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Miguel de Luna as arbitrista
(2023)
This article deals with Miguel de Luna, a Morisco from Granada, who is most famous for his involvement in the Lead Books of Sacromonte affair. In the following pages I will, however, focus on a facet of his life that has been rather neglected. Rather than recount again his activities as translator for Arabic, I will shed light on his work as physician and claim that his medical paper on the benefits of bathing and the reopening of public baths in Granada may very well put him in league with the arbitristas, a group of intellectuals who advised the monarch in economic and financial matters.
Physical fitness of primary school children differs depending on their timing of school enrollment
(2023)
Previous research has shown that children who were enrolled to school according to the legal key date (i.e., keyage children, between eight and nine years in third grade) exhibited a linear physical fitness development in the ninth year of life. In contrast, children who were enrolled with a delay (i.e., older-than-keyage children [OTK], between nine and ten years in third grade) exhibited a lower physical fitness compared to what would be expected for their age. In these studies, cross-sectional age differences within third grade and timing of school enrollment were confounded. The present study investigated the longitudinal development of keyage and OTK children from third to fifth grade. This design also afforded a comparison of the two groups at the same average chronological age, that is a dissociation of the effects of timing of school enrollment and age. We tested six physical fitness components: cardiorespiratory endurance, coordination, speed, power of lower and upper limbs, and static balance. 1502 children (i.e., 1206 keyage and 296 OTK children) from 35 schools were tested in third, fourth, and fifth grade. Except for cardiorespiratory endurance, both groups developed from third to fourth and from fourth to fifth grade and keyage children outperformed OTK children at the average ages of 9.5 or 10.5 years. For cardiorespiratory endurance, there was no significant gain from fourth to fifth grade and keyage and OTK children did not differ significantly at 10.5 years of age. One reason for a delayed school enrollment could be that a child is (or is perceived as) biologically younger than their chronological age at the school entry examination, implying a negative correlation between chronological and biological age for OTK children. Indeed, a simple reflection of chronological age brought the developmental rate of the chronologically youngest OTK children in line with the developmental rate observed for keyage children, but did not eliminate all differences. The mapping of chronological and biological age of OTK children and other possible reasons for lower physical fitness of OTK children remain a task for future research.
Protein-protein-interactions play an important role in many cellular functions. Quantitative non-invasive techniques are applied in living cells to evaluate such interactions, thereby providing a broader understanding of complex biological processes. Fluorescence fluctuation spectroscopy describes a group of quantitative microscopy approaches for the characterization of molecular interactions at single cell resolution. Through the obtained molecular brightness, it is possible to determine the oligomeric state of proteins. This is usually achieved by fusing fluorescent proteins (FPs) to the protein of interest. Recently, the number of novel green FPs has increased, with consequent improvements to the quality of fluctuation-based measurements. The photophysical behavior of FPs is influenced by multiple factors (including photobleaching, protonation-induced "blinking" and long-lived dark states). Assessing these factors is critical for selecting the appropriate fluorescent tag for live cell imaging applications. In this work, we focus on novel green FPs that are extensively used in live cell imaging. A systematic performance comparison of several green FPs in living cells under different pH conditions using Number & Brightness (N & B) analysis and scanning fluorescence correlation spectroscopy was performed. Our results show that the new FP Gamillus exhibits higher brightness at the cost of lower photostability and fluorescence probability (pf), especially at lower pH. mGreenLantern, on the other hand, thanks to a very high pf, is best suited for multimerization quantification at neutral pH. At lower pH, mEGFP remains apparently the best choice for multimerization investigation. These guidelines provide the information needed to plan quantitative fluorescence microscopy involving these FPs, both for general imaging or for protein-protein-interactions quantification via fluorescence fluctuation-based methods.
Genomic and epigenomic determinants of heat stress-induced transcriptional memory in Arabidopsis
(2023)
Background
Transcriptional regulation is a key aspect of environmental stress responses. Heat stress induces transcriptional memory, i.e., sustained induction or enhanced re-induction of transcription, that allows plants to respond more efficiently to a recurrent HS. In light of more frequent temperature extremes due to climate change, improving heat tolerance in crop plants is an important breeding goal. However, not all heat stress-inducible genes show transcriptional memory, and it is unclear what distinguishes memory from non-memory genes. To address this issue and understand the genome and epigenome architecture of transcriptional memory after heat stress, we identify the global target genes of two key memory heat shock transcription factors, HSFA2 and HSFA3, using time course ChIP-seq.
Results
HSFA2 and HSFA3 show near identical binding patterns. In vitro and in vivo binding strength is highly correlated, indicating the importance of DNA sequence elements. In particular, genes with transcriptional memory are strongly enriched for a tripartite heat shock element, and are hallmarked by several features: low expression levels in the absence of heat stress, accessible chromatin environment, and heat stress-induced enrichment of H3K4 trimethylation. These results are confirmed by an orthogonal transcriptomic data set using both de novo clustering and an established definition of memory genes.
Conclusions
Our findings provide an integrated view of HSF-dependent transcriptional memory and shed light on its sequence and chromatin determinants, enabling the prediction and engineering of genes with transcriptional memory behavior.
Spatial and temporal variation in perceived predation risk is an important determinant of movement and foraging activity of animals. Foraging in this landscape of fear, individuals need to decide where and when to move, and what resources to choose. Foraging theory predicts the outcome of these decisions based on energetic trade-offs, but complex interactions between perceived predation risk and preferences of foragers for certain functional traits of their resources are rarely considered. Here, we studied the interactive effects of perceived predation risk on food trait preferences and foraging behavior in bank voles (Myodes glareolus) in experimental landscapes. Individuals (n = 19) were subjected for periods of 24 h to two extreme, risk-uniform landscapes (either risky or safe), containing 25 discrete food patches, filled with seeds of four plant species in even amounts. Seeds varied in functional traits: size, nutrients, and shape. We evaluated whether and how risk modifies forager preference for functional traits. We also investigated whether perceived risk and distance from shelter affected giving-up density (GUD), time in patches, and number of patch visits. In safe landscapes, individuals increased time spent in patches, lowered GUD and visited distant patches more often compared to risky landscapes. Individuals preferred bigger seeds independent of risk, but in the safe treatment they preferred fat-rich over carb-rich seeds. Thus, higher densities of resource levels remained in risky landscapes, while in safe landscapes resource density was lower and less diverse due to selective foraging. Our results suggest that the interaction of perceived risk and dietary preference adds an additional layer to the cascading effects of a landscape of fear which affects biodiversity at resource level.
Ore precipitation in porphyry copper systems is generally characterized by metal zoning (Cu-Mo to Zn-Pb-Ag), which is suggested to be variably related to solubility decreases during fluid cooling, fluid-rock interactions, partitioning during fluid phase separation and mixing with external fluids. Here, we present new advances of a numerical process model by considering published constraints on the temperature- and salinity-dependent solubility of Cu, Pb and Zn in the ore fluid. We quantitatively investigate the roles of vapor-brine separation, halite saturation, initial metal contents, fluid mixing and remobilization as first-order controls of the physical hydrology on ore formation. The results show that the magmatic vapor and brine phases ascend with different residence times but as miscible fluid mixtures, with salinity increases generating metal-undersaturated bulk fluids. The release rates of magmatic fluids affect the location of the thermohaline fronts, leading to contrasting mechanisms for ore precipitation: higher rates result in halite saturation without significant metal zoning, lower rates produce zoned ore shells due to mixing with meteoric water. Varying metal contents can affect the order of the final metal precipitation sequence. Redissolution of precipitated metals results in zoned ore shell patterns in more peripheral locations and also decouples halite saturation from ore precipitation.
The oil palm (Elaeis guineensis Jacq.) produces a large amount of oil from the fruit. However, increasing the oil production in this fruit is still challenging. A recent study has shown that starch metabolism is essential for oil synthesis in fruit-producing species. Therefore, the transcriptomic analysis by RNA-seq was performed to observe gene expression alteration related to starch metabolism genes throughout the maturity stages of oil palm fruit with different oil yields. Gene expression profiles were examined with three different oil yields group (low, medium, and high) at six fruit development phases (4, 8, 12, 16, 20, and 22 weeks after pollination). We successfully identified and analyzed differentially expressed genes in oil palm mesocarps during development. The results showed that the transcriptome profile for each developmental phase was unique. Sucrose flux to the mesocarp tissue, rapid starch turnover, and high glycolytic activity have been identified as critical factors for oil production in oil palms. For starch metabolism and the glycolytic pathway, we identified specific gene expressions of enzyme isoforms (isozymes) that correlated with oil production, which may determine the oil content. This study provides valuable information for creating new high-oil-yielding palm varieties via breeding programs or genome editing approaches.
Starch has been a convenient, economically important polymer with substantial applications in the food and processing industry. However, native starches present restricted applications, which hinder their industrial usage. Therefore, modification of starch is carried out to augment the positive characteristics and eliminate the limitations of the native starches. Modifications of starch can result in generating novel polymers with numerous functional and value-added properties that suit the needs of the industry. Here, we summarize the possible starch modifications in planta and outside the plant system (physical, chemical, and enzymatic) and their corresponding applications. In addition, this review will highlight the implications of each starch property adjustment.
Keeping cool on hot days
(2023)
Long-lived organisms are likely to respond to a rapidly changing climate with behavioral flexibility. Animals inhabiting the arid parts of southern Africa face a particularly rapid rise in temperature which in combination with food and water scarcity places substantial constraints on the ability of animals to tolerate heat. We investigated how three species of African antelope-springbok Antidorcas marsupialis, kudu Tragelaphus strepsiceros and eland T. oryx-differing in body size, habitat preference and movement ecology, change their activity in response to extreme heat in an arid savanna. Serving as a proxy for activity, dynamic body acceleration data recorded every five minutes were analyzed for seven to eight individuals per species for the three hottest months of the year. Activity responses to heat during the hottest time of day (the afternoons) were investigated and diel activity patterns were compared between hot and cool days. Springbok, which prefer open habitat, are highly mobile and the smallest of the species studied, showed the greatest decrease in activity with rising temperature. Furthermore, springbok showed reduced mean activity over the 24 h cycle on hot days compared to cool days. Large-bodied eland seemed less affected by afternoon heat than springbok. While eland also reduced diurnal activity on hot days compared to cool days, they compensated for this by increasing nocturnal activity, possibly because their predation risk is lower. Kudu, which are comparatively sedentary and typically occupy shady habitat, seemed least affected during the hottest time of day and showed no appreciable difference in diel activity patterns between hot and cool days. The interplay between habitat preference, body size, movement patterns, and other factors seems complex and even sub-lethal levels of heat stress have been shown to impact an animal's long-term survival and reproduction. Thus, differing heat tolerances among species could result in a shift in the composition of African herbivore communities as temperatures continue to rise, with significant implications for economically important wildlife-based land use and conservation.
