In a previous work, we explored zone broadening and the achievable plate numbers in linear drift tube ion mobility-mass spectrometry through developing a plate-height model . On the basis of these findings, the present theoretical study extends the model by exploring peak-to-peak resolution and peak capacity in ion mobility separations. The first part provides a critical overview of chromatography-influenced resolution equations, including refinement of existing formulae. Furthermore, we present exact resolution equations for drift tube ion mobility spectrometry based on first principles. Upon implementing simple modifications, these exact formulae could be readily extended to traveling wave ion mobility separations and to cases when ion mobility spectrometry is coupled to mass spectrometry. The second part focuses on peak capacity. The well-known assumptions of constant plate number and constant peak width form the basis of existing approximate solutions. To overcome their limitations, an exact peak capacity equation is derived for drift tube ion mobility spectrometry. This exact solution is rooted in a suitable physical model of peak broadening, accounting for the finite injection pulse and subsequent diffusional spreading. By borrowing concepts from the theoretical toolbox of chromatography, we believe that the present study will help in integrating ion mobility spectrometry into the unified language of separation science.View less
The Covid-19 disease has caused a world-wide pandemic with more than 60 million positive cases and more than 1.4 million deaths by the end of November 2020. As long as effective medical treatment and vaccination are not available, non-pharmaceutical interventions such as social distancing, self-isolation and quarantine as well as far-reaching shutdowns of economic activity and public life are the only available strategies to prevent the virus from spreading. These interventions must meet conflicting requirements where some objectives, like the minimization of disease-related deaths or the impact on health systems, demand for stronger counter-measures, while others, such as social and economic costs, call for weaker counter-measures. Therefore, finding the optimal compromise of counter-measures requires the solution of a multi-objective optimization problem that is based on accurate prediction of future infection spreading for all combinations of counter-measures under consideration. We present a strategy for construction and solution of such a multi-objective optimization problem with real-world applicability. The strategy is based on a micro-model allowing for accurate prediction via a realistic combination of person-centric data-driven human mobility and behavior, stochastic infection models and disease progression models including micro-level inclusion of governmental intervention strategies. For this micro-model, a surrogate macro-model is constructed and validated that is much less computationally expensive and can therefore be used in the core of a numerical solver for the multi-objective optimization problem. The resulting set of optimal compromises between counter-measures (Pareto front) is discussed and its meaning for policy decisions is outlined.View less
A new all-Manganese flow battery (all-MFB) as a non-aqueous hybrid redox-flow battery is reported. The discharged active material [Cat]2[MnIICl4] (Cat = organic cation) utilized in both half-cells supports a long cycle life. The reversible oxidation of [MnIICl4]2− to [MnIIICl5]2− at the positive electrode and manganese metal deposition from [MnIICl4]2− at the negative electrode give a cell voltage of 2.59 V. Suitable electrolytes are prepared and optimized, followed by a characterization in static battery cells and in a pumped flow-cell. Several electrode materials, solvents, and membranes are tested for their feasibility in the all-MFB. An electrolyte consisting of [EMP]2[MnCl4] and some solvent γ-butyrolactone is cycled 500 times, both in a static as well as a flow-cell, over a period of two months, with coulombic efficiencies up to 83%. With the electrolytes prepared in this work, energy densities up to 74 Wh L−1 are possible, exceeding the VRFB benchmark system, using solely the cheap and abundant element manganese as the active material. Although further optimizations are necessary, this system represents a new and promising setup toward sustainable stationary energy storage.View less
The indole alkaloid yohimbine is an alpha-2 receptor antagonist used for its sympathomimetic effects. Several cases of yohimbine intoxication have been reported and the most recent one involved four individuals taking a yohimbine-containing drug powder. All individuals developed severe intoxication symptoms and were admitted to the hospital. Even though all individuals were assumed to have taken the same dose of the drug powder, toxicology analyses revealed yohimbine blood concentrations of 249–5631 ng/mL, amounting to a 22-fold difference. The reason for this high variability remained to be elucidated. We used recently reported knowledge on the metabolism of yohimbine together with state-of-the art nonlinear mixed-effects modelling and simulation and show that a patient’s cytochrome P450 2D6 (CYP2D6) phenotype can explain the large differences observed in the measured concentration after intake of the same yohimbine dose. Our findings can be used both for the identification of safe doses in therapeutic use of yohimbine and for an explanation of individual cases of overdosing.View less
