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Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
Digital terrain models (DTMs) are a fundamental source of information in Earth sciences. DTM-based studies, however, can contain remarkable biases if limitations and inaccuracies in these models are disregarded. In this work, four freely available datasets, including Shuttle Radar Topography Mission C-Band Synthetic Aperture Radar (SRTM C-SAR V3 DEM), Advanced Spaceborne Thermal Emission and Reflection Radiometer Global Digital Elevation Map (ASTER GDEM V2), and two nationwide airborne light detection and ranging (LiDAR)-derived DTMs (at 5-m and 1-m spatial resolution, respectively) were analysed in three geomorphologically contrasting, small (3–5 km2) catchments located in Mediterranean landscapes under intensive human influence (Mallorca Island, Spain). Vertical accuracy as well as the influence of each dataset’s characteristics on hydrological and geomorphological modelling applicability were assessed by using ground-truth data, classic geometric and morphometric parameters, and a recently proposed index of sediment connectivity. Overall vertical accuracy—expressed as the root mean squared error (RMSE) and normalised median deviation (NMAD)—revealed the highest accuracy for the 1-m (RMSE = 1.55 m; NMAD = 0.44 m) and 5-m LiDAR DTMs (RMSE = 1.73 m; NMAD = 0.84 m). Vertical accuracy of the SRTM data was lower (RMSE = 6.98 m; NMAD = 5.27 m), but considerably higher than for the ASTER data (RMSE = 16.10 m; NMAD = 11.23 m). All datasets were affected by systematic distortions. Propagation of these errors and coarse horizontal resolution caused negative impacts on flow routing, stream network, and catchment delineation, and to a lower extent, on the distribution of slope values. These limitations should be carefully considered when applying DTMs for catchment hydrogeomorphological modelling.
This study examines the access to healthcare for children and adolescents with three common chronic diseases (type-1 diabetes (T1D), obesity, or juvenile idiopathic arthritis (JIA)) within the 4th (Delta), 5th (Omicron), and beginning of the 6th (Omicron) wave (June 2021 until July 2022) of the COVID-19 pandemic in Germany in a cross-sectional study using three national patient registries. A paper-and-pencil questionnaire was given to parents of pediatric patients (<21 years) during the routine check-ups. The questionnaire contains self-constructed items assessing the frequency of healthcare appointments and cancellations, remote healthcare, and satisfaction with healthcare. In total, 905 parents participated in the T1D-sample, 175 in the obesity-sample, and 786 in the JIA-sample. In general, satisfaction with healthcare (scale: 0–10; 10 reflecting the highest satisfaction) was quite high (median values: T1D 10, JIA 10, obesity 8.5). The proportion of children and adolescents with canceled appointments was relatively small (T1D 14.1%, JIA 11.1%, obesity 20%), with a median of 1 missed appointment, respectively. Only a few parents (T1D 8.6%; obesity 13.1%; JIA 5%) reported obstacles regarding health services during the pandemic. To conclude, it seems that access to healthcare was largely preserved for children and adolescents with chronic health conditions during the COVID-19 pandemic in Germany.
Classroom noise impairs students' cognition and learning. At a first glance, it seems useful to prevent the negative effects of noise on academic learning by wearing noise-cancelling (NC) headphones during class. The literature and guidelines emphasize the academic benefits of wearing NC headphones (decreased auditory distraction, increased concentration, learning improvement, and decreased distress). These benefits are particularly expected for students with special needs. None of the recommendations to wear NC headphones during class refer to any empirical studies, indicating a potential research gap and lack of evidence. Therefore, the question arises: Is there any empirical evidence supporting academic benefits of wearing NC headphones during class for typically developing students or students with special needs? A total of 13 empirical studies (quantitative and qualitative) were identified through a systematic scoping review of the existing literature. A wide range of outcomes (cognition, learning, academic performance, behaviour, and emotions) were reported related to the use of NC headphones. Most of the studies refer to specific groups of students with special needs (learning disabilities, autism, ADHD, etc.). In view of the limited number of studies, small sample sizes, and lack of replication studies, all studies give the impression of being pilot studies on the academic benefits of wearing NC headphones. The practice of wearing NC headphones during class is an understudied topic. The current body of evidence does not meet the standards for evidence-based practices in both general and special education. Implications for educational practice and future research are discussed.
