县域内义务教育学校财政拨款充足性估算——基于B、J和S县所辖小学数据的包络分析

我国义务教育财政投入不足备受社会关注,但究竟什么是义务教育财政投入的充足性,国内已有研究基本上是描述性的,至今并没有给出明确的含义及标准。已有国外研究和实践表明,确立学校财政拨款充足标准,必须要与教育结果关联,且要考虑学校所处环境对教育结果的影响,同时还需要排除学校低效率行为。基于此,本文在明确我国义务教育学校财政拨款充足性含义及标准的基础上,构建了包含环境因素的学校拨款充足模型,运用拓展的线性包络分析方法排除学校低效率行为,以经济发展不同水平的B县、S县和J县所辖小学为典型案例,对各县所辖每一所学校达到该县设定教育结果水平所需最低成本进行估算。结果表明:达到各县确认的优秀教育结果水平,排除低效率行为,超过60%的学校无需追加财政拨款。今后在加大义务教育财政投入的同时,还应注重资金使用效率并建立相应的问责机制。

USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway.Recent studies have revealed that posttranslational modifications,such as ubiquitination,regulate NOTCH1 stability,activity,and localization.However,the specific deubiquitinase that affects NOTCH1 protein stability remains unestablished.Here,we report that ubiquitin-specific protease 7(USP7)can stabilize NOTCH1.USP7 deubiquitinated NOTCH1 in vivo and in vitro,whereas knockdown of USP7 increased the ubiquitination of NOTCH1.USP7 interacted with NOTCH1 protein in T-ALL cells,and the MATH and UBL domains of USP7 were responsible for this interaction.Depletion of USP7 significantly suppressed the proliferation of T-ALL cells in vitro and in vivo,accompanied by downregulation of the NOTCH1 protein level.Similarly,pharmacologic inhibition of USP7 led to apoptosis of T-ALL cells.More importantly,we found that USP7 was significantly upregulated in human T-ALL cell lines and patient samples,and a USP7 inhibitor exhibited cell cytotoxicity toward primary T-ALL cells,indicating the clinical relevance of these findings.Overall,our results demonstrate that USP7 is a novel deubiquitinase that stabilizes NOTCH1.Therefore,USP7 may be a promising therapeutic target in the currently incurable T-ALL.

Ubiquitin-specific protease 47 regulates intestinal inflammation through deubiquitination of TRAF6 in epithelial cells

Deubiquitinates(DUBs) alter the stabilities, localizations or activities of substrates by removing their ubiquitin conjugates,which are closely related to the development of inflammatory response. Here, we show that ubiquitin-specific protease 47(USP47) prevents inflammation development in inflammatory bowel disease(IBD). Compared with wild-type mice, Usp47 knockout mice are more susceptible to dextran sodium sulfate(DSS)-induced acute and chronic colitis with higher inflammatory cytokines expression and severe intestinal tissue damage. Chimeric mouse experiments suggest that non-hematopoietic cells mainly contribute to the phenotype. And, DSS-induced colitis of the Usp47 knockout mice depends on commensal bacteria.Mechanistically, down-regulation of USP47 aggravates the activation of NF-κB signaling pathway by increasing the K63-linked poly-ubiquitination of tumor necrosis factor receptor-associated factor 6(TRAF6) in intestinal epithelial cells. Furthermore, the expression of USP47, negatively correlated with the degree of inflammation, is lower at colonic inflammatory lesions than that non-inflammatory sites from the intestine from ulcerative colitis(UC) and Crohn's disease(CD) patients. These data, taken together, indicate that USP47 regulates intestinal inflammation through de-ubiquitination of K63-linked poly-ubiquitination TRAF6 in intestinal epithelial cells.

Dimensional synthesis of a novel 5-DOF reconfigurable hybrid perfusion manipulator for large-scale spherical honeycomb perfusion

A novel hybrid perfusion manipulator(HPM)with five degrees of freedom(DOFs)is introduced by combining the 5PUS-PRPU(P,R,U and S represent prismatic,revolute,universal and spherical joint,respectively)parallel mechanism with the 5PRR reconfigurable base to enhance the perfusion efficiency of the large-scale spherical honeycomb thermal protection layer.This study mainly presents the dimensional synthesis of the proposed HPM.First,the inverse kinematics,including the analytic expression of the rotation angles of the U joint in the PUS limb,is obtained,and mobility analysis is conducted based on screw theory.The Jacobian matrix of 5PUS-PRPU is also determined with screw theory and used for the establishment of the objective function.Second,a global and comprehensive objective function(GCOF)is proposed to represent the Jacobian matrix’s condition number.With the genetic algorithm,dimensional synthesis is conducted by minimizing GCOF subject to the given variable constraints.The values of the designed variables corresponding to different configurations of the reconfigurable base are then obtained.Lastly,the optimal structure parameters of the proposed 5-DOF HPM are determined.Results show that the HPM with the optimized parameters has an enlarged orientation workspace,and the maximum angle of the reconfigurable base is decreased,which is conducive to improving the overall stiffness of HPM.