Otoancorin(OTOA)is a glycosylphosphatidylinositol(GPI)-anchored protein mediating the attachment of the tectorial membrane(TM)to the spiral limbus(SL)in the inner ear.Homozygous or compound heterozygous mutations in O...Otoancorin(OTOA)is a glycosylphosphatidylinositol(GPI)-anchored protein mediating the attachment of the tectorial membrane(TM)to the spiral limbus(SL)in the inner ear.Homozygous or compound heterozygous mutations in OTOA cause autosomal recessive deafness(DFNB22).We performed short-read exome sequencing(SRS)in a 10-monthold boy with sensorineural hearing loss,identifying a potential p.Glu787*variant in OTOA.Interestingly,this variant is common among normal-hearing individuals,leading us to question its pathogenic potential.展开更多
In order to achieve omnidirectional locomotion on rough terrain with multi-legged biomimetic robot,a free gait generation approach is proposed based on local rules.The phase coordinates of each operation leg was estab...In order to achieve omnidirectional locomotion on rough terrain with multi-legged biomimetic robot,a free gait generation approach is proposed based on local rules.The phase coordinates of each operation leg was established according to the motion task and a universal depiction of leg-end locomotion was implemented;the mathematical relation of gait pattern and walking velocity of multi-legged robot was put forward;combined polynomial curve was adopted to generate the leg-end trajectory,which was capable of accomplishing walking missions and accommodating to landform conditions;a distributed network of local rules for gait control was constructed based on a set of local rules operating between adjacent legs.In the simulation experiments,adaptive regulation of inter-leg phase sequence,omnidirectional locomotion and ground accommodation were realized.Moreover,statically stable free gait was obtained simultaneously,which provided multi-legged robot with the capability of walking on irregular terrain reliably and expeditiously.展开更多
Xu et al used the HOMA2 model to estimate theβ-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels.This method is based o...Xu et al used the HOMA2 model to estimate theβ-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels.This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities,which led to type 2 diabetes.However,significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids(FFAs)into the blood circulation,which leads to a marked reduction in membrane flexibility.These data favor a FFA-glucose-insulin axis.The authors are invited to extend their study with the introduction of the saturation index(number of carbon-carbon double bonds per 100 fatty-acyl chains),as observed in erythrocytes.展开更多
在面向卫星物联网的免授权随机接入(Grant-free Random Access,GFRA)系统中,受大规模连接和设备随机激活的影响,前导碰撞成为用户接入性能提升的主要制约因素。鉴于此,借助正交与非正交序列在前导检测和冲突抑制方面的各自优势,提出一...在面向卫星物联网的免授权随机接入(Grant-free Random Access,GFRA)系统中,受大规模连接和设备随机激活的影响,前导碰撞成为用户接入性能提升的主要制约因素。鉴于此,借助正交与非正交序列在前导检测和冲突抑制方面的各自优势,提出一种基于混合ZC(Zadoff-Chu)序列的大容量前导设计和检测方法。该方法利用正交ZC序列与其循环移位映射的不同根ZC序列级联来构建前导序列,并采用一种基于假设检验的两阶段干扰消除活跃用户检测算法,以确保大规模接入场景下的高精度用户识别。此外,对所提前导结构进行扩展,将相位旋转因子与多段非正交序列相结合,在不增加峰均比的前提下进一步扩大前导集容量。所提方法较现有复合和正交前导方法具有显著改善的多用户识别性能,在相同活跃用户下,成功检测概率最大提升约30.3%。展开更多
As an important building block for the synthesis of angiotensin-converting enzyme inhibitors,ethyl(R)-2-hy-droxyl-4-phenylbutanoate[(R)-HPBE]has attracted increasing attention.The key to industrial biosynthesis of(R)-...As an important building block for the synthesis of angiotensin-converting enzyme inhibitors,ethyl(R)-2-hy-droxyl-4-phenylbutanoate[(R)-HPBE]has attracted increasing attention.The key to industrial biosynthesis of(R)-HPBE is a biocatalyst that efficiently reduces ethyl 2-oxo-4-phenylbutanoate(OPBE)with high R-enantiose-lectivity.This paper proposed a strategy for identifying key residues involved in enantioselectivity control based on per-residue free energy decomposition and sequence conservatism analysis.Using this strategy,4 noncon-servative sites with high energy contribution to binding of OPBE were chosen as engineering targets,generating variant Mu27 with 99%conversion and 98%(R)ee value at substrate loading of up to 500 mmol/L.MD simu-lations suggested the higher stability and formation probability of Mu27-OPBEproR prereaction state as key rea-sons for the excellent R-enantioselectivity of Mu27 towards OPBE.The success in this study provides a viable approach for rational design of alcohol dehydrogenases with high enantioselectivity towards unnatural substrates.展开更多
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2021R1C1C1007980 to B.J.K.)Chungnam National University Sejong Hospital Research Fund,2022,and Chungnam National University(to B.J.K.)+6 种基金supported by the Basic Science Research Program through the NRF,funded by the Ministry of Education(No.2021R1A2C2092038 to B.Y.C.)Bio Core Facility Center program(No.NRF-2022M3A9G1014007 to B.Y.C.)the Basic Research Laboratory program through the NRF,funded by the Ministry of Education(No.RS-2023-0021971031482092640001 to B.Y.C.)the Technology Innovation Program(No.K_G012002572001 to B.Y.C.)funded By the Ministry of Trade,Industry&Energy(MOTIE,Korea)funded by SNUBH(Seoul National University Bundang Hospital)intramural research fund(No.13-2022-0010,02-2017-0060,16-2023-0002,13-2023-0002,16-2022-0005,13-2024-0004,and 13-2017-0013 to B.Y.C.)supported by the National Institute on Deafness and Other Communication Disorders(NIDCD)part of the US National Institutes of Health(No.R01DC018814 to S.P.).
