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Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes. By using a novel Medical-In silico approach that combines conventional cell culture experiments with machine learning algorithms, we aimed to reduce a significant part of the expensive and time-consuming cell culture experiments and data generation by using computational intelligence (refinement and replacement). Cardiomyocytes exposed to HS showed an activation of the intrinsic apoptosis signal pathway via cytochrome C and the activation of caspase 3 (both p < 0.001). Notably, the exposure of HS resulted in the induction of necroptosis by tumor necrosis factor α and receptor interaction protein 3 (p < 0.05; p < 0.01) and, hence, an increased level of necrotic cardiomyocytes. In conclusion, using this novel Medical-In silico approach, our data suggest (i) that HS induces necroptosis in cardiomyocytes by phosphorylation (activation) of receptor-interacting protein 3, (ii) that HS is a therapeutic target in trauma- or sepsis-associated cardiomyopathy, and (iii) indicate that this proof-of-concept is a first step toward simulating the extent of activated components in the pro-apoptotic pathway induced by HS with only a small data set gained from the in vitro experiments by using machine learning algorithms.
Hydrochar derived from Argan nut shell (ANS) was synthesized and applied to remove bisphenol A (BPA) and diuron. The results indicated that the hydrochar prepared at 200 °C (HTC@ANS-200) possessed a higher specific surface area (42 m2/g) than hydrochar (HTC@ANS-180) prepared at 180 °C (17 m2/g). The hydrochars exhibited spherical particles, which are rich in functional groups. The HTC@ANS-200 exhibited high adsorption efficiency, of about 92% of the BPA removal and 95% of diuron removal. The maximum Langmuir adsorption capacities of HTC@ANS-200 at room temperature were 1162.79 mg/for Bisphenol A and 833.33 mg/g for diuron (higher than most reported adsorbents). The adsorption process was spontaneous (− ΔG°) and exothermic (− ΔH°). Excellent reusability was reclaimed after five cycles, the removal efficiency showed a weak decrease of 4% for BPA and 1% for diuron. The analysis of Fourier transforms infrared spectrometry demonstrated that the aromatic C=C and OH played major roles in the adsorption mechanisms of BPA and diuron in this study. The high adsorption capacity was attributed to the beneficial porosity (The pore size of HTC@ANS-200 bigger than the size of BPA and diuron molecule) and surface functional groups. BPA and diuron adsorption occurred also via multiple adsorption mechanisms, including pore filling, π–π interactions, and hydrogen bonding interactions on HTC@ANS-200.
Purification of mRNA with oligo(dT)-functionalized magnetic particles involves a series of magnetic separations for buffer exchange and washing. Magnetic particles interact and agglomerate with each other when a magnetic field is applied, which can result in a decreased total surface area and thus a decreased yield of mRNA. In addition, agglomeration may also be caused by mRNA loading on the magnetic particles. Therefore, it is of interest how the individual steps of magnetic separation and subsequent redispersion in the buffers used affect the particle size distribution. The lysis/binding buffer is the most important buffer for the separation of mRNA from the multicomponent suspension of cell lysate. Therefore, monodisperse magnetic particles loaded with mRNA were dispersed in the lysis/binding buffer and in the reference system deionized water, and the particle size distributions were measured. A concentration-dependent agglomeration tendency was observed in deionized water. In contrast, no significant agglomeration was detected in the lysis/binding buffer. With regard to magnetic particle recycling, the influence of different storage and drying processes on particle size distribution was investigated. Agglomeration occurred in all process alternatives. For de-agglomeration, ultrasonic treatment was examined. It represents a suitable method for reproducible restoration of the original particle size distribution.
