The optimization of two-scale structures can adapt to the different needs of materials in various regions by reasonably arranging different microstructures at the macro scale,thereby considerably improving structural ...The optimization of two-scale structures can adapt to the different needs of materials in various regions by reasonably arranging different microstructures at the macro scale,thereby considerably improving structural performance.Here,a multiple variable cutting(M-VCUT)level set-based data-driven model of microstructures is presented,and a method based on this model is proposed for the optimal design of two-scale structures.The geometry of the microstructure is described using the M-VCUT level set method,and the effective mechanical properties of microstructures are computed by the homogenization method.Then,a database of microstructures containing their geometric and mechanical parameters is constructed.The two sets of parameters are adopted as input and output datasets,and a mapping relationship between the two datasets is established to build the data-driven model of microstructures.During the optimization of two-scale structures,the data-driven model is used for macroscale finite element and sensitivity analyses.The efficiency of the analysis and optimization of two-scale structures is improved because the computational costs of invoking such a data-driven model are much smaller than those of homogenization.展开更多
Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmaco...Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic efficacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.展开更多
Viruses in the family Reoviridae are non-enveloped particles comprising a segmented double-stranded RNA genome surrounded by a two-layered or multi-layered icosahedral protein capsid.These viruses are classified into ...Viruses in the family Reoviridae are non-enveloped particles comprising a segmented double-stranded RNA genome surrounded by a two-layered or multi-layered icosahedral protein capsid.These viruses are classified into two sub-families based on their particle structural organization.Recent studies have focused on high-resolution three-dimensional structures of reovirus particles by using cryo-electron microscopy (cryo-EM) to approach the resolutions seen in X-ray crystallographic structures.The results of cryo-EM image reconstructions allow tracing of most of the protein side chains,and thus permit integration of structural and functional information into a coherent mechanism for reovirus assembly and entry.展开更多
GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this ...GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this study, we determined crystal structures of CaZ＋-bound GCaMP6 monomer and dimer and presented detailed structural analyses in comparison with its par- ent version GCaMP5G. Our analyses reveal the structural basis for the outperformance of this newly developed Ca2＋ indicator. Three substitution mutations and the resulting changes of local structure and interaction explain the ultrasensitivity and in- creased fluorescence intensity common to all three versions of GCaMP6. Each particular substitution in the three GCaMP6 is also structurally consistent with their differential sensitivity and intensity, maximizing the potential of using GCaMP6 in solving diverse problems in neuronal research and calcium signaling. Our studies shall also be beneficial to further structure-guided optimization of GCaMP and facilitate the design of novel calcium indicators.展开更多
Purpose–The purpose of this paper is to provide an effective and simple technique to structural damage identification,particularly to identify a crack in a structure.Artificial neural networks approach is an alternat...Purpose–The purpose of this paper is to provide an effective and simple technique to structural damage identification,particularly to identify a crack in a structure.Artificial neural networks approach is an alternative to identify the extent and location of the damage over the classical methods.Radial basis function(RBF)networks are good at function mapping and generalization ability among the various neural network approaches.RBF neural networks are chosen for the present study of crack identification.Design/methodology/approach–Analyzing the vibration response of a structure is an effective way to monitor its health and even to detect the damage.A novel two-stage improved radial basis function(IRBF)neural network methodology with conventional RBF in the first stage and a reduced search space moving technique in the second stage is proposed to identify the crack in a cantilever beam structure in the frequency domain.Latin hypercube sampling(LHS)technique is used in both stages to sample the frequency modal patterns to train the proposed network.Study is also conducted with and without addition of 5%white noise to the input patterns to simulate the experimental errors.Findings–The results show a significant improvement in identifying the location and magnitude of a crack by the proposed IRBF method,in comparison with conventional RBF method and other classical methods.In case of crack location in a beam,the average identification error over 12 test cases was 0.69 per cent by IRBF network compared to 4.88 per cent by conventional RBF.Similar improvements are reported when compared to hybrid CPN BPN networks.It also requires much less computational effort as compared to other hybrid neural network approaches and classical methods.Originality/value–The proposed novel IRBF crack identification technique is unique in originality and not reported elsewhere.It can identify the crack location and crack depth with very good accuracy,less computational effort and ease of implementation.展开更多
From the view of the physical model,structure and function characteristics,the material basis and clinical application of Yin-Yang theory,analysing and thinking combined with modern medical theory,this paper finds tha...From the view of the physical model,structure and function characteristics,the material basis and clinical application of Yin-Yang theory,analysing and thinking combined with modern medical theory,this paper finds that as one of the most basic and important theory of traditional Chinese medicine(TCM),Yin-Yang theory reveals the understanding of human physiology in TCM,which has many consensuses with modern medicine,so it is worth studying further.展开更多
胆盐水解酶(Bile salt hydrolase,BSH)广泛存在于哺乳动物胃肠道中,是肠道菌群在生长、繁殖过程中产生的一种胞内酶,可以调节宿主的胆汁酸平衡,影响脂质代谢,有控制胆固醇、调节肠道疾病的作用,并且BSH这种调控作用可以实现益生菌部分...胆盐水解酶(Bile salt hydrolase,BSH)广泛存在于哺乳动物胃肠道中,是肠道菌群在生长、繁殖过程中产生的一种胞内酶,可以调节宿主的胆汁酸平衡,影响脂质代谢,有控制胆固醇、调节肠道疾病的作用,并且BSH这种调控作用可以实现益生菌部分益生功能,因此BSH一直是研究热点。BSH结构和底物特异性的详细知识是开发BSH相关产品的坚实基础。本文介绍了BSH的来源及活性检测方法,BSH基因结构、酶学性质及底物识别机制,最后讨论了BSH在畜禽业食品工业及医药等方面的应用,期望为胆盐水解酶的深入研究及其在食品、保健品及医药方面的开发利用提供参考。展开更多
基金supported by the National Natural Science Foundation of China(Grant No.12272144).
