Two large earthquakes(an earthquake doublet)occurred in south-central Turkey on February 6,2023,causing massive damages and casualties.The magnitudes and the relative sizes of the two mainshocks are essential informat...Two large earthquakes(an earthquake doublet)occurred in south-central Turkey on February 6,2023,causing massive damages and casualties.The magnitudes and the relative sizes of the two mainshocks are essential information for scientific research and public awareness.There are obvious discrepancies among the results that have been reported so far,which may be revised and updated later.Here we applied a novel and reliable long-period coda moment magnitude method to the two large earthquakes.The moment magnitudes(with one standard error)are 7.95±0.013 and 7.86±0.012,respectively,which are larger than all the previous reports.The first mainshock,which matches the largest recorded earthquakes in the Turkish history,is slightly larger than the second one by 0.11±0.035 in magnitude or by 0.04 to 0.18 at 95%confidence level.展开更多
Construction of high-order difference schemes based on Taylor series expansion has long been a hot topic in computational mathematics, while its application in comprehensive weather models is still very rare. Here, th...Construction of high-order difference schemes based on Taylor series expansion has long been a hot topic in computational mathematics, while its application in comprehensive weather models is still very rare. Here, the properties of high-order finite difference schemes are studied based on idealized numerical testing, for the purpose of their application in the Global/Regional Assimilation and Prediction System(GRAPES) model. It is found that the pros and cons due to grid staggering choices diminish with higher-order schemes based on linearized analysis of the one-dimensional gravity wave equation. The improvement of higher-order difference schemes is still obvious for the mesh with smooth varied grid distance. The results of discontinuous square wave testing also exhibits the superiority of high-order schemes. For a model grid with severe non-uniformity and non-orthogonality, the advantage of high-order difference schemes is inapparent, as shown by the results of two-dimensional idealized advection tests under a terrain-following coordinate. In addition, the increase in computational expense caused by high-order schemes can be avoided by the precondition technique used in the GRAPES model. In general, a high-order finite difference scheme is a preferable choice for the tropical regional GRAPES model with a quasi-uniform and quasi-orthogonal grid mesh.展开更多
KMT2D,a H3K4me1 methyltransferase primarily regulating enhancers,is a leading cause of KABUKI syndrome.This multisystem disorder leads to craniofacial and cognitive abnormalities,possibly through neural crest and neur...KMT2D,a H3K4me1 methyltransferase primarily regulating enhancers,is a leading cause of KABUKI syndrome.This multisystem disorder leads to craniofacial and cognitive abnormalities,possibly through neural crest and neuronal lineages.However,the impacted cell-of-origin and molecular mechanism of KMT2D during the development of KABUKI disease remains unknown.Here we have optimized a brain organoid model to investigate neural crest and neuronal differentiation.To pinpoint KMT2D's enhancer target,we developed a genome-wide cis-regulatory element explorer(GREE)based on single-cell multiomic integration.Single cell RNA-seq revealed that KMT2D-knockout(KO)and patient-derived organoids exhibited neural crest deformities and GABAergic overproduction.Mechanistically,GREE identified that KMT2D targets a roof-plate-like niche cell and activates the niche cell-specific WNT3A enhancer,providing the microenvironment for neural crest and neuronal development.Interestingly,KMT2D-mutated mice displayed decreased WNT3A expression in the diencephalon roof plate,indicating impaired niche cell function.Deleting the WNT3A enhancer in the organoids presented phenotypic similarities to KMT2D-depletion,emphasizing the WNT3A enhancer as the predominant target of KMT2D.Conversely,reactivating WNT signaling in KMT2D-KO rescued the lineage defects by restoring the microenvironment.Overall,our discovery of KMT2D's primary target provides insights for reconciling complex phenotypes of KABUKI syndrome and establishes a new paradigm for dissecting the mechanisms of genetic disorders from genotype to phenotype.展开更多
基金the National Key R&D Program of China(No.2022YFF0800601)the National Natural Science Foundation of China(No.U1939204).
