Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated ...Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus,the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.展开更多
MicroRNAs (miRNAs) are a class of ~22 nucleotides long non coding RNA molecules which play an important role in gene regulation at the post transcriptional level. The conserved nature of miRNAs provides the basis of n...MicroRNAs (miRNAs) are a class of ~22 nucleotides long non coding RNA molecules which play an important role in gene regulation at the post transcriptional level. The conserved nature of miRNAs provides the basis of new miRNA identification through homology search. In an attempt to identify new conserved miRNAs in tea, previously known plant miRNAs were used for searching their homolog in a tea Expressed Sequence Tags and full length nucleotide sequence database. The sequences showing homolog no more than four mismatches were predicted for their fold back structures and passed through a series of filtration criteria, finally led us to identify 13 conserved miRNAs in tea belonging to 9 miRNA families. A total of 37 potential target genes in Arabidopsis were identified subsequently for 7 miRNA families based on their sequence complementarity which encode transcription factors (8%), enzymes (30%) and transporters (14%) as well as other proteins involved in physiological and metabolic processes (48%). Overall, our findings will accelerate the way for further researches of miRNAs and their functions in tea.展开更多
Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identifi...Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identification of a potent DHODH inhibitor by proteomic profiling.Cell-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer cells.Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic acid.Moreover,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid.These results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell growth.Thus,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.展开更多
Ship type identification is an important part of electronic reconnaissance. However, in the existing methods, such as statistical-based methods and fuzzy-mathematics-based methods, the information acquired by the pass...Ship type identification is an important part of electronic reconnaissance. However, in the existing methods, such as statistical-based methods and fuzzy-mathematics-based methods, the information acquired by the passive sensor is not fully utilized, and there is a certain ambiguity in the assignment relationship of the emitters-ship. They can’t conclude the accurate and reliable assignment relationship of the emitters-ship. Therefore, this paper proposes a comprehensive correlation discriminant method to obtain a more reliable and comprehensive emitters-ship assignment, and then uses information entropy method to identify the type of the target ship on the basis of this association and assign the credibility. The simulation results show that this algorithm can effectively solve the problem of target ship type identification using the information of multi-passive sensors.展开更多
On the basis of target transfer function with the early time and late time response together, a method for solving the feature coefficients of target is investigated by utilizing approximation theory and method. Then,...On the basis of target transfer function with the early time and late time response together, a method for solving the feature coefficients of target is investigated by utilizing approximation theory and method. Then, the feature coefficients are classified by the minimum distance criterion to identify targets automatically.展开更多
In this paper,a new radar target identification scheme is presented based on adaptivediscrimination waveform synthesis and a nearest neighbor neural network.It can directly use theimpulse response of the target to syn...In this paper,a new radar target identification scheme is presented based on adaptivediscrimination waveform synthesis and a nearest neighbor neural network.It can directly use theimpulse response of the target to synthesize discrimination waveform,so the poles extractionprocedure is not required.Particularly,it can successfully operate on the case that the poles ofthe target are weakly dependent on the aspect angle.展开更多
In this paper, by using the biorthogonal quadrature filters, the biorthogonal mul-tiresolution analysis of finite dimension space equipped with inner product and the fast discrete wavelet transform (FDWT) are construc...In this paper, by using the biorthogonal quadrature filters, the biorthogonal mul-tiresolution analysis of finite dimension space equipped with inner product and the fast discrete wavelet transform (FDWT) are constructed. The dual transform method is proposed and the radar data storage is reduced by it. The method of choosing the wavelet coefficients, and the methods of correlation and nearest neighbor classification in wavelet domain based on the compressed data, are presented. The experimental results of the classification, using the high resolution range returns from six kinds of aircrafts, show that the methods of transform, compression and recognition are efficient.展开更多