文摘Otoancorin(OTOA)is a glycosylphosphatidylinositol(GPI)-anchored protein mediating the attachment of the tectorial membrane(TM)to the spiral limbus(SL)in the inner ear.Homozygous or compound heterozygous mutations in OTOA cause autosomal recessive deafness(DFNB22).We performed short-read exome sequencing(SRS)in a 10-monthold boy with sensorineural hearing loss,identifying a potential p.Glu787*variant in OTOA.Interestingly,this variant is common among normal-hearing individuals,leading us to question its pathogenic potential.
基金Sponsored by the National High Technology Research and Development Program of China(Grant No. 2006AA04Z245)the Program for Changjiang Scholars and Innovative Research Team in University(Grant No. IRT0423)
文摘In order to achieve omnidirectional locomotion on rough terrain with multi-legged biomimetic robot,a free gait generation approach is proposed based on local rules.The phase coordinates of each operation leg was established according to the motion task and a universal depiction of leg-end locomotion was implemented;the mathematical relation of gait pattern and walking velocity of multi-legged robot was put forward;combined polynomial curve was adopted to generate the leg-end trajectory,which was capable of accomplishing walking missions and accommodating to landform conditions;a distributed network of local rules for gait control was constructed based on a set of local rules operating between adjacent legs.In the simulation experiments,adaptive regulation of inter-leg phase sequence,omnidirectional locomotion and ground accommodation were realized.Moreover,statically stable free gait was obtained simultaneously,which provided multi-legged robot with the capability of walking on irregular terrain reliably and expeditiously.
文摘Xu et al used the HOMA2 model to estimate theβ-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels.This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities,which led to type 2 diabetes.However,significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids(FFAs)into the blood circulation,which leads to a marked reduction in membrane flexibility.These data favor a FFA-glucose-insulin axis.The authors are invited to extend their study with the introduction of the saturation index(number of carbon-carbon double bonds per 100 fatty-acyl chains),as observed in erythrocytes.
文摘在面向卫星物联网的免授权随机接入(Grant-free Random Access,GFRA)系统中,受大规模连接和设备随机激活的影响,前导碰撞成为用户接入性能提升的主要制约因素。鉴于此,借助正交与非正交序列在前导检测和冲突抑制方面的各自优势,提出一种基于混合ZC(Zadoff-Chu)序列的大容量前导设计和检测方法。该方法利用正交ZC序列与其循环移位映射的不同根ZC序列级联来构建前导序列,并采用一种基于假设检验的两阶段干扰消除活跃用户检测算法,以确保大规模接入场景下的高精度用户识别。此外,对所提前导结构进行扩展,将相位旋转因子与多段非正交序列相结合,在不增加峰均比的前提下进一步扩大前导集容量。所提方法较现有复合和正交前导方法具有显著改善的多用户识别性能,在相同活跃用户下,成功检测概率最大提升约30.3%。
基金This study is financially supported by the National Key Research and Development Program of China(No.2018YFA0901800 to H.Yu and L.Ye)Zhejiang Provincial Natural Science Foundation of China(No.LY18B060001 to L.Ye and No.LZ20B060002 to H.Yu)Natural Science Foundation of China(No.21776244 to H.Yu).We are grateful to the constructive suggestions from academician Fen-Er Chen(Department of Chemistry,Fudan University,Shanghai,China)and the support of Discovery Studio software from Fuzhou University platform.
文摘As an important building block for the synthesis of angiotensin-converting enzyme inhibitors,ethyl(R)-2-hy-droxyl-4-phenylbutanoate[(R)-HPBE]has attracted increasing attention.The key to industrial biosynthesis of(R)-HPBE is a biocatalyst that efficiently reduces ethyl 2-oxo-4-phenylbutanoate(OPBE)with high R-enantiose-lectivity.This paper proposed a strategy for identifying key residues involved in enantioselectivity control based on per-residue free energy decomposition and sequence conservatism analysis.Using this strategy,4 noncon-servative sites with high energy contribution to binding of OPBE were chosen as engineering targets,generating variant Mu27 with 99%conversion and 98%(R)ee value at substrate loading of up to 500 mmol/L.MD simu-lations suggested the higher stability and formation probability of Mu27-OPBEproR prereaction state as key rea-sons for the excellent R-enantioselectivity of Mu27 towards OPBE.The success in this study provides a viable approach for rational design of alcohol dehydrogenases with high enantioselectivity towards unnatural substrates.