Salmonella enterica subspecies enterica serovar Derby (S. Derby) is one of the most frequent causes for salmonellosis in humans and animals. Understanding the genetic diversity of S. Derby, as well as the nature and origin of its resistance to antimicrobial treatment are thus the key to epidemiological control and surveillance. Here, we report an analysis of 15 S. Derby strains isolated from pig and cattle in slaughterhouses across Germany (2000–2015), which belonged to multilocus sequence types (ST) ST39, ST40 and ST682. Strains were compared to publicly available S. Derby sequence data of these three STs from Germany, comprising 65 isolates collected between 2004 and 2018 from different sources (i.e., pigs, humans, cattle, wild boar, and poultry). A total of 80 sequences (ST39 = 34, ST40 = 21, and ST682 = 25) were analyzed to assess genetic diversity, to identify virulence-associated and antimicrobial resistance genes (ARGs), and to characterize plasmid content. Strains belonging to all three STs were identified in each source examined. Strains with the same ST were closely related regardless of origin. Altogether, 72.5% of the isolates carried at least one resistance gene, furthermore ST40 carried most of the ARGs and the plasmid replicons. The IncI1 replicon was detected in eleven isolates, four of them carried IncI1 plasmid ST26 with clonal complex 2. The comparison of these four isolates with an IncI1 ST26 plasmid reported in 2010 from a German pig (JX566770), showed only variations in a region carrying different ARGs and mobile genetic elements. The strains of our collection had similar genetic diversity as the strains taken from the public database. Moreover, we found that strains harboring multidrug resistant IncI plasmid were found in different animal species, indicating that S. Derby may be implicated in the spread of antimicrobial resistance among animal species. Results may contribute to the knowledge about the diversity in S. Derby in Germany, which may be useful for the future surveillance and antimicrobial resistance of this serovar.View less
Incompatible measurements, i.e., measurements that cannot be simultaneously performed, are necessary to observe nonlocal correlations. It is natural to ask, e.g., how incompatible the measurements have to be to achieve a certain violation of a Bell inequality. In this paper, we provide the direct link between Bell nonlocality and the quantification of measurement incompatibility. This includes quantifiers for both incompatible and genuine-multipartite incompatible measurements. Our method straightforwardly generalizes to include constraints on the system's dimension (semi-device-independent approach) and on projective measurements, providing improved bounds on incompatibility quantifiers, and to include the prepare-and-measure scenario.View less
Metal-sulfur batteries (MSBs) are considered up-and-coming future-generation energy storage systems because of their prominent theoretical energy density. However, the practical applications of MSBs are still hampered by several critical challenges, i.e., the shuttle effects, sluggish redox kinetics, and low conductivity of sulfur species. Recently, benefiting from the high surface area, regulated networks, molecular/atomic-level reactive sites, the metal-organic frameworks (MOFs)-derived nanostructures have emerged as efficient and durable multifaceted electrodes in MSBs. Herein, a timely review is presented on recent advancements in designing MOF-derived electrodes, including fabricating strategies, composition management, topography control, and electrochemical performance assessment. Particularly, the inherent charge transfer, intrinsic polysulfide immobilization, and catalytic conversion on designing and engineering of MOF nanostructures for efficient MSBs are systematically discussed. In the end, the essence of how MOFs’ nanostructures influence their electrochemical properties in MSBs and conclude the future tendencies regarding the construction of MOF-derived electrodes in MSBs is exposed. It is believed that this progress review will provide significant experimental/theoretical guidance in designing and understanding the MOF-derived nanostructures as multifaceted electrodes, thus offering promising orientations for the future development of fast-kinetic and robust MSBs in broad energy fields.View less
