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Individual contribution of PDE4B and PDE4D subfamilies to the prevention of object location memory impairments induced by sleep deprivation
No full textInsufficient sleep compromises the cAMP signaling pathway in the hippocampus, negatively impacting hippocampus-dependent memory. In the current study, we explored whether selective PDE4B or selective PDE4D inhibition can improve hippocampus-dependent spatial memory in the object location test (OLT) in mice after sleep deprivation (SD). The results demonstrated that SD impaired the OLT performance, and both A-33 and zatolmilast protected against the negative consequences of SD when administered at the start and middle of the SD period. These findings suggest that both PDE4B and PDE4D subfamilies contribute to the beneficial effect of PDE4 inhibition against SD-induced memory consolidation impairment.</p
Overcoming Challenges to the EU as a Global Actor
No full textThe European Union (EU) is at the centre of geopolitical tensions characterized by the war in Ukraine, wavering security support from the US, tensions in the Middle East and the IndoPacific, as well as climate, energy and trade concerns. This geopolitical landscape requires the EU to act more effectively, coherently and sustainably to finally become the global actor it aspires to be. This paper introduces a Special Issue that analyses some of the most pressing challenges the EU is facing, as well as pathways to overcome these hurdles and improve its external engagement. After introducing the concepts underlying the analysis, the paper presents the contributions to the Special Issue and suggests future research areas that may aid the EU in overcoming its challenges as a global actor
Synchronously modulating the universal diffusion of cations and anions by separator integration:A versatile approach toward safe and high-performance lithium-metal batteries
No full textDespite the great potential of lithium metal batteries (LMBs) for next-generation energy storage systems, the practical application still suffers from safety issues and capacity fading due to irregular ion diffusion from both anode and cathode. Herein, a sandwich separator consisting of PP substrate and two-side coated NH2-MIL-101 (NM) layers (NM-PP-NM) is designed to integrally modulate the interfacial diffusion of both anions and cations. Ordered micropores of NM endow separator with physical confinement toward cations (Li+, Fe2+, and Mn2+) and anions (polysulfide anions and electrolyte anions), contributing to regulated multi-ion diffusion. Moreover, chemisorptions between NM and ions (polysulfide, Fe2+, and Mn2+) validated by density functional theory simulations effectively alleviate the undesirable cathode crossover. Meanwhile, amino groups can participate in the formation of solid electrolyte interface and improve interfacial stability. Due to the modulated Li+ flux and uniform Li plating/stripping, a desirable lifespan of ∼2600 h with ultralow overpotential for a Li-Li symmetrical cell is achieved by equipping the NM-PP-NM separator. Benefit from the regulated diffusion of both anions and cations, NM-PP-NM exhibits excellent versatility in various LMBs, including lithium-sulfur, Li-LiFePO4, and Li-LiNi0.8Mn0.1Co0.1O2 (NMC811) battery systems. Both the safety and electrochemical performances of the above LMBs are greatly enhanced, emphasizing the versatility and potential of the developed multifunctional integration strategy for separator modification.</p
Preparing to Hit the Ground Running:Adding RISC-V Support to EESSI
No full textRISC-V-based high-performance processors and accelerators gain more interest for running scientific workloads. While RISC-V is already supported in Linux distributions such as Debian Sid and Ubuntu, a comprehensive stack of performance-optimized software installations is missing. For x86_64 and aarch64, EESSI already streams such software installations to any machine worldwide. Hence, we were also interested in whether one could provide such software stacks for RISC-V-based systems. The benefit would not only be that a stack with software installations optimized for RISC-V becomes easily accessible, but it would also integrate a development environment with toolchains and dependencies. This would help port more software to RISC-V, thereby increasing the platform’s viability for running scientific workloads. In this paper, we describe our work on supporting the RISC-V ISA in EESSI - what issues we encountered and how we solved them. We explain our progress on implementing the core components of EESSI - CernVM-FS and Gentoo Prefix - and discuss lessons learned that could provide valuable insights for software developers porting codes to RISC-V. In summary, our experience is that researchers will soon use RISC-V...</p
