A new extended exponential lifetime model called Harris extended-exponential(HEE)distribution for data modelling with increasing and decreasing hazard rate shapes has been considered.In the reliability context,researc...A new extended exponential lifetime model called Harris extended-exponential(HEE)distribution for data modelling with increasing and decreasing hazard rate shapes has been considered.In the reliability context,researchers prefer to use censoring plans to collect data in order to achieve a compromise between total test time and/or test sample size.So,this study considers both maximum likelihood and Bayesian estimates of the Harris extended-exponential distribution parameters and some of its reliability indices using a progressive Type-II censoring strategy.Under the premise of independent gamma priors,the Bayesian estimation is created using the squared-error and general entropy loss functions.Due to the challenging form of the joint posterior distribution,to evaluate the Bayes estimates,samples from the full conditional distributions are generated using Markov Chain Monte Carlo techniques.For each unknown parameter,the highest posterior density credible intervals and asymptotic confidence intervals are also determined.Through a simulated study,the usefulness of the various suggested strategies is assessed.The optimal progressive censoring plans are also shown,and various optimality criteria are investigated.Two actual data sets,taken from engineering and veterinary medicine areas,are analyzed to show how the offered point and interval estimators can be used in practice and to verify that the proposed model furnishes a good fit than other lifetimemodels:alpha power exponential,generalized-exponential,Nadarajah-Haghighi,Weibull,Lomax,gamma and exponential distributions.Numerical evaluations revealed that in the presence of progressively Type-II censored data,the Bayes estimation method against the squared-error(symmetric)loss is advised for getting the point and interval estimates of the HEE distribution.展开更多
InAs/GaSb type-II superlattce (T2SL) photodetector structures at the MWIR regime were grown by molecular beam epitaxy. The growth temperature and group-V soaking times were optimized with respect to interface and tran...InAs/GaSb type-II superlattce (T2SL) photodetector structures at the MWIR regime were grown by molecular beam epitaxy. The growth temperature and group-V soaking times were optimized with respect to interface and transport quality. Novel strain compensation schemes with insertion of InSb layers were proposed and tested to be efficient to tune the overall strain between tensile and compressive without degradation of interface and optical quality. The effect of the proposed methods is modeled by analytic functions.? Band structure calculations were also carried out for the proposed T2SL structures to assist optimizing sample designs. Single pixel photodiodes with a low dark current were demonstrated.展开更多
An inverse problemin practical scientific investigations is the process of computing unknown parameters from a set of observations where the observations are only recorded indirectly,such as monitoring and controlling...An inverse problemin practical scientific investigations is the process of computing unknown parameters from a set of observations where the observations are only recorded indirectly,such as monitoring and controlling quality in industrial process control.Linear regression can be thought of as linear inverse problems.In other words,the procedure of unknown estimation parameters can be expressed as an inverse problem.However,maximum likelihood provides an unstable solution,and the problembecomes more complicated if unknown parameters are estimated from different samples.Hence,researchers search for better estimates.We study two joint censoring schemes for lifetime products in industrial process monitoring.In practice,this type of data can be collected in fields such as the medical industry and industrial engineering.In this study,statistical inference for the Chen lifetime products is considered and analyzed to estimate underlying parameters.Maximum likelihood and Bayes’rule are both studied for model parameters.The asymptotic distribution of maximumlikelihood estimators and the empirical distributions obtained withMarkov chainMonte Carlo algorithms are utilized to build the interval estimators.Theoretical results using tables and figures are adopted through simulation studies and verified in an analysis of the lifetime data.We briefly describe the performance of developed methods.展开更多
