For the first time,proteolysis-targeting chimeras(PROTAC)technology was utilized to achieve the isoform-selective degradation of class I phosphoinositide 3-kinases(PI3Ks)in this study.Through screening and optimizatio...For the first time,proteolysis-targeting chimeras(PROTAC)technology was utilized to achieve the isoform-selective degradation of class I phosphoinositide 3-kinases(PI3Ks)in this study.Through screening and optimization,the PROTAC molecule ZM-PI05 was identified as a selective degrader of p110αin multiple breast cancer cells.More importantly,the degrader can down-regulate p85 regulatory subunit simultaneously,thereby inhibiting the non-enzymatic functions of PI3K that are independent on p110catalytic subunits.Therefore,compared with PI3K inhibitor copanlisib,ZM-PI05 displayed the stronger anti-proliferative activity on breast cancer cells.In brief,a selective and efficient PROTAC molecule was developed to induce the degradation of p110αand concurrent reduction of p85 proteins,providing a tool compound for the biological study of PI3K-αby blocking its enzymatic and non-enzymatic functions.展开更多
离群点检测任务是指检测与正常数据在特征属性上存在显著差异的异常数据。大多数基于聚类的离群点检测方法主要从全局角度对数据集中的离群点进行检测,而对局部离群点的检测性能较弱。基于此,本文通过引入快速搜索和发现密度峰值方法改...离群点检测任务是指检测与正常数据在特征属性上存在显著差异的异常数据。大多数基于聚类的离群点检测方法主要从全局角度对数据集中的离群点进行检测,而对局部离群点的检测性能较弱。基于此,本文通过引入快速搜索和发现密度峰值方法改进K-means聚类算法,提出了一种名为KLOD(local outlier detection based on improved K-means and least-squares methods)的局部离群点检测方法,以实现对局部离群点的精确检测。首先,利用快速搜索和发现密度峰值方法计算数据点的局部密度和相对距离,并将二者相乘得到γ值。其次,将γ值降序排序,利用肘部法则选择γ值最大的k个数据点作为K-means聚类算法的初始聚类中心。然后,通过K-means聚类算法将数据集聚类成k个簇,计算数据点在每个维度上的目标函数值并进行升序排列。接着,确定数据点的每个维度的离散程度并选择适当的拟合函数和拟合点,通过最小二乘法对升序排列的每个簇的每1维目标函数值进行函数拟合并求导,以获取变化率。最后,结合信息熵,将每个数据点的每个维度目标函数值乘以相应的变化率进行加权,得到最终的异常得分,并将异常值得分较高的top-n个数据点视为离群点。通过人工数据集和UCI数据集,对KLOD、LOF和KNN方法在准确度上进行仿真实验对比。结果表明KLOD方法相较于KNN和LOF方法具有更高的准确度。本文提出的KLOD方法能够有效改善K-means聚类算法的聚类效果,并且在局部离群点检测方面具有较好的精度和性能。展开更多
Objective: To discuss some key points about nursing in the use of DDG-3300K liver reserve function analyzer in patients at the department of infectious diseases. Method: DDG-3300K liver reserve function analyzer was a...Objective: To discuss some key points about nursing in the use of DDG-3300K liver reserve function analyzer in patients at the department of infectious diseases. Method: DDG-3300K liver reserve function analyzer was applied to 5464 patients at the department of infectious diseases. The reasons for failed detection and complications related to the detection were analyzed, and the measures for improving the nursing procedures were proposed. Result: Among the 5464 patients, the detections were successful at the first attempt in 5458 patients;2 patients had leakage of liquid;2 patients were poorly prepared, and 1 case failed because of mistaken selection of CO mode, which led to adverse drug reactions;1 case did not finish the detection due to anaphylactic shock;8 patients had nausea and 6 patients had skin rash on the four limbs and torso during the detection. Conclusion: It is necessary to formulate the nursing procedures for the use of DDG-3300K liver reserve function analyzer. Moreover, preparatory work, health education, refined nursing procedures and skillful operations are closely related to the success rate and accuracy of the detection.展开更多
In this context, we mainly study the behavior in the neighborhood of finite singular points for k-regular functions in R1^n with values in R0、n. We get a Laurent expansion of them in an open set, prove its uniqueness...In this context, we mainly study the behavior in the neighborhood of finite singular points for k-regular functions in R1^n with values in R0、n. We get a Laurent expansion of them in an open set, prove its uniqueness, give the definitions of k-poles, isolated and essential singular points and removable singularity, discuss some properties, and further obtain the residue theorems.展开更多
In this paper, we obtain the convexity of new general integral operator on some classes of k-uniformly p-valent a-convex functions of complex order. These results extend some known theorems.
