Double-Stranded RNA-Dependent Protein Kinase (PKR) Is Regulated by Reovirus Structural Proteins

AbstractReovirus σ3 is a virion outer shell protein that also binds dsRNA and stimulates translation by blocking activation of the dsRNA-dependent protein kinase, PKR. Purified σ3 was shown by gel shift assay to bind specifically to RNA duplexes of minimal length 32–45 base pairs. PKR binding to dsRNA was prevented by σ3, and translation inhibition of luciferase reporter by PKR expression in transfected cells was reversed by σ3. Association of σ3 with its outer capsid partner μ1/μ1C eliminated dsRNA binding and prevented restoration of protein synthesis. Analyses of σ3 mutants demonstrated a direct correlation between dsRNA binding and reversal of the down-regulation of translation by PKR. In infected cells, σ3 was stable but dsRNA binding decreased, presumably due to μ1/μ1C complex formation. The results suggest a functional transition from early inhibition of PKR activation by σ3 to its association with μ1/μ1C in capsid structures

Noise-Aware and Equitable Urban Air Traffic Management: An Optimization Approach

Urban air mobility (UAM), a transformative concept for the transport of passengers and cargo, faces several integration challenges in complex urban environments. Community acceptance of aircraft noise is among the most noticeable of these challenges when launching or scaling up a UAM system. Properly managing community noise is fundamental to establishing a UAM system that is environmentally and socially sustainable. In this work, we develop a holistic and equitable approach to manage UAM air traffic and its community noise impact in urban environments. The proposed approach is a hybrid approach that considers a mix of different noise mitigation strategies, including limiting the number of operations, cruising at higher altitudes, and ambient noise masking. We tackle the problem through the lens of network system control and formulate a multi-objective optimization model for managing traffic flow in a multi-layer UAM network while concurrently pursuing demand fulfillment, noise control, and energy saving. Further, we use a social welfare function in the optimization model as the basis for the efficiency-fairness trade-off in both demand fulfillment and noise control. We apply the proposed approach to a comprehensive case study in the city of Austin and perform design trade-offs through both visual and quantitative analyses.Comment: 30 pages, 15 figure

HDR Video Reconstruction with a Large Dynamic Dataset in Raw and sRGB Domains

High dynamic range (HDR) video reconstruction is attracting more and more attention due to the superior visual quality compared with those of low dynamic range (LDR) videos. The availability of LDR-HDR training pairs is essential for the HDR reconstruction quality. However, there are still no real LDR-HDR pairs for dynamic scenes due to the difficulty in capturing LDR-HDR frames simultaneously. In this work, we propose to utilize a staggered sensor to capture two alternate exposure images simultaneously, which are then fused into an HDR frame in both raw and sRGB domains. In this way, we build a large scale LDR-HDR video dataset with 85 scenes and each scene contains 60 frames. Based on this dataset, we further propose a Raw-HDRNet, which utilizes the raw LDR frames as inputs. We propose a pyramid flow-guided deformation convolution to align neighboring frames. Experimental results demonstrate that 1) the proposed dataset can improve the HDR reconstruction performance on real scenes for three benchmark networks; 2) Compared with sRGB inputs, utilizing raw inputs can further improve the reconstruction quality and our proposed Raw-HDRNet is a strong baseline for raw HDR reconstruction. Our dataset and code will be released after the acceptance of this paper

Long-term behavior of connections for glubam-concrete composite beams

Glubam-concrete composite (BCC) structure is a construction technique where glue-laminated bamboo beam is connected to an upper concrete slab using different types of connectors. The long-term behavior and creep mechanism of BCC system are very complex due to different time-dependent behavior of three components. This paper performed a series long-term push-out tests on four types of connections under static load. The tests lasted for a period of seven months in uncontrolled sheltered indoor condition. Important results such as the relative slip-time curves are presented in order to characterize time-dependent behavior of connectors. Furthermore creep coefficient constitutive models are provided for predicting the long-term behavior of connections

中小学校园公共空间自然可视率量化研究

In order to solve the problem that the traditional method is very complex in safety assessment of primary and secondary school, which cannot get an objective result quickly. The method of calculating the natural visibility ratio within the students' effective range of visibility is studied based on graph theory, which can assess the safety level of public space in a quantitative way. Through this method, 42 primary and secondary schools were used to investigate to get the value of natural visibility ratio, and which was used to analyse the natural visibility level of those schools. The results show that natural visibility ratio can quality identify potential unsafe factors in campus. There is a strong negative correlation between campus average natural visibility ratio and building density. Therefore, the natural visibility ratio is beneficial to quality and objectively evaluate the safety of the campus, and to improve campus planning and design by predicting the level of visibility in public space

Phosphorylation-Dependent 14-3-3 Binding to LRRK2 Is Impaired by Common Mutations of Familial Parkinson's Disease

