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Institute
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- Department Sport- und Gesundheitswissenschaften (13)
Der Band stellt ein Modell für einen differenzierenden Literaturunterricht vor, der individuelle Förderung für unterschiedliche Bereiche von Heterogenität ermöglicht.
Eine ergiebige Differenzierung nutzt die Aspekte Ziele, Themen und Methoden des Unterrichts sowie Lenkung und Aufgabenformat. Diese Aspekte werden mit Blick auf die einzelnen Phasen des Unterrichts präzisiert. Dabei werden Leistungsunterschiede, sprachliche, kulturelle und soziale sowie individuelle Voraussetzungen der einzelnen Schüler:innen deutlicher adressiert.
Einzelne exemplarische Aufgabensets mit ausführlicher Erläuterung dienen der Veranschaulichung des Modells. Zudem werden Unterrichtseinheiten vorgestellt, die systematisch Möglichkeiten der Differenzierung nutzen.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
The “HPI Future SOC Lab” is a cooperation of the Hasso Plattner Institute (HPI) and industry partners. Its mission is to enable and promote exchange and interaction between the research community and the industry partners.
The HPI Future SOC Lab provides researchers with free of charge access to a complete infrastructure of state of the art hard and software. This infrastructure includes components, which might be too expensive for an ordinary research environment, such as servers with up to 64 cores and 2 TB main memory. The offerings address researchers particularly from but not limited to the areas of computer science and business information systems. Main areas of research include cloud computing, parallelization, and In-Memory technologies.
This technical report presents results of research projects executed in 2019. Selected projects have presented their results on April 9th and November 12th 2019 at the Future SOC Lab Day events.
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.
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.
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.
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.
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.
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.