Male frog advertisement calls are species-specific vocalizations used to attract females for breeding. However, it is possible for environmental or biological sounds to overlap these calls in both frequency and duration resulting in signal confusion, influencing female decision and/or location abilities. It is therefore important for vocal species competing for the same acoustic space to partition their calls either spatially or temporally (via call alternation or suppression). However, frog species previously isolated from each other may not have developed appropriate adaptive behaviors, resulting in acoustic competition. This study applied rhythm analysis to track changes in calling behavior, namely changes in calling frequency (as in beats per second), of the wallum sedgefrog and the eastern sedgefrog when vocalizing alone versus in the presence of each other to assess potential acoustic competition. Our main findings demonstrated that both species significantly altered their calling behavior when exposed to each other. While we expected the increased calling activity of one species to inhibit the activity of the other to avoid signal confusion, we instead found that both species greatly increased the beat frequency of their calls when calling in the presence of each other. We also found evidence of beat frequency development in the wallum sedgefrog whereby there was always a strong initial increase in call frequency in reaction to the first vocal interruption by the eastern sedgefrog. These results support the hypothesis that the eastern sedgefrog and the wallum sedgefrog are in competition for the acoustic space in habitats where they occur together. This highlights a new threat to the vulnerable wallum sedgefrog species and may serve to inform future management practices. Using rhythm analyses to track changes in acoustic behavior can help inform on important population dynamics such as health, trajectory, and response to management, and therefore be of great benefit to the conservation of vocal species.View less
In a green energy economy, electrocatalysis is essential for chemical energy conversion and to produce value added chemicals from regenerative resources. To be widely applicable, an electrocatalyst should comprise the Earth's crust's most abundant elements. The most abundant 3d metal, iron, with its multiple accessible redox states has been manifold applied in chemocatalytic processes. However, due to the low conductivity of FeIIIOxHy phases, its applicability for targeted electrocatalytic oxidation reactions such as water oxidation is still limited. Herein, it is shown that iron incorporated in conductive intermetallic iron silicide (FeSi) can be employed to meet this challenge. In contrast to silicon-poor iron–silicon alloys, intermetallic FeSi possesses an ordered structure with a peculiar bonding situation including covalent and ionic contributions together with conducting electrons. Using in situ X-ray absorption and Raman spectroscopy, it could be demonstrated that, under the applied corrosive alkaline conditions, the FeSi partly forms a unique, oxidic iron(III) phase consisting of edge and corner sharing [FeO6] octahedra together with oxidized silicon species. This phase is capable of driving the oxyge evolution reaction (OER) at high efficiency under ambient and industrially relevant conditions (500 mA cm−2 at 1.50 ± 0.025 VRHE and 65 °C) and to selectively oxygenate 5-hydroxymethylfurfural (HMF).View less
Background Understanding subnational variation in age-specific fertility rates (ASFRs) and total fertility rates (TFRs), and geographical clustering of high fertility and its determinants in low-income and middle-income countries, is increasingly needed for geographical targeting and prioritising of policy. We aimed to identify variation in fertility rates, to describe patterns of key selected fertility determinants in areas of high fertility.
Methods We did a subnational analysis of ASFRs and TFRs from the most recent publicly available and nationally representative cross-sectional Demographic and Health Surveys and Multiple Indicator Cluster Surveys collected between 2010 and 2016 for 70 low-income, lower-middle-income, and upper-middle-income countries, across 932 administrative units. We assessed the degree of global spatial autocorrelation by using Moran's I statistic and did a spatial cluster analysis using the Getis-Ord Gi* local statistic to examine the geographical clustering of fertility and key selected fertility determinants. Descriptive analysis was used to investigate the distribution of ASFRs and of selected determinants in each cluster.
Findings TFR varied from below replacement (2·1 children per women) in 36 of the 932 subnational regions (mainly located in India, Myanmar, Colombia, and Armenia), to rates of 8 and higher in 14 subnational regions, located in sub-Saharan Africa and Afghanistan. Areas with high-fertility clusters were mostly associated with areas of low prevalence of women with secondary or higher education, low use of contraception, and high unmet needs for family planning, although exceptions existed.