The main purpose of this paper is to obtain the inference of parameters of heterogeneous population represented by finite mixture of two Pareto (MTP) distributions of the second kind. The constant-partially accelerate...The main purpose of this paper is to obtain the inference of parameters of heterogeneous population represented by finite mixture of two Pareto (MTP) distributions of the second kind. The constant-partially accelerated life tests are applied based on progressively type-II censored samples. The maximum likelihood estimates (MLEs) for the considered parameters are obtained by solving the likelihood equations of the model parameters numerically. The Bayes estimators are obtained by using Markov chain Monte Carlo algorithm under the balanced squared error loss function. Based on Monte Carlo simulation, Bayes estimators are compared with their corresponding maximum likelihood estimators. The two-sample prediction technique is considered to derive Bayesian prediction bounds for future order statistics based on progressively type-II censored informative samples obtained from constant-partially accelerated life testing models. The informative and future samples are assumed to be obtained from the same population. The coverage probabilities and the average interval lengths of the confidence intervals are computed via a Monte Carlo simulation to investigate the procedure of the prediction intervals. Analysis of a simulated data set has also been presented for illustrative purposes. Finally, comparisons are made between Bayesian and maximum likelihood estimators via a Monte Carlo simulation study.展开更多
In this paper,we propose a new extension of the traditional Rayleigh distribution called the modified Kies Rayleigh distribution.The new distribution contains one scale and one shape parameter and its hazard rate func...In this paper,we propose a new extension of the traditional Rayleigh distribution called the modified Kies Rayleigh distribution.The new distribution contains one scale and one shape parameter and its hazard rate function can be increasing and bathtub-shaped.Some mathematical properties of the new distribution are derived including quantiles and moments.The parameters of modified Kies Rayleigh distribution are estimated based on progressively Type-II censored data.For this purpose,we consider two estimation methods,namely maximum likelihood and maximum product of spacing estimation methods.To compare the efficiency of the proposed estimators,a simulation study is carried out.To show the applicability of the new model as well as the estimation methods,one real data for failure times of software is analyzed.Based on the empirical parts,we can conclude that the proposed model can be considered as a good model in the field of life testing and reliability analysis compared with other competing models.展开更多
In this paper, based on a new type of censoring scheme called an adaptive type-II progressive censoring scheme introduce by Ng et al. [1], Naval Research Logistics is considered. Based on this type of censoring the ma...In this paper, based on a new type of censoring scheme called an adaptive type-II progressive censoring scheme introduce by Ng et al. [1], Naval Research Logistics is considered. Based on this type of censoring the maximum likelihood estimation (MLE), Bayes estimation, and parametric bootstrap method are used for estimating the unknown parameters. Also, we propose to apply Markov chain Monte Carlo (MCMC) technique to carry out a Bayesian estimation procedure and in turn calculate the credible intervals. Point estimation and confidence intervals based on maximum likelihood and bootstrap method are also proposed. The approximate Bayes estimators obtained under the assumptions of non-informative priors, are compared with the maximum likelihood estimators. Numerical examples using real data set are presented to illustrate the methods of inference developed here. Finally, the maximum likelihood, bootstrap and the different Bayes estimates are compared via a Monte Carlo simulation study.展开更多
Field equations in the presence of perfect fluid distribution are obtained in a scalar tensor theory of gravitation proposed by Brans and Dicke[1] with the aid of Bianchi type-II, VIII & IX metrics. Exact prefect ...Field equations in the presence of perfect fluid distribution are obtained in a scalar tensor theory of gravitation proposed by Brans and Dicke[1] with the aid of Bianchi type-II, VIII & IX metrics. Exact prefect fluid Bianchi type- IX cosmological model is presented since other models doesn’t exist in Brans-Dicke scalar tensor theory of gravitation. Some physical properties of the model are also discussed.展开更多
We present a theoretical study on the terahertz (THz) optoelectronic properties of long-period InAs/GaSb type-II super lattices (SLs). The eight-band k·p model is used to calculate the electronic structures of su...We present a theoretical study on the terahertz (THz) optoelectronic properties of long-period InAs/GaSb type-II super lattices (SLs). The eight-band k·p model is used to calculate the electronic structures of such SLs and on the basis of band structures, the Boltzmann equation approach is employed to calculate the optical absorption coefficients for the corresponding SL systems. It is found that long-period InAs/GaSb type-II SLs have a considerable absorption in the THz bandwidth. By examining the dependence of THz absorption coefficient on the InAs/GaSb layer widths, we demonstrate that with a proper choice of InAs/GaSb layer widths, an optimized THz absorption can be achieved. This study is pertinent to the potential application of InAs/GaSb type-II SLs as THz photo detectors.展开更多