The heat is on
(2023)
Climate conditions severely impact the activity and, consequently, the fitness of wildlife species across the globe. Wildlife can respond to new climatic conditions, but the pace of human-induced change limits opportunities for adaptation or migration. Thus, how these changes affect behavior, movement patterns, and activity levels remains unclear. In this study, we investigate how extreme weather conditions affect the activity of European hares (Lepus europaeus) during their peak reproduction period. When hares must additionally invest energy in mating, prevailing against competitors, or lactating, we investigated their sensitivities to rising temperatures, wind speed, and humidity. To quantify their activity, we used the overall dynamic body acceleration (ODBA) calculated from tri-axial acceleration measurements of 33 GPS-collared hares. Our analysis revealed that temperature, humidity, and wind speed are important in explaining changes in activity, with a strong response for high temperatures above 25 & DEG;C and the highest change in activity during temperature extremes of over 35 & DEG;C during their inactive period. Further, we found a non-linear relationship between temperature and activity and an interaction of activity changes between day and night. Activity increased at higher temperatures during the inactive period (day) and decreased during the active period (night). This decrease was strongest during hot tropical nights. At a stage of life when mammals such as hares must substantially invest in reproduction, the sensitivity of females to extreme temperatures was particularly pronounced. Similarly, both sexes increased their activity at high humidity levels during the day and low wind speeds, irrespective of the time of day, while the effect of humidity was stronger for males. Our findings highlight the importance of understanding the complex relationships between extreme weather conditions and mammal behavior, critical for conservation and management. With ongoing climate change, extreme weather events such as heat waves and heavy rainfall are predicted to occur more often and last longer. These events will directly impact the fitness of hares and other wildlife species and hence the population dynamics of already declining populations across Europe.
The active global SARS-CoV-2 pandemic caused more than 426 million cases and 5.8 million deaths worldwide. The development of completely new drugs for such a novel disease is a challenging, time intensive process. Despite researchers around the world working on this task, no effective treatments have been developed yet. This emphasizes the importance of drug repurposing, where treatments are found among existing drugs that are meant for different diseases. A common approach to this is based on knowledge graphs, that condense relationships between entities like drugs, diseases and genes. Graph neural networks (GNNs) can then be used for the task at hand by predicting links in such knowledge graphs. Expanding on state-of-the-art GNN research, Doshi et al. recently developed the Dr-COVID model. We further extend their work using additional output interpretation strategies. The best aggregation strategy derives a top-100 ranking of 8,070 candidate drugs, 32 of which are currently being tested in COVID-19-related clinical trials. Moreover, we present an alternative application for the model, the generation of additional candidates based on a given pre-selection of drug candidates using collaborative filtering. In addition, we improved the implementation of the Dr-COVID model by significantly shortening the inference and pre-processing time by exploiting data-parallelism. As drug repurposing is a task that requires high computation and memory resources, we further accelerate the post-processing phase using a new emerging hardware-we propose a new approach to leverage the use of high-capacity Non-Volatile Memory for aggregate drug ranking.
Psychology and nutritional science research has highlighted the impact of negative emotions and cognitive load on calorie consumption behaviour using subjective questionnaires. Isolated studies in other domains objectively assess cognitive load without considering its effects on eating behaviour. This study aims to explore the potential for developing an integrated eating behaviour assistant system that incorporates cognitive load factors. Two experimental sessions were conducted using custom-developed experimentation software to induce different stimuli. During these sessions, we collected 30 h of physiological, food consumption, and affective states questionnaires data to automatically detect cognitive load and analyse its effect on food choice. Utilising grid search optimisation and leave-one-subject-out cross-validation, a support vector machine model achieved a mean classification accuracy of 85.12% for the two cognitive load tasks using eight relevant features. Statistical analysis was performed on calorie consumption and questionnaire data. Furthermore, 75% of the subjects with higher negative affect significantly increased consumption of specific foods after high-cognitive-load tasks. These findings offer insights into the intricate relationship between cognitive load, affective states, and food choice, paving the way for an eating behaviour assistant system to manage food choices during cognitive load. Future research should enhance system capabilities and explore real-world applications.
The detection of communities in graph datasets provides insight about a graph's underlying structure and is an important tool for various domains such as social sciences, marketing, traffic forecast, and drug discovery. While most existing algorithms provide fast approaches for community detection, their results usually contain strictly separated communities. However, most datasets would semantically allow for or even require overlapping communities that can only be determined at much higher computational cost. We build on an efficient algorithm, FOX, that detects such overlapping communities. FOX measures the closeness of a node to a community by approximating the count of triangles which that node forms with that community. We propose LAZYFOX, a multi-threaded adaptation of the FOX algorithm, which provides even faster detection without an impact on community quality. This allows for the analyses of significantly larger and more complex datasets. LAZYFOX enables overlapping community detection on complex graph datasets with millions of nodes and billions of edges in days instead of weeks. As part of this work, LAZYFOX's implementation was published and is available as a tool under an MIT licence at https://github.com/TimGarrels/LazyFox.
Background
The aggregation of a series of N-of-1 trials presents an innovative and efficient study design, as an alternative to traditional randomized clinical trials. Challenges for the statistical analysis arise when there is carry-over or complex dependencies of the treatment effect of interest.
Methods
In this study, we evaluate and compare methods for the analysis of aggregated N-of-1 trials in different scenarios with carry-over and complex dependencies of treatment effects on covariates. For this, we simulate data of a series of N-of-1 trials for Chronic Nonspecific Low Back Pain based on assumed causal relationships parameterized by directed acyclic graphs. In addition to existing statistical methods such as regression models, Bayesian Networks, and G-estimation, we introduce a carry-over adjusted parametric model (COAPM).
Results
The results show that all evaluated existing models have a good performance when there is no carry-over and no treatment dependence. When there is carry-over, COAPM yields unbiased and more efficient estimates while all other methods show some bias in the estimation. When there is known treatment dependence, all approaches that are capable to model it yield unbiased estimates. Finally, the efficiency of all methods decreases slightly when there are missing values, and the bias in the estimates can also increase.
Conclusions
This study presents a systematic evaluation of existing and novel approaches for the statistical analysis of a series of N-of-1 trials. We derive practical recommendations which methods may be best in which scenarios.
Giving emotional intelligence to machines can facilitate the early detection and prediction of mental diseases and symptoms. Electroencephalography (EEG)-based emotion recognition is widely applied because it measures electrical correlates directly from the brain rather than indirect measurement of other physiological responses initiated by the brain. Therefore, we used non-invasive and portable EEG sensors to develop a real-time emotion classification pipeline. The pipeline trains different binary classifiers for Valence and Arousal dimensions from an incoming EEG data stream achieving a 23.9% (Arousal) and 25.8% (Valence) higher F1-Score on the state-of-art AMIGOS dataset than previous work. Afterward, the pipeline was applied to the curated dataset from 15 participants using two consumer-grade EEG devices while watching 16 short emotional videos in a controlled environment. Mean F1-Scores of 87% (Arousal) and 82% (Valence) were achieved for an immediate label setting. Additionally, the pipeline proved to be fast enough to achieve predictions in real-time in a live scenario with delayed labels while continuously being updated. The significant discrepancy from the readily available labels on the classification scores leads to future work to include more data. Thereafter, the pipeline is ready to be used for real-time applications of emotion classification.
Oxygen (O-2) availability in soils is vital for plant growth and productivity. The transport and consumption of O-2 in the root zone is closely linked to soil moisture content, the spatial distribution of roots, as well as structure and heterogeneity of the surrounding soil. In this study, we measure three-dimensional root system architecture and the spatiotemporal dynamics of soil moisture (& theta;) and O-2 concentrations in the root zone of maize (Zea mays) via non-invasive imaging, and then construct and parameterize a reactive transport model based on the experimental data. The combination of three non-invasive imaging methods allowed for a direct comparison of simulation results with observations at high spatial and temporal resolution. In three different modeling scenarios, we investigated how the results obtained for different levels of conceptual complexity in the model were able to match measured & theta; and O-2 concentration patterns. We found that the modeling scenario that considers heterogeneous soil structure and spatial variability of hydraulic parameters (permeability, porosity, and van Genuchten & alpha; and n), better reproduced the measured & theta; and O-2 patterns relative to a simple model with a homogenous soil domain. The results from our combined imaging and modeling analysis reveal that experimental O-2 and water dynamics can be reproduced quantitatively in a reactive transport model, and that O-2 and water dynamics are best characterized when conditions unique to the specific system beyond the distribution of roots, such as soil structure and its effect on water saturation and macroscopic gas transport pathways, are considered.
This review discusses picosecond ultrasonics experiments using ultrashort hard x-ray probe pulses to extract the transient strain response of laser-excited nanoscopic structures from Bragg-peak shifts. This method provides direct, layer-specific, and quantitative information on the picosecond strain response for structures down to few-nm thickness. We model the transient strain using the elastic wave equation and express the driving stress using Gruneisen parameters stating that the laser-induced stress is proportional to energy density changes in the microscopic subsystems of the solid, i.e., electrons, phonons and spins. The laser-driven strain response can thus serve as an ultrafast proxy for local energy-density and temperature changes, but we emphasize the importance of the nanoscale morphology for an accurate interpretation due to the Poisson effect. The presented experimental use cases encompass ultrathin and opaque metal-heterostructures, continuous and granular nanolayers as well as negative thermal expansion materials, that each pose a challenge to established all-optical techniques.
Using time-resolved x-ray diffraction, we demonstrate the manipulation of the picosecond strain response of a metallic heterostructure consisting of a dysprosium (Dy) transducer and a niobium (Nb) detection layer by an external magnetic field. We utilize the first-order ferromagnetic–antiferromagnetic phase transition of the Dy layer, which provides an additional large contractive stress upon laser excitation compared to its zerofield response. This enhances the laser-induced contraction of the transducer and changes the shape of the picosecond strain pulses driven in Dy and detected within the buried Nb layer. Based on our experiment with rare-earth metals we discuss required properties for functional transducers, which may allow for novel field-control of the emitted picosecond strain pulses.
Satisfaction and frustration of the needs for autonomy, competence, and relatedness, as assessed with the 24-item Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), have been found to be crucial indicators of individuals’ psychological health. To increase the usability of this scale within a clinical and health services research context, we aimed to validate a German short version (12 items) of this scale in individuals with depression including the examination of the relations from need frustration and need satisfaction to ill-being and quality of life (QOL). This cross-sectional study involved 344 adults diagnosed with depression (Mage (SD) = 47.5 years (11.1); 71.8% females). Confirmatory factor analyses indicated that the short version of the BPNSFS was not only reliable, but also fitted a six-factor structure (i.e., satisfaction/frustration X type of need). Subsequent structural equation modeling showed that need frustration related positively to indicators of ill-being and negatively to QOL. Surprisingly, need satisfaction did not predict differences in ill-being or QOL. The short form of the BPNSFS represents a practical instrument to measure need satisfaction and frustration in people with depression. Further, the results support recent evidence on the importance of especially need frustration in the prediction of psychopathology.
Background Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders.
Methods Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP).
Results The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: & beta; = -0.35; NVS: & beta; = 0.39; CS: & beta; = -0.12; SP: & beta; = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association.
Limitations The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for.
Conclusion Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.
Research within the framework of Basic Psychological Need Theory (BPNT) finds strong associations between basic need frustration and depressive symptoms. This study examined the role of rumination as an underlying mechanism in the association between basic psychological need frustration and depressive symptoms. A cross-sectional sample of N = 221 adults (55.2% female, mean age = 27.95, range = 18–62, SD = 10.51) completed measures assessing their level of basic psychological need frustration, rumination, and depressive symptoms. Correlational analyses and multiple mediation models were conducted. Brooding partially mediated the relation between need frustration and depressive symptoms. BPNT and Response Styles Theory are compatible and can further advance knowledge about depression vulnerabilities.
