrammetry with multi-view stereo) and light detection and ranging from airborne platforms. Two approaches were implemented to achieve the corresponding objectives. First, by calculating linear regression models using the accumulated sediment yield and the corresponding catchment area (on a log–log scale), the range of the variability in the spatial distribution of erosion values within the sites. Second, we use volume calculations to determine the total and the mean sediment yield (as well as erosion rates) of the entire sites. Subsequently, both the sites and the different time periods of both approaches are compared. Based on the slopes of the calculated regression lines, it can be shown that the highest variability in the sediment yield at the sites occurs in the first time period (mainly 1950s to 1970s). This can be attributed to the fact that within some sites the sediment yield per square metre increases clearly more strongly (regression lines with slopes up to 1.5). In contrast, in the later time periods (1970s to mid-2000s and mid-2000s to 2017/2019), there is generally a decrease in 10 out of 12 cases (regression lines with slopes around 1). However, even at sites with an increase in the variability in the sediment yield over time, the earlier high variabilities are no longer reached. This means that the spatial pattern of erosion in the gully heads changes over time as it becomes more uniform. Furthermore, using sediment volume calculations and corresponding erosion rates, we show a generally decreasing trend in geomorphic activity (amount of sediment yield) between the different time periods in 10 out of 12 sites, while 2 sites show an opposite trend, where morphodynamics increase and remain at the same level. Finally, we summarise the results of long-term changes in the morphodynamics of geomorphologically active areas on lateral moraines by presenting the “sediment activity concept”, which, in contrast to theoretical models, is based on actually calculated erosion. The level of geomorphic activity depends strongly on the characteristics of the sites, such as size, slope length, and slope gradient, some of which are associated with deeply incised gullies. It is noticeable that especially areas with influence of dead ice over decades in the lower slope area show high geomorphic activity. Furthermore, we show that system internal factors, as well as the general paraglacial adjustment process, have a greater influence on long-term morphodynamics than changing external weather and climate conditions, which, however, had a slight impact mainly in the last, i.e. most recent, time period (mid-2000s to 2017/2019) and may have led to an increase in erosion at the sites

Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES

Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart—yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells. Dose-dependent EOMES induction alone can fully replace a cocktail of signaling molecules otherwise essential for the specification of cardiogenic mesoderm. Highly efficient cardiomyocyte programming by EOMES mechanistically involves autocrine activation of canonical WNT signaling via the WNT3 ligand, which necessitates a shutdown of this axis at a subsequent stage. Our findings provide insights into human germ layer induction and bear biotechnological potential for the robust production of cardiomyocytes from engineered stem cells

<i>mi</i>R-625-3<i>p</i> regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells

Oxaliplatin resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Herein, we show that miR-625-3p functionally induces oxaliplatin resistance in CRC cells, and identify the signalling networks affected by miR-625-3p. We show that the p38 MAPK activator MAP2K6 is a direct target of miR-625-3p, and, accordingly, is downregulated in non-responder patients of oxaliplatin therapy. miR-625-3p-mediated resistance is reversed by anti-miR-625-3p treatment and ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, reduction of p38 signalling by using siRNAs, chemical inhibitors or expression of a dominant-negative MAP2K6 protein induces resistance to oxaliplatin. Transcriptome, proteome and phosphoproteome profiles confirm inactivation of MAP2K6-p38 signalling as one likely mechanism of oxaliplatin resistance. Our study shows that miR-625-3p induces oxaliplatin resistance by abrogating MAP2K6-p38-regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p

Standardization and control of Grignard reactions in a universal chemical synthesis machine using online NMR

A big problem with the chemistry literature is that it is not standardized with respect to precise operational parameters, and real time corrections are hard to make without expert knowledge. This lack of context means difficult reproducibility because many steps are ambiguous, and hence depend on tacit knowledge. Here we present the integration of online NMR into an automated chemical synthesis machine (CSM aka. ‘Chemputer’ which is capable of small-molecule synthesis using a universal programming language) to allow automated analysis and adjustment of reactions on the fly. The system was validated and benchmarked by using Grignard reactions which were chosen due to their importance in synthesis. The system was monitored in real time using online-NMR, and spectra were measured continuously during the reactions. This shows that the synthesis being done in the Chemputer can be dynamically controlled in response to feedback optimizing the reaction conditions according to the user requirements

Feasible mitigation actions in developing countries

Energy use is not only crucial for economic development, but is also the main driver of greenhouse-gas emissions. Developing countries can reduce emissions and thrive only if economic growth is disentangled from energy-related emissions. Although possible in theory, the required energy-system transformation would impose considerable costs on developing nations. Developed countries could bear those costs fully, but policy design should avoid a possible 'climate rent curse', that is, a negative impact of financial inflows on recipients' economies. Mitigation measures could meet further resistance because of adverse distributional impacts as well as political economy reasons. Hence, drastically re-orienting development paths towards low-carbon growth in developing countries is not very realistic. Efforts should rather focus on 'feasible mitigation actions' such as fossil-fuel subsidy reform, decentralized modern energy and fuel switching in the power sector