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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.
1. Recent reports on insect decline have highlighted the need for long-term data on insect communities towards identifying their trends and drivers.
2. With the launch of many new insect monitoring schemes to investigate insect communities over large spatial and temporal scales, Malaise traps have become one of the most important tools due to the broad spectrum of species collected and reduced capture bias through passive sampling of insects day and night. However, Malaise traps can vary in size, shape, and colour, and it is unknown how these differences affect biomass, species richness, and composition of trap catch, making it difficult to compare results between studies.
3. We compared five Malaise trap types (three variations of the Townes and two variations of the Bartak Malaise trap) to determine their effects on biomass and species richness as identified by metabarcoding.
4. Insect biomass varied by 20%–55%, not strictly following trap size but varying with trap type. Total species richness was 20%–38% higher in the three Townes trap models compared to the Bartak traps. Bartak traps captured lower richness of highly mobile taxa but increased richness of ground-dwelling taxa. The white roofed Townes trap captured a higher richness of pollinators.
5. We find that biomass, total richness, and taxa group specific richness are all sensitive to Malaise trap type. Trap type should be carefully considered and aligned to match monitoring and research questions. Additionally, our estimates of trap type effects can be used to adjust results to facilitate comparisons across studies.
The implementation of single-use technologies offers several major advantages, e.g. prevention of cross-contamination, especially when spore-forming microorganisms are present. This study investigated the application of a single-use bioreactor in batch fermentation of filamentous fungus Penicillium sp. (IBWF 040-09) from the Institute of Biotechnology and Drug Research (IBWF), which is capable of intracellular production of a protease inhibitor against parasitic proteases as a secondary metabolite. Several modifications to the SU bioreactor were suggested in this study to allow the fermentation in which the fungus forms pellets. Simultaneously, fermentations in conventional glass bioreactor were also conducted as reference. Although there are significant differences in the construction material and gassing system, the similarity of the two types of bioreactors in terms of fungal metabolic activity and the reproducibility of fermentations could be demonstrated using statistic methods. Under the selected cultivation conditions, growth rate, yield coefficient, substrate uptake rate, and formation of intracellular protease-inhibiting substance in the single-use bioreactor were similar to those in the glass bioreactor.
This study introduced an automated long-term fermentation process for fungals grown in pellet form. The goal was to reduce the overgrowth of bioreactor internals and sensors while better rheological properties in the fermentation broth, such as oxygen transfer and mixing time, can be achieved. Because this could not be accomplished with continuous culture and fed-batch fermentation, repeated-batch fermentation was implemented with the help of additional bioreactor internals (“sporulation supports”). This should capture some biomass during fermentation. After harvesting the suspended biomass, intermediate cleaning was performed using a cleaning device. The biomass retained on the sporulation support went through the sporulation phase. The spores were subsequently used as inocula for the next batch. The reason for this approach was that the retained pellets could otherwise cause problems (e.g., overgrowth on sensors) in subsequent batches because the fungus would then show undesirable hyphal growth. Various sporulation supports were tested for sufficient biomass fixation to start the next batch. A reproducible spore concentration within the range of the requirements could be achieved by adjusting the sporulation support (design and construction material), and an intermediate cleaning adapted to this.
Zur Optimierung von Zulaufsatzkultur-Fermentationen von methylotrophen Organismen wird eine Online-Messmethode vorgestellt, mit der die Methanol-Konzentration im Medium während einer Fermentation durch ein Spülgaspervaporations-Prinzip bestimmt werden kann. Im Gegensatz zu anderen Analysemethoden bietet die Messmethode die Möglichkeit, die Substratkonzentration bei Prozessen mit Methanol als zentralem Substrat über eine Regelung auf einem definierten Wert zu halten. Es werden Schwierigkeiten, aber auch deren Überwindung bei der Adaption der Messmethode auf Fermentationsprozesse dargestellt.