We study the diffusive motion of a particle in a subharmonic potential of the form U(x) = |x|( c ) (0 < c < 2) driven by long-range correlated, stationary fractional Gaussian noise xi ( alpha )(t) with 0 < alpha <= 2. In the absence of the potential the particle exhibits free fractional Brownian motion with anomalous diffusion exponent alpha. While for an harmonic external potential the dynamics converges to a Gaussian stationary state, from extensive numerical analysis we here demonstrate that stationary states for shallower than harmonic potentials exist only as long as the relation c > 2(1 - 1/alpha) holds. We analyse the motion in terms of the mean squared displacement and (when it exists) the stationary probability density function. Moreover we discuss analogies of non-stationarity of Levy flights in shallow external potentials.
Der vorliegende Abschlussbericht umfasst die Ergebnisse der wissenschaftlichen Evaluation der Werkstatt „Schule leiten“. Bei dieser Werkstatt handelt es sich um ein 18-monatiges Fortbildungsangebot für Schulleitungen, das durch die Deutsche Schulakademie konzipiert und in Kooperation mit dem saarländischen Kultusministerium für Bildung und Kultur sowie dem saarländischen Landesinstitut für Pädagogik und Medien durchgeführt wurde. Im Zeitraum 2016–2020 absolvierten jeweils zwei Personen des Schulleitungsteams allgemeinbildender Schulen erstmalig in insgesamt drei Durchgängen verschiedene Angebote der Werkstatt. Weiterhin erhielten die Teilnehmenden die Aufgaben, im Zuge ihres Fortbildungsbesuches ein individuelles Schulentwicklungsprojekt zu planen, zu entwickeln und unter Anleitung der Werkstatt in der Schule zu implementieren. Zur Überprüfung der wahrgenommenen Qualität sowie der Wirksamkeit des Fortbildungsangebotes wurde die Universität Potsdam, Arbeitsbereich Prof. Dr. Dirk Richter, beauftragt. Der vorliegende Bericht präsentiert die Evaluationsergebnisse der Durchgänge 2 und 3.
Im Zentrum der Evaluation stehen die folgenden Forschungsfragen: (1) Wie beurteilen die Teilnehmenden die Qualität der Werkstatt „Schule leiten“? (2) Inwiefern hat die Werkstatt „Schule leiten“ dazu beigetragen, die Leitungskompetenzen (u.a. Einstellungen und Führungshandeln) der Teilnehmenden zu stärken? sowie (3) Wie haben sich schulische Strukturen und Prozesse zur Förderung von Schulentwicklung in den teilnehmenden Schulen durch die Werkstatt „Schule leiten“ verändert? Zur Beantwortung der Fragestellungen wurden eine Reihe schriftlicher Befragungen mit den teilnehmenden Schulleitungen sowie den Lehrkräften der teilnehmenden Schulen durchgeführt. Diese Befragungen erfolgten sowohl begleitend zum Fortbildungsprogramm (nach Absolvieren der einzelnen Angebote) sowie in einem Prä-Post-Follow-Up-Design. Weiterhin wurden im Rahmen einer qualitativen Begleitstudie verschiedene Personen (Schulleitung, Mitglieder des Schulleitungsteams, Lehrkräfte) von insgesamt fünf Schulen über drei Zeitpunkte dazu befragt, wie die Planung, Entwicklung und Implementation der Schulentwicklungsprojekte erfolgten.