Laboratory protocols using magnetic beads have gained importance in the purification of mRNA for vaccines. Here, the produced mRNA hybridizes specifically to oligo(dT)-functionalized magnetic beads after cell lysis. The mRNA-loaded magnetic beads can be selectively separated using a magnet. Subsequently, impurities are removed by washing steps and the mRNA is eluted. Magnetic separation is utilized in each step, using different buffers such as the lysis/binding buffer. To reduce the time required for purification of larger amounts of mRNA vaccine for clinical trials, high-gradient magnetic separation (HGMS) is suitable. Thereby, magnetic beads are selectively retained in a flow-through separation chamber. To meet the requirements of biopharmaceutical production, a disposable HGMS separation chamber with a certified material (United States Pharmacopeia Class VI) was developed which can be manufactured using 3D printing. Due to the special design, the filter matrix itself is not in contact with the product. The separation chamber was tested with suspensions of oligo(dT)-functionalized Dynabeads MyOne loaded with synthetic mRNA. At a concentration of cB = 1.6–2.1 g·L–1 in lysis/binding buffer, these 1 μm magnetic particles are retained to more than 99.39% at volumetric flows of up to 150 mL·min–1 with the developed SU-HGMS separation chamber. When using the separation chamber with volumetric flow rates below 50 mL·min–1, the retained particle mass is even more than 99.99%.
1. Among the many concerns for biodiversity in the Anthropocene, recent reports of flying insect loss are particularly alarming, given their importance as pollinators, pest control agents, and as a food source. Few insect monitoring programmes cover the large spatial scales required to provide more generalizable estimates of insect responses to global change drivers.
2. We ask how climate and surrounding habitat affect flying insect biomass using data from the first year of a new monitoring network at 84 locations across Germany comprising a spatial gradient of land cover types from protected to urban and crop areas.
3. Flying insect biomass increased linearly with temperature across Germany. However, the effect of temperature on flying insect biomass flipped to negative in the hot months of June and July when local temperatures most exceeded long-term averages.
4. Land cover explained little variation in insect biomass, but biomass was lowest in forests. Grasslands, pastures, and orchards harboured the highest insect biomass. The date of peak biomass was primarily driven by surrounding land cover, with grasslands especially having earlier insect biomass phenologies.
5. Standardised, large-scale monitoring provides key insights into the underlying processes of insect decline and is pivotal for the development of climate-adapted strategies to promote insect diversity. In a temperate climate region, we find that the positive effects of temperature on flying insect biomass diminish in a German summer at locations where temperatures most exceeded long-term averages. Our results highlight the importance of local adaptation in climate change-driven impacts on insect communities.
This article presents experience curves and cost-benefit analyses for electric and plug-in hybrid cars sold in Germany. We find that between 2010 and 2016, the prices and price differentials relative to conventional cars declined at learning rates of 23 ± 2% and 32 ± 2% for electric cars and 6 ± 1% and 37 ± 2% for plug-in hybrids. If trends persist, price beak-even with conventional cars may be reached after another 7 ± 1 million electric cars and 5 ± 1 million plug-in hybrids are produced. The user costs of electric and plug-in hybrid cars relative to their conventional counterparts are declining annually by 14% and 26%. Also the costs for mitigating CO2 and air pollutant emissions through the deployment of electrified cars tend to decline. However, at current levels, NOX and particle emissions are still mitigated at lower costs by state-of-the-art after-treatment systems than through the electrification of powertrains. Overall, the observation of robust technological learning suggests policy makers should focus their support on non-cost market barriers for the electrification of road transport, addressing specifically the availability of recharging infrastructure.
Passenger cars in Europe have become both heavier and more powerful over the past decades. This trend has increased vehicle utility but it might have also offset technical improvements in powertrain efficiency. Here, we analyze efficiency trade-offs and CO2 emissions for three popular compact cars in Germany. We find that mass, power, and front area of model variants has increased by 66%, 147%, and 22%, respectively between 1980 and 2018. In the same period, fuel consumption decreased 14% for gasoline models but it increased 9% for diesel models. However, if vehicle mass, power, and front area had remained at 1980 levels, technical efficiency improvements would have decreased the fuel consumption of gasoline and diesel models by 23% and 24%, respectively. The related efficiency trade-offs amount to 24 g CO2/km or 13% of the current fuel consumption for gasoline models and 40 g CO2/km or 25% of the current fuel consumption for diesel models. These findings suggest that about half of the technical efficiency improvements in gasoline models and all of the technical efficiency improvements in diesel models are offset through other vehicle attributes. By accounting for the observed efficiency trade-offs, climate policy could become more effective.
