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The spin forming parameters of bimetallic composite pipe were optimized by FEM and experiment, and the torque and the residual contact pressure were analyzed during forming process. Adoption of The orthogonal test of four factors and five levels to gain the optimal spinning parameters (δ = 0.16mm, Ψ = 0.4mm, β = 3.0∘, f = 0.5) and the effects of factors on analysis indicators under the condition of maximum residual contact pressure and small torque. The simulation results showed that the residual contact pressure was nearly 1MPa higher and the torque was lower about 160N·m than unoptimized results. It proved that the orthogonal test method was effective for the optimization of spinning parameters of bimetal composite tube. The accuracy of numerical simulation value was verified by the drawing experiment of the composite tube.

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) mediates vascular endothelial growth factor (VEGF)-stimulated endothelial cytoskeleton remodeling and migration; however, the underlying mechanisms are elusive. Covalent adduction of a NO moiety (NO(•)) to cysteines called S-nitrosylation (SNO) is a key NO signaling pathway. The small actin-binding protein cofilin-1 (CFL1) is essential for actin cytoskeleton remodeling. We investigated whether S-nitrosylation regulates CFL1 function and endothelial cytoskeleton remodeling and migration upon VEGF stimulation. VEGF rapidly stimulated S-nitrosylation of CFL1, which was blocked by NO Synthase inhibition and eNOS knockdown by specific eNOS-siRNA. Cys80 and Cys139 were identified as the major SNO-sites in CFL1 by LC-MS/MS. The actin severing activity of recombinant SNO-mimetic CFL1 (C80/139A DMA-CFL1), but not SNO-deficient CFL1 (C80/139S DMS-CFL1), was significantly greater than that of wild-type CFL1 (wt-CFL1). When wt-CFL1 and its mutants were overexpressed in endothelial cells, basal actin bound wt-CFL1 was undetectable but significantly increased by VEGF; basal actin bound DMA-CFL1 was readily high and basal actin bound DMS-CFL1 was detectable but low, and both were unresponsive to VEGF. Treatment with VEGF significantly increased filamentous (F-) actin and filopodium formation and cell migration in endothelial cells. Overexpression of wt-CFL1 inhibited VEGF-induced F-actin formation. Overexpression of DMA but not DMS CFL1 decreased basal but not VEGF-stimulated F-actin formation. Overexpression of DMA but not DMS CFL1 suppressed VEGF-stimulated filopodium formation and migration in endothelial cells. Thus, S-nitrosylation of CFL1 provides a novel signaling pathway post-NO biosynthesis via eNOS-derived NO for endothelial cytoskeleton remodeling and migration upon VEGF stimulation.

There have been mixed results in studies investigating proportional reasoning in young children. The current study aimed to examine whether providing visual scaling cues and structuring the reasoning process can improve proportional reasoning in 5- to 6-year-old children. In a series of computerized tasks, children compared the sweetness of 2 mixtures. Each mixture was represented by a juice rectangle stacked on top of a water rectangle. Two rectangles shared the same width but were of same or different heights. The mixtures were scaled by either changing their widths or their heights. In Experiment 1, children's performance was poor when judging equivalent proportions. In Experiment 2, the 2 mixtures were individually previewed to encourage individual estimation of each mixture and thereby allow participants to strategically reason about the relative proportions. Children performed significantly better than in Experiment 1. In Experiment 3, children explicitly rated the sweetness of each preview mixture. Performance did not improve relative to Experiment 2. Throughout all 3 experiments, children were more sensitive in detecting equivalence when scaling occurred along the width compared with the height, demonstrating the effectiveness of visual-spatial scaling cues. Together, these experiments suggested that visuospatial scaling cues and structuring the 2-step reasoning process using previews can improve 5- to 6-year-olds' proportional reasoning with certain limitations.

Background: Navigating the environment, or wayfinding, is integral to independent living. Laboratory studies have consistently indicated an impairment in wayfinding in people with Down syndrome (DS). However, very little is known regarding their real-life wayfinding abilities. Method: Eighty-six parents of children with DS completed an online survey on their children's wayfinding behaviours and their own feelings and expectations about their children's wayfinding. Results: Parents reported their children had few wayfinding skills, yet much confidence in their own abilities. Many parents had taught/planned to teach their children wayfinding skills. Parents also expressed concerns over their children's independent wayfinding. Parents teaching wayfinding and parents' concern predicted their assessment of their children's wayfinding competence and knowledge. Children's age and sex, as well as parents' concerns predicted assessment of children's confidence in wayfinding. Conclusions: Our results identified key factors related to wayfinding behaviours in people with DS. Parental factors are especially important in predicting their children's wayfinding behaviour.

Protein-protein interactions (PPIs) are fundamental to the structure and function of protein complexes. Resolving the physical contacts between proteins as they occur in cells is critical to uncovering the molecular details underlying various cellular activities. To advance the study of PPIs in living cells, we have developed a new in vivo cross-linking mass spectrometry platform that couples a novel membrane-permeable, enrichable, and MS-cleavable cross-linker with multistage tandem mass spectrometry. This strategy permits the effective capture, enrichment, and identification of in vivo cross-linked products from mammalian cells and thus enables the determination of protein interaction interfaces. The utility of the developed method has been demonstrated by profiling PPIs in mammalian cells at the proteome scale and the targeted protein complex level. Our work represents a general approach for studying in vivo PPIs and provides a solid foundation for future studies toward the complete mapping of PPI networks in living systems.

Lysine 48 (K48)-polyubiquitination is the predominant mechanism for mediating selective protein degradation, but the underlying molecular basis of selecting ubiquitin (Ub) K48 for linkage-specific chain synthesis remains elusive. Here, we present biochemical, structural, and cell-based evidence demonstrating a pivotal role for the Ub Y59-E51 loop in supporting K48-polyubiquitination. This loop is established by a hydrogen bond between Ub Y59s hydroxyl group and the backbone amide of Ub E51, as substantiated by NMR spectroscopic analysis. Loop residues Y59 and R54 are specifically required for the receptor activity enabling K48 to attack the donor Ub-E2 thiol ester in reconstituted ubiquitination catalyzed by Skp1-Cullin1-F-box (SCF)(βTrCP) E3 ligase and Cdc34 E2-conjugating enzyme. When introduced into mammalian cells, loop-disruptive mutant Ub(R54A/Y59A) diminished the production of K48-polyubiquitin chains. Importantly, conditional replacement of human endogenous Ub by Ub(R54A/Y59A) or Ub(K48R) yielded profound apoptosis at a similar extent, underscoring the global impact of the Ub Y59-E51 loop in cellular K48-polyubiquitination. Finally, disulfide cross-linking revealed interactions between the donor Ub-bound Cdc34 acidic loop and the Ub K48 site, as well as residues within the Y59-E51 loop, suggesting a mechanism in which the Ub Y59-E51 loop helps recruit the E2 acidic loop that aligns the receptor Ub K48 to the donor Ub for catalysis.