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    2819 research outputs found

    Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling

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    Abstract Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs). Targeting of Bmpr2 reduced sprouting angiogenesis in zebrafish and BMPR2-deficient human ECs formed fewer filopodia, affecting cell migration and actomyosin localization. Spheroid assays revealed a reduced sprouting of BMPR2-deficient ECs in fibrin gels. Even more strikingly, in mosaic spheroids, BMPR2-deficient ECs failed to acquire tip-cell positions. Yet, 3D traction force microscopy revealed that these distinct cell behaviors of BMPR2-deficient tip cells cannot be explained by differences in force-induced matrix deformations, even though these cells adopted distinct cone-shaped morphologies. Notably, BMPR2 positively regulates local CDC42 activity at the plasma membrane to promote filopodia formation. Our findings reveal that BMPR2 functions as a nexus integrating biochemical and biomechanical processes crucial for TCs during angiogenesis

    Complex compositional and metabolic response of river sediment microbiomes to multiple anthropogenic stressors

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    Rivers face constant anthropogenic stress, resulting in significant changes in microbial community composition. What remains unclear is whether stream microbiomes exhibit distinct resilience patterns in composition and/or activity upon exposure to different stressors. By subjecting 64 river-connected mesocosms to multiple stressors, we show that sediment microbiomes of small lowland rivers are highly sensitive to low flow velocity. This stress results in altered community compositions incapable of mitigating the applied stressor within a two-week timeframe despite functional stability (inferred via metagenomics). Transcriptomics revealed a systematic heat shock response in the community and a highly active, metabolically versatile, uncharacterized anaerobic keystone species. Increases in temperature (+ 3.5°C) or salinity (+ 0.5 mS/cm) elicited minor responses at community and transcriptomic levels (e.g., upregulation of photosystems). Following a two-week recovery, transcriptomic-inferred stress responses vanished completely, underscoring the river microbiome resilience. Given the complex community responses observed at the activity and compositional levels, we conclude that maintaining natural river flow is vital to preventing energy loss and reduced microbiome activity in river sediments

    Assessing the Use of Mixed Reality as a Valid Tool for Human-Robot Interaction Studies in the Context of Space Exploration

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    Mixed Reality (MR) is a technology with strong potential for advancing research in Human-Robot Interaction (HRI) for space exploration. Apart from the efficiency and high flexibility MR can offer, we argue that its benefits for HRI research in space contexts lies particularly in its ability to aid human-in-the-loop development, offer realistic hybrid simulations, and foster broader participation in HRI research in the space exploration context. However, we believe that this is only plausible if MR-based simulations can yield comparable results to fully physical approaches in human-centred studies. In this position paper, we highlight several arguments in favour of MR as a tool for space HRI research, while emphasising the importance of the open question regarding its scientific validity. We believe MR could become a central tool for preparing for future human-robotic space exploration missions and significantly diversify research in this domain

    MARCUS: Molecular Annotation and Recognition for Curating Unravelled Structures

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    The exponential growth of chemical literature necessitates the development of automated tools for extracting and curating molecular information from unstructured scientific publications into open-access chemical databases. Current optical chemical structure recognition (OCSR) and named entity recognition solutions operate in isolation, which limits their scalability for comprehensive literature curation. Here we present MARCUS (Molecular Annotation and Recognition for Curating Unravelled Structures), a tool to aid curators in performing literature curation in the field of natural products. This integrated web-based platform combines automated text annotation, multi-engine OCSR, and direct submission capabilities to the COCONUT database. MARCUS employs a fine-tuned GPT-4 model to extract chemical entities and utilises an ensemble approach integrating DECIMER, MolNexTR, and MolScribe for structure recognition. The platform aims to streamline the data extraction workflow from PDF upload to database submission, significantly reducing curation time. MARCUS bridges the gap between unstructured chemical literature and machine-actionable databases, enabling FAIR data principles and facilitating AI-driven chemical discovery. Through open-source code, accessible models, and comprehensive documentation, the web application enhances accessibility and promotes community-driven development. This approach facilitates unrestricted use and encourages the collaborative advancement of automated chemical literature curation tools. We dedicate MARCUS to Dr Marcus Ennis, the longest-serving curator of the ChEBI database, on the occasion of his 75th birthday

    Electrodeposition of Mo-Rich NiMo Catalysts: Effect of Deposition Parameters and Oxygen Content on the Alkaline Hydrogen Evolution Reaction Activity