Interpretation Substantial within-country variation in the distribution of fertility rates highlights the need for tailored programmes and strategies in high-fertility cluster areas to increase the use of contraception and access to secondary education, and to reduce unmet need for family planning.View less
Background In German veterinary education interdisciplinary lectures (ILs) are an important and mandatory part of the curriculum as their merging character builds a useful preparation for the future profession as a veterinarian. These lectures should enable students to work on practically-relevant and interdisciplinary cases, which should ideally be defined jointly by lecturers from different disciplines.
Methods In order to give students the opportunity to work on these cases and at the same time have contact with their lecturers and fellow students, the Faculty of Veterinary Medicine, Freie Universität Berlin, has converted its former in-class ILs (face-to-face delivery format) into a blended learning format. The mandatory lectures comprise 196 curricular hours and are delivered over the course of three semesters within the veterinary curriculum. The new concept was developed over a period of three academic years and extensively evaluated (old-new-comparison) with regard to its acceptance and compliance with national requirements for interdisciplinary teaching.
Results A total of 306 students were asked to evaluate different aspects of the newly implemented format. Overall, more than 79% of the students attending the newly implemented blended learning format responded positively, and the evaluation showed a significant improvement of learning motivation and acceptance when compared to the traditional teaching format.
Conclusion The results indicated that blended learning is a suitable option for teaching mandatory ILs in clinical medicine and veterinary public health.View less
Background: Despite concerns about causing bacterial resistance and serious side effects, oral cephalosporins and fluoroquinolones are still frequently prescribed in Germany. We aimed to test a method for the detection of regional quality differences in the use of oral cephalosporins and fluoroquinolones and to apply this to the German federal states. Methods: Use of antibiotics from 2014–2019 was analyzed using dispensing data from community pharmacies claimed to the statutory health insurance (SHI) funds. Quality of regional antibiotic use in 2019 was assessed by calculating indicators based on defined daily doses per 1000 SHI-insured persons per day (DID). Oral cephalosporin and fluoroquinolone use was followed by linear regression analyses. Results: The method used was suitable to find meaningful quality differences in ambulatory oral cephalosporin and fluoroquinolone use between the German federal states. In 2019, DID varied from 1.62 in Brandenburg to 3.17 in Rhineland-Palatinate for cephalosporins and from 0.47 in Brandenburg to 0.89 in Saarland for fluoroquinolones. The city-states Hamburg, Bremen, and Berlin showed highest quality with the applied indicator set. From 2014–2019, a significant decrease in utilization of oral cephalosporins was found in all federal states. During 2017–2019, all states showed a significant decline of fluoroquinolone use.View less
The cultural effects of globalization constitute one of the most important challenges for the discipline of art history today. The aim of this publication is to take a critical look at art historical narratives. Based on transcultural object biographies, the volume brings together analyses of objects and images that circulate in transcultural contact zones: their histories of origin, circulation and perception slice through space and time. The histories of these objects and images thus demonstrate in exemplary fashion how knowledge and understanding can be generated, communicated or also challenged in cultural contact zones. Hence, the publication is designed as a methodological contribution to a transcultural art and cultural history. It is also conceived as an instrument for teaching and contains a critical-discursive glossary of key-terms that combines theory and practice of transcultural art history.View less
The liver is composed of different cell populations. Interactions of different cell populations can be investigated by a newly established indirect co-culture system consisting of immortalised primary human hepatocytes and human monocyte derived macrophages (MDMs). Using the time-dependent cytokine secretion of the co-cultures and single cultures, correlation networks (including the cytokines G-CSF, CCL3, MCP-1, CCL20, FGF, TGF-β1, GM-CSF, IL-8 IL-6, IL-1β, and IL-18) were generated and the correlations were validated by application of IL-8 and TNF-α-neutralising antibodies. The data reveal that IL-8 is crucial for the interaction between hepatocytes and macrophages in vitro. In addition, transcriptome analyses showed that a change in the ratio between macrophages and hepatocytes may trigger pro-inflammatory signalling pathways of the acute phase response and the complement system (release of, e.g., certain cyto- and chemokines). Using diclofenac and LPS showed that the release of cytokines is increasing with higher ratios of MDMs. Altogether, we could demonstrate that the current co-culture system is better suited to mirror the in vivo situation when compared to previously established co-culture systems composed of HepG2 and differentiated THP-1 cells. Further, our data reveal that the cytokine IL-8 is crucial for the interaction between hepatocytes and macrophages in vitro.View less