In order to improve the identification capability of ultra wide-band radar,this paper in-troduces a step-variant multiresolution approach for the time-shift parameter estimation. Subsequently,combining with the approa...In order to improve the identification capability of ultra wide-band radar,this paper in-troduces a step-variant multiresolution approach for the time-shift parameter estimation. Subsequently,combining with the approach,a Geometrical Theory of Diffraction(GTD) model-based time-shift Invariant method to target identification using Matching Pursuits and Likelihood Ratio Test(IMPLRT) is developed. Simulation results using measured scattering signatures of two targets in an ultra wide-band chamber are presented contrasting the performance of the IMPLRT to the Wang's MPLRT technique.展开更多
OBJECTIVE Our group mainly focuses on the target identification and pharmacological mechanism study of TCM.We deeply identified the direct targets of the active ingredients in TCM using molecule probe-'Target Fish...OBJECTIVE Our group mainly focuses on the target identification and pharmacological mechanism study of TCM.We deeply identified the direct targets of the active ingredients in TCM using molecule probe-'Target Fishing' technology in chemical biology,and explored the related signaling pathways to explain the traditional efficiency of TCM.METHODS We synthesized biotin-tagged mole.cule probe by connecting biotin tag to TCM active molecule using PGE as a linker.Then,the biotintagged molecule probe was bound to the surface of solid beads by strong biotin-avidin interaction.Thus,the molecule probe-bound beads were mixed with cell lysates to capture the potential targets and identified by MS.RESULTS Our study found that SA which was an anti-inflammatory compound.could selectively bind to IMPDH2 in microglial cells,and SA showed weaker anti-inflammatory effect on IMPDH2-knock down microglial cells,suggesting IMPDH2 as a key anti-inflammatory target for SA.Ad.ditionally,handelin was a key anti-inflammatory compound.We identified the target protein of handelin as Hsp70 from microglial cells using target pull-down technology.Moreover,handelin showed weaker anti-inflammatory effect on Hsp70-knock down microglial cells,revealing that Hsp70 was the direct antiinflammatory target of handelin.CONCLUSION Our study provided methodology references for TCM target identification in the future,and also showed a new insight for exploring the pharmacological mechanism of TCM active ingredients.More importantly,we can perform scientific annotation for TCM efficiency by clarifying the biological functions of each target protein,showing important significance on modernization and internationalization of TCM.展开更多
This paper proposes a hybrid method, called CNOP–4 DVar, for the identification of sensitive areas in targeted observations, which takes the advantages of both the conditional nonlinear optimal perturbation(CNOP) and...This paper proposes a hybrid method, called CNOP–4 DVar, for the identification of sensitive areas in targeted observations, which takes the advantages of both the conditional nonlinear optimal perturbation(CNOP) and four-dimensional variational assimilation(4 DVar) methods. The proposed CNOP–4 DVar method is capable of capturing the most sensitive initial perturbation(IP), which causes the greatest perturbation growth at the time of verification;it can also identify sensitive areas by evaluating their assimilation effects for eliminating the most sensitive IP. To alleviate the dependence of the CNOP–4 DVar method on the adjoint model, which is inherited from the adjoint-based approach, we utilized two adjointfree methods, NLS-CNOP and NLS-4 DVar, to solve the CNOP and 4 DVar sub-problems, respectively. A comprehensive performance evaluation for the proposed CNOP–4 DVar method and its comparison with the CNOP and CNOP–ensemble transform Kalman filter(ETKF) methods based on 10 000 observing system simulation experiments on the shallow-water equation model are also provided. The experimental results show that the proposed CNOP–4 DVar method performs better than the CNOP–ETKF method and substantially better than the CNOP method.展开更多
Aiming at the effective realization of particle filter for maneuvering target tracking in multi-sensor measurements,a novel multi-sensor multiple model particle filtering algorithm with correlated noises is proposed.C...Aiming at the effective realization of particle filter for maneuvering target tracking in multi-sensor measurements,a novel multi-sensor multiple model particle filtering algorithm with correlated noises is proposed.Combined with the kinetic evolution equation of target state,a multi-sensor multiple model particle filter is firstly constructed,which is also used as the basic framework of a new algorithm.In the new algorithm,in order to weaken the adverse influence from random measurement noises in the measuring process of particle weight,a weight optimization strategy is introduced to improve the reliability and stability of particle weight.In addition,considering the correlated noise existing in the practical engineering,a decoupling method of correlated noise is given by the rearrangement and transformation of the state transition equation and measurement equation.Since the weight optimization strategy and noise decoupling method adopt respectively the center fusion structure and the off-line way,it improves the adverse effect effectively on computational complexity for increasing state dimension and sensor number.Finally,the theoretical analysis and experimental results show the feasibility and efficiency of the proposed algorithm.展开更多