Background: As electric kick scooters, three-wheelers, and passenger cars enter the streets, efficiency trade-offs across vehicle types gain practical relevance for consumers and policy makers. Here, we compile a comprehensive dataset of 428 electric vehicles, including seven vehicle types and information on certified and real-world energy consumption. Regression analysis is applied to quantify trade-offs between energy consumption and other vehicle attributes.
Results: Certified and real-world energy consumption of electric vehicles increase by 60% and 40%, respectively, with each doubling of vehicle mass, but only by 5% with each doubling of rated motor power. These findings hold roughly also for passenger cars whose energy consumption tends to increase 0.6 ± 0.1 kWh/100 km with each 100 kg of vehicle mass. Battery capacity and vehicle mass are closely related. A 10 kWh increase in battery capacity increases the mass of electric cars by 15 kg, their drive range by 40–50 km, and their energy consumption by 0.7–1.0 kWh/100 km. Mass-produced state-of-the-art electric passenger cars are 2.1 ± 0.8 kWh/100 km more efficient than first-generation vehicles, produced at small scale.
Conclusion: Efficiency trade-offs in electric vehicles differ from those in conventional cars—the latter showing a strong dependency of fuel consumption on rated engine power. Mass-related efficiency trade-offs in electric vehicles are large and could be tapped by stimulating mode shift from passenger cars to light electric road vehicles. Electric passenger cars still offer potentials for further efficiency improvements. These could be exploited through a dedicated energy label with battery capacity as utility parameter.
Intraspecific diet specialization, usually driven by resource availability, competition and predation, is common in natural populations. However, the role of parasites on diet specialization of their hosts has rarely been studied. Eye flukes can impair vision ability of their hosts and have been associated with alterations of fish feeding behavior. Here it was assessed whether European perch (Perca fluviatilis) alter their diet composition as a consequence of infection with eye flukes. Young-of-the-year (YOY) perch from temperate Lake Müggelsee (Berlin, Germany) were sampled in two years, eye flukes counted and fish diet was evaluated using both stomach content and stable isotope analyses. Perch diet was dominated by zooplankton and benthic macroinvertebrates. Both methods indicated that with increasing eye fluke infection intensity fish had a more selective diet, feeding mainly on the benthic macroinvertebrate Dikerogammarus villosus, while less intensively infected fish appeared to be generalist feeders showing no preference for any particular prey type. Our results show that infection with eye flukes can indirectly affect interaction of the host with lower trophic levels by altering the diet composition and highlight the underestimated role of parasites in food web studies.
The current work investigates the capability of a tailored multivariate curve resolution–alternating least squares (MCR-ALS) algorithm to analyse glucose, phosphate, ammonium and acetate dynamics simultaneously in an E. coli BL21 fed-batch fermentation. The high-cell-density (HCDC) process is monitored by ex situ online attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy and several in situ online process sensors. This approach efficiently utilises automatically generated process data to reduce the time and cost consuming reference measurement effort for multivariate calibration. To determine metabolite concentrations with accuracies between ±0.19 and ±0.96·gL−l, the presented utilisation needs primarily — besides online sensor measurements — single FTIR measurements for each of the components of interest. The ambiguities in alternating least squares solutions for concentration estimation are reduced by the insertion of analytical process knowledge primarily in the form of elementary carbon mass balances. Thus, in this way, the established idea of mass balance constraints in MCR combines with the consistency check of measured data by carbon balances, as commonly applied in bioprocess engineering. The constraints are calculated based on online process data and theoretical assumptions. This increased calculation effort is able to replace, to a large extent, the need for manually conducted quantitative chemical analysis, leads to good estimations of concentration profiles and a better process understanding.