In this paper, an interpolating method for bivariate cubic splines with C2-join on type-II triangular at a rectangular domain is given, and the approximation degree, inter- polating existence and uniqueness of the cub...In this paper, an interpolating method for bivariate cubic splines with C2-join on type-II triangular at a rectangular domain is given, and the approximation degree, inter- polating existence and uniqueness of the cubic splines are studied.展开更多
In this paper,we present an investigation of type-II 'W' quantum wells for the InAs/Ga 1 x In x Sb/AlSb family,where 'W' denotes the conduction profile of the material.We focus our attention on using t...In this paper,we present an investigation of type-II 'W' quantum wells for the InAs/Ga 1 x In x Sb/AlSb family,where 'W' denotes the conduction profile of the material.We focus our attention on using the eight-band k · p model to calculate the band structures within the framework of finite element method.For the sake of clarity,the simulation in this paper is simplified and based on only one period-AlSb/InAs/Ga 1 x In x Sb/InAs/AlSb.The obtained numerical results include the energy levels and wavefunctions of carriers.We discuss the variations of the electronic properties by changing several important parameters,such as the thickness of either InAs or Ga 1 x In x Sb layer and the alloy composition in Ga 1 x In x Sb separately.In the last part,in order to compare the eight-band k · p model,we recalculate the conduction bands of the 'W' structure using the one-band k · p model and then discuss the difference between the two results,showing that conduction bands are strongly coupled with valence bands in the narrow band gap structure.The in-plane energy dispersions,which illustrate the suppression of the Auger recombination process,are also obtained.展开更多
Objective: To investigate the effect of acupuncture on high hemagglutination state, blood sugar raising hormone and immunocyte factor levels in type II diabetes patients. Methods: A total of 120 inpatients and outpati...Objective: To investigate the effect of acupuncture on high hemagglutination state, blood sugar raising hormone and immunocyte factor levels in type II diabetes patients. Methods: A total of 120 inpatients and outpatients were randomly divided into acupuncture plus medication group (n=52) and medication group (n=50). In addition, 18 type II diabetes patients formed acupuncture group for comparing their therapeutic effects. Main acupoints used were Pishu (BL 20), Geshu (BL 17), Yishu, Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), etc.. combined with other acupoints according to different sydroms. These acupoints were stimulated by manipulaing the filiform needles with uniform reinforcing and reducing method for 15 min and then stimulated electrically for 15 min with an electroacupuncture therapeutic apparatus. Western medicines used were Glipizide, Dimethyldiguanide Hydrochloride, etc.. The treatment was given once daily, with 10 sessions being a therapeutic course, 2～3 courses altogether. Indexes of external thrombosis length (ETL), platelet agglutination rate (PAgR), fibrinogen (FG), activated partial thromboplastin time (APTT), fasting blood glucose (FBG), prothrombin time(PT), adrenocoticortropic hormone (ACTH), cortisol (CS), growth hormone (GH), glucagon (GL), tumor necrosis factor alpha (TNF α), interleukin 6 (IL 6), insulin (INS) and C peptide (C P) were determined using radioimmunoassay. Results: After 2～3 courses of treatment, both acupuncture group and medication plus acupuncture group could significantly improve high hemagglutination state, lower blood sugar raising hormone level, regulate immunocyte factor level and raise the sensitivity of insulin, which were apparently superior to those of medication group (P<0.05～0.01). Conclusion: Acupuncture therapy can effectively regulate plasma blood sugar raising hormone, immunocyte factor levels, increase the sensitivity of insulin to target cells, resist blood coagulation and improve microcirculation.展开更多
Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allo...Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical evaluation.Recently,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.Here,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i.We also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62,which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases.Collectively,62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.展开更多
A novel extended Lindley lifetime model that exhibits unimodal or decreasing density shapes as well as increasing,bathtub or unimodal-then-bathtub failure rates, named the Marshall-Olkin-Lindley (MOL) model is studied...A novel extended Lindley lifetime model that exhibits unimodal or decreasing density shapes as well as increasing,bathtub or unimodal-then-bathtub failure rates, named the Marshall-Olkin-Lindley (MOL) model is studied.In this research, using a progressive Type-II censored, various inferences of the MOL model parameters oflife are introduced. Utilizing the maximum likelihood method as a classical approach, the estimators of themodel parameters and various reliability measures are investigated. Against both symmetric and asymmetric lossfunctions, the Bayesian estimates are obtained using the Markov Chain Monte Carlo (MCMC) technique with theassumption of independent gamma priors. From the Fisher information data and the simulatedMarkovian chains,the approximate asymptotic interval and the highest posterior density interval, respectively, of each unknownparameter are calculated. Via an extensive simulated study, the usefulness of the various suggested strategies isassessedwith respect to some evaluationmetrics such as mean squared errors, mean relative absolute biases, averageconfidence lengths, and coverage percentages. Comparing the Bayesian estimations based on the asymmetric lossfunction to the traditional technique or the symmetric loss function-based Bayesian estimations, the analysisdemonstrates that asymmetric loss function-based Bayesian estimations are preferred. Finally, two data sets,representing vinyl chloride and repairable mechanical equipment items, have been investigated to support theapproaches proposed and show the superiority of the proposed model compared to the other fourteen lifetimemodels.展开更多
基金This research was funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project Number(PNURSP2023R175),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘A new extended exponential lifetime model called Harris extended-exponential(HEE)distribution for data modelling with increasing and decreasing hazard rate shapes has been considered.In the reliability context,researchers prefer to use censoring plans to collect data in order to achieve a compromise between total test time and/or test sample size.So,this study considers both maximum likelihood and Bayesian estimates of the Harris extended-exponential distribution parameters and some of its reliability indices using a progressive Type-II censoring strategy.Under the premise of independent gamma priors,the Bayesian estimation is created using the squared-error and general entropy loss functions.Due to the challenging form of the joint posterior distribution,to evaluate the Bayes estimates,samples from the full conditional distributions are generated using Markov Chain Monte Carlo techniques.For each unknown parameter,the highest posterior density credible intervals and asymptotic confidence intervals are also determined.Through a simulated study,the usefulness of the various suggested strategies is assessed.The optimal progressive censoring plans are also shown,and various optimality criteria are investigated.Two actual data sets,taken from engineering and veterinary medicine areas,are analyzed to show how the offered point and interval estimators can be used in practice and to verify that the proposed model furnishes a good fit than other lifetimemodels:alpha power exponential,generalized-exponential,Nadarajah-Haghighi,Weibull,Lomax,gamma and exponential distributions.Numerical evaluations revealed that in the presence of progressively Type-II censored data,the Bayes estimation method against the squared-error(symmetric)loss is advised for getting the point and interval estimates of the HEE distribution.
文摘InAs/GaSb type-II superlattce (T2SL) photodetector structures at the MWIR regime were grown by molecular beam epitaxy. The growth temperature and group-V soaking times were optimized with respect to interface and transport quality. Novel strain compensation schemes with insertion of InSb layers were proposed and tested to be efficient to tune the overall strain between tensile and compressive without degradation of interface and optical quality. The effect of the proposed methods is modeled by analytic functions.? Band structure calculations were also carried out for the proposed T2SL structures to assist optimizing sample designs. Single pixel photodiodes with a low dark current were demonstrated.
基金Let Pub(www.letpub.com)for its linguistic assistance during the preparation of this manuscript.This study was funded by Taif University Researchers Supporting Project number(TURSP-2020/279),Taif University,Taif,Saudi Arabia.
文摘An inverse problemin practical scientific investigations is the process of computing unknown parameters from a set of observations where the observations are only recorded indirectly,such as monitoring and controlling quality in industrial process control.Linear regression can be thought of as linear inverse problems.In other words,the procedure of unknown estimation parameters can be expressed as an inverse problem.However,maximum likelihood provides an unstable solution,and the problembecomes more complicated if unknown parameters are estimated from different samples.Hence,researchers search for better estimates.We study two joint censoring schemes for lifetime products in industrial process monitoring.In practice,this type of data can be collected in fields such as the medical industry and industrial engineering.In this study,statistical inference for the Chen lifetime products is considered and analyzed to estimate underlying parameters.Maximum likelihood and Bayes’rule are both studied for model parameters.The asymptotic distribution of maximumlikelihood estimators and the empirical distributions obtained withMarkov chainMonte Carlo algorithms are utilized to build the interval estimators.Theoretical results using tables and figures are adopted through simulation studies and verified in an analysis of the lifetime data.We briefly describe the performance of developed methods.
文摘The main purpose of this paper is to obtain the inference of parameters of heterogeneous population represented by finite mixture of two Pareto (MTP) distributions of the second kind. The constant-partially accelerated life tests are applied based on progressively type-II censored samples. The maximum likelihood estimates (MLEs) for the considered parameters are obtained by solving the likelihood equations of the model parameters numerically. The Bayes estimators are obtained by using Markov chain Monte Carlo algorithm under the balanced squared error loss function. Based on Monte Carlo simulation, Bayes estimators are compared with their corresponding maximum likelihood estimators. The two-sample prediction technique is considered to derive Bayesian prediction bounds for future order statistics based on progressively type-II censored informative samples obtained from constant-partially accelerated life testing models. The informative and future samples are assumed to be obtained from the same population. The coverage probabilities and the average interval lengths of the confidence intervals are computed via a Monte Carlo simulation to investigate the procedure of the prediction intervals. Analysis of a simulated data set has also been presented for illustrative purposes. Finally, comparisons are made between Bayesian and maximum likelihood estimators via a Monte Carlo simulation study.
基金the Deanship Scientific Research(DSR)King Abdulaziz University,Jeddah under Grant No.(G:337-130-1441).
文摘In this paper,we propose a new extension of the traditional Rayleigh distribution called the modified Kies Rayleigh distribution.The new distribution contains one scale and one shape parameter and its hazard rate function can be increasing and bathtub-shaped.Some mathematical properties of the new distribution are derived including quantiles and moments.The parameters of modified Kies Rayleigh distribution are estimated based on progressively Type-II censored data.For this purpose,we consider two estimation methods,namely maximum likelihood and maximum product of spacing estimation methods.To compare the efficiency of the proposed estimators,a simulation study is carried out.To show the applicability of the new model as well as the estimation methods,one real data for failure times of software is analyzed.Based on the empirical parts,we can conclude that the proposed model can be considered as a good model in the field of life testing and reliability analysis compared with other competing models.
文摘In this paper, based on a new type of censoring scheme called an adaptive type-II progressive censoring scheme introduce by Ng et al. [1], Naval Research Logistics is considered. Based on this type of censoring the maximum likelihood estimation (MLE), Bayes estimation, and parametric bootstrap method are used for estimating the unknown parameters. Also, we propose to apply Markov chain Monte Carlo (MCMC) technique to carry out a Bayesian estimation procedure and in turn calculate the credible intervals. Point estimation and confidence intervals based on maximum likelihood and bootstrap method are also proposed. The approximate Bayes estimators obtained under the assumptions of non-informative priors, are compared with the maximum likelihood estimators. Numerical examples using real data set are presented to illustrate the methods of inference developed here. Finally, the maximum likelihood, bootstrap and the different Bayes estimates are compared via a Monte Carlo simulation study.
文摘Field equations in the presence of perfect fluid distribution are obtained in a scalar tensor theory of gravitation proposed by Brans and Dicke[1] with the aid of Bianchi type-II, VIII & IX metrics. Exact prefect fluid Bianchi type- IX cosmological model is presented since other models doesn’t exist in Brans-Dicke scalar tensor theory of gravitation. Some physical properties of the model are also discussed.
文摘We present a theoretical study on the terahertz (THz) optoelectronic properties of long-period InAs/GaSb type-II super lattices (SLs). The eight-band k·p model is used to calculate the electronic structures of such SLs and on the basis of band structures, the Boltzmann equation approach is employed to calculate the optical absorption coefficients for the corresponding SL systems. It is found that long-period InAs/GaSb type-II SLs have a considerable absorption in the THz bandwidth. By examining the dependence of THz absorption coefficient on the InAs/GaSb layer widths, we demonstrate that with a proper choice of InAs/GaSb layer widths, an optimized THz absorption can be achieved. This study is pertinent to the potential application of InAs/GaSb type-II SLs as THz photo detectors.
文摘In this paper, an interpolating method for bivariate cubic splines with C2-join on type-II triangular at a rectangular domain is given, and the approximation degree, inter- polating existence and uniqueness of the cubic splines are studied.
基金supported by the National Natural Science Foundation of China (Grant No. 60636030)
文摘In this paper,we present an investigation of type-II 'W' quantum wells for the InAs/Ga 1 x In x Sb/AlSb family,where 'W' denotes the conduction profile of the material.We focus our attention on using the eight-band k · p model to calculate the band structures within the framework of finite element method.For the sake of clarity,the simulation in this paper is simplified and based on only one period-AlSb/InAs/Ga 1 x In x Sb/InAs/AlSb.The obtained numerical results include the energy levels and wavefunctions of carriers.We discuss the variations of the electronic properties by changing several important parameters,such as the thickness of either InAs or Ga 1 x In x Sb layer and the alloy composition in Ga 1 x In x Sb separately.In the last part,in order to compare the eight-band k · p model,we recalculate the conduction bands of the 'W' structure using the one-band k · p model and then discuss the difference between the two results,showing that conduction bands are strongly coupled with valence bands in the narrow band gap structure.The in-plane energy dispersions,which illustrate the suppression of the Auger recombination process,are also obtained.