In September 2011, an infectious disease suspected to be postweaning multisystemic wasting syndrome (PMWS) broke out in some pig farm in Taizhou. The inguinal lymph node, liver and lung tissues were collected and gr...In September 2011, an infectious disease suspected to be postweaning multisystemic wasting syndrome (PMWS) broke out in some pig farm in Taizhou. The inguinal lymph node, liver and lung tissues were collected and grinded into tissue suspension. The suspension was subjected to PCR detection, and the positive product was sequenced. The suspension of positive samples was filtered with 0.22 μm filter membrane, and the filtrate was inoculated onto PK15 cells. After five generations of blind passages, the cell viral liquid was collected and extracted for DNA, which was subjected to PCR detection and indirect immunofluorescence. The results showed that the isolate was porcine circovirus type 2 (PCV2) and designated as TAIZ110926. The target sequence was committed to NCBI with a serial number: KF039888.展开更多
Electronic throttle control (ETC) system has worked its way to becoming a standard subsystem in most of the current automobiles as it has contributed much to the improvement of fuel economy, emissions, drivability and...Electronic throttle control (ETC) system has worked its way to becoming a standard subsystem in most of the current automobiles as it has contributed much to the improvement of fuel economy, emissions, drivability and safety. Precision control of the subsystem, which consists of a dc motor driving a throttle plate, a pre-loaded return spring and a set of gear train to regulate airflow into the engine, seems rather straightforward and yet complex. The difficulties lie in the unknown system parameters, hard nonlinearity of the pre-loaded spring that pulls the throttle plate to its default position, and friction, among others. In this paper, we extend our previous results obtained for the modeling, unknown system parameters identification and control of a commercially available Bosch’s DV-E5 ETC system. Details of modeling and parameters identification based on laboratory experiments, data analysis, and knowledge of the system are provided. The parameters identification results were verified and validated by a real-time PID control implemented with an xPC Target. A nonlinear control design was then proposed utilizing the input-output feedback linearization approach and technique. In view of a recent massive auto recalls due to the controversial uncontrollable engine accelerations, the results of this paper may inspire further research interest on the drive-by-wire technology.展开更多
Inertial characteristics of non-cooperative targets are crucial for space capture and sub-sequent on-orbit servicing.Previous methods for identifying inertial parameters involve proximity operations,which are associat...Inertial characteristics of non-cooperative targets are crucial for space capture and sub-sequent on-orbit servicing.Previous methods for identifying inertial parameters involve proximity operations,which are associated with the risk of collision with non-cooperative targets.This paper introduces a long-range,contactless method for identifying the inertial parameters of a non-cooperative target during the pre-capture phase.Specifically,electrostatic interaction is used as an external excitation to alter the target's motion.A force estimation algorithm that uses measure-ments from visual and potential sensors is proposed to estimate the electrostatic interaction and eliminate the need for force sensors.Furthermore,a recursive estimation-identification framework is presented to concurrently estimate the coupled motion state,weak electrostatic interaction,and inertial parameters of the target.The simulation results show that the proposed method extends the identification distance to 170 times that of the previous method while maintaining high identifica-tion precision forall parameters.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 81503039)
文摘Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus,the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.
文摘MicroRNAs (miRNAs) are a class of ~22 nucleotides long non coding RNA molecules which play an important role in gene regulation at the post transcriptional level. The conserved nature of miRNAs provides the basis of new miRNA identification through homology search. In an attempt to identify new conserved miRNAs in tea, previously known plant miRNAs were used for searching their homolog in a tea Expressed Sequence Tags and full length nucleotide sequence database. The sequences showing homolog no more than four mismatches were predicted for their fold back structures and passed through a series of filtration criteria, finally led us to identify 13 conserved miRNAs in tea belonging to 9 miRNA families. A total of 37 potential target genes in Arabidopsis were identified subsequently for 7 miRNA families based on their sequence complementarity which encode transcription factors (8%), enzymes (30%) and transporters (14%) as well as other proteins involved in physiological and metabolic processes (48%). Overall, our findings will accelerate the way for further researches of miRNAs and their functions in tea.
基金supported by AMED Grants(Nos.JP16cm0106112 and JP16cm0106002)JSPS KAKENHI Grants(Nos.JP17H06412,18H05503,JP19K05744,JP20K05857,JP20H05620,JP21H04720,JP22H04922,and JP22K05363).
文摘Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identification of a potent DHODH inhibitor by proteomic profiling.Cell-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer cells.Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic acid.Moreover,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid.These results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell growth.Thus,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.
