国产盐酸拓扑替康治疗晚期卵巢癌的疗效观察

目的评价国产盐酸拓扑替康治疗晚期卵巢癌的疗效和安全性。方法对84例晚期卵巢癌患者采用盐酸拓扑替康1.25 mg/m2静滴1-5 d,每21 d重复。治疗2周期后评价疗效,有效病例4周后确认疗效。结果84例中可评价疗效72例,可评价毒性84例。完全缓解2例,部分缓解14例,总有效率22.2%,其中初治和复治患者有效率分别为25.0%和20.8%。主要毒副作用为中性粒细胞减少和白细胞减少,两者III/IV度毒性分别为26.1%和26.1%。非血液学毒性轻微。结论国产盐酸拓扑替康单药治疗晚期卵巢癌,特别是复发病例疗效较好,耐受性良好。     

Robust Fuzzy Sampled-Data Control for Dynamic Positioning Ships

A robust H∞sampled-data stabilization problem for nonlinear dynamic positioning(DP) ships with Takagi-Sugeno(T-S) fuzzy models is discussed in this paper. Input delay approach is used to convert the sampleddata DP ship system to a fuzzy system with time-varying delay. Adequate conditions are derived to determine the system's asymptotical stability and achieve H∞performance via Lyapunov stability theorems. Then, the fuzzy sampled-data controller is obtained by analyzing the stabilization condition. Simulation result shows that the proposed method and the designed controller for a DP ship are effective so that the DP ship can maintain the desired position, heading and velocities in the existence of varying environment disturbances.     

mTOR信号通路与肿瘤的研究进展

哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)是一种丝/苏氨酸蛋白激酶,在细胞生长、增殖、分化、细胞周期调控等多个方面起到重要作用.近年来发现mTOR相关的信号通路复杂且涉及面广泛,其中多个元素的调控异常都与肿瘤的发生密切相关.mTOR抑制剂能够抑制由于该信号通路异常引起的癌基因的转化、肿瘤的生长和肿瘤血管生成.到目前为止,4种mTOR抑制剂被有效地应用于临床,有的已进入Ⅱ、Ⅲ期临床试验.因此,对mTOR信号通路的深入研究对肿瘤的靶向性治疗具有重要意义.     

复方风湿宁治疗类风湿性关节炎的临床研究

典型类风湿性关节炎１５０例，随机分为复方风湿宁组（１２０例）和消炎痛对照组（３０例）。临床研究结果：复方风湿宁有效率９８．３３％，临床治愈２６．６７％，显效６４．１６％，缓解（有效）７．５％，无效１．６７％。其效果优良，起效快，消关节肿胀和止痛作用好，血沉和ＲＦ的复常与降低率高，撤除激素的作用强，疗效稳定，副作用少。疗效显著优于消炎痛和目前临床应用的同类抗风湿药。并对国内外近年研究的新药进行了引证和讨论。     

髓样细胞白血病-1基因在多发性骨髓瘤发病中的分子机制

目的通过检测骨髓瘤细胞中依赖IL-6与否的髓样细胞白血病-1(mcl-1)基因的表达,阐明mcl-1基因在多发性骨髓瘤发病中的信号转导通路。方法应用JAK特异性抑制剂AG490、蛋白激酶抑制剂LY294002、ERK1/2信号通路的特异性阻断剂PD98059,分别研究了JAK/STAT通路、ras/MAPK通路及PI3K/Akt三大信号途径与mcl-1基因在多发性骨髓瘤中的关系。结果在骨髓瘤细胞8226和U266中,抑制ERK1/2活性不能改变mcl-1的表达;高浓度的AG490不能抑制STAT3的酪氨酸磷酸化;LY294002可抑制8226细胞和ANBL-6细胞的增殖,但不抑制mcl-1的表达。结论 Ras/MAPK通路以及PI3K通路在mcl-1基因的调节中无作用,但STAT的作用仍然需要进一步探讨。     

选择性PDGF受体酪氨酸激酶抑制剂对兔PVR的治疗作用

目的　评价一种新的血小板源性生长因子 (platelet derivedgrowthfactor,PDGF)受体酪氨酸激酶抑制剂AG12 95对兔增殖性玻璃体视网膜病变 (proliferativevitreoretinopathy ,PVR)的治疗作用。 方法　兔结膜成纤维细胞 (rabbitconjunctivalfibroblastscells,RCF)培养 ,用MTT分析法检测PDGF AA和 BB以及AG12 95对兔RCF的增殖状况的影响。建立PVR动物模型 ,玻璃体腔内给予AG12 95 ,用牵引性视网膜脱离 (tractionalretinaldetach ment,TRD)的发生率判断药物的体内疗效。眼视网膜电生理检查和HE染色分析药物的毒性。结果　 10 μmol·L-1和 10 0 μmol·L-1两种浓度的AG12 95均可显著抑制由PDGF AA和 BB诱导的成纤维细胞的增生 ,10 0 μmol·L-1AG12 95可减缓兔TRD的发生 ,但其作用仅持续至第 2 1d。在AG12 95治疗组中 ,未发现明显的网膜毒性。结论　PDGF受体酪氨酸激酶抑制剂AG12 95可减缓兔TRD的发生。     

Time-series forecasting using autoregression enhanced k-nearest neighbors method

This study proposes two metrics using the nearest neighbors method to improve the accuracy of time-series forecasting. These two metrics can be treated as a hybrid forecasting approach to combine linear and non-linear forecasting techniques. One metric redefines the distance in k-nearest neighbors based on the coefficients of autoregression (AR) in time series. Meanwhile, an improvement to Kulesh’s adaptive metrics in the nearest neighbors is also presented. To evaluate the performance of the two proposed metrics, three types of time-series data, namely deterministic synthetic data, chaotic time-series data and real time-series data, are predicted. Experimental results show the superiority of the proposed AR-enhanced k-nearest neighbors methods to the traditional k-nearest neighbors metric and Kulesh’s adaptive metrics.     

Grain refining mechanism of carbon inoculation on Mg-Al alloy

The processing parameters and refining mechanism of Mg-Al alloy treated with a newly developed carbon inoculant under different conditions were investigated experimentally in this work. Results show that the finest ??-Mg grain in AZ91D alloy can be obtained after processing at about 740°C, and the average grain size of ??-Mg grain decreases from about 180.4 to 85.6 ??m by adding mass fraction w _in = 1% inoculant into melt. However, no evident refinement was achieved with excessive inoculant for Mn-free Mg-9Al alloy. Scanning electron microscope (SEM