文摘The optimization of two-scale structures can adapt to the different needs of materials in various regions by reasonably arranging different microstructures at the macro scale,thereby considerably improving structural performance.Here,a multiple variable cutting(M-VCUT)level set-based data-driven model of microstructures is presented,and a method based on this model is proposed for the optimal design of two-scale structures.The geometry of the microstructure is described using the M-VCUT level set method,and the effective mechanical properties of microstructures are computed by the homogenization method.Then,a database of microstructures containing their geometric and mechanical parameters is constructed.The two sets of parameters are adopted as input and output datasets,and a mapping relationship between the two datasets is established to build the data-driven model of microstructures.During the optimization of two-scale structures,the data-driven model is used for macroscale finite element and sensitivity analyses.The efficiency of the analysis and optimization of two-scale structures is improved because the computational costs of invoking such a data-driven model are much smaller than those of homogenization.
基金This work was supported by Natural Science Foundation of Guangdong Province(grant number 2022A1515010552,China)National Natural Science Foundation of China(grant number U1832101 and 81373473).
文摘Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic efficacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.
基金supported by grants from the National Natural Science Foundation of China(31172434,31372565)
文摘Viruses in the family Reoviridae are non-enveloped particles comprising a segmented double-stranded RNA genome surrounded by a two-layered or multi-layered icosahedral protein capsid.These viruses are classified into two sub-families based on their particle structural organization.Recent studies have focused on high-resolution three-dimensional structures of reovirus particles by using cryo-electron microscopy (cryo-EM) to approach the resolutions seen in X-ray crystallographic structures.The results of cryo-EM image reconstructions allow tracing of most of the protein side chains,and thus permit integration of structural and functional information into a coherent mechanism for reovirus assembly and entry.
基金supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute to Shao Fenggrant from the National Basic Research Program of China (2011CB910304 and 2011CB911103) to Wang DaChengNational Natural Science Foundation of China (31100535) to Ding JingJin
文摘GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this study, we determined crystal structures of CaZ＋-bound GCaMP6 monomer and dimer and presented detailed structural analyses in comparison with its par- ent version GCaMP5G. Our analyses reveal the structural basis for the outperformance of this newly developed Ca2＋ indicator. Three substitution mutations and the resulting changes of local structure and interaction explain the ultrasensitivity and in- creased fluorescence intensity common to all three versions of GCaMP6. Each particular substitution in the three GCaMP6 is also structurally consistent with their differential sensitivity and intensity, maximizing the potential of using GCaMP6 in solving diverse problems in neuronal research and calcium signaling. Our studies shall also be beneficial to further structure-guided optimization of GCaMP and facilitate the design of novel calcium indicators.
文摘Purpose–The purpose of this paper is to provide an effective and simple technique to structural damage identification,particularly to identify a crack in a structure.Artificial neural networks approach is an alternative to identify the extent and location of the damage over the classical methods.Radial basis function(RBF)networks are good at function mapping and generalization ability among the various neural network approaches.RBF neural networks are chosen for the present study of crack identification.Design/methodology/approach–Analyzing the vibration response of a structure is an effective way to monitor its health and even to detect the damage.A novel two-stage improved radial basis function(IRBF)neural network methodology with conventional RBF in the first stage and a reduced search space moving technique in the second stage is proposed to identify the crack in a cantilever beam structure in the frequency domain.Latin hypercube sampling(LHS)technique is used in both stages to sample the frequency modal patterns to train the proposed network.Study is also conducted with and without addition of 5%white noise to the input patterns to simulate the experimental errors.Findings–The results show a significant improvement in identifying the location and magnitude of a crack by the proposed IRBF method,in comparison with conventional RBF method and other classical methods.In case of crack location in a beam,the average identification error over 12 test cases was 0.69 per cent by IRBF network compared to 4.88 per cent by conventional RBF.Similar improvements are reported when compared to hybrid CPN BPN networks.It also requires much less computational effort as compared to other hybrid neural network approaches and classical methods.Originality/value–The proposed novel IRBF crack identification technique is unique in originality and not reported elsewhere.It can identify the crack location and crack depth with very good accuracy,less computational effort and ease of implementation.
文摘From the view of the physical model,structure and function characteristics,the material basis and clinical application of Yin-Yang theory,analysing and thinking combined with modern medical theory,this paper finds that as one of the most basic and important theory of traditional Chinese medicine(TCM),Yin-Yang theory reveals the understanding of human physiology in TCM,which has many consensuses with modern medicine,so it is worth studying further.
文摘胆盐水解酶(Bile salt hydrolase,BSH)广泛存在于哺乳动物胃肠道中,是肠道菌群在生长、繁殖过程中产生的一种胞内酶,可以调节宿主的胆汁酸平衡,影响脂质代谢,有控制胆固醇、调节肠道疾病的作用,并且BSH这种调控作用可以实现益生菌部分益生功能,因此BSH一直是研究热点。BSH结构和底物特异性的详细知识是开发BSH相关产品的坚实基础。本文介绍了BSH的来源及活性检测方法,BSH基因结构、酶学性质及底物识别机制,最后讨论了BSH在畜禽业食品工业及医药等方面的应用,期望为胆盐水解酶的深入研究及其在食品、保健品及医药方面的开发利用提供参考。