BackgroundIn spring of 2020, the Sars-CoV-2 incidence rate increased rapidly in Germany and around the world. Throughout the next 2 years, schools were temporarily closed and social distancing measures were put in place to slow the spread of the Covid-19 virus. Did these social restrictions and temporary school lockdowns affect children's physical fitness? The EMOTIKON project annually tests the physical fitness of all third-graders in the Federal State of Brandenburg, Germany. The tests assess cardiorespiratory endurance (6-min-run test), coordination (star-run test), speed (20-m sprint test), lower (powerLOW, standing long jump test), and upper (powerUP, ball-push test) limbs muscle power, and static balance (one-legged stance test with eyes closed). A total of 125,893 children were tested in the falls from 2016 to 2022. Primary analyses focused on 98,510 keyage third-graders (i.e., school enrollment according to the legal key date, aged 8 to 9 years) from 515 schools. Secondary analyses included 27,383 older-than-keyage third-graders (i.e., OTK, delayed school enrollment or repetition of a grade, aged 9 to 10 years), who have been shown to exhibit lower physical fitness than expected for their age. Linear mixed models fitted pre-pandemic quadratic secular trends, and took into account differences between children and schools.ResultsThird-graders exhibited lower cardiorespiratory endurance, coordination, speed and powerUP in the Covid pandemic cohorts (2020-2022) compared to the pre-pandemic cohorts (2016-2019). Children's powerLOW and static balance were higher in the pandemic cohorts compared to the pre-pandemic cohorts. From 2020 to 2021, coordination, powerLOW and powerUP further declined. Evidence for some post-pandemic physical fitness catch-up was restricted to powerUP. Cohen's |ds| for comparisons of the pandemic cohorts 2020-2022 with pre-pandemic cohorts 2016-2019 ranged from 0.02 for powerLOW to 0.15 for coordination. Within the pandemic cohorts, keyage children exhibited developmental losses ranging from approximately 1 month for speed to 5 months for cardiorespiratory endurance. For powerLOW and static balance, the positive pandemic effects translate to developmental gains of 1 and 7 months, respectively. Pre-pandemic secular trends may account for some of the observed differences between pandemic and pre-pandemic cohorts, especially in powerLOW, powerUP and static balance. The pandemic further increased developmental delays of OTK children in cardiorespiratory endurance, powerUP and balance.ConclusionsThe Covid-19 pandemic was associated with declines in several physical fitness components in German third-graders. Pandemic effects are still visible in 2022. Health-related interventions should specifically target those physical fitness components that were negatively affected by the pandemic (cardiorespiratory endurance, coordination, speed).
How to not induce SNAs
(2023)
People respond faster to smaller numbers in their left space and to larger numbers in their right space. Here we argue that movements in space contribute to the formation of spatial-numerical associations (SNAs). We studied the impact of continuous isometric forces along the horizontal or vertical cardinal axes on SNAs while participants performed random number production and arithmetic verification tasks. Our results suggest that such isometric directional force do not suffice to induce SNAs.
The use of automated tools to reconstruct lipid metabolic pathways is not warranted in plants. Here, the authors construct Plant Lipid Module for Arabidopsis rosette using constraint-based modeling, demonstrate its integration in other plant metabolic models, and use it to dissect the genetic architecture of lipid metabolism.
Lipids play fundamental roles in regulating agronomically important traits. Advances in plant lipid metabolism have until recently largely been based on reductionist approaches, although modulation of its components can have system-wide effects. However, existing models of plant lipid metabolism provide lumped representations, hindering detailed study of component modulation. Here, we present the Plant Lipid Module (PLM) which provides a mechanistic description of lipid metabolism in the Arabidopsis thaliana rosette. We demonstrate that the PLM can be readily integrated in models of A. thaliana Col-0 metabolism, yielding accurate predictions (83%) of single lethal knock-outs and 75% concordance between measured transcript and predicted flux changes under extended darkness. Genome-wide associations with fluxes obtained by integrating the PLM in diel condition- and accession-specific models identify up to 65 candidate genes modulating A. thaliana lipid metabolism. Using mutant lines, we validate up to 40% of the candidates, paving the way for identification of metabolic gene function based on models capturing natural variability in metabolism.
Progressive habitat fragmentation threatens plant species with narrow habitat requirements. While local environmental conditions define population growth rates and recruitment success at the patch level, dispersal is critical for population viability at the landscape scale. Identifying the dynamics of plant meta-populations is often confounded by the uncertainty about soil-stored population compartments. We combined a landscape-scale assessment of an amphibious plant's population structure with measurements of dispersal complexity in time to track dispersal and putative shifts in functional connectivity. Using 13 microsatellite markers, we analyzed the genetic structure of extant Oenanthe aquatica populations and their soil seed banks in a kettle hole system to uncover hidden connectivity among populations in time and space. Considerable spatial genetic structure and isolation-by-distance suggest limited gene flow between sites. Spatial isolation and patch size showed minor effects on genetic diversity. Genetic similarity found among extant populations and their seed banks suggests increased local recruitment, despite some evidence of migration and recent colonization. Results indicate stepping-stone dispersal across adjacent populations. Among permanent and ephemeral demes the resulting meta-population demography could be determined by source-sink dynamics. Overall, these spatiotemporal connectivity patterns support mainland-island dynamics in our system, highlighting the importance of persistent seed banks as enduring sources of genetic diversity.
Metabolic engineering of microalgae offers a promising solution for sustainable biofuel production, and rational design of engineering strategies can be improved by employing metabolic models that integrate enzyme turnover numbers. However, the coverage of turnover numbers for Chlamydomonas reinhardtii, a model eukaryotic microalga accessible to metabolic engineering, is 17-fold smaller compared to the heterotrophic cell factory Saccharomyces cerevisiae. Here we generate quantitative protein abundance data of Chlamydomonas covering 2337 to 3708 proteins in various growth conditions to estimate in vivo maximum apparent turnover numbers. Using constrained-based modeling we provide proxies for in vivo turnover numbers of 568 reactions, representing a 10-fold increase over the in vitro data for Chlamydomonas. Integration of the in vivo estimates instead of in vitro values in a metabolic model of Chlamydomonas improved the accuracy of enzyme usage predictions. Our results help in extending the knowledge on uncharacterized enzymes and improve biotechnological applications of Chlamydomonas.
The study addresses the question, if observed changes in terms of Arctic-midlatitude linkages during winter are driven by Arctic Sea ice decline alone or if the increase of global sea surface temperatures plays an additional role. We compare atmosphere-only model experiments with ECHAM6 to ERA-Interim Reanalysis data. The model sensitivity experiment is implemented as a set of four combinations of sea ice and sea surface temperature boundary conditions. Atmospheric circulation regimes are determined and evaluated in terms of their cyclone and blocking characteristics and changes in frequency during winter. As a prerequisite, ECHAM6 reproduces general features of circulation regimes very well. Tropospheric changes induced by the change of boundary conditions are revealed and further impacts on the large-scale circulation up into the stratosphere are investigated. In early winter, the observed increase of atmospheric blocking in the region between Scandinavia and the Urals are primarily related to the changes in sea surface temperatures. During late winter, we f nd a weakened polar stratospheric vortex in the reanalysis that further impacts the troposphere. In the model sensitivity study a climatologically weakened polar vortex occurs only if sea ice is reduced and sea surface temperatures are increased together. This response is delayed compared to the reanalysis. The tropospheric response during late winter is inconclusive in the model, which is potentially related to the weak and delayed response in the stratosphere. The model experiments do not reproduce the connection between early and late winter as interpreted from the reanalysis. Potentially explaining this mismatch, we identify a discrepancy of ECHAM6 to reproduce the weakening of the stratospheric polar vortex through blocking induced upward propagation of planetary waves.
Caenorhabditis elegans (C. elegans) is gaining recognition and importance as an organismic model for toxicity testing in line with the 3Rs principle (replace, reduce, refine). In this study, we explored the use of C. elegans to examine the toxicities of alkylating sulphur mustard analogues, specifically the monofunctional agent 2-chloroethyl-ethyl sulphide (CEES) and the bifunctional, crosslinking agent mechlorethamine (HN2). We exposed wild-type worms at different life cycle stages (from larvae L1 to adulthood day 10) to CEES or HN2 and scored their viability 24 h later. The susceptibility of C. elegans to CEES and HN2 paralleled that of human cells, with HN2 exhibiting higher toxicity than CEES, reflected in LC50 values in the high µM to low mM range. Importantly, the effects were dependent on the worms’ developmental stage as well as organismic age: the highest susceptibility was observed in L1, whereas the lowest was observed in L4 worms. In adult worms, susceptibility to alkylating agents increased with advanced age, especially to HN2. To examine reproductive effects, L4 worms were exposed to CEES and HN2, and both the offspring and the percentage of unhatched eggs were assessed. Moreover, germline apoptosis was assessed by using ced-1p::GFP (MD701) worms. In contrast to concentrations that elicited low toxicities to L4 worms, CEES and HN2 were highly toxic to germline cells, manifesting as increased germline apoptosis as well as reduced offspring number and percentage of eggs hatched. Again, HN2 exhibited stronger effects than CEES. Compound specificity was also evident in toxicities to dopaminergic neurons–HN2 exposure affected expression of dopamine transporter DAT-1 (strain BY200) at lower concentrations than CEES, suggesting a higher neurotoxic effect. Mechanistically, nicotinamide adenine dinucleotide (NAD+) has been linked to mustard agent toxicities. Therefore, the NAD+-dependent system was investigated in the response to CEES and HN2 treatment. Overall NAD+ levels in worm extracts were revealed to be largely resistant to mustard exposure except for high concentrations, which lowered the NAD+ levels in L4 worms 24 h post-treatment. Interestingly, however, mutant worms lacking components of NAD+-dependent pathways involved in genome maintenance, namely pme-2, parg-2, and sirt-2.1 showed a higher and compound-specific susceptibility, indicating an active role of NAD+ in genotoxic stress response. In conclusion, the present results demonstrate that C. elegans represents an attractive model to study the toxicology of alkylating agents, which supports its use in mechanistic as well as intervention studies with major strength in the possibility to analyze toxicities at different life cycle stages.
The deficiency of a (bio)chemical reaction network can be conceptually interpreted as a measure of its ability to support exotic dynamical behavior and/or multistationarity. The classical definition of deficiency relates to the capacity of a network to permit variations of the complex formation rate vector at steady state, irrespective of the network kinetics. However, the deficiency is by definition completely insensitive to the fine details of the directionality of reactions as well as bounds on reaction fluxes. While the classical definition of deficiency can be readily applied in the analysis of unconstrained, weakly reversible networks, it only provides an upper bound in the cases where relevant constraints on reaction fluxes are imposed. Here we propose the concept of effective deficiency, which provides a more accurate assessment of the network’s capacity to permit steady state variations at the complex level for constrained networks of any reversibility patterns. The effective deficiency relies on the concept of nonstoichiometric balanced complexes, which we have already shown to be present in real-world biochemical networks operating under flux constraints. Our results demonstrate that the effective deficiency of real-world biochemical networks is smaller than the classical deficiency, indicating the effects of reaction directionality and flux bounds on the variation of the complex formation rate vector at steady state.
HARE
(2023)
Sensor-based human activity recognition is becoming ever more prevalent. The increasing importance of distinguishing human movements, particularly in healthcare, coincides with the advent of increasingly compact sensors. A complex sequence of individual steps currently characterizes the activity recognition pipeline. It involves separate data collection, preparation, and processing steps, resulting in a heterogeneous and fragmented process. To address these challenges, we present a comprehensive framework, HARE, which seamlessly integrates all necessary steps. HARE offers synchronized data collection and labeling, integrated pose estimation for data anonymization, a multimodal classification approach, and a novel method for determining optimal sensor placement to enhance classification results. Additionally, our framework incorporates real-time activity recognition with on-device model adaptation capabilities. To validate the effectiveness of our framework, we conducted extensive evaluations using diverse datasets, including our own collected dataset focusing on nursing activities. Our results show that HARE’s multimodal and on-device trained model outperforms conventional single-modal and offline variants. Furthermore, our vision-based approach for optimal sensor placement yields comparable results to the trained model. Our work advances the field of sensor-based human activity recognition by introducing a comprehensive framework that streamlines data collection and classification while offering a novel method for determining optimal sensor placement.
