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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%.
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.
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.
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.
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.
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.
This study compares the environmental impacts of petrol, diesel, natural gas, and electric vehicles using a process-based attributional life cycle assessment (LCA) and the ReCiPe characterization method that captures 18 impact categories and the single score endpoints. Unlike common practice, we derive the cradle-to-grave inventories from an originally combustion engine VW Caddy that was disassembled and electrified in our laboratory, and its energy consumption was measured on the road. Ecoivent 2.2 and 3.0 emission inventories were contrasted exhibiting basically insignificant impact deviations. Ecoinvent 3.0 emission inventory for the diesel car was additionally updated with recent real-world close emission values and revealed strong increases over four midpoint impact categories, when matched with the standard Ecoinvent 3.0 emission inventory. Producing batteries with photovoltaic electricity instead of Chinese coal-based electricity decreases climate impacts of battery production by 69%. Break-even mileages for the electric VW Caddy to pass the combustion engine models under various conditions in terms of climate change impact ranged from 17,000 to 310,000 km. Break-even mileages, when contrasting the VW Caddy and a mini car (SMART), which was as well electrified, did not show systematic differences. Also, CO2-eq emissions in terms of passenger kilometers travelled (54–158 g CO2-eq/PKT) are fairly similar based on 1 person travelling in the mini car and 1.57 persons in the mid-sized car (VW Caddy). Additionally, under optimized conditions (battery production and use phase utilizing renewable electricity), the two electric cars can compete well in terms of CO2-eq emissions per passenger kilometer with other traffic modes (diesel bus, coach, trains) over lifetime. Only electric buses were found to have lower life cycle carbon emissions (27–52 g CO2-eq/PKT) than the two electric passenger cars.
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.
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.
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.
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.
Since operational managers often monitor large numbers of wind turbines (WTs), they depend on a toolset to provide them with highly condensed information to identify and prioritize low performing WTs or schedule preventive maintenance measures. Power curves are a frequently used tool to assess the performance of WTs. The power curve health value (HV) used in this work is supposed to detect power curve anomalies since small deviations in the power curve are not easy to identify. It evaluates deviations in the linear region of power curves by performing a principal component analysis. To calculate the HV, the standard deviation in direction of the second principal component of a reference data set is compared to the standard deviation of a combined data set consisting of the reference data and data of the evaluated period. This article examines the applicability of this HV for different purposes as well as its sensitivities and provides a modified HV approach to make it more robust and suitable for heterogeneous data sets. The modified HV was tested based on ENGIE's open data wind farm and data of on- and offshore WTs from the WInD-Pool. It proved to detect anomalies in the linear region of the power curve in a reliable and sensitive manner and was also eligible to detect long term power curve degradation. Also, about 7 % of all corrective maintenance measures were preceded by high HVs with a median alarm horizon of three days. Overall, the HV proved to be a promising tool for various applications.
A comprehensive overview is provided evaluating direct real-world CO2 emissions of both diesel and petrol cars newly registered in Europe between 1995 and 2015. Before 2011, European diesel cars emitted less CO2 per kilometre than petrol cars, but since then there is no appreciable difference in per-km CO2 emissions between diesel and petrol cars. Real-world CO2 emissions of diesel cars have not declined appreciably since 2001, while the CO2 emissions of petrol cars have been stagnant since 2012. When adding black carbon related CO2-equivalents, such as from diesel cars without particulate filters, diesel cars were discovered to have had much higher climate relevant emissions until the year 2001 when compared to petrol cars. From 2001 to 2015 CO2-equivalent emissions from new diesel cars and petrol cars were hardly distinguishable. Lifetime use phase CO2-equivalent emissions of all European passenger vehicles were modelled for 1995–2015 based on three scenarios: the historic case, another scenario freezing percentages of diesel cars at the low levels from the early 1990s (thus avoiding the observed “boom” in new diesel registrations), and an advanced mitigation scenario based on high proportions of petrol hybrid cars and cars burning gaseous fuels. The difference in CO2-equivalent emissions between the historical case and the scenario avoiding the diesel car boom is only 0.4%. The advanced mitigation scenario would have been able to achieve a 3.4% reduction in total CO2-equivalent emissions over the same time frame. The European diesel car boom appears to have been ineffective at reducing climate-warming emissions from the European transport sector.
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.
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.
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.
Fuzzy system based on two-step cascade genetic optimization strategy for tobacco tar prediction
(2019)
There are many challenges in accurately measuring cigarette tar constituents. These include the need for standardized smoke generation methods related to unstable mixtures. In this research were developed algorithms using fusion of artificial intelligence methods to predict tar concentration. Outputs of development are three fuzzy structures optimized with genetic algorithms resulting in genetic algorithm (GA)-FUZZY, GA-adaptive neuro fuzzy inference system (ANFIS), GA-GA-FUZZY algorithms. Proposed algorithms are used for the tar prediction in the cigarette production process. The results of prediction are compared with gas chromatograph (high-performance liquid chromatography (HPLC)) readings.
A new comprehensive evaluation system presented here allows to compare and to quantify education for a sustainable development (ESD) in degree programs. The evaluation is based on a criteria system working with three hierarchic levels. The highest level considers a list of 35 indicator terms. Primarily, the two most popular undergraduate (bachelor’s) degree programs in Germany (mechanical engineering, ME, and business administration, BA) have been reviewed for ESD contents based on the new evaluation scheme. Additionally we reviewed and quantified ESD subjects and their temporal changes in the entire bandwidth of degree programs of a university (Umwelt-Campus Birkenfeld, University of Applied Sciences Trier), back to 1999. Moreover, a spot check on international ME and BA bachelor’s degree programs was performed. Through our reviews, we found a high number of elective classes dedicated to ESD particularly in BA bachelor programs. However, the percentage of compulsory classes related to ESD is relatively low with 5-6 % in both ME and BA programs, respectively. The spot check on degree programs outside Germany revealed similar results. Analysing the time trend at Umwelt-Campus Birkenfeld, a considerable share of ESD that was part of the original diploma degrees was moved to what are now master’s degrees.
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.
Global change effects on biodiversity and human wellbeing call for improved long-term environmental data as a basis for science, policy and decision making, including increased interoperability, multifunctionality, and harmonization. Based on the example of two global initiatives, the International Long-Term Ecological Research (ILTER) network and the Group on Earth Observations Biodiversity Observation Network (GEO BON), we propose merging the frameworks behind these initiatives, namely ecosystem integrity and essential biodiversity variables, to serve as an improved guideline for future site-based long-term research and monitoring in terrestrial, freshwater and coastal ecosystems. We derive a list of specific recommendations of what and how to measure at a monitoring site and call for an integration of sites into co-located site networks across individual monitoring initiatives, and centered on ecosystems. This facilitates the generation of linked comprehensive ecosystem monitoring data, supports synergies in the use of costly infrastructures, fosters cross-initiative research and provides a template for collaboration beyond the ILTER and GEO BON communities.