In vitro and in vivo lipopolysaccharide-driven activation of human neutrophils in healthy volunteers as a tool for clinical drug development
No full textNeutrophils are an emerging target for therapeutical intervention in both autoimmune diseases as well as cancer. Since healthy humans lack constitutive neutrophil activation, induction of neutrophil activation is necessary to evaluate investigational compounds and can be achieved via intravenous administration of lipopolysaccharides (LPS). Furthermore, LPS stimulation can be performed ex vivo during clinical trials, and in vitro for pre-clinical analysis. Therefore, we aimed to provide a time course of neutrophil responses after in vivo LPS administration using samples from human endotoxemia trials and compared this to in vitro LPS stimulated whole blood cultures. We performed shotgun proteomics on in vivo stimulated neutrophils, and measured neutrophil activation by flow cytometry using CD11b and CD62L as activation markers and elastase, MPO, LL37 and nucleosome levels as degranulation and NETosis markers. Neutrophil numbers rapidly increased after LPS administration. In line, we found significant increases in neutrophil activation and degranulation markers both in vitro as well as in vivo, which all returned to baseline within 24 h. Degranulation proteins and NETosis related nucleosomes rapidly increased after LPS administration (1 h after exposure) in vivo, while higher concentrations of LPS were necessary in vitro. Lastly, shotgun proteomics revealed little but significant differences in the neutrophil proteome after in vivo LPS administration, pointing to degranulation after LPS stimulation. Both, the in vitro whole blood LPS stimulation assay and the human endotoxemia model, could be valuable tools for evaluation of the effects of future drugs modulating neutrophil responses during preclinical and clinical development.</p
Creativity and technology in translation
No full textCreativity is often considered the decisive factor that distinguishes professional translations from machine-generated content. However, creativity is quite an elusive concept that is difficult to identify, measure, and compare. Although translators have employed their creativity for centuries, there is limited data that describes creativity in translation, including the creative person, the process, the product, and the environment. This lack of data becomes even more pronounced when technology is integrated into the translation workflow. This chapter seeks to address this gap. It provides an overview of creativity concepts in both the social sciences and translation studies and analyses existing research on creativity, technology, and translation. In doing so, it focuses on experiments that explore creativity, including cases where it is mediated by technology. Based on the available data, the chapter discusses the constraints that technology may impose on creativity and offers suggestions on how technology and creativity could be better understood or studied from a human-centred perspective
The Emerging Green Energy Corridor in the Caspian Region
No full textSince the start of the full-scale war in Ukraine in 2022, the European Union has been seeking alternative sources for critical raw materials and renewable energy resources. Through its External Energy Engagement Strategy and REPowerEU initiatives, the EU is working to decrease its reliance on Russian fossil fuels, form sustainable energy partnerships, and foster a worldwide transition to green energy. Among the regions that can meet these needs is the Caspian Sea, which boasts strong potential for renewable energy and has played a major role in supplying oil and gas to the EU, particularly through Azerbaijan and Kazakhstan. Countries in the South Caucasus and Central Asia have been investing in renewable energy sources and exploring avenues to export green energy to Europe. Several memoranda of understanding (MOUs) have been signed between European and regional countries, as well as among the Caspian countries themselves. Noteworthy projects include the Black Sea Electricity Cable Project, the Green Hydrogen Project, and the Caspian Electricity Cable Project. Azerbaijan hosted the 29th Conference of the Parties (COP29), the annual United Nations climate change meeting, in Baku in November 2024. During that summit, Azerbaijan, Kazakhstan, and Uzbekistan reached an agreement to develop the Caspian Green Energy Corridor, a project that aims to export renewable electricity to Europe through high-voltage cables laid beneath the Caspian and Black Seas. But all these ambitions must contend with the region’s serious environmental challenges.</p