Several lines of research have demonstrated spatial-numerical associations in both adults and children, which are thought to be based on a spatial representation of numerical information in the form of a mental number line. The acquisition of increasingly precise mental number line representations is assumed to support arithmetic learning in children. It is further suggested that sensorimotor experiences shape the development of number concepts and arithmetic learning, and that mental arithmetic can be characterized as “motion along a path” and might constitute shifts in attention along the mental number line. The present study investigated whether movements in physical space influence mental arithmetic in primary school children, and whether the expected effect depends on concurrency of body movements and mental arithmetic. After turning their body towards the left or right, 48 children aged 8 to 10 years solved simple subtraction and addition problems. Meanwhile, they either walked or stood still and looked towards the respective direction. We report a congruency effect between body orientation and operation type, i.e., higher performance for the combinations leftward orientation and subtraction and rightward orientation and addition. We found no significant difference between walking and looking conditions. The present results suggest that mental arithmetic in children is influenced by preceding sensorimotor cues and not necessarily by concurrent body movements.
Einleitung
(2023)
Introduction LingoTalk is a German speech-language app designed to enhance lexical retrieval in individuals with aphasia. It incorporates automatic speech recognition (ASR) to provide therapist-independent feedback. The execution and effectiveness of a self-administered intervention with LingoTalk was explored in a case series study.
Methods Three individuals with chronic aphasia participated in a highly individualized, supervised self-administered intervention lasting 3 weeks. The LingoTalk app closely monitored the frequency, intensity and progress of the intervention. Treatment efficacy was assessed using a multiple baseline design, examining both item-specific treatment effects and generalization to untreated items, an untreated task, and spontaneous speech.
Results All participants successfully completed the intervention with LingoTalk, although one participant was not able to use the ASR feature. None of the participants fully adhered to the treatment protocol. All participants demonstrated significant and sustained improvement in the naming of practiced items, although there was limited evidence of generalization. Additionally, there was a slight reduction in word-finding difficulties during spontaneous speech.
Discussion This small-scale study indicates that self-administered intervention with LingoTalk can improve oral naming of treated items. Thus, it has the potential to complement face-to-face speech-language therapy, such as within in a “flipped speech room” approach. The choice of feedback mode is discussed. Transparent progress monitoring of the intervention appears to positively influence patients' motivation.
Introduction Vagally mediated heart rate variability is an index of autonomic nervous system activity that is associated with a large variety of outcome variables including psychopathology and self-regulation. While practicing heart rate variability biofeedback over several weeks has been reliably associated with a number of positive outcomes, its acute effects are not well known. As the strongest association with vagally mediated heart rate variability has been found particularly within the attention-related subdomain of self-regulation, we investigated the acute effect of heart rate variability biofeedback on attentional control using the revised Attention Network Test.
Methods Fifty-six participants were tested in two sessions. In one session each participant received a heart rate variability biofeedback intervention, and in the other session a control intervention of paced breathing at a normal ventilation rate. After the biofeedback or control intervention, participants completed the Attention Network Test using the Orienting Score as a measure of attentional control.
Results Mixed models revealed that higher resting baseline vagally mediated heart rate variability was associated with better performance in attentional control, which suggests more efficient direction of attention to target stimuli. There was no significant main effect of the intervention on attentional control. However, an interaction effect indicated better performance in attentional control after biofeedback in individuals who reported higher current stress levels.
Discussion The results point to acute beneficial effects of heart rate variability biofeedback on cognitive performance in highly stressed individuals. Although promising, the results need to be replicated in larger or more targeted samples in order to reach stronger conclusions about the effects.
Our subject is a new catalogue of radar-based heavy rainfall events (CatRaRE) over Germany and how it relates to the concurrent atmospheric circulation. We classify daily ERA5 fields of convective indices according to CatRaRE, using an array of 13 statistical methods, consisting of 4 conventional (“shallow”) and 9 more recent deep machine learning (DL) algorithms; the classifiers are then applied to corresponding fields of
simulated present and future atmospheres from the Coordinated Regional Climate Downscaling Experiment (CORDEX) project. The inherent uncertainty of the DL results from the stochastic nature of their optimization is addressed by employing an ensemble approach using 20 runs for each network. The shallow random forest method performs best with an equitable threat score (ETS) around 0.52, followed by the DL networks ALL-CNN and ResNet with an ETS near 0.48. Their success can be understood as a result of conceptual simplicity and parametric parsimony, which obviously best fits the relatively simple classification task. It is found that, on summer days, CatRaRE convective atmospheres over Germany occur with a probability of about 0.5. This probability is projected to increase, regardless of method, both in ERA5-reanalyzed and CORDEX-simulated atmospheres: for the historical period we find a centennial increase of about 0.2 and for the future period one of slightly below 0.1.
BACKGROUND: Patients with diabetes exhibit an increased prevalence for emotional disorders compared with healthy humans, partially due to a shared pathogenesis including hormone resistance and inflammation, which is also linked to intestinal dysbiosis. The preventive intake of probiotic lactobacilli has been shown to improve dysbiosis along with mood and metabolism. Yet, a potential role of Lactobacillus rhamnosus (Lacticaseibacillus rhamnosus 0030) (LR) in improving emotional behavior in established obesity and the underlying mechanisms are unknown.
METHODS: Female and male C57BL/6N mice were fed a low-fat diet (10% kcal from fat) or high-fat diet (HFD) (45% kcal from fat) for 6 weeks, followed by daily oral gavage of vehicle or 1 3 10 8 colony-forming units of LR, and assessment of anxiety- and depressive-like behavior. Cecal microbiota composition was analyzed using 16S ribosomal RNA sequencing, plasma and cerebrospinal fluid were collected for metabolomic analysis, and gene expression of different brain areas was assessed using reverse transcriptase quantitative polymerase chain reaction.
RESULTS: We observed that 12 weeks of HFD feeding induced hyperinsulinemia, which was attenuated by LR application only in female mice. On the contrary, HFD-fed male mice exhibited increased anxiety- and depressive-like behavior, where the latter was specifically attenuated by LR application, which was independent of metabolic changes. Furthermore, LR application restored the HFD-induced decrease of tyrosine hydroxylase, along with normalizing cholecystokinin gene expression in dopaminergic brain regions; both tyrosine hydroxylase and cholecystokinin are involved in signaling pathways impacting emotional disorders.
CONCLUSIONS: Our data show that LR attenuates depressive-like behavior after established obesity, with changes in the dopaminergic system in male mice, and mitigates hyperinsulinemia in obese female mice.
Introduction Early linguistic background, and in particular, access to language, lays the foundation of future reading skills in deaf and hard-of-hearing signers. The current study aims to estimate the impact of two factors – early access to sign and/or spoken language – on reading fluency in deaf and hard-of-hearing adult Russian Sign Language speakers.
Methods In the eye-tracking experiment, 26 deaf and 14 hard-of-hearing native Russian Sign Language speakers read 144 sentences from the Russian Sentence Corpus. Analysis of global eye-movement trajectories (scanpaths) was used to identify clusters of typical reading trajectories. The role of early access to sign and spoken language as well as vocabulary size as predictors of the more fluent reading pattern was tested.
Results Hard-of-hearing signers with early access to sign language read more fluently than those who were exposed to sign language later in life or deaf signers without access to speech sounds. No association between early access to spoken language and reading fluency was found.
Discussion Our results suggest a unique advantage for the hard-of-hearing individuals from having early access to both sign and spoken language and support the existing claims that early exposure to sign language is beneficial not only for deaf but also for hard-of-hearing children.
We review an approach for reconstructing oscillatory networks’ undirected and directed connectivity from data. The technique relies on inferring the phase dynamics model. The central assumption is that we observe the outputs of all network nodes. We distinguish between two cases. In the first one, the observed signals represent smooth oscillations, while in the second one, the data are pulse-like and can be viewed as point processes. For the first case, we discuss estimating the true phase from a scalar signal, exploiting the protophase-to-phase transformation. With the phases at hand, pairwise and triplet synchronization indices can characterize the undirected connectivity. Next, we demonstrate how to infer the general form of the coupling functions for two or three oscillators and how to use these functions to quantify the directional links. We proceed with a different treatment of networks with more than three nodes. We discuss the difference between the structural and effective phase connectivity that emerges due to high-order terms in the coupling functions. For the second case of point-process data, we use the instants of spikes to infer the phase dynamics model in the Winfree form directly. This way, we obtain the network’s coupling matrix in the first approximation in the coupling strength.
Introduction This study examined the effects of an 8-week backward running (BR) vs. forward running (FR) training programmes on measures of physical fitness in young female handball players.
Methods Twenty-nine players participated in this study. Participants were randomly assigned to a FR training group, BR training group, and a control group.
Results and discussion Within-group analysis indicated significant, small-to-large improvements in all performance tests (effect size [g] = 0.36 to 1.80), except 5-m forward sprint-time in the BR group and 5- and 10-m forward sprint-time in the FR group. However, the CG significantly decreased forward sprint performance over 10-m and 20-m (g = 0.28 to 0.50) with no changes in the other fitness parameters. No significant differences in the amount of change scores between the BR and FR groups were noted. Both training interventions have led to similar improvements in measures of muscle power, change of direction (CoD) speed, sprint speed either forward or backward, and repeated sprint ability (RSA) in young female handball players, though BR training may have a small advantage over FR training for 10-m forward sprint time and CoD speed, while FR training may provide small improvements over BR training for RSAbest. Practitioners are advised to consider either FR or BR training to improve various measures of physical fitness in young female handball players.
DUO-GAIT
(2023)
In recent years, there has been a growing interest in developing and evaluating gait analysis algorithms based on inertial measurement unit (IMU) data, which has important implications, including sports, assessment of diseases, and rehabilitation. Multi-tasking and physical fatigue are two relevant aspects of daily life gait monitoring, but there is a lack of publicly available datasets to support the development and testing of methods using a mobile IMU setup. We present a dataset consisting of 6-minute walks under single- (only walking) and dual-task (walking while performing a cognitive task) conditions in unfatigued and fatigued states from sixteen healthy adults. Especially, nine IMUs were placed on the head, chest, lower back, wrists, legs, and feet to record under each of the above-mentioned conditions. The dataset also includes a rich set of spatio-temporal gait parameters that capture the aspects of pace, symmetry, and variability, as well as additional study-related information to support further analysis. This dataset can serve as a foundation for future research on gait monitoring in free-living environments.
This study focuses on three key aspects: (a) crude throat swab samples in a viral transport medium (VTM) as templates for RT-LAMP reactions; (b) a biotinylated DNA probe with enhanced specificity for LFA readouts; and (c) a digital semi-quantification of LFA readouts. Throat swab samples from SARS-CoV-2 positive and negative patients were used in their crude (no cleaning or pre-treatment) forms for the RT-LAMP reaction. The samples were heat-inactivated but not treated for any kind of nucleic acid extraction or purification. The RT-LAMP (20 min processing time) product was read out by an LFA approach using two labels: FITC and biotin. FITC was enzymatically incorporated into the RT-LAMP amplicon with the LF-LAMP primer, and biotin was introduced using biotinylated DNA probes, specifically for the amplicon region after RT-LAMP amplification. This assay setup with biotinylated DNA probe-based LFA readouts of the RT-LAMP amplicon was 98.11% sensitive and 96.15% specific. The LFA result was further analysed by a smartphone-based IVD device, wherein the T-line intensity was recorded. The LFA T-line intensity was then correlated with the qRT-PCR Ct value of the positive swab samples. A digital semi-quantification of RT-LAMP-LFA was reported with a correlation coefficient of R2 = 0.702. The overall RT-LAMP-LFA assay time was recorded to be 35 min with a LoD of three RNA copies/µL (Ct-33). With these three advancements, the nucleic acid testing-point of care technique (NAT-POCT) is exemplified as a versatile biosensor platform with great potential and applicability for the detection of pathogens without the need for sample storage, transportation, or pre-processing.