文摘Two large earthquakes(an earthquake doublet)occurred in south-central Turkey on February 6,2023,causing massive damages and casualties.The magnitudes and the relative sizes of the two mainshocks are essential information for scientific research and public awareness.There are obvious discrepancies among the results that have been reported so far,which may be revised and updated later.Here we applied a novel and reliable long-period coda moment magnitude method to the two large earthquakes.The moment magnitudes(with one standard error)are 7.95±0.013 and 7.86±0.012,respectively,which are larger than all the previous reports.The first mainshock,which matches the largest recorded earthquakes in the Turkish history,is slightly larger than the second one by 0.11±0.035 in magnitude or by 0.04 to 0.18 at 95%confidence level.
基金supported by the National Natural Science Foundation of China (Grant No. U1811464)。
文摘Construction of high-order difference schemes based on Taylor series expansion has long been a hot topic in computational mathematics, while its application in comprehensive weather models is still very rare. Here, the properties of high-order finite difference schemes are studied based on idealized numerical testing, for the purpose of their application in the Global/Regional Assimilation and Prediction System(GRAPES) model. It is found that the pros and cons due to grid staggering choices diminish with higher-order schemes based on linearized analysis of the one-dimensional gravity wave equation. The improvement of higher-order difference schemes is still obvious for the mesh with smooth varied grid distance. The results of discontinuous square wave testing also exhibits the superiority of high-order schemes. For a model grid with severe non-uniformity and non-orthogonality, the advantage of high-order difference schemes is inapparent, as shown by the results of two-dimensional idealized advection tests under a terrain-following coordinate. In addition, the increase in computational expense caused by high-order schemes can be avoided by the precondition technique used in the GRAPES model. In general, a high-order finite difference scheme is a preferable choice for the tropical regional GRAPES model with a quasi-uniform and quasi-orthogonal grid mesh.
基金supported by National Science Foundation of China(32225012)National Key R&D Program of China(2019YFA0110200)+5 种基金Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong SAR,China,Youth Innovation Promotion Association,Chinese Academy of Sciences(Jie Wang),National Science Foundation of China(32000414,32000503,and 32000501)The Science and Technology Program of Guangzhou 201804020052 and 202102021039the Pearl River Talent Recruitment Program(2021ZT09Y233)Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,(GIBHBRP23-01,GIBHBRP23-02)Frontier Science Research Program of the CAS ZDBS-LY-SM007Science and Technology Planning Project of Guangdong Province,China(2023B1212060050 and 2023B1212120009)。
文摘KMT2D,a H3K4me1 methyltransferase primarily regulating enhancers,is a leading cause of KABUKI syndrome.This multisystem disorder leads to craniofacial and cognitive abnormalities,possibly through neural crest and neuronal lineages.However,the impacted cell-of-origin and molecular mechanism of KMT2D during the development of KABUKI disease remains unknown.Here we have optimized a brain organoid model to investigate neural crest and neuronal differentiation.To pinpoint KMT2D's enhancer target,we developed a genome-wide cis-regulatory element explorer(GREE)based on single-cell multiomic integration.Single cell RNA-seq revealed that KMT2D-knockout(KO)and patient-derived organoids exhibited neural crest deformities and GABAergic overproduction.Mechanistically,GREE identified that KMT2D targets a roof-plate-like niche cell and activates the niche cell-specific WNT3A enhancer,providing the microenvironment for neural crest and neuronal development.Interestingly,KMT2D-mutated mice displayed decreased WNT3A expression in the diencephalon roof plate,indicating impaired niche cell function.Deleting the WNT3A enhancer in the organoids presented phenotypic similarities to KMT2D-depletion,emphasizing the WNT3A enhancer as the predominant target of KMT2D.Conversely,reactivating WNT signaling in KMT2D-KO rescued the lineage defects by restoring the microenvironment.Overall,our discovery of KMT2D's primary target provides insights for reconciling complex phenotypes of KABUKI syndrome and establishes a new paradigm for dissecting the mechanisms of genetic disorders from genotype to phenotype.