Background: Recent studies show that mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the cause of the most common inherited and some sporadic forms of Parkinson's disease (PD). The molecular mechanism underlying the pathogenic role of LRRK2 mutations in PD remains unknown.Methodology/Principal Findings: Using affinity purification and mass spectrometric analysis, we investigated phosphorylation sites and binding proteins of LRRK2 purified from mouse brain. We identified multiple phosphorylation sites at N-terminus of LRRK2 including S910, S912, S935 and S973. Focusing on the high stoichiometry S935 phosphorylation site, we developed an anti-pS935 specific antibody and showed that LRRK2 is constitutively phosphorylated at S935 in various tissues (including brain) and at different ages in mice. We find that 14-3-3 proteins (especially isoforms γ and η) bind LRRK2 and this binding depends on phosphorylation of S935. The binding of 14-3-3, with little effect on dimer formation of LRRK2, confers protection of the phosphorylation status of S935. Furthermore, we show that protein kinase A (PKA), but not LRRK2 kinase itself, can cause the phosphorylation of LRRK2 at S935 in vitro and in cell culture, suggesting that PKA is a potential upstream kinase that regulates LRRK2 function. Finally, our study indicates that the common PD-related mutations of LRRK2, R1441G, Y1699C and G2019S, decrease homeostatic phosphorylation levels of S935 and impair 14-3-3 binding of LRRK2.Conclusions/Significance: LRRK2 is extensively phosphorylated in vivo, and the phosphorylation of specific sites (e.g. S935) determines 14-3-3 binding of LRRK2. We propose that 14-3-3 is an important regulator of LRRK2-mediated cellular functions. Our study suggests that PKA, a cAMP-dependent kinase involved in regulating dopamine physiology, is a potential upstream kinase that phosphorylates LRRK2 at S935. Furthermore, the reduction of phosphorylation/14-3-3 binding of LRRK2 due to the common familial PD-related mutations provides novel insight into the pathogenic mechanism of LRRK2-linked PD.</p

Plant beta-turnover rather than nestedness shapes overall taxonomic and phylogenetic beta-diversity triggered by favorable spatial–environmental conditions in large-scale Chinese grasslands

IntroductionAlthough it is widely acknowledged that biodiversity maintains plant community assembly processes, exploring the patterns and drivers of beta-diversity (β-diversity; species variation among local plant communities) has received much less attention compared to alpha-diversity (α-diversity; species variation within a local plant community). Here, we aim to examine the patterns and spatial–environmental drivers of taxonomic and phylogenetic β-diversity, and their components such as species turnover and nestedness, in large-scale Leymus chinensis grassland communities.MethodsWe collected plant community data from 166 sites across widely distributed L. chinensis communities in northern China, and then calculated the taxonomic and phylogenetic β-diversity indices (overall, turnover and nestedness) using a pairwise dissimilarity approach. To assess the effects and to explain the variation in the patterns of β-diversity, we collected data on geospatial, climate and soil conditions. We applied descriptive statistics, Mental correlations, and multiple linear regression models to assess the patterns and spatial–environmental drivers of β-diversity.ResultsThe β-turnover, as compared to β-nestedness, exhibited a predominant influence, constituting 92.6% of the taxonomic β-diversity and 80.4% of the phylogenetic β-diversity. Most of the spatial–environmental variables were significantly positively correlated with the overall taxonomic and phylogenetic β-diversity and β-turnover, but not with β-nestedness. Climatic factors such as MAP and MAT were the strongest predictors of both taxonomic and phylogenetic β-diversity and β-turnover. The variance partitioning analysis showed that the combined effects of spatial and environmental factors accounted for 19% and 16% of the variation in the taxonomic and phylogenetic β-diversity (overall), 17% and 12% of the variation in the β-turnover, and 7% and 1% of the variation in the β-nestedness, respectively, which were higher than independent effects of either spatial or environmental factors.DiscussionAt larger spatial scales, the turnover component of β-diversity may be associated with the species complementarity effect, but dominant or functionally important species can vary among communities due to the species selection effect. By incorporating β-diversity into grassland management strategies, we can enhance the provision of vital ecosystem services that bolster human welfare, serving as a resilient barrier against the adverse effects of climate change at regional and global scales

Phosphorylation-Dependent 14-3-3 Binding to LRRK2 Is Impaired by Common Mutations of Familial Parkinson's Disease

) are the cause of the most common inherited and some sporadic forms of Parkinson's disease (PD). The molecular mechanism underlying the pathogenic role of LRRK2 mutations in PD remains unknown. and in cell culture, suggesting that PKA is a potential upstream kinase that regulates LRRK2 function. Finally, our study indicates that the common PD-related mutations of LRRK2, R1441G, Y1699C and G2019S, decrease homeostatic phosphorylation levels of S935 and impair 14-3-3 binding of LRRK2., and the phosphorylation of specific sites (e.g. S935) determines 14-3-3 binding of LRRK2. We propose that 14-3-3 is an important regulator of LRRK2-mediated cellular functions. Our study suggests that PKA, a cAMP-dependent kinase involved in regulating dopamine physiology, is a potential upstream kinase that phosphorylates LRRK2 at S935. Furthermore, the reduction of phosphorylation/14-3-3 binding of LRRK2 due to the common familial PD-related mutations provides novel insight into the pathogenic mechanism of LRRK2-linked PD