Productive biofilms are gaining growing interest in research due to their potential of producing valuable compounds and bioactive substances such as antibiotics. This is supported by recent developments in biofilm photobioreactors that established the controlled phototrophic cultivation of algae and cyanobacteria. Cultivation of biofilms can be challenging due to the need of surfaces for biofilm adhesion. The total production of biomass, and thus production of e.g. bioactive substances, within the bioreactor volume highly depends on the available cultivation surface. To achieve an enlargement of surface area for biofilm photobioreactors, biocarriers can be implemented in the cultivation. Thereby, material properties and design of the biocarriers are important for initial biofilm formation and growth of cyanobacteria. In this study, special biocarriers were designed and additively manufactured to investigate different polymeric materials and surface designs regarding biofilm adhesion of the terrestrial cyanobacterium Nostoc flagelliforme (CCAP 1453/33). Properties of 3D-printed materials were characterized by determination of wettability, surface roughness, and density. To evaluate the influence of wettability on biofilm formation, material properties were specifically modified by gas-phase fluorination and biofilm formation was analyzed on biocarriers with basic and optimized geometry in shaking flask cultivation. We found that different polymeric materials revealed no significant differences in wettability and with identical surface design no significant effect on biomass adhesion was observed. However, materials treated with fluorination as well as optimized biocarrier design showed improved wettability and an increase in biomass adhesion per biocarrier surface.
We present the concrete realization of a virtual laboratory equipped with a pedagogical agent. Its functionality and media didactics takes into account the results of an usability test on a prototype system, and the students' demand on such an automated assistance as obtained from a preliminary survey. The pedagogical agent mediates between the content and the learner by activating him or her. To provide information about the learner's skills, we propose a pragmatic and simplified competence model that is based on fundamental representations in physics (experiment, figure, text and equation). Moreover, an automated feedback relates the student's self-assessment with the submitted answer to the correctness of the respective task. In consequence, the pedagogical agent enables mental reflection for a crucial review of the own learning process. Interestingly, learning pathways can be envisioned, thus, giving valuable insight into individual strengths and weaknesses.
Modeling and executing knowledge-intensive processes (KiPs) are challenging with state-of-the-art approaches, and the specific demands of KiPs are the subject of ongoing research. In this context, little attention has been paid to the ontology-driven combination of data-centric and semantic business process modeling, which finds additional motivation by enabling the division of labor between humans and artificial intelligence. Such approaches have characteristics that could allow support for KiPs based on the inferencing capabilities of reasoners. We confirm this as we show that reasoners can infer the executability of tasks based on a currently researched ontology- and data-driven business process model (ODD-BP model). Further support for KiPs by the proposed inference mechanism results from its ability to infer the relevance of tasks, depending on the extent to which their execution would contribute to process progress. Besides these contributions along with the execution perspective (start-to-end direction), we will also show how our approach can help to reach specific process goals by inferring the relevance of process elements regarding their support to achieve such goals (end-to-start direction). The elements with the most valuable process progress can be identified in the intersection of both, the execution and goal perspective. This paper will introduce this new approach and verifies its practicability with an evaluation of a KiP in the field of emergency call centers.
Local biodiversity trends over time are likely to be decoupled from global trends, as local processes may compensate or counteract global change. We analyze 161 long-term biological time series (15–91 years) collected across Europe, using a comprehensive dataset comprising ~6,200 marine, freshwater and terrestrial taxa. We test whether (i) local long-term biodiversity trends are consistent among biogeoregions, realms and taxonomic groups, and (ii) changes in biodiversity correlate with regional climate and local conditions. Our results reveal that local trends of abundance, richness and diversity differ among biogeoregions, realms and taxonomic groups, demonstrating that biodiversity changes at local scale are often complex and cannot be easily generalized. However, we find increases in richness and abundance with increasing temperature and naturalness as well as a clear spatial pattern in changes in community composition (i.e. temporal taxonomic turnover) in most biogeoregions of Northern and Eastern Europe.