Introduction
Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method's susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks.
Methods
We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling.
Results
The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity.
Discussion
Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation.
Introduction General and particularly sport-specific testing is an integral aspect of performance optimization in artistic gymnastics. In artistic gymnastics, however, only non-specific field tests have been used to assess endurance performance (e.g., Multistage Shuttle Run Test; Cooper's Test).
Methods This study aimed to examine the validity of a new sport-specific endurance test in artistic gymnastics. Fourteen elite-level gymnasts (i.e., eight males and six females) participated in this study. The newly developed artistic gymnastics-specific endurance test (AGSET) was conducted on two different occasions seven days apart to determine its reliability. To assess the concurrent validity of AGSET, participants performed the multistage shuttle run test (MSRT). Maximum oxygen uptake (VO2max) and respiratory exchange ratio (RER) were directly assessed using a portable gas analyzer system during both protocols. Additionally, the total time maintained (TTM) during the AGSET, maximum heart rate (HRmax), maximal aerobic speed (MAS), and blood lactate concentration (BLa) during the two protocols were collected.
Results The main findings indicated that all variables derived from the AGSET (i.e., VO2max, MAS, HRmax, BLa, and RER) displayed very good relative (all intraclass correlation coefficients [ICC] > 0.90) and absolute (all typical errors of measurement [TEM] < 5%) reliability. Further, results showed that the ability of the AGSET to detect small changes in VO2max, MAS, BLa, and RER was good (smallest worthwhile change [SWC0.2] > TEM), except HRmax (SWC0.2 < TEM). Additionally, results showed a nearly perfect association between the VO2max values derived from the AGSET and MSRT (r = 0.985; coefficient of determination [R-2] = 97%) with no statistically significant differences (p>0.05). The mean (bias) +/- 95% limits of agreement between the two protocols were 0.28 +/- 0.55 mlminkg-1.
Discussion AGSET seems to present very good reliability and concurrent validity for assessing endurance performance in elite artistic gymnastics. In addition, the newly developed protocol presents a good ability to detect small changes in performance.
Background
There is consistent evidence that the COVID-19 pandemic is associated with an increased psychosocial burden on children and adolescents and their parents. Relatively little is known about its particular impact on high-risk groups with chronic physical health conditions (CCs). Therefore, the primary aim of the study is to analyze the multiple impacts on health care and psychosocial well-being on these children and adolescents and their parents.
Methods
We will implement a two-stage approach. In the first step, parents and their underage children from three German patient registries for diabetes, obesity, and rheumatic diseases, are invited to fill out short questionnaires including questions about corona-specific stressors, the health care situation, and psychosocial well-being. In the next step, a more comprehensive, in-depth online survey is carried out in a smaller subsample.
Discussion
The study will provide insights into the multiple longer-term stressors during the COVID-19 pandemic in families with a child with a CC. The simultaneous consideration of medical and psycho-social endpoints will help to gain a deeper understanding of the complex interactions affecting family functioning, psychological well-being, and health care delivery.
Background
Teleost fishes comprise more than half of the vertebrate species. Within teleosts, most phylogenies consider the split between Osteoglossomorpha and Euteleosteomorpha/Otomorpha as basal, preceded only by the derivation of the most primitive group of teleosts, the Elopomorpha. While Osteoglossomorpha are generally species poor, the taxon contains the African weakly electric fish (Mormyroidei), which have radiated into numerous species. Within the mormyrids, the genus Campylomormyrus is mostly endemic to the Congo Basin. Campylomormyrus serves as a model to understand mechanisms of adaptive radiation and ecological speciation, especially with regard to its highly diverse species-specific electric organ discharges (EOD). Currently, there are few well-annotated genomes available for electric fish in general and mormyrids in particular. Our study aims at producing a high-quality genome assembly and to use this to examine genome evolution in relation to other teleosts. This will facilitate further understanding of the evolution of the osteoglossomorpha fish in general and of electric fish in particular.
Results
A high-quality weakly electric fish (C. compressirostris) genome was produced from a single individual with a genome size of 862 Mb, consisting of 1,497 contigs with an N50 of 1,399 kb and a GC-content of 43.69%. Gene predictions identified 34,492 protein-coding genes, which is a higher number than in the two other available Osteoglossomorpha genomes of Paramormyrops kingsleyae and Scleropages formosus. A Computational Analysis of gene Family Evolution (CAFE5) comparing 33 teleost fish genomes suggests an overall faster gene family turnover rate in Osteoglossomorpha than in Otomorpha and Euteleosteomorpha. Moreover, the ratios of expanded/contracted gene family numbers in Osteoglossomorpha are significantly higher than in the other two taxa, except for species that had undergone an additional genome duplication (Cyprinus carpio and Oncorhynchus mykiss). As potassium channel proteins are hypothesized to play a key role in EOD diversity among species, we put a special focus on them, and manually curated 16 Kv1 genes. We identified a tandem duplication in the KCNA7a gene in the genome of C. compressirostris.
Conclusions
We present the fourth genome of an electric fish and the third well-annotated genome for Osteoglossomorpha, enabling us to compare gene family evolution among major teleost lineages. Osteoglossomorpha appear to exhibit rapid gene family evolution, with more gene family expansions than contractions. The curated Kv1 gene family showed seven gene clusters, which is more than in other analyzed fish genomes outside Osteoglossomorpha. The KCNA7a, encoding for a potassium channel central for EOD production and modulation, is tandemly duplicated which may related to the diverse EOD observed among Campylomormyrus species.
Background
Machine learning models promise to support diagnostic predictions, but may not perform well in new settings. Selecting the best model for a new setting without available data is challenging. We aimed to investigate the transportability by calibration and discrimination of prediction models for cognitive impairment in simulated external settings with different distributions of demographic and clinical characteristics.
Methods
We mapped and quantified relationships between variables associated with cognitive impairment using causal graphs, structural equation models, and data from the ADNI study. These estimates were then used to generate datasets and evaluate prediction models with different sets of predictors. We measured transportability to external settings under guided interventions on age, APOE & epsilon;4, and tau-protein, using performance differences between internal and external settings measured by calibration metrics and area under the receiver operating curve (AUC).
Results
Calibration differences indicated that models predicting with causes of the outcome were more transportable than those predicting with consequences. AUC differences indicated inconsistent trends of transportability between the different external settings. Models predicting with consequences tended to show higher AUC in the external settings compared to internal settings, while models predicting with parents or all variables showed similar AUC.
Conclusions
We demonstrated with a practical prediction task example that predicting with causes of the outcome results in better transportability compared to anti-causal predictions when considering calibration differences. We conclude that calibration performance is crucial when assessing model transportability to external settings.
The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes.
Quantifying the resilience of vegetated ecosystems is key to constraining both present-day and future global impacts of anthropogenic climate change. Here we apply both empirical and theoretical resilience metrics to remotely-sensed vegetation data in order to examine the role of water availability and variability in controlling vegetation resilience at the global scale. We find a concise global relationship where vegetation resilience is greater in regions with higher water availability. We also reveal that resilience is lower in regions with more pronounced inter-annual precipitation variability, but find less concise relationships between vegetation resilience and intra-annual precipitation variability. Our results thus imply that the resilience of vegetation responds differently to water deficits at varying time scales. In view of projected increases in precipitation variability, our findings highlight the risk of ecosystem degradation under ongoing climate change.
Vegetation dynamics depend on both the amount of precipitation and its variability over time. Here, the authors show that vegetation resilience is greater where water availability is higher and where precipitation is more stable from year to year.
Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models
(2023)
Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We previously proposed a first approach to leverage the knowledge in QSP models to derive simpler, mechanism-based pharmacodynamic (PD) models. Their complexity, however, is typically still too large to be used in the population analysis of clinical data. Here, we extend the approach beyond state reduction to also include the simplification of reaction rates, elimination of reactions, and analytic solutions. We additionally ensure that the reduced model maintains a prespecified approximation quality not only for a reference individual but also for a diverse virtual population. We illustrate the extended approach for the warfarin effect on blood coagulation. Using the model-reduction approach, we derive a novel small-scale warfarin/international normalized ratio model and demonstrate its suitability for biomarker identification. Due to the systematic nature of the approach in comparison with empirical model building, the proposed model-reduction algorithm provides an improved rationale to build PD models also from QSP models in other applications.
Economic evaluation of digital therapeutic care apps for unsupervised treatment of low back pain
(2023)
Background:
Digital therapeutic care (DTC) programs are unsupervised app-based treatments that provide video exercises and educational material to patients with nonspecific low back pain during episodes of pain and functional disability. German statutory health insurance can reimburse DTC programs since 2019, but evidence on efficacy and reasonable pricing remains scarce. This paper presents a probabilistic sensitivity analysis (PSA) to evaluate the efficacy and cost-utility of a DTC app against treatment as usual (TAU) in Germany.
Objective:
The aim of this study was to perform a PSA in the form of a Monte Carlo simulation based on the deterministic base case analysis to account for model assumptions and parameter uncertainty. We also intend to explore to what extent the results in this probabilistic analysis differ from the results in the base case analysis and to what extent a shortage of outcome data concerning quality-of-life (QoL) metrics impacts the overall results.
Methods:
The PSA builds upon a state-transition Markov chain with a 4-week cycle length over a model time horizon of 3 years from a recently published deterministic cost-utility analysis. A Monte Carlo simulation with 10,000 iterations and a cohort size of 10,000 was employed to evaluate the cost-utility from a societal perspective. Quality-adjusted life years (QALYs) were derived from Veterans RAND 6-Dimension (VR-6D) and Short-Form 6-Dimension (SF-6D) single utility scores. Finally, we also simulated reducing the price for a 3-month app prescription to analyze at which price threshold DTC would result in being the dominant strategy over TAU in Germany.
Results:
The Monte Carlo simulation yielded on average a euro135.97 (a currency exchange rate of EUR euro1=US $1.069 is applicable) incremental cost and 0.004 incremental QALYs per person and year for the unsupervised DTC app strategy compared to in-person physiotherapy in Germany. The corresponding incremental cost-utility ratio (ICUR) amounts to an additional euro34,315.19 per additional QALY. DTC yielded more QALYs in 54.96% of the iterations. DTC dominates TAU in 24.04% of the iterations for QALYs. Reducing the app price in the simulation from currently euro239.96 to euro164.61 for a 3-month prescription could yield a negative ICUR and thus make DTC the dominant strategy, even though the estimated probability of DTC being more effective than TAU is only 54.96%.
Conclusions:
Decision-makers should be cautious when considering the reimbursement of DTC apps since no significant treatment effect was found, and the probability of cost-effectiveness remains below 60% even for an infinite willingness-to-pay threshold. More app-based studies involving the utilization of QoL outcome parameters are urgently needed to account for the low and limited precision of the available QoL input parameters, which are crucial to making profound recommendations concerning the cost-utility of novel apps.