Die Befunde der Evaluation deuten insgesamt darauf hin, dass die Qualität der Werkstatt „Schule leiten“ als Gesamtprogramm sowie die einzelnen Angebote der Werkstatt sehr positiv bewertet werden. Dabei nehmen die Teilnehmenden von Durchgang 2 die Werkstatt in einer Reihe von Merkmalen positiver wahr als die Teilnehmenden von Durchgang 3. Weiterhin deuten die Ergebnisse darauf hin, dass sich bestimmte Facetten des Führungshandelns der Teilnehmenden im zeitlichen Verlauf positiv verändert haben. Hierfür existieren Hinweise sowohl aus Perspektive der Teilnehmenden selbst als auch aus Perspektive der Lehrkräfte ihrer Schulen. Motivationale Merkmale der Teilnehmenden sowie Aspekte des Führungshandelns, die sich auf Tätigkeiten zur Unterstützung der innerschulischen Kooperation beziehen, bleiben aus Perspektive der Teilnehmenden hingegen weitestgehend konstant. Hinsichtlich der Veränderungen schulischer Strukturen zur Schulentwicklung deuten die Ergebnisse auf eine positive Entwicklung der wahrgenommenen Offenheit gegenüber Kooperation im Kollegium aus Perspektive der Lehrkräfte hin. Die Befunde der qualitativen Begleitstudie liefern weitere Informationen über die wahrgenommene Qualität der Werkstatt sowie über Veränderungen aufseiten der Teilnehmenden und der schulischen Strukturen.
Identifying abrupt transitions is a key question in various disciplines. Existing transition detection methods, however, do not rigorously account for time series uncertainties, often neglecting them altogether or assuming them to be independent and qualitatively similar. Here, we introduce a novel approach suited to handle uncertainties by representing the time series as a time-ordered sequence of probability density functions. We show how to detect abrupt transitions in such a sequence using the community structure of networks representing probabilities of recurrence. Using our approach, we detect transitions in global stock indices related to well-known periods of politico-economic volatility. We further uncover transitions in the El Niño-Southern Oscillation which coincide with periods of phase locking with the Pacific Decadal Oscillation. Finally, we provide for the first time an ‘uncertainty-aware’ framework which validates the hypothesis that ice-rafting events in the North Atlantic during the Holocene were synchronous with a weakened Asian summer monsoon.
In this paper, we propose a consistent mechanism of protein microcapsule formation upon ultrasound treatment. Aqueous suspensions of bovine serum albumin (BSA) microcapsules filled with toluene are prepared by use of high-intensity ultrasound following a reported method. Stabilization of the oil-in-water emulsion by the adsorption of the protein molecules at the interface of the emulsion droplets is accompanied by the creation of the cross-linked capsule shell due to formation of intermolecular disulfide bonds caused by highly reactive species like superoxide radicals generated sonochemically. The evidence for this mechanism, which until now remained elusive and was not proven properly, is presented based on experimental data from SDS-PAGE, Raman spectroscopy and dynamic light scattering.
Continental rift systems form by propagation of isolated rift segments that interact, and eventually evolve into continuous zones of deformation. This process impacts many aspects of rifting including rift morphology at breakup, and eventual ocean-ridge segmentation. Yet, rift segment growth and interaction remain enigmatic. Here we present geological data from the poorly documented Ririba rift (South Ethiopia) that reveals how two major sectors of the East African rift, the Kenyan and Ethiopian rifts, interact. We show that the Ririba rift formed from the southward propagation of the Ethiopian rift during the Pliocene but this propagation was short-lived and aborted close to the Pliocene-Pleistocene boundary. Seismicity data support the abandonment of laterally offset, overlapping tips of the Ethiopian and Kenyan rifts. Integration with new numerical models indicates that rift abandonment resulted from progressive focusing of the tectonic and magmatic activity into an oblique, throughgoing rift zone of near pure extension directly connecting the rift sectors.
Abgelegte Musik
(2023)
ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans
(2020)
Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence.
Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication.
Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low.
Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
The crises of both the climate and the biosphere are manifestations of the imbalance between human extractive, and polluting activities and the Earth’s regenerative capacity. Planetary boundaries define limits for biophysical systems and processes that regulate the stability and life support capacity of the Earth system, and thereby also define a safe operating space for humanity on Earth. Budgets associated to planetary boundaries can be understood as global commons: common pool resources that can be utilized within finite limits. Despite the analytical interpretation of planetary boundaries as global commons, the planetary boundaries framework is missing a thorough integration into economic theory. We aim to bridge the gap between welfare economic theory and planetary boundaries as derived in the natural sciences by presenting a unified theory of cost-benefit and cost-effectiveness analysis. Our pragmatic approach aims to overcome shortcomings of the practical applications of CEA and CBA to environmental problems of a planetary scale. To do so, we develop a model framework and explore decision paradigms that give guidance to setting limits on human activities. This conceptual framework is then applied to planetary boundaries. We conclude by using the realized insights to derive a research agenda that builds on the understanding of planetary boundaries as global commons.