文摘Ship type identification is an important part of electronic reconnaissance. However, in the existing methods, such as statistical-based methods and fuzzy-mathematics-based methods, the information acquired by the passive sensor is not fully utilized, and there is a certain ambiguity in the assignment relationship of the emitters-ship. They can’t conclude the accurate and reliable assignment relationship of the emitters-ship. Therefore, this paper proposes a comprehensive correlation discriminant method to obtain a more reliable and comprehensive emitters-ship assignment, and then uses information entropy method to identify the type of the target ship on the basis of this association and assign the credibility. The simulation results show that this algorithm can effectively solve the problem of target ship type identification using the information of multi-passive sensors.
文摘On the basis of target transfer function with the early time and late time response together, a method for solving the feature coefficients of target is investigated by utilizing approximation theory and method. Then, the feature coefficients are classified by the minimum distance criterion to identify targets automatically.
文摘In this paper,a new radar target identification scheme is presented based on adaptivediscrimination waveform synthesis and a nearest neighbor neural network.It can directly use theimpulse response of the target to synthesize discrimination waveform,so the poles extractionprocedure is not required.Particularly,it can successfully operate on the case that the poles ofthe target are weakly dependent on the aspect angle.
文摘In this paper, by using the biorthogonal quadrature filters, the biorthogonal mul-tiresolution analysis of finite dimension space equipped with inner product and the fast discrete wavelet transform (FDWT) are constructed. The dual transform method is proposed and the radar data storage is reduced by it. The method of choosing the wavelet coefficients, and the methods of correlation and nearest neighbor classification in wavelet domain based on the compressed data, are presented. The experimental results of the classification, using the high resolution range returns from six kinds of aircrafts, show that the methods of transform, compression and recognition are efficient.
文摘In order to improve the identification capability of ultra wide-band radar,this paper in-troduces a step-variant multiresolution approach for the time-shift parameter estimation. Subsequently,combining with the approach,a Geometrical Theory of Diffraction(GTD) model-based time-shift Invariant method to target identification using Matching Pursuits and Likelihood Ratio Test(IMPLRT) is developed. Simulation results using measured scattering signatures of two targets in an ultra wide-band chamber are presented contrasting the performance of the IMPLRT to the Wang's MPLRT technique.
基金supported by National Natural Science Foundation of China(81773932)
文摘OBJECTIVE Our group mainly focuses on the target identification and pharmacological mechanism study of TCM.We deeply identified the direct targets of the active ingredients in TCM using molecule probe-'Target Fishing' technology in chemical biology,and explored the related signaling pathways to explain the traditional efficiency of TCM.METHODS We synthesized biotin-tagged mole.cule probe by connecting biotin tag to TCM active molecule using PGE as a linker.Then,the biotintagged molecule probe was bound to the surface of solid beads by strong biotin-avidin interaction.Thus,the molecule probe-bound beads were mixed with cell lysates to capture the potential targets and identified by MS.RESULTS Our study found that SA which was an anti-inflammatory compound.could selectively bind to IMPDH2 in microglial cells,and SA showed weaker anti-inflammatory effect on IMPDH2-knock down microglial cells,suggesting IMPDH2 as a key anti-inflammatory target for SA.Ad.ditionally,handelin was a key anti-inflammatory compound.We identified the target protein of handelin as Hsp70 from microglial cells using target pull-down technology.Moreover,handelin showed weaker anti-inflammatory effect on Hsp70-knock down microglial cells,revealing that Hsp70 was the direct antiinflammatory target of handelin.CONCLUSION Our study provided methodology references for TCM target identification in the future,and also showed a new insight for exploring the pharmacological mechanism of TCM active ingredients.More importantly,we can perform scientific annotation for TCM efficiency by clarifying the biological functions of each target protein,showing important significance on modernization and internationalization of TCM.
基金partially supported by the National Key R&D Program of China (Grant No. 2016YFA0600203)the National Natural Science Foundation of China (Grant No. 41575100)
文摘This paper proposes a hybrid method, called CNOP–4 DVar, for the identification of sensitive areas in targeted observations, which takes the advantages of both the conditional nonlinear optimal perturbation(CNOP) and four-dimensional variational assimilation(4 DVar) methods. The proposed CNOP–4 DVar method is capable of capturing the most sensitive initial perturbation(IP), which causes the greatest perturbation growth at the time of verification;it can also identify sensitive areas by evaluating their assimilation effects for eliminating the most sensitive IP. To alleviate the dependence of the CNOP–4 DVar method on the adjoint model, which is inherited from the adjoint-based approach, we utilized two adjointfree methods, NLS-CNOP and NLS-4 DVar, to solve the CNOP and 4 DVar sub-problems, respectively. A comprehensive performance evaluation for the proposed CNOP–4 DVar method and its comparison with the CNOP and CNOP–ensemble transform Kalman filter(ETKF) methods based on 10 000 observing system simulation experiments on the shallow-water equation model are also provided. The experimental results show that the proposed CNOP–4 DVar method performs better than the CNOP–ETKF method and substantially better than the CNOP method.
