Non-uniform rational B-spline(NURBS)curves are combined with the Kriging model to present a prediction method of the rail grinding profile for a grinding train.As a worn rail profile is a free-form curve,the parameter...Non-uniform rational B-spline(NURBS)curves are combined with the Kriging model to present a prediction method of the rail grinding profile for a grinding train.As a worn rail profile is a free-form curve,the parameterized model of a rail profile is constructed by using the cubic NURBS curve.Taking the removed area of the rail profile cross-section by grinding as the calculation index of the grinding amount,the grinding amount calculation model of a grinding wheel is established based on the area integral formula of the cubic NURBS curve.To predict the grinding amount of a grinding wheel in different modes,a Kriging model of the grinding amount is constructed,taking the travel speed of a grinding train,the grinding angle and grinding pressure of a grinding wheel as the variables,and considering the grinding amount of a grinding wheel as the response.On this basis,the prediction method of the rail grinding profile is presented based on the order-forming mechanisms.The effectiveness of this method is verified based on a practical application.展开更多
The normalized central moments are widely used in pattern recognition because of scale and translation invariance. The moduli of normalized central moments of the 1-dimensional complex range profiles are used here as ...The normalized central moments are widely used in pattern recognition because of scale and translation invariance. The moduli of normalized central moments of the 1-dimensional complex range profiles are used here as feature vector for radar target recognition. The common feature extraction method for high resolution range profile obtained by using Fourier-modified direct Mellin transform is inefficient and unsatisfactory in recognition rate And. generally speaking, the automatic target recognition method based on inverse synthetic aperture radar 2-dimensional imaging is not competent for real time object identification task because it needs complicated motion compensation which is sometimes too difficult to carry out. While the method applied here is competent for real-time recognition because of its computational efficiency. The result of processing experimental data indicates that this method is good at recognition.展开更多
Liquid chromatography-mass spectrometry （LC-MS）-based metabolomics has been facilitated by the con- struction of MSz spectral tag （MS2T） library from the total scan ESI MS/MS data, and the development of widely ta...Liquid chromatography-mass spectrometry （LC-MS）-based metabolomics has been facilitated by the con- struction of MSz spectral tag （MS2T） library from the total scan ESI MS/MS data, and the development of widely targeted metabolomics method using MS/MS data gathered from authentic standards. In this report, a novel strategy called step- wise multiple ion monitoring-enhanced product ions （stepwise MIM-EPI） was developed to construct the MS2T library, in which stepwise MIM was used as survey scans to trigger the acquisition of EPI. A total number of 698 （almost） non- redundant metabolites with MS2 spectra were obtained, of which 135 metabolites were identified/annotated. Integrating the data gathered from our MS2T library and other available multiple reaction monitoring （MRM） information, a widely targeted metabolomics method was developed to quantify 277 metabolites, including some phytohormones. Evaluation of the dehydration responses and natural variations of these metabolites in rice leaf not only suggested the coordinated regulation of abscisic acid （ABA） with metabolites such as serotonin derivative（s）, polyamine conjugates under drought stress, but also revealed some C-glycosylated flavones as the potential markers for the discrimination of indica and japonica rice subspecies. The new MS2T library construction and widely targeted metabolomics strategy could be used as a tool for rice functional genomics.展开更多
Great success has been witnessed in last decades,some new techniques and strategies have been widely used in drug discovery.In this roadmap,several representative techniques and strategies are highlighted to show rece...Great success has been witnessed in last decades,some new techniques and strategies have been widely used in drug discovery.In this roadmap,several representative techniques and strategies are highlighted to show recent advances in this filed.(A)A DOX protocol has been developed for accurate protein-ligand binding structure prediction,in which first principle method was used to rank the binding poses.Validation against crystal structures have found that DOX prediction achieved an impressive success rate of 99%,indicating significant improvement over molecular docking method.(B)Virtual target profiling is a compound-centric strategy enabling a parallel implementation of interrogating compounds against various targets in a single screen,which has been used in hit/lead identification,drug repositioning,and mechanism-of-action studies.Current and emerging methods for virtual target profiling are briefly summarized herein.