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    Electrodeposited Mo-rich NiMo catalysts offer enhanced catalytic activity for the alkaline hydrogen evolution reaction (HER) and provide an electrically conductive, binder-free substrate connection, making them promising catalysts for green hydrogen production. However, creating Mo-rich deposits is challenging, as the codeposition process typically favors Ni. Optimal deposition conditions for Mo-rich NiMo catalysts remain insufficiently explored. This article investigates Mo-rich NiMo electrodeposition from an ammonia-free citrate bath using NaSO4 as a chlorine-free support electrolyte. The effects of the deposition parameters, 1) sodium molybdate concentration in the electrolyte, 2) deposition current density, and 3) enhanced mass transport via working electrode rotation on the alkaline HER activity, were studied. The electrodeposits, containing 44–66 wt% Mo, exhibited increased surface area due to a rough, cracked morphology and variable oxygen content of the catalyst. The oxygen content was linked to HER activity, revealing an inhibiting effect. The lowest overpotential of 118 mV at −10  mA cm−2 for the alkaline HER was achieved using an electrolyte with 0.02 mol L−1 sodium molybdate, a deposition current density of 600 mA cm−2, without electrode rotation. Respective samples combined a favorable Ni:Mo ratio comprising 56 wt% Mo content with increased surface area and low oxygen content

    Benchmarking Hyper-Breakpoints for Efficient Virtual Machine Introspection

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    Virtual Machine Introspection (VMI) is a powerful technology used to detect and analyze malicious software inside Virtual Machines (VMs) from outside. Asynchronously accessing the VM ’s memory can be insufficient for efficiently monitoring what is happening inside of a VM. Active VMI introduces breakpoints to intercept VM execution at relevant points. Especially for frequently visited breakpoints, and even more so for production systems, it is crucial to keep their performance overhead as low as possible. In this paper, we provide a systematization of existing VMI breakpoint implementation variants, propose workloads to quantify the different performance penalties of breakpoints, and implement them in the benchmarking application bpbench. We used this benchmark to measure that, on an Intel Core i5 7300U, SmartVMI’s breakpoints take around 81 μs to handle, and keeping the breakpoint invisible costs an additional 21 μs per read access. The availability of bpbench facilitates the comparison of disparate breakpoint mechanisms and their performance optimization with immediate feedback

    Transformation: acceptance factors for electrifying corporate fleets in service companies—an extension of the UTAUT and an empirical study with decision-makers

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    From 2035 onwards, the European Union will no longer register any new vehicles that are not powered in a climate-neutral way. In alignment with this policy, Germany aims to perceived carbon neutrality by 2045, with the electrification of transport playing a central role. Corporate fleets are particularly well-suited for electrification due to their relatively short ownership cycles and frequent vehicle renewals. However, the pace of adoption in organizations remains slow. The success of such technological transitions depends largely on acceptance at the decision-making level. This study investigates the determinants of organizational decision-makers’ behavioral intention to electrify their corporate fleets prior to implementation. To this end, the newly developed Acceptance Model for Electrification (eAM) integrates the two-stage innovation decision-making process within companies. The model accounts for 60% of the variance in behavioral intention. Drawing on the findings, this paper proposes practical recommendations for policy development

    Interpolyelectrolyte complexes of in vivo produced dsRNA with chitosan and alginate for enhanced plant protection against tobacco mosaic virus

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    We developed a formulation of long double-stranded RNA (dsRNA) using interpolyelectrolyte complexes (IPECs) composed of the biopolymers chitosan and alginate, in order to protect the dsRNA from biotic and abiotic factors. Our primary objectives were to enhance stability of dsRNA against environmental nucleases and, secondarily, to mitigate the negative charge of the dsRNA, which may promote foliar uptake. Our approach relies on submicron particles with adjustable surface charge being either positive or negative. Following this approach, we obtained a high encapsulation efficiency of 94 %. Subsequently, we investigated the influence of the charge ratio and total polymer content on the size, size distribution and ζ-potential of the IPECs. We discovered that formulating at low polymer concentrations ≤0.05 g/L with charge ratios of ≤0.9 (+/ ) and ≥ 1.25 (+/ ), respectively, produced <100 nm particles. Furthermore, the IPEC formulation protected dsRNA from enzymatic degradation by RNase III and micrococcal nuclease. In addition, we observed outstanding protection of formulated dsRNA from heat degradation. Experiments on Nicotiana benthamiana plants showed that formulated dsRNA offered protection against tobacco mosaic virus. In essence, this formulation demonstrates versatility for the production of IPECs with customizable size, surface charge, and nucleic acid content

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