The detrital zircons in tills overlying the Guichon Creek batholith, British Columbia, Canada, have trace element concentrations and ages similar to those of zircons from the bedrock samples from which they are interpreted to have been sourced. Rocks from the core of the batholith that host porphyry copper mineralization have distinct zircon compositions relative to the distal, barren margin. We analyzed 296 zircons separated from 12 subglacial till samples to obtain U-Pb ages and trace element compositions. Laser ablation U-Pb ages of the detrital zircons overlap within error with chemical abrasion-thermal ionization mass spectrometry U-Pb ages of the Late Triassic Guichon Creek batholith and confirm that the detrital zircons are likely derived from the batholith. The youngest intrusions of the batholith produced the Highland Valley Copper porphyry deposits and contain distinctive zircons with elevated Eu/EuN* >0.4 attributed to high magmatic water contents and oxidation states, indicating higher porphyry copper potential. Zircon from till samples adjacent to and 9 km down-ice from the mineralized centers have mean Eu/EuN* >0.4, which are indicative of potential porphyry copper mineralization. Detrital zircon grains from more distal up- and down-ice locations (10–15 km) have zircon Eu/EuN* mean values of 0.26 to 0.37, reflecting background values. We conclude that detrital zircon compositions in glacial sediments transported several kilometers can be used to establish the regional potential for porphyry copper mineralization.View less
H3K9 methylation maintains cell identity orchestrating stable silencing and anchoring of alternate fate genes within the heterochromatic compartment underneath the nuclear lamina (NL). However, how cell type–specific genomic regions are specifically targeted to the NL is still elusive. Using fibro-adipogenic progenitors (FAPs) as a model, we identified Prdm16 as a nuclear envelope protein that anchors H3K9-methylated chromatin in a cell-specific manner. We show that Prdm16 mediates FAP developmental capacities by orchestrating lamina-associated domain organization and heterochromatin sequestration at the nuclear periphery. We found that Prdm16 localizes at the NL where it cooperates with the H3K9 methyltransferases G9a/GLP to mediate tethering and silencing of myogenic genes, thus repressing an alternative myogenic fate in FAPs. Genetic and pharmacological disruption of this repressive pathway confers to FAP myogenic competence, preventing fibro-adipogenic degeneration of dystrophic muscles. In summary, we reveal a druggable mechanism of heterochromatin perinuclear sequestration exploitable to reprogram FAPs in vivo.View less
Introduction Oxidative stress and inflammation are known to play a critical role in ageing and chronic disease development and could therefore represent important targets for developing dietary strategies for disease prevention. We aimed to systematically review the results from observational studies and intervention trials published in the last 5 years on the associations between dietary patterns and biomarkers of oxidative stress and inflammation.
Methods A systematic search of the PubMed, MEDLINE and Web of Science (January 2015 to October 2020) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality of selected studies was evaluated based on the NUTRIGRADE and BIOCROSS assessment tools.
Results In total, 29 studies among which 16 observational studies and 13 intervention studies were found eligible for review. Overall, results indicated an inverse association between plant-based diets - the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diet - and oxidative stress and proinflammatory biomarkers. In observational studies, inverse associations were further revealed for the vegetarian diet, the USDA Healthy Eating Index (HEI) - based diet and the paleolithic diet, whereas a positive association was seen for western and fast food diets. Quality assessment suggested that majority of dietary intervention studies (n = 12) were of low to moderate quality.
Conclusions This study provides evidence that the plant-based dietary patterns are associated with lowered levels of oxidative stress and inflammation and may provide valid means for chronic disease prevention. Future large-scale intervention trials using validated biomarkers are warranted to confirm these findings.View less
Carbon dots have been previosly immobilized on titanium dioxide to generate photocatalysts for pollutant degradation and water splitting. Here we demonstrate that these nanocomposites are valuable photocatalysts for metallaphotocatalytic carbon–heteroatom cross-couplings. These sustainable materials show a large applicability, high photostability, excellent reusability, and broadly absorb across the visible-light spectrum.