(C)Research on targeted autophagy to treat diseases has received encouraging progress.However,due to the complexity of autophagy and disease,experimental and in silico methods should be performed synergistically for the entire process.This part focuses on in silico methods in autophagy research to promote their use in medicinal research.(D)Histone deacetylases(HDACs)play important roles in various biological functions through the deacetylation of lysine residues.Recent studies demonstrated that HDACs,which possess low deacetylase activities,exhibited more efficient defatty-acylase activities.Here,we review the defatty-acylase activity of HDACs and describe examples for the design of isoform selective HDAC inhibitor.(E)The FDA approval of three kinase allosteric inhibitors and some others entering clinical study has spurred considerable interests in this targeted drug discovery area.(F)Recent advances are reviewed in structure-based design of novel antiviral agents to combat drug resistance.(G)Since nitric oxide(NO)exerts anticancer activity depending on its concentration,optimal levels of NO in cancer cells is desirable.In this minireview,we briefly describe recent advances in the research of NO-based anticancer agents by our group and present some opinions on the future development of these agents.(H)The field of photoactivation strategies have been extensively developed for controlling chemical and biological processes with light.This review will summarize and provide insight into recent research advances in the understanding of photoactivatable molecules including photoactivatable caged prodrugs and photoswitchable molecules.展开更多
Despite increased international efforts to control schistosomiasis using preventive chemotherapy,several challenges still exist in reaching the target populations.Until recently,preschool-aged children had been exclud...Despite increased international efforts to control schistosomiasis using preventive chemotherapy,several challenges still exist in reaching the target populations.Until recently,preschool-aged children had been excluded from the recommended target population for mass drug administration,i.e.primary school children aged 6-15 years.Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010.The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug,praziquantel.The currently available formulation of praziquantel presents several problems.First,it is a large tablet,making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake.Second,it is bitter so it is often mixed with a sweetener to make it palatable for young children.Third,the current formulation of 600 mg does not allow for flexible dose adjustments for this age group.Thus,there is a need to formulate a child-appropriate praziquantel tablet.This paper discusses the target product profile for paediatric praziquantel,as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children.展开更多
基金Project(51405516)supported by the National Natural Science Foundation of ChinaProject(2015JJ2168)supported by the Natural Science Foundation of Hunan Province,China
文摘Non-uniform rational B-spline(NURBS)curves are combined with the Kriging model to present a prediction method of the rail grinding profile for a grinding train.As a worn rail profile is a free-form curve,the parameterized model of a rail profile is constructed by using the cubic NURBS curve.Taking the removed area of the rail profile cross-section by grinding as the calculation index of the grinding amount,the grinding amount calculation model of a grinding wheel is established based on the area integral formula of the cubic NURBS curve.To predict the grinding amount of a grinding wheel in different modes,a Kriging model of the grinding amount is constructed,taking the travel speed of a grinding train,the grinding angle and grinding pressure of a grinding wheel as the variables,and considering the grinding amount of a grinding wheel as the response.On this basis,the prediction method of the rail grinding profile is presented based on the order-forming mechanisms.The effectiveness of this method is verified based on a practical application.
文摘The normalized central moments are widely used in pattern recognition because of scale and translation invariance. The moduli of normalized central moments of the 1-dimensional complex range profiles are used here as feature vector for radar target recognition. The common feature extraction method for high resolution range profile obtained by using Fourier-modified direct Mellin transform is inefficient and unsatisfactory in recognition rate And. generally speaking, the automatic target recognition method based on inverse synthetic aperture radar 2-dimensional imaging is not competent for real time object identification task because it needs complicated motion compensation which is sometimes too difficult to carry out. While the method applied here is competent for real-time recognition because of its computational efficiency. The result of processing experimental data indicates that this method is good at recognition.