We present a new algorithm for solving the common problem of flow trapped in closed depressions within digital elevation models, as encountered in many applications relying on flow routing. Unlike other approaches (e.g., the Priority-Flood depression filling algorithm), this solution is based on the explicit computation of the flow paths both within and across the depressions through the construction of a graph connecting together all adjacent drainage basins. Although this represents many operations, a linear time complexity can be reached for the whole computation, making it very efficient. Compared to the most optimized solutions proposed so far, we show that this algorithm of flow path enforcement yields the best performance when used in landscape evolution models. In addition to its efficiency, our proposed method also has the advantage of letting the user choose among different strategies of flow path enforcement within the depressions (i.e., filling vs. carving). Furthermore, the computed graph of basins is a generic structure that has the potential to be reused for solving other problems as well, such as the simulation of erosion. This sequential algorithm may be helpful for those who need to, e.g., process digital elevation models of moderate size on single computers or run batches of simulations as part of an inference study.
In this paper, we define a variant of Roe algebras for spaces with cylindrical ends and use this to study questions regarding existence and classification of metrics of positive scalar curvature on such manifolds which are collared on the cylindrical end.
We discuss how our constructions are related to relative higher index theory as developed by Chang, Weinberger, and Yu and use this relationship to define higher rho-invariants for positive scalar curvature metrics on manifolds with boundary.
This paves the way for the classification of these metrics.
Finally, we use the machinery developed here to give a concise proof of a result of Schick and the author, which relates the relative higher index with indices defined in the presence of positive scalar curvature on the boundary.
We present a prototype of an integrated reasoning environment for educational purposes. The presented tool is a fragment of a proof assistant and automated theorem prover. We describe the existing and planned functionality of the theorem prover and especially the functionality of the educational fragment. This currently supports working with terms of the untyped lambda calculus and addresses both undergraduate students and researchers. We show how the tool can be used to support the students' understanding of functional programming and discuss general problems related to the process of building theorem proving software that aims at supporting both research and education.
This research paper aims to introduce a novel practitioner-oriented and research-based taxonomy of video genres. This taxonomy can serve as a scaffolding strategy to support educators throughout the entire educational system in creating videos for pedagogical purposes. A taxonomy of video genres is essential as videos are highly valued resources among learners. Although the use of videos in education has been extensively researched and well-documented in systematic research reviews, gaps remain in the literature. Predominantly, researchers employ sophisticated quantitative methods and similar approaches to measure the performance of videos. This trend has led to the emergence of a strong learning analytics research tradition with its embedded literature. This body of research includes analysis of performance of videos in online courses such as Massive Open Online Courses (MOOCs). Surprisingly, this same literature is limited in terms of research outlining approaches to designing and creating educational videos, which applies to both video-based learning and online courses. This issue results in a knowledge gap, highlighting the need for developing pedagogical tools and strategies for video making. These can be found in frameworks, guidelines, and taxonomies, which can serve as scaffolding strategies. In contrast, there appears to be very few frameworks available for designing and creating videos for pedagogica purposes, apart from a few well-known frameworks. In this regard, this research paper proposes a novel taxonomy of video genres that educators can utilize when creating videos intended for use in either video-based learning environments or online courses. To create this taxonomy, a large number of videos from online courses were collected and analyzed using a mixed-method research design approach.
A treemap is a visualization that has been specifically designed to facilitate the exploration of tree-structured data and, more general, hierarchically structured data. The family of visualization techniques that use a visual metaphor for parent-child relationships based “on the property of containment” (Johnson, 1993) is commonly referred to as treemaps. However, as the number of variations of treemaps grows, it becomes increasingly important to distinguish clearly between techniques and their specific characteristics. This paper proposes to discern between Space-filling Treemap TS, Containment Treemap TC, Implicit Edge Representation Tree TIE, and Mapped Tree TMT for classification of hierarchy visualization techniques and highlights their respective properties. This taxonomy is created as a hyponymy, i.e., its classes have an is-a relationship to one another: TS TC TIE TMT. With this proposal, we intend to stimulate a discussion on a more unambiguous classification of treemaps and, furthermore, broaden what is understood by the concept of treemap itself.