The study explores differences between three user types in the top tweets about the 2015 “refugee crisis” in Germany and presents the results of a quantitative content analysis. All tweets with the keyword “Flüchtlinge” posted for a monthlong period following September 13, 2015, the day Germany decided to implement border controls, were collected (N = 763,752). The top 2,495 tweets according to number of retweets were selected for analysis. Differences between news media, public and private actor tweets in topics, tweet characteristics such as tone and opinion expression, links, and specific sentiments toward refugees were analyzed. We found strong differences between the tweets. Public actor tweets were the main source of positive sentiment toward refugees and the main information source on refugee support. News media tweets mostly reflected traditional journalistic norms of impartiality and objectivity, whereas private actor tweets were more diverse in sentiments toward refugees.
The color red has been implicated in a variety of social processes, including those involving mating. While previous research suggests that women sometimes wear red strategically to increase their attractiveness, the replicability of this literature has been questioned. The current research is a reasonably powered conceptual replication designed to strengthen this literature by testing whether women are more inclined to display the color red 1) during fertile (as compared with less fertile) days of the menstrual cycle, and 2) when expecting to interact with an attractive man (as compared with a less attractive man and with a control condition). Analyses controlled for a number of theoretically relevant covariates (relationship status, age, the current weather). Only the latter hypothesis received mixed support (mainly among women on hormonal birth control), whereas results concerning the former hypothesis did not reach significance. Women (N = 281) displayed more red when expecting to interact with an attractive man; findings did not support the prediction that women would increase their display of red on fertile days of the cycle. Findings thus suggested only mixed replicability for the link between the color red and psychological processes involving romantic attraction. They also illustrate the importance of further investigating the boundary conditions of color effects on everyday social processes.
Background: Patients with subjective cognitive decline (SCD) report memory deterioration and are at an increased risk of converting to Alzheimer's disease (AD) although psychophysical testing does not reveal any cognitive deficit.
Objective: Here, gustatory function is investigated as a potential predictor for an increased risk of progressive cognitive decline indicating higher AD risk in SCD.
Methods: Measures of smell and taste perception as well as neuropsychological data were assessed in patients with subjective cognitive decline (SCD): Subgroups with an increased likelihood of the progression to preclinical AD (SCD+) and those with a lower likelihood (SCD-) were compared to healthy controls (HC), patients with mild cognitive impairment and AD patients. The Sniffin' Sticks test contained 12 items with different qualities and taste was measured with 32 taste stripes (sweet, salty, bitter, sour) of different concentration.
Results: Only taste was able to distinguish between HC/SCD- and SCD+ patients.
Conclusion: This study provides a first hint of taste as a more sensitive marker than smell for detecting preclinical AD in SCD. Longitudinal observation of cognition and pathology are necessary to further evaluate taste perception as a predictor of pathological objective decline in cognition.
Finger-based representation of numbers is a high-level cognitive strategy to assist numerical and arithmetic processing in children and adults. It is unclear whether this paradigm builds on simple perceptual features or comprises several attributes through embodiment. Here we describe the development and initial testing of an experimental setup to study embodiment during a finger-based numerical task using Virtual Reality (VR) and a low-cost tactile stimulator that is easy to build. Using VR allows us to create new ways to study finger-based numerical representation using a virtual hand that can be manipulated in ways our hand cannot, such as decoupling tactile and visual stimuli. The goal is to present a new methodology that can allow researchers to study embodiment through this new approach, maybe shedding new light on the cognitive strategy behind the finger-based representation of numbers. In this case, a critical methodological requirement is delivering precisely targeted sensory stimuli to specific effectors while simultaneously recording their behavior and engaging the participant in a simulated experience. We tested the device's capability by stimulating users in different experimental configurations. Results indicate that our device delivers reliable tactile stimulation to all fingers of a participant's hand without losing motion tracking quality during an ongoing task. This is reflected by an accuracy of over 95% in participants detecting stimulation of a single finger or multiple fingers in sequential stimulation as indicated by experiments with sixteen participants. We discuss possible application scenarios, explain how to apply our methodology to study the embodiment of finger-based numerical representations and other high-level cognitive functions, and discuss potential further developments of the device based on the data obtained in our testing.
Cell-level systems biology model to study inflammatory bowel diseases and their treatment options
(2023)
To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options.
Fetal alcohol-spectrum disorder (FASD) is underdiagnosed and often misdiagnosed as attention-deficit/hyperactivity disorder (ADHD). Here, we develop a screening tool for FASD in youth with ADHD symptoms. To develop the prediction model, medical record data from a German University outpatient unit are assessed including 275 patients aged 0-19 years old with FASD with or without ADHD and 170 patients with ADHD without FASD aged 0-19 years old. We train 6 machine learning models based on 13 selected variables and evaluate their performance. Random forest models yield the best prediction models with a cross-validated AUC of 0.92 (95% confidence interval [0.84, 0.99]). Follow-up analyses indicate that a random forest model with 6 variables - body length and head circumference at birth, IQ, socially intrusive behaviour, poor memory and sleep disturbance - yields equivalent predictive accuracy. We implement the prediction model in a web-based app called FASDetect - a user-friendly, clinically scalable FASD risk calculator that is freely available at https://fasdetect.dhc-lab.hpi.de.
Purpose
Due to the increasing application of genome analysis and interpretation in medical disciplines, professionals require adequate education. Here, we present the implementation of personal genotyping as an educational tool in two genomics courses targeting Digital Health students at the Hasso Plattner Institute (HPI) and medical students at the Technical University of Munich (TUM).
Methods
We compared and evaluated the courses and the students ' perceptions on the course setup using questionnaires.
Results
During the course, students changed their attitudes towards genotyping (HPI: 79% [15 of 19], TUM: 47% [25 of 53]). Predominantly, students became more critical of personal genotyping (HPI: 73% [11 of 15], TUM: 72% [18 of 25]) and most students stated that genetic analyses should not be allowed without genetic counseling (HPI: 79% [15 of 19], TUM: 70% [37 of 53]). Students found the personal genotyping component useful (HPI: 89% [17 of 19], TUM: 92% [49 of 53]) and recommended its inclusion in future courses (HPI: 95% [18 of 19], TUM: 98% [52 of 53]).
Conclusion
Students perceived the personal genotyping component as valuable in the described genomics courses. The implementation described here can serve as an example for future courses in Europe.
Entrepreneurship education research has a strong “output” focus on impact studies but pays much less attention to the “inside” or process perspective of the way entrepreneurship education occurs. In particular, the scattered previous entrepreneurship curriculum research has not managed to provide a current and comprehensive overview of the curricular elements that constitute entrepreneurship education. To overcome this shortcoming, we aim to identify the teaching objectives, teaching contents, teaching methods, and assessment methods discussed in entrepreneurship curriculum research. To this end, we conducted a systematic literature review on the four entrepreneurship curriculum dimensions and collected all mentioned curriculum items. We used a two-stage coding procedure to find the genuinely entrepreneurship-specific items. Among numerous items (also from business management and other subjects), we found 26 objectives, 34 contents, 11 teaching methods, and 7 assessment methods that were entrepreneurship-specific. Most of these items were addressed by only a few scholarly papers.
This study provides a synthesis of corpus-based and experimental investigations of word-order preferences in German infinitival complementation. We carried out a systematic analysis of present-day German corpora to establish frequency distributions of different word-order options: extraposition, intraposition, and 'third construction'. We then examined, firstly, whether and to what extent corpus frequencies and processing economy constraints can predict the acceptability of these three word-order variants, and whether subject raising and subject control verbs form clearly distinguishable subclasses of infinitive-embedding verbs in terms of their word-order behaviour. Secondly, our study looks into the issue of coherence by comparing acceptability ratings for monoclausal coherent and biclausal incoherent construals of intraposed infinitives, and by examining whether a biclausal incoherent analysis gives rise to local and/or global processing difficulty. Taken together, our results revealed that (i) whilst the extraposition pattern consistently wins out over all other word-order variants for control verbs, neither frequency nor processing-based approaches to word-order variation can account for the acceptability of low-frequency variants, (ii) there is considerable verb-specific variation regarding word-order preferences both between and within the two sets of raising and control verbs under investigation, and (iii) although monoclausal coherent intraposition is rated above biclausal incoherent intraposition, the latter is not any more difficult to process than the former. Our findings indicate that frequency of occurrence and processing-related constraints interact with idiosyncratic lexical properties of individual verbs in determining German speakers' structural preferences.
Cosmic-ray neutron sensing (CRNS) allows for the estimation of root-zone soil water content (SWC) at the scale of several hectares. In this paper, we present the data recorded by a dense CRNS network operated from 2019 to 2022 at an agricultural research site in Marquardt, Germany - the first multi-year CRNS cluster. Consisting, at its core, of eight permanently installed CRNS sensors, the cluster was supplemented by a wealth of complementary measurements: data from seven additional temporary CRNS sensors, partly co-located with the permanent ones; 27 SWC profiles (mostly permanent); two groundwater observation wells; meteorological records; and Global Navigation Satellite System reflectometry (GNSS-R). Complementary to these continuous measurements, numerous campaign-based activities provided data by mobile CRNS roving, hyperspectral im-agery via UASs, intensive manual sampling of soil properties (SWC, bulk density, organic matter, texture, soil hydraulic properties), and observations of biomass and snow (cover, depth, and density). The unique temporal coverage of 3 years entails a broad spectrum of hydro-meteorological conditions, including exceptional drought periods and extreme rainfall but also episodes of snow coverage, as well as a dedicated irrigation experiment. Apart from serving to advance CRNS-related retrieval methods, this data set is expected to be useful for vari-ous disciplines, for example, soil and groundwater hydrology, agriculture, or remote sensing. Hence, we show exemplary features of the data set in order to highlight the potential for such subsequent studies. The data are available at doi.org/10.23728/b2share.551095325d74431881185fba1eb09c95 (Heistermann et al., 2022b).
Introduction Flux phenotypes from different organisms and growth conditions allow better understanding of differential metabolic networks functions. Fluxes of metabolic reactions represent the integrated outcome of transcription, translation, and post-translational modifications, and directly affect growth and fitness. However, fluxes of intracellular metabolic reactions cannot be directly measured, but are estimated via metabolic flux analysis (MFA) that integrates data on isotope labeling patterns of metabolites with metabolic models. While the application of metabolomics technologies in photosynthetic organisms have resulted in unprecedented data from 13CO2-labeling experiments, the bottleneck in flux estimation remains the application of isotopically nonstationary MFA (INST-MFA). INST-MFA entails fitting a (large) system of coupled ordinary differential equations, with metabolite pools and reaction fluxes as parameters. Here, we focus on the Calvin-Benson cycle (CBC) as a key pathway for carbon fixation in photosynthesizing organisms and ask if approaches other than classical INST-MFA can provide reliable estimation of fluxes for reactions comprising this pathway.
Methods First, we show that flux estimation with the labeling patterns of all CBC intermediates can be formulated as a single constrained regression problem, avoiding the need for repeated simulation of time-resolved labeling patterns.
Results We then compare the flux estimates of the simulation-free constrained regression approach with those obtained from the classical INST-MFA based on labeling patterns of metabolites from the microalgae Chlamydomonas reinhardtii, Chlorella sorokiniana and Chlorella ohadii under different growth conditions.
Discussion Our findings indicate that, in data-rich scenarios, simulation-free regression-based approaches provide a suitable alternative for flux estimation from classical INST-MFA since we observe a high qualitative agreement (rs=0.89) to predictions obtained from INCA, a state-of-the-art tool for INST-MFA.