基金the National High Technology R&D Program of China (863 Program)，the Major State Basic Research Development Program of China (973 Program)，by the National Natural Science Foundation of China，by the Program for New Century Excellent Talents in University of Ministry of Education in China (NCET-09-0401).A patent for this method has been approved by the State Intellectual Property Office of China
文摘Liquid chromatography-mass spectrometry （LC-MS）-based metabolomics has been facilitated by the con- struction of MSz spectral tag （MS2T） library from the total scan ESI MS/MS data, and the development of widely targeted metabolomics method using MS/MS data gathered from authentic standards. In this report, a novel strategy called step- wise multiple ion monitoring-enhanced product ions （stepwise MIM-EPI） was developed to construct the MS2T library, in which stepwise MIM was used as survey scans to trigger the acquisition of EPI. A total number of 698 （almost） non- redundant metabolites with MS2 spectra were obtained, of which 135 metabolites were identified/annotated. Integrating the data gathered from our MS2T library and other available multiple reaction monitoring （MRM） information, a widely targeted metabolomics method was developed to quantify 277 metabolites, including some phytohormones. Evaluation of the dehydration responses and natural variations of these metabolites in rice leaf not only suggested the coordinated regulation of abscisic acid （ABA） with metabolites such as serotonin derivative（s）, polyamine conjugates under drought stress, but also revealed some C-glycosylated flavones as the potential markers for the discrimination of indica and japonica rice subspecies. The new MS2T library construction and widely targeted metabolomics strategy could be used as a tool for rice functional genomics.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81973173 and 81773571),Jiangsu Province Funds for Excellent Young Scientists(No.BK20170088),the Six Talent Peaks Project(No.YY-023)and the 333 Project of Jiangsu Province.
文摘Great success has been witnessed in last decades,some new techniques and strategies have been widely used in drug discovery.In this roadmap,several representative techniques and strategies are highlighted to show recent advances in this filed.(A)A DOX protocol has been developed for accurate protein-ligand binding structure prediction,in which first principle method was used to rank the binding poses.Validation against crystal structures have found that DOX prediction achieved an impressive success rate of 99%,indicating significant improvement over molecular docking method.(B)Virtual target profiling is a compound-centric strategy enabling a parallel implementation of interrogating compounds against various targets in a single screen,which has been used in hit/lead identification,drug repositioning,and mechanism-of-action studies.Current and emerging methods for virtual target profiling are briefly summarized herein.(C)Research on targeted autophagy to treat diseases has received encouraging progress.However,due to the complexity of autophagy and disease,experimental and in silico methods should be performed synergistically for the entire process.This part focuses on in silico methods in autophagy research to promote their use in medicinal research.(D)Histone deacetylases(HDACs)play important roles in various biological functions through the deacetylation of lysine residues.Recent studies demonstrated that HDACs,which possess low deacetylase activities,exhibited more efficient defatty-acylase activities.Here,we review the defatty-acylase activity of HDACs and describe examples for the design of isoform selective HDAC inhibitor.(E)The FDA approval of three kinase allosteric inhibitors and some others entering clinical study has spurred considerable interests in this targeted drug discovery area.(F)Recent advances are reviewed in structure-based design of novel antiviral agents to combat drug resistance.(G)Since nitric oxide(NO)exerts anticancer activity depending on its concentration,optimal levels of NO in cancer cells is desirable.In this minireview,we briefly describe recent advances in the research of NO-based anticancer agents by our group and present some opinions on the future development of these agents.(H)The field of photoactivation strategies have been extensively developed for controlling chemical and biological processes with light.This review will summarize and provide insight into recent research advances in the understanding of photoactivatable molecules including photoactivatable caged prodrugs and photoswitchable molecules.
基金The discussion presented in this paper is based on current and previous collaborative work funded by the Thrasher Research Fund,the WHO and the Wellcome Trust。
文摘Despite increased international efforts to control schistosomiasis using preventive chemotherapy,several challenges still exist in reaching the target populations.Until recently,preschool-aged children had been excluded from the recommended target population for mass drug administration,i.e.primary school children aged 6-15 years.Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010.The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug,praziquantel.The currently available formulation of praziquantel presents several problems.First,it is a large tablet,making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake.Second,it is bitter so it is often mixed with a sweetener to make it palatable for young children.Third,the current formulation of 600 mg does not allow for flexible dose adjustments for this age group.Thus,there is a need to formulate a child-appropriate praziquantel tablet.This paper discusses the target product profile for paediatric praziquantel,as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children.