Pollen records from Siberia are mostly absent in global or Northern Hemisphere synthesis works. Here we present a taxonomically harmonized and temporally standardized pollen dataset that was synthesized using 173 palynological records from Siberia and adjacent areas (northeastern Asia, 42-75 degrees N, 50-180 degrees E). Pollen data were taxonomically harmonized, i.e. the original 437 taxa were assigned to 106 combined pollen taxa. Age-depth models for all records were revised by applying a constant Bayesian age-depth modelling routine. The pollen dataset is available as count data and percentage data in a table format (taxa vs. samples), with age information for each sample. The dataset has relatively few sites covering the last glacial period between 40 and 11.5 ka (calibrated thousands of years before 1950 CE) particularly from the central and western part of the study area. In the Holocene period, the dataset has many sites from most of the area, with the exception of the central part of Siberia. Of the 173 pollen records, 81 % of pollen counts were downloaded from open databases (GPD, EPD, PANGAEA) and 10 % were contributions by the original data gatherers, while a few were digitized from publications. Most of the pollen records originate from peatlands (48 %) and lake sediments (33 %). Most of the records (83 %) have >= 3 dates, allowing the establishment of reliable chronologies. The dataset can be used for various purposes, including pollen data mapping (example maps for Larix at selected time slices are shown) as well as quantitative climate and vegetation reconstructions. The datasets for pollen counts and pollen percentages are available at https://doi.org/10.1594/PANGAEA.898616 (Cao et al., 2019a), also including the site information, data source, original publication, dating data, and the plant functional type for each pollen taxa.
A tale of shifting relations
(2021)
Understanding the dynamics between the East Asian summer (EASM) and winter monsoon (EAWM) is needed to predict their variability under future global warming scenarios. Here, we investigate the relationship between EASM and EAWM as well as the mechanisms driving their variability during the last 10,000 years by stacking marine and terrestrial (non-speleothem) proxy records from the East Asian realm. This provides a regional and proxy independent signal for both monsoonal systems. The respective signal was subsequently analysed using a linear regression model. We find that the phase relationship between EASM and EAWM is not time-constant and significantly depends on orbital configuration changes. In addition, changes in the Atlantic Meridional Overturning circulation, Arctic sea-ice coverage, El Niño-Southern Oscillation and Sun Spot numbers contributed to millennial scale changes in the EASM and EAWM during the Holocene. We also argue that the bulk signal of monsoonal activity captured by the stacked non-speleothem proxy records supports the previously argued bias of speleothem climatic archives to moisture source changes and/or seasonality.
Sustainable development goals (SDGs) have set the 2030 agenda to transform our world by tackling multiple challenges humankind is facing to ensure well-being, economic prosperity, and environmental protection. In contrast to conventional development agendas focusing on a restricted set of dimensions, the SDGs provide a holistic and multidimensional view on development. Hence, interactions among the SDGs may cause diverging results. To analyze the SDG interactions we systematize the identification of synergies and trade-offs using official SDG indicator data for 227 countries. A significant positive correlation between a pair of SDG indicators is classified as a synergy while a significant negative correlation is classified as a trade-off. We rank synergies and trade-offs between SDGs pairs on global and country scales in order to identify the most frequent SDG interactions. For a given SDG, positive correlations between indicator pairs were found to outweigh the negative ones in most countries. Among SDGs the positive and negative correlations between indicator pairs allowed for the identification of particular global patterns. SDG 1 (No poverty) has synergetic relationship with most of the other goals, whereas SDG 12 (Responsible consumption and production) is the goal most commonly associated with trade-offs. The attainment of the SDG agenda will greatly depend on whether the identified synergies among the goals can be leveraged. In addition, the highlighted trade-offs, which constitute obstacles in achieving the SDGs, need to be negotiated and made structurally nonobstructive by deeper changes in the current strategies.