基金supported by National Key R&D Program of China(Nos.2021YFA1302100,2021YFA1300200,2020YFE0202200)National Natural Science Foundation of China(Nos.82125034,82330115)。
文摘For the first time,proteolysis-targeting chimeras(PROTAC)technology was utilized to achieve the isoform-selective degradation of class I phosphoinositide 3-kinases(PI3Ks)in this study.Through screening and optimization,the PROTAC molecule ZM-PI05 was identified as a selective degrader of p110αin multiple breast cancer cells.More importantly,the degrader can down-regulate p85 regulatory subunit simultaneously,thereby inhibiting the non-enzymatic functions of PI3K that are independent on p110catalytic subunits.Therefore,compared with PI3K inhibitor copanlisib,ZM-PI05 displayed the stronger anti-proliferative activity on breast cancer cells.In brief,a selective and efficient PROTAC molecule was developed to induce the degradation of p110αand concurrent reduction of p85 proteins,providing a tool compound for the biological study of PI3K-αby blocking its enzymatic and non-enzymatic functions.
文摘离群点检测任务是指检测与正常数据在特征属性上存在显著差异的异常数据。大多数基于聚类的离群点检测方法主要从全局角度对数据集中的离群点进行检测,而对局部离群点的检测性能较弱。基于此,本文通过引入快速搜索和发现密度峰值方法改进K-means聚类算法,提出了一种名为KLOD(local outlier detection based on improved K-means and least-squares methods)的局部离群点检测方法,以实现对局部离群点的精确检测。首先,利用快速搜索和发现密度峰值方法计算数据点的局部密度和相对距离,并将二者相乘得到γ值。其次,将γ值降序排序,利用肘部法则选择γ值最大的k个数据点作为K-means聚类算法的初始聚类中心。然后,通过K-means聚类算法将数据集聚类成k个簇,计算数据点在每个维度上的目标函数值并进行升序排列。接着,确定数据点的每个维度的离散程度并选择适当的拟合函数和拟合点,通过最小二乘法对升序排列的每个簇的每1维目标函数值进行函数拟合并求导,以获取变化率。最后,结合信息熵,将每个数据点的每个维度目标函数值乘以相应的变化率进行加权,得到最终的异常得分,并将异常值得分较高的top-n个数据点视为离群点。通过人工数据集和UCI数据集,对KLOD、LOF和KNN方法在准确度上进行仿真实验对比。结果表明KLOD方法相较于KNN和LOF方法具有更高的准确度。本文提出的KLOD方法能够有效改善K-means聚类算法的聚类效果,并且在局部离群点检测方面具有较好的精度和性能。
文摘Objective: To discuss some key points about nursing in the use of DDG-3300K liver reserve function analyzer in patients at the department of infectious diseases. Method: DDG-3300K liver reserve function analyzer was applied to 5464 patients at the department of infectious diseases. The reasons for failed detection and complications related to the detection were analyzed, and the measures for improving the nursing procedures were proposed. Result: Among the 5464 patients, the detections were successful at the first attempt in 5458 patients;2 patients had leakage of liquid;2 patients were poorly prepared, and 1 case failed because of mistaken selection of CO mode, which led to adverse drug reactions;1 case did not finish the detection due to anaphylactic shock;8 patients had nausea and 6 patients had skin rash on the four limbs and torso during the detection. Conclusion: It is necessary to formulate the nursing procedures for the use of DDG-3300K liver reserve function analyzer. Moreover, preparatory work, health education, refined nursing procedures and skillful operations are closely related to the success rate and accuracy of the detection.
基金Supported by the National Natural Science Foundation of China (10471107)the Specialized Research Fund for the Doctoral Program of Higher Education of China (20060486001)
文摘In this context, we mainly study the behavior in the neighborhood of finite singular points for k-regular functions in R1^n with values in R0、n. We get a Laurent expansion of them in an open set, prove its uniqueness, give the definitions of k-poles, isolated and essential singular points and removable singularity, discuss some properties, and further obtain the residue theorems.
基金Foundation item： Supported by the Natural Science Foundation of Inner Mongolia（2009MS0113） Sup- ported by the Higher School Research Foundation of Inner Mongolia（NJzy08150）
文摘In this paper, we obtain the convexity of new general integral operator on some classes of k-uniformly p-valent a-convex functions of complex order. These results extend some known theorems.