The plasma membrane of mammalian cells links transmembrane receptors, various structural components, and membrane-binding proteins to subcellular processes, allowing inter- and intracellular communication. Therefore, membrane-binding proteins, together with structural components such as actin filaments, modulate the cell membrane in their flexibility, stiffness, and curvature. Investigating membrane components and curvature in cells remains challenging due to the diffraction limit in light microscopy. Preparation of 5–15-nm-thin plasma membrane sheets and subsequent inspection by metal replica transmission electron microscopy (TEM) reveal detailed information about the cellular membrane topology, including the structure and curvature. However, electron microscopy cannot identify proteins associated with specific plasma membrane domains. Here, we describe a novel adaptation of correlative super-resolution light microscopy and platinum replica TEM (CLEM-PREM), allowing the analysis of plasma membrane sheets with respect to their structural details, curvature, and associated protein composition. We suggest a number of shortcuts and troubleshooting solutions to contemporary PREM protocols. Thus, implementation of super-resolution stimulated emission depletion (STED) microscopy offers significant reduction in sample preparation time and reduced technical challenges for imaging and analysis. Additionally, highly technical challenges associated with replica preparation and transfer on a TEM grid can be overcome by scanning electron microscopy (SEM) imaging. The combination of STED microscopy and platinum replica SEM or TEM provides the highest spatial resolution of plasma membrane proteins and their underlying membrane and is, therefore, a suitable method to study cellular events like endocytosis, membrane trafficking, or membrane tension adaptations.
The motion picture industry is subject to extensive business and management research conducted on a wide range of topics. Due to high research productivity, it is challenging to keep track of the abundance of publications. Against this background, we employ a bibliographic coupling analysis to gain a comprehensive understanding of current research topics. The following themes were defined: Key factors for success, word of mouth and social media, organizational and pedagogical dimensions, advertising—product placement and online marketing, tourism, the influence of data, the influence of culture, revenue maximization and purchase decisions, and the perception and identification of audiences. Based on the cluster analysis, we suggest the following future research opportunities: Exploring technological innovations, especially the influence of social media and streaming platforms in the film industry; the in-depth analysis of the use of artificial intelligence in film production, both in terms of its creative potential and ethical and legal challenges; the exploration of the representation of wokeness and minorities in films and their cultural and economic significance; and, finally, a detailed examination of the long-term effects of the COVID-19 pandemic and other crises on the film industry, especially in terms of changed consumption habits and structural adjustments.
Introduction Climbing is an increasingly popular activity and imposes specific physiological demands on the human body, which results in unique injury presentations. Of particular concern are overuse injuries (non-traumatic injuries). These injuries tend to present in the upper body and might be preventable with adequate knowledge of risk factors which could inform about injury prevention strategies. Research in this area has recently emerged but has yet to be synthesized comprehensively. Therefore, the aim of this study was to conduct a systematic review of the potential risk factors and injury prevention strategies for overuse injuries in adult climbers.
Methods This systematic review was conducted in accordance with the PRISMA guidelines. Databases were searched systematically, and articles were deemed eligible based upon specific criteria. Research included was original and peer-reviewed, involving climbers, and published in English, German or Czech. Outcomes included overuse injury, and at least one or more variable indicating potential risk factors or injury prevention strategies. The methodological quality of the included studies was assessed with the Downs and Black Quality Index. Data were extracted from included studies and reported descriptively for population, climbing sport type, study design, injury definition and incidence/prevalence, risk factors, and injury prevention strategies.
Results Out of 1,183 records, a total of 34 studies were included in the final analysis. Higher climbing intensity, bouldering, reduced grip/finger strength, use of a “crimp” grip, and previous injury were associated with an increased risk of overuse injury. Additionally, a strength training intervention prevented shoulder and elbow injuries. BMI/body weight, warm up/cool downs, stretching, taping and hydration were not associated with risk of overuse injury. The evidence for the risk factors of training volume, age/years of climbing experience, and sex was conflicting.
Discussion This review presents several risk factors which appear to increase the risk of overuse injury in climbers. Strength and conditioning, load management, and climbing technique could be targeted in injury prevention programs, to enhance the health and wellbeing of climbing athletes. Further research is required to investigate the conflicting findings reported across included studies, and to investigate the effectiveness of injury prevention programs.
Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023404031).
Comparamos la labialización no asimiladora de nasales finales en español en tres corpus de español americano (mexicano, colombiano y paraguayo). Si bien es conocida la labialización no asimiladora en español yucateco, es en gran parte desconocida en otras regiones de habla hispana, por lo que a menudo se atribuye a la influencia maya. Ahora bien, se han señalado casualmente hábitos de pronunciación similares tanto en Paraguay como en Colombia. Comparando empíricamente la labialización en tres corpus constituidos sobre la misma base metodológica, concluimos que la evidencia a favor del contacto lingüístico es como mucho sumamente indirecta. Independientemente de esto, encontramos que la diferencia más marcada es que la tasa de labialización parece ser determinada por la duración de la pausa subsiguiente en los datos de la península yucateca, mas no en aquellos de Colombia y Paraguay. Argumentamos que es cierto que el contacto puede eventualmente haber desencadenado el desarrollo de este rasgo en el español yucateco, puesto que el español actual casi no conoce nasales labiales finales, pero el maya sí. Sin embargo, el perfil lingüístico (hablantes monolingües vs. bilingües) no tiene ningún efecto en nuestros datos yucatecos y paraguayos, y en el total de nuestros datos tampoco encontramos evidencia en favor de la hipótesis que el contacto lingüístico hubiera jugado un rol (importante) en el desarrollo de las labiales nasales en las tres variedades.
El artículo analiza la corrupción como un fenómeno complejo y con frecuencia ambiguo, relacionado con comportamientos y mentalidades individuales y colectivas, que son percibidos como ilegítimos o inmorales y, por lo tanto, desviados de normas establecidas. Más allá de un acercamiento reduccionista u objetivista a lugares comunes de la corrupción política, o a delitos tipificados por la ley, esta contribución pretende destacar la relevancia del análisis histórico del discurso en el estudio del tema. Este enfoque nos permite reconstruir contextos en los que se identifica la corrupción, así como analizar relatos, no siempre unánimes, sobre estas prácticas. El trabajo se adentra en una época lejana, pero a la vez cercana a nuestro tiempo, el último siglo la República romana. La evidencia nos permite evaluar críticamente aspectos fundamentales de la construcción retórica de la corrupción y de sus zonas grises, como la distinción, a menudo borrosa, entre regalo y soborno.
In many churches nowadays, there has been a standardized approach to premarital counseling for couples involving social, pastoral, and psychological perspectives. In contrast, many rabbis and other Jewish officials still concentrate on legal aspects alone. The need for resolving important issues on the verge of wedlock is too often left to secular experts in law, psychology, or counseling. However, in recent years, this lack of formal training for marriage preparation has also been acknowledged by the Jewish clergy in order to incorporate it in the preparatory period before the bond is tied. This case study focuses on Jewish and Roman Catholic conceptions of marriage, past and present. We intend to do a comparative analysis of the prerequisites of religious marriage based on the assumption that both Judaism and the Roman Catholic Church have a distinct legal framework to assess marriage preparation.
In this visualization, the authors show changes in family patterns by different race groups across two cohorts. Using data from the National Longitudinal Survey of Youth 1979 (born from 1957 to 1965) and 1997 (born from 1980 to 1984), the authors visualize the relationship-parenthood state distributions at each age between 15 and 35 years by race and cohort. The results suggest the rise of cohabiting mothers and the decline of married and divorced mothers among women born from 1980 to 1984. Black women born from 1980 to 1984 were more likely to experience single/childless and single/parent status compared with Black women born from 1957 to 1965. Although with some visible postponement in the recent cohort, white women in both cohorts were more likely to experience married/parent status than other race groups. The decline in married/parent status across the two generations was sharpest among Hispanic women. These descriptive findings highlight the importance of identifying race when discussing changes in family formation and dissolution trends across generations.
Die islamische Speiseordnung
(2024)
Hässlich aber gut
(2024)
The paper argues that economists’ position-taking in discourses of crises should be understood in the light of economists’ positions in the academic field of economics. This hypothesis is investigated by performing a multiple correspondence analysis (MCA) on a prosopographical data set of 144 French economists who positioned themselves between 2008 and 2021 in controversies over the euro crisis, the French political economic model, and French economics. In these disciplinary controversies, different forms of (post-)national academic capital are used by economists to either initiate change or defend the status quo. These strategies are then interpreted as part of more general power struggles over the basic national or post-national constitution and legitimate governance of economy and society.
Kaschrut
(2024)
Background
Many high-income countries are grappling with severe labour shortages in the healthcare sector. Refugees and recent migrants present a potential pool for staff recruitment due to their higher unemployment rates, younger age, and lower average educational attainment compared to the host society's labour force. Despite this, refugees and recent migrants, often possessing limited language skills in the destination country, are frequently excluded from traditional recruitment campaigns conducted solely in the host country’s language. Even those with intermediate language skills may feel excluded, as destination-country language advertisements are perceived as targeting only native speakers. This study experimentally assesses the effectiveness of a recruitment campaign for nursing positions in a German care facility, specifically targeting Arabic and Ukrainian speakers through Facebook advertisements.
Methods
We employ an experimental design (AB test) approximating a randomized controlled trial, utilizing Facebook as the delivery platform. We compare job advertisements for nursing positions in the native languages of Arabic and Ukrainian speakers (treatment) with the same advertisements displayed in German (control) for the same target group in the context of a real recruitment campaign for nursing jobs in Berlin, Germany. Our evaluation includes comparing link click rates, visits to the recruitment website, initiated applications, and completed applications, along with the unit cost of these indicators. We assess statistical significance in group differences using the Chi-squared test.
Results
We find that recruitment efforts in the origin language were 5.6 times (Arabic speakers) and 1.9 times (Ukrainian speakers) more effective in initiating nursing job applications compared to the standard model of German-only advertisements among recent migrants and refugees. Overall, targeting refugees and recent migrants was 2.4 (Ukrainians) and 10.8 (Arabic) times cheaper than targeting the reference group of German speakers indicating higher interest among these groups.
Conclusions
The results underscore the substantial benefits for employers in utilizing targeted recruitment via social media aimed at foreign-language communities within the country. This strategy, which is low-cost and low effort compared to recruiting abroad or investing in digitalization, has the potential for broad applicability in numerous high-income countries with sizable migrant communities. Increased employment rates among underemployed refugee and migrant communities, in turn, contribute to reducing poverty, social exclusion, public expenditure, and foster greater acceptance of newcomers within the receiving society.
Die deutsch-kubanische Forschungs- und Digitalisierungsinitiative „Proyecto Humboldt Digital“ (ProHD) hat während ihrer Projektlaufzeit (2019–2023) wichtige Quellen zum Thema „Humboldt und Kuba“ erstmals digital erschlossen. Als Kooperation zwischen der Berlin-Brandenburgischen Akademie der Wissenschaften und der Oficina del Historiador de la Ciudad de La Habana hat ProHD damit wichtige Akzente für die Archivdigitalisierung, die digitale Editionsphilologie und die digitale Wissenschaftskommunikation in Kuba gesetzt. Das Korpus der erschlossenen Bestände wird hier in fünf Schlaglichtern vorgestellt: 1) Quellen zur Humboldt’schen Forschungsreise, 2) Juan Luis de la Cuesta, 3) Materialien zu Kuba aus dem Humboldt-Nachlass, 4) Zensur und Beschlagnahme des Essai politique sur l’île de Cuba, 5) Francisco de Arango y Parreño.