Background: High numbers of consumable medical materials (eg, sterile needles and swabs) are used during the daily routine of intensive care units (ICUs) worldwide. Although medical consumables largely contribute to total ICU hospital expenditure, many hospitals do not track the individual use of materials. Current tracking solutions meeting the specific requirements of the medical environment, like barcodes or radio frequency identification, require specialized material preparation and high infrastructure investment. This impedes the accurate prediction of consumption, leads to high storage maintenance costs caused by large inventories, and hinders scientific work due to inaccurate documentation. Thus, new cost-effective and contactless methods for object detection are urgently needed.
Objective: The goal of this work was to develop and evaluate a contactless visual recognition system for tracking medical consumable materials in ICUs using a deep learning approach on a distributed client-server architecture.
Methods: We developed Consumabot, a novel client-server optical recognition system for medical consumables, based on the convolutional neural network model MobileNet implemented in Tensorflow. The software was designed to run on single-board computer platforms as a detection unit. The system was trained to recognize 20 different materials in the ICU, while 100 sample images of each consumable material were provided. We assessed the top-1 recognition rates in the context of different real-world ICU settings: materials presented to the system without visual obstruction, 50% covered materials, and scenarios of multiple items. We further performed an analysis of variance with repeated measures to quantify the effect of adverse real-world circumstances.
Results: Consumabot reached a >99% reliability of recognition after about 60 steps of training and 150 steps of validation. A desirable low cross entropy of <0.03 was reached for the training set after about 100 iteration steps and after 170 steps for the validation set. The system showed a high top-1 mean recognition accuracy in a real-world scenario of 0.85 (SD 0.11) for objects presented to the system without visual obstruction. Recognition accuracy was lower, but still acceptable, in scenarios where the objects were 50% covered (P<.001; mean recognition accuracy 0.71; SD 0.13) or multiple objects of the target group were present (P=.01; mean recognition accuracy 0.78; SD 0.11), compared to a nonobstructed view. The approach met the criteria of absence of explicit labeling (eg, barcodes, radio frequency labeling) while maintaining a high standard for quality and hygiene with minimal consumption of resources (eg, cost, time, training, and computational power).
Conclusions: Using a convolutional neural network architecture, Consumabot consistently achieved good results in the classification of consumables and thus is a feasible way to recognize and register medical consumables directly to a hospital’s electronic health record. The system shows limitations when the materials are partially covered, therefore identifying characteristics of the consumables are not presented to the system. Further development of the assessment in different medical circumstances is needed.
The aim of this work was to develop and evaluate the reinforcement learning algorithm VentAI, which is able to suggest a dynamically optimized mechanical ventilation regime for critically-ill patients. We built, validated and tested its performance on 11,943 events of volume-controlled mechanical ventilation derived from 61,532 distinct ICU admissions and tested it on an independent, secondary dataset (200,859 ICU stays; 25,086 mechanical ventilation events). A patient “data fingerprint” of 44 features was extracted as multidimensional time series in 4-hour time steps. We used a Markov decision process, including a reward system and a Q-learning approach, to find the optimized settings for positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2) and ideal body weight-adjusted tidal volume (Vt). The observed outcome was in-hospital or 90-day mortality. VentAI reached a significantly increased estimated performance return of 83.3 (primary dataset) and 84.1 (secondary dataset) compared to physicians’ standard clinical care (51.1). The number of recommended action changes per mechanically ventilated patient constantly exceeded those of the clinicians. VentAI chose 202.9% more frequently ventilation regimes with lower Vt (5–7.5 mL/kg), but 50.8% less for regimes with higher Vt (7.5–10 mL/kg). VentAI recommended 29.3% more frequently PEEP levels of 5–7 cm H2O and 53.6% more frequently PEEP levels of 7–9 cmH2O. VentAI avoided high (>55%) FiO2 values (59.8% decrease), while preferring the range of 50–55% (140.3% increase). In conclusion, VentAI provides reproducible high performance by dynamically choosing an optimized, individualized ventilation strategy and thus might be of benefit for critically ill patients.