资源环境科技发展态势分析平台

Graphene films grown by chemical vapour deposition have unusual physical and chemical properties that offer promise for applications such as flexible electronics and high-frequency transistors(1-10). However, wrinkles invariably form during growth because of the strong coupling to the substrate, and these limit the large-scale homogeneity of the film(1-4,11,12). Here we develop a proton-assisted method of chemical vapour deposition to grow ultra-flat graphene films that are wrinkle-free. Our method of proton penetration(13-17) and recombination to form hydrogen can also reduce the wrinkles formed during traditional chemical vapour deposition of graphene. Some of the wrinkles disappear entirely, owing to the decoupling of van der Waals interactions and possibly an increase in distance from the growth surface. The electronic band structure of the as-grown graphene films shows a V-shaped Dirac cone and a linear dispersion relation within the atomic plane or across an atomic step, confirming the decoupling from the substrate. The ultra-flat nature of the graphene films ensures that their surfaces are easy to clean after a wet transfer process. A robust quantum Hall effect appears even at room temperature in a device with a linewidth of 100 micrometres. Graphene films grown by proton-assisted chemical vapour deposition should largely retain their intrinsic performance, and our method should be easily generalizable to other nanomaterials for strain and doping engineering.

Genetic variations underlying susceptibility to complex autoimmune and allergic diseases are concentrated within noncoding regulatory elements termed enhancers(1). The functions of a large majority of disease-associated enhancers are unknown, in part owing to their distance from the genes they regulate, a lack of understanding of the cell types in which they operate, and our inability to recapitulate the biology of immune diseases in vitro. Here, using shared synteny to guide loss-of-function analysis of homologues of human enhancers in mice, we show that the prominent autoimmune and allergic disease risk locus at chromosome 11q13.5(2-7) contains a distal enhancer that is functional in CD4(+) regulatory T (T-reg) cells and required for T-reg-mediated suppression of colitis. The enhancer recruits the transcription factors STAT5 and NF-kappa B to mediate signal-driven expression of Lrrc32, which encodes the protein glycoprotein A repetitions predominant (GARP). Whereas disruption of the Lrrc32 gene results in early lethality, mice lacking the enhancer are viable but lack GARP expression in Foxp3(+) T-reg cells, which are unable to control colitis in a cell-transfer model of the disease. In human T-reg cells, the enhancer forms conformational interactions with the promoter of LRRC32 and enhancer risk variants are associated with reduced histone acetylation and GARP expression. Finally, functional fine-mapping of 11q13.5 using CRISPR-activation (CRISPRa) identifies a CRISPRa-responsive element in the vicinity of risk variant rs11236797 capable of driving GARP expression. These findings provide a mechanistic basis for association of the 11q13.5 risk locus with immune-mediated diseases and identify GARP as a potential target in their therapy.

Shared synteny guides loss-of-function analysis of human enhancer homologues in mice, identifying a distal enhancer at the autoimmune and allergic disease risk locus at chromosome 11q13.5 whose function in regulatory T cells provides a mechanistic basis for its role in disease.