基金Supported by the National Natural Science Foundation of China(No.61300214)the National Natural Science Foundation of Henan Province(No.132300410148)+1 种基金the Post-doctoral Science Foundation of China(No.2014M551999)the Funding Scheme of Young Key Teacher ofHenan Province Universities(No.2013GGJS-026)
文摘Aiming at the effective realization of particle filter for maneuvering target tracking in multi-sensor measurements,a novel multi-sensor multiple model particle filtering algorithm with correlated noises is proposed.Combined with the kinetic evolution equation of target state,a multi-sensor multiple model particle filter is firstly constructed,which is also used as the basic framework of a new algorithm.In the new algorithm,in order to weaken the adverse influence from random measurement noises in the measuring process of particle weight,a weight optimization strategy is introduced to improve the reliability and stability of particle weight.In addition,considering the correlated noise existing in the practical engineering,a decoupling method of correlated noise is given by the rearrangement and transformation of the state transition equation and measurement equation.Since the weight optimization strategy and noise decoupling method adopt respectively the center fusion structure and the off-line way,it improves the adverse effect effectively on computational complexity for increasing state dimension and sensor number.Finally,the theoretical analysis and experimental results show the feasibility and efficiency of the proposed algorithm.
基金Supported by Key Project of Jiangsu Agri-animal Husbandry Vocational College(ZD201104)College Students'Innovation and Enterpreneurship Training Program of Jiangsu Province(201312806014Y)Special Fund for Fenghuang talents in Jiangsu Agri-animal Husbandry Vocational College
文摘In September 2011, an infectious disease suspected to be postweaning multisystemic wasting syndrome (PMWS) broke out in some pig farm in Taizhou. The inguinal lymph node, liver and lung tissues were collected and grinded into tissue suspension. The suspension was subjected to PCR detection, and the positive product was sequenced. The suspension of positive samples was filtered with 0.22 μm filter membrane, and the filtrate was inoculated onto PK15 cells. After five generations of blind passages, the cell viral liquid was collected and extracted for DNA, which was subjected to PCR detection and indirect immunofluorescence. The results showed that the isolate was porcine circovirus type 2 (PCV2) and designated as TAIZ110926. The target sequence was committed to NCBI with a serial number: KF039888.
文摘Electronic throttle control (ETC) system has worked its way to becoming a standard subsystem in most of the current automobiles as it has contributed much to the improvement of fuel economy, emissions, drivability and safety. Precision control of the subsystem, which consists of a dc motor driving a throttle plate, a pre-loaded return spring and a set of gear train to regulate airflow into the engine, seems rather straightforward and yet complex. The difficulties lie in the unknown system parameters, hard nonlinearity of the pre-loaded spring that pulls the throttle plate to its default position, and friction, among others. In this paper, we extend our previous results obtained for the modeling, unknown system parameters identification and control of a commercially available Bosch’s DV-E5 ETC system. Details of modeling and parameters identification based on laboratory experiments, data analysis, and knowledge of the system are provided. The parameters identification results were verified and validated by a real-time PID control implemented with an xPC Target. A nonlinear control design was then proposed utilizing the input-output feedback linearization approach and technique. In view of a recent massive auto recalls due to the controversial uncontrollable engine accelerations, the results of this paper may inspire further research interest on the drive-by-wire technology.
基金supported by the National Natural Science Foundation of China (No.6200326).
文摘Inertial characteristics of non-cooperative targets are crucial for space capture and sub-sequent on-orbit servicing.Previous methods for identifying inertial parameters involve proximity operations,which are associated with the risk of collision with non-cooperative targets.This paper introduces a long-range,contactless method for identifying the inertial parameters of a non-cooperative target during the pre-capture phase.Specifically,electrostatic interaction is used as an external excitation to alter the target's motion.A force estimation algorithm that uses measure-ments from visual and potential sensors is proposed to estimate the electrostatic interaction and eliminate the need for force sensors.Furthermore,a recursive estimation-identification framework is presented to concurrently estimate the coupled motion state,weak electrostatic interaction,and inertial parameters of the target.The simulation results show that the proposed method extends the identification distance to 170 times that of the previous method while maintaining high identifica-tion precision forall parameters.