La traduction en langue chinoise du premier volume du monumental ouvrage scientifique d'Alexander von Humboldt, intitulé «Cosmos», a vu le jour en 2023 sous l՚égide de la prestigieuse maison d՚édition de l՚Université de Pékin. Dans sa postface éclairée, la traductrice émérite, Gao Hong, éclaire la lanterne des lecteurs chinois sur la fresque cosmique esquissée par Humboldt, révélant ainsi les intrications entre les phénomènes naturels et leur pertinence à l՚échelle de l'univers tout entier. Gao Hong narre son propre périple aux côtés de Humboldt, tout en distillant ses réflexions personnelles sur cette fresque cosmique. «Cosmos» d՚Humboldt, œuvre scientifique par excellence, transcende également les sphères esthétiques et artistiques, exprimant invariablement une profonde vénération pour l՚univers. Restituer en chinois la «beauté géométrique» de la langue allemande, empreinte d՚une rigueur structurelle, constitue un défi singulier, le chinois se caractérisant par sa fluidité, sa souplesse et sa poésie imagée, en totale antithèse avec l՚allemand. En qualité de traducteur, il importe de naviguer librement entre ces deux mondes linguistiques distincts.
In dem Aufsatz wird ein Brief erstmalig veröffentlicht, in dem Alexander von Humboldt im Jahr 1849 bei einem Minister der liberalen Regierung von Kurhessen die Verdienste eines an der Universität in Marburg lehrenden jungen Professors hervorhob. Die Rede ist hier von dem später durch bahnbrechende Entdeckungen berühmten Physiologen Carl Ludwig. Vermittelt wurde das Schreiben durch den Humboldt nahestehenden Mediziner und Physiologen Emil du Bois-Reymond. Der Empfehlungsbrief, mit dem Humboldt versuchte, Ludwigs finanzielle Situation zu verbessern, ist ein Beispiel für die Förderung junger Forscher wie auch freier wissenschaftlicher Institutionen durch Humboldt.
Off-road adventures
(2024)
This article focuses on the visual qualities of Alexander von Humboldt’s statistical tables in his Political Essay on the Kingdom of New Spain (1808–1811, 2nd ed. 1825–1827) with special attention to how such composites of numbers, alphabetical script, and semiotic elements relate to narrative writing. I argue that Humboldt’s tables/tableaus open up spaces inside his narrative that fragment the reading process, inviting new conversations, connections, and ideas.
To achieve the Paris climate target, deep emissions reductions have to be complemented with carbon dioxide removal (CDR). However, a portfolio of CDR options is necessary to reduce risks and potential negative side effects. Despite a large theoretical potential, ocean-based CDR such as ocean alkalinity enhancement (OAE) has been omitted in climate change mitigation scenarios so far. In this study, we provide a techno-economic assessment of large-scale OAE using hydrated lime ('ocean liming'). We address key uncertainties that determine the overall cost of ocean liming (OL) such as the CO2 uptake efficiency per unit of material, distribution strategies avoiding carbonate precipitation which would compromise efficiency, and technology availability (e.g., solar calciners). We find that at economic costs of 130–295 $/tCO2 net-removed, ocean liming could be a competitive CDR option which could make a significant contribution towards the Paris climate target. As the techno-economic assessment identified no showstoppers, we argue for more research on ecosystem impacts, governance, monitoring, reporting, and verification, and technology development and assessment to determine whether ocean liming and other OAE should be considered as part of a broader CDR portfolio.
In this paper, we present data from an elicitation study and a corpus study that support the observation that the Yucatec Maya progressive aspect auxiliary táan is replaced by the habitual auxiliary k in sentences with contrastively focused fronted objects. Focus has been extensively studied in Yucatec, yet the incompatibility of object fronting and progressive aspect in Yucatec Maya remains understudied. Both our experimental results and our corpus study point in the direction that this incompatibility may very well be categorical. Theoretically, we take a progressive reading to be derived from an imperfectivity operator in combination with a singular operator, and we propose that this singular operator implicates the negation of event plurality, leading to an exhaustive interpretation which ranks below corrective focus on a contrastive focus scale. This means that, in a sentence with object focus fronting, the use of the marked auxiliary táan (as opposed to the more general k) would trigger two contrastive foci, which would be an unlikely and probably dispreferred speech act.
“Ick bin een Berlina”
(2024)
Background: Robots are increasingly used as interaction partners with humans. Social robots are designed to follow expected behavioral norms when engaging with humans and are available with different voices and even accents. Some studies suggest that people prefer robots to speak in the user’s dialect, while others indicate a preference for different dialects.
Methods: Our study examined the impact of the Berlin dialect on perceived trustworthiness and competence of a robot. One hundred and twenty German native speakers (Mage = 32 years, SD = 12 years) watched an online video featuring a NAO robot speaking either in the Berlin dialect or standard German and assessed its trustworthiness and competence.
Results: We found a positive relationship between participants’ self-reported Berlin dialect proficiency and trustworthiness in the dialect-speaking robot. Only when controlled for demographic factors, there was a positive association between participants’ dialect proficiency, dialect performance and their assessment of robot’s competence for the standard German-speaking robot. Participants’ age, gender, length of residency in Berlin, and device used to respond also influenced assessments. Finally, the robot’s competence positively predicted its trustworthiness.
Discussion: Our results inform the design of social robots and emphasize the importance of device control in online experiments.
Systematic review and meta-analysis of ex-post evaluations on the effectiveness of carbon pricing
(2024)
Today, more than 70 carbon pricing schemes have been implemented around the globe, but their contributions to emissions reductions remains a subject of heated debate in science and policy. Here we assess the effectiveness of carbon pricing in reducing emissions using a rigorous, machine-learning assisted systematic review and meta-analysis. Based on 483 effect sizes extracted from 80 causal ex-post evaluations across 21 carbon pricing schemes, we find that introducing a carbon price has yielded immediate and substantial emission reductions for at least 17 of these policies, despite the low level of prices in most instances. Statistically significant emissions reductions range between –5% to –21% across the schemes (–4% to –15% after correcting for publication bias). Our study highlights critical evidence gaps with regard to dozens of unevaluated carbon pricing schemes and the price elasticity of emissions reductions. More rigorous synthesis of carbon pricing and other climate policies is required across a range of outcomes to advance our understanding of “what works” and accelerate learning on climate solutions in science and policy.
Organizational commitments to equality change how people view women’s and men’s professional success
(2024)
To address women’s underrepresentation in high-status positions, many organizations have committed to gender equality. But is women’s professional success viewed less positively when organizations commit to women’s advancement? Do equality commitments have positive effects on evaluations of successful men? We fielded a survey experiment with a national probability sample in Germany (N = 3229) that varied employees’ gender and their organization’s commitment to equality. Respondents read about a recently promoted employee and rated how decisive of a role they thought intelligence and effort played in getting the employee promoted from 1 “Not at all decisive” to 7 “Very decisive” and the fairness of the promotion from 1 “Very unfair” to 7 “Very fair.” When organizations committed to women’s advancement rather than uniform performance standards, people believed intelligence and effort were less decisive in women’s promotions, but that intelligence was more decisive in men’s promotions. People viewed women’s promotions as least fair and men’s as most fair in organizations committed to women’s advancement. However, women’s promotions were still viewed more positively than men’s in all conditions and on all outcomes, suggesting people believed that organizations had double standards for success that required women to be smarter and work harder to be promoted, especially in organizations that did not make equality commitments.
Zuerst erschienen in:
Alexander von Humboldt-Stiftung. Mitteilungen, 5. Jg., Heft 38, Oktober 1980, S. 27–36.
Existing curricula for entrepreneurship education do not necessarily represent the best way of teaching. How could entrepreneurship curricula be improved? To answer this question, we aim to identify and rank desirable teaching objectives, teaching contents, teaching methods, and assessment methods for higher entrepreneurship education. To this end, we employ an international real-time Delphi study with an expert panel consisting of entrepreneurship education instructors and researchers. The study reveals 17 favorable objectives, 17 items of content, 25 teaching methods, and 15 assessment methods, which are ranked according to their desirability and the group consensus. We contribute to entrepreneurship curriculum research by adding a normative perspective.
Back to bureaucracy?
(2024)
In this contribution, the emergence of the neo-Weberian state (NWS) is analyzed with regard to German public administration. Drawing on the concept of a governance space, which consists of a hierarchy, markets, and networks, we distinguish between four empirical manifestations of the NWS, namely, the NWS as (1) come back of the public/ re-municipalization; (2) re-hierarchization; (3) de-agencification; (4) de-escalation in performance management. These movements can, on the one hand, be interpreted as a (partial) reversal of New Public Management (NPM) approaches and a “swinging back of the pendulum” (see Kuhlmann & Wollmann, 2019) toward public and classical Weberian principles (e.g., hierarchy, regulation, institutional re-aggregation). This reversal re-strengthened the hierarchy within the overall governance space to the detriment of, but without completely replacing, market mechanisms and networks. NPM’s failure to deliver what it promised and its inappropriateness as a response to more recent challenges connected to crises and wicked problems have engendered a partial return of the public and a move away from the economization logic of NPM. On the other hand, post-NPM reversals and managerial de-escalation gave rise to hybrid models that merge NPM and classic Weberian administration. While some well-functioning combinations of NPM and Weberianism exist, the hybridization of “old” and “neo” elements has also provoked ambivalent and negative assessments regarding the actual functioning of the NWS in Germany. Our analysis suggests that the NWS is only partially suitable as a model for reform and future administrative modernization, largely depending on the context surrounding reform and implementation practices.
This article analyses the institutional design variants of local crisis governance responses to the COVID-19 pandemic and their entanglement with other locally impactful crises from a cross-country comparative perspective (France, Germany, Poland, Sweden, and the UK/England). The pandemic offers an excellent empirical lens for scrutinizing the phenomenon of polycrises governance because it occurred while European countries were struggling with the impacts of several prior, ongoing, or newly arrived crises. Our major focus is on institutional design variants of crisis governance (dependent variable) and the influence of different administrative cultures on it (independent variable). Furthermore, we analyze the entanglement and interaction of institutional responses to other (previous or parallel) crises (polycrisis dynamics). Our findings reveal a huge variance of institutional designs, largely evoked by country-specific administrative cultures and profiles. The degree of de-/centralization and the intensity of coordination or decoupling across levels of government differs significantly by country. Simultaneously, all countries were affected by interrelated and entangled crises, resulting in various patterns of polycrisis dynamics. While policy failures and “fatal remedies” from previous crises have partially impaired the resilience and crisis preparedness of local governments, we have also found some learning effects from previous crises.
In Hellboy (2004, Sony Pictures), Guillermo del Toro presents a mythic hero (half human/half demon) seemingly made from the same mold as the classical hero Heracles (Hercules). Hellboy’s modern world is shaped by a cosmology not unlike that of Greek mythology, and as is true for Heracles, his unique pedigree and superior physicality empower him to mediate between the forces of supernaturality and humanity. Hellboy’s experiences evoke comparison with most characters and exploits in the Heraclean mythological corpus; his good character precludes comparison with others. Hellboy must contend with his own versions of Hera, Eurystheus, and a Nemean Lion/Hydra-like monster. He, too, relies on his own superhuman strength, innate cunning and an Athena-like protector to be successful at his job. Both heroes navigate a difficult path to their very different destinies. But in the end, Hellboy’s compassion, humility, unerring moral compass, and genuinely altruistic motivations make him both a better man and a better mythic hero, one worthy even of being loved.