文摘Objective: To investigate the effect of acupuncture on high hemagglutination state, blood sugar raising hormone and immunocyte factor levels in type II diabetes patients. Methods: A total of 120 inpatients and outpatients were randomly divided into acupuncture plus medication group (n=52) and medication group (n=50). In addition, 18 type II diabetes patients formed acupuncture group for comparing their therapeutic effects. Main acupoints used were Pishu (BL 20), Geshu (BL 17), Yishu, Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), etc.. combined with other acupoints according to different sydroms. These acupoints were stimulated by manipulaing the filiform needles with uniform reinforcing and reducing method for 15 min and then stimulated electrically for 15 min with an electroacupuncture therapeutic apparatus. Western medicines used were Glipizide, Dimethyldiguanide Hydrochloride, etc.. The treatment was given once daily, with 10 sessions being a therapeutic course, 2～3 courses altogether. Indexes of external thrombosis length (ETL), platelet agglutination rate (PAgR), fibrinogen (FG), activated partial thromboplastin time (APTT), fasting blood glucose (FBG), prothrombin time(PT), adrenocoticortropic hormone (ACTH), cortisol (CS), growth hormone (GH), glucagon (GL), tumor necrosis factor alpha (TNF α), interleukin 6 (IL 6), insulin (INS) and C peptide (C P) were determined using radioimmunoassay. Results: After 2～3 courses of treatment, both acupuncture group and medication plus acupuncture group could significantly improve high hemagglutination state, lower blood sugar raising hormone level, regulate immunocyte factor level and raise the sensitivity of insulin, which were apparently superior to those of medication group (P<0.05～0.01). Conclusion: Acupuncture therapy can effectively regulate plasma blood sugar raising hormone, immunocyte factor levels, increase the sensitivity of insulin to target cells, resist blood coagulation and improve microcirculation.
基金We thank Prof.Junying Yuan(IRCBC of CAS,Shanghai,China)and Dr.Jidong Zhu(Etern Therapeutics,Shanghai,China)for their generous help on this work,Dr.Sudan He(ISM of CAMS,Suzhou,China)for providing RIPK3-FKBP NIH/3T3 cells,and National Facility for Protein Science in Shanghai(China)for the help in animal studies.This work was supported by grants from the National Natural Science Foundation of China(Grants Nos.21837004,82151212,and 32170755)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39050500,China)Shanghai Municipal Science and Technology Major Project(Grant No.2019SHZDZX02,China).
文摘Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical evaluation.Recently,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.Here,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i.We also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62,which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases.Collectively,62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.
文摘A novel extended Lindley lifetime model that exhibits unimodal or decreasing density shapes as well as increasing,bathtub or unimodal-then-bathtub failure rates, named the Marshall-Olkin-Lindley (MOL) model is studied.In this research, using a progressive Type-II censored, various inferences of the MOL model parameters oflife are introduced. Utilizing the maximum likelihood method as a classical approach, the estimators of themodel parameters and various reliability measures are investigated. Against both symmetric and asymmetric lossfunctions, the Bayesian estimates are obtained using the Markov Chain Monte Carlo (MCMC) technique with theassumption of independent gamma priors. From the Fisher information data and the simulatedMarkovian chains,the approximate asymptotic interval and the highest posterior density interval, respectively, of each unknownparameter are calculated. Via an extensive simulated study, the usefulness of the various suggested strategies isassessedwith respect to some evaluationmetrics such as mean squared errors, mean relative absolute biases, averageconfidence lengths, and coverage percentages. Comparing the Bayesian estimations based on the asymmetric lossfunction to the traditional technique or the symmetric loss function-based Bayesian estimations, the analysisdemonstrates that asymmetric loss function-based Bayesian estimations are preferred. Finally, two data sets,representing vinyl chloride and repairable mechanical equipment items, have been investigated to support theapproaches proposed and show the superiority of the proposed model compared to the other fourteen lifetimemodels.
