This paper proposes a system representation for unifying control design and numerical calculation in nonlinear optimal control problems with inequality constraints in terms of the symplectic structure. The symplectic ...This paper proposes a system representation for unifying control design and numerical calculation in nonlinear optimal control problems with inequality constraints in terms of the symplectic structure. The symplectic structure is derived from Hamiltonian systems that are equivalent to Hamilton-Jacobi equations. In the representation, the constraints can be described as an input-state transformation of the system. Therefore, it can be seamlessly applied to the stable manifold method that is a precise numerical solver of the Hamilton-Jacobi equations. In conventional methods, e.g., the penalty method or the barrier method, it is difficult to systematically assign the weights of penalty functions that are used for realizing the constraints. In the proposed method, we can separate the adjustment of weights with respect to objective functions from that of penalty functions. Furthermore, the proposed method can extend the region of computable solutions in a state space. The validity of the method is shown by a numerical example of the optimal control of a vehicle model with steering limitations.展开更多
Background Estrogen receptor alpha （ER α） is the most important endocrine therapy responsiveness predictor for women with breast cancer. The accuracy of the prediction of the response to endocrine therapy was thoug...Background Estrogen receptor alpha （ER α） is the most important endocrine therapy responsiveness predictor for women with breast cancer. The accuracy of the prediction of the response to endocrine therapy was thought to be affected by involving the estrogen receptor coregulatory proteins and cross-talk between ER and other growth factor-signaling networks. Nuclear corepressor 1 （NCOR1） is one of the ER a transcription repressor. The objective of the study is to investigate the expression of NCOR1 at the protein level and pursue its predictive value for breast cancer endocrine therapy. Methods In the present study, the level of expression of NCOR1 protein has been assessed by immunohistochemistry in 104 cases of invasive carcinoma of the breast. Associations between NCOR1 protein expression and different clinicopathological factors and survival were sought. Results It was found that NCOR1 was expressed at significantly higher levels in responsive patients treated with endocrine therapy as first-line treatment on relapse. Responsive patients also had a significantly longer post-relapse survival and overall survival. No NCOR1 expression difference was found between patient by age, tumor size, lymph node status, different histological grade groups and human epidermal growth factor receptor 2 （HER2） status. Multivariate analysis showed that NCOR1 is an independent prognostic factor for over-all survival. Conclusions In breast cancer, NCOR1 protein expression level predicts response to endocrine therapy as first-line treatment for breast cancer patients on relapse and NCOR1 protein level assay may increase the accuracy in the endocrine treatment determination and, therefore, improving the patients survival.展开更多
Individuals which have invaded urbanized environments are reported to engage in riskier behav-iors,possibly influenced by the scarcity of predators in urbanized areas.Here,we studied the risk-taking behavior of birds ...Individuals which have invaded urbanized environments are reported to engage in riskier behav-iors,possibly influenced by the scarcity of predators in urbanized areas.Here,we studied the risk-taking behavior of birds which had invaded a new natural environment,rather than an artificial urban environment,using recently established populations of the bull-headed shrike Lanius bu-cephalus,which naturally colonized three subtropical islands in Japan.We compared flight initi-ation distance(FID),the distance at which an individual approached by a human initiates flight,be-tween the islands and the temperate mainland.FID was longer for the insular shrikes compared with the mainland shrikes after controlling for other factors,indicating that the individuals which had invaded a new natural environment had a lower propensity for risk-taking.A possible explan-ation for these results is that low risk-taking behavior might be adaptive on the islands due to predation by the black rat Rattus rattus,an unfamiliar predator not found in shrike habitats on the temperate mainland.Further studies are needed to examine the nest predation rate,predator species,and nest site selection of these insular shrike populations.展开更多
Despite several advances in targeted therapies for breast cancer,breast-cancer-associated death remains high in women.This is partially due to the lack of reliable markers predicting metastatic disease or recurrence a...Despite several advances in targeted therapies for breast cancer,breast-cancer-associated death remains high in women.This is partially due to the lack of reliable markers predicting metastatic disease or recurrence after initial therapy.Recent research into the clinical validity of circulating cancer-specific biomarkers as a“liquid biopsy”is of growing interest.Of these,exosomal microRNAs(miRNAs)are promising candidate biomarkers for clinical use in breast cancer.In addition to their diagnostic value,exosomal miRNAs play an important role in predicting clinical outcome or treatment response.In this review,it is focused on the findings concerning exosomal miRNAs in relation to disease detection,prognostic impact and therapeutic effect in breast cancer,and discuss their clinical utility.展开更多
文摘This paper proposes a system representation for unifying control design and numerical calculation in nonlinear optimal control problems with inequality constraints in terms of the symplectic structure. The symplectic structure is derived from Hamiltonian systems that are equivalent to Hamilton-Jacobi equations. In the representation, the constraints can be described as an input-state transformation of the system. Therefore, it can be seamlessly applied to the stable manifold method that is a precise numerical solver of the Hamilton-Jacobi equations. In conventional methods, e.g., the penalty method or the barrier method, it is difficult to systematically assign the weights of penalty functions that are used for realizing the constraints. In the proposed method, we can separate the adjustment of weights with respect to objective functions from that of penalty functions. Furthermore, the proposed method can extend the region of computable solutions in a state space. The validity of the method is shown by a numerical example of the optimal control of a vehicle model with steering limitations.
文摘Background Estrogen receptor alpha （ER α） is the most important endocrine therapy responsiveness predictor for women with breast cancer. The accuracy of the prediction of the response to endocrine therapy was thought to be affected by involving the estrogen receptor coregulatory proteins and cross-talk between ER and other growth factor-signaling networks. Nuclear corepressor 1 （NCOR1） is one of the ER a transcription repressor. The objective of the study is to investigate the expression of NCOR1 at the protein level and pursue its predictive value for breast cancer endocrine therapy. Methods In the present study, the level of expression of NCOR1 protein has been assessed by immunohistochemistry in 104 cases of invasive carcinoma of the breast. Associations between NCOR1 protein expression and different clinicopathological factors and survival were sought. Results It was found that NCOR1 was expressed at significantly higher levels in responsive patients treated with endocrine therapy as first-line treatment on relapse. Responsive patients also had a significantly longer post-relapse survival and overall survival. No NCOR1 expression difference was found between patient by age, tumor size, lymph node status, different histological grade groups and human epidermal growth factor receptor 2 （HER2） status. Multivariate analysis showed that NCOR1 is an independent prognostic factor for over-all survival. Conclusions In breast cancer, NCOR1 protein expression level predicts response to endocrine therapy as first-line treatment for breast cancer patients on relapse and NCOR1 protein level assay may increase the accuracy in the endocrine treatment determination and, therefore, improving the patients survival.
基金This study was supported by the National Muscum of Nature and Scicnee,Tokyo(Nos 20183001 and 20193001 to S.H.).
文摘Individuals which have invaded urbanized environments are reported to engage in riskier behav-iors,possibly influenced by the scarcity of predators in urbanized areas.Here,we studied the risk-taking behavior of birds which had invaded a new natural environment,rather than an artificial urban environment,using recently established populations of the bull-headed shrike Lanius bu-cephalus,which naturally colonized three subtropical islands in Japan.We compared flight initi-ation distance(FID),the distance at which an individual approached by a human initiates flight,be-tween the islands and the temperate mainland.FID was longer for the insular shrikes compared with the mainland shrikes after controlling for other factors,indicating that the individuals which had invaded a new natural environment had a lower propensity for risk-taking.A possible explan-ation for these results is that low risk-taking behavior might be adaptive on the islands due to predation by the black rat Rattus rattus,an unfamiliar predator not found in shrike habitats on the temperate mainland.Further studies are needed to examine the nest predation rate,predator species,and nest site selection of these insular shrike populations.
文摘Despite several advances in targeted therapies for breast cancer,breast-cancer-associated death remains high in women.This is partially due to the lack of reliable markers predicting metastatic disease or recurrence after initial therapy.Recent research into the clinical validity of circulating cancer-specific biomarkers as a“liquid biopsy”is of growing interest.Of these,exosomal microRNAs(miRNAs)are promising candidate biomarkers for clinical use in breast cancer.In addition to their diagnostic value,exosomal miRNAs play an important role in predicting clinical outcome or treatment response.In this review,it is focused on the findings concerning exosomal miRNAs in relation to disease detection,prognostic impact and therapeutic effect in breast cancer,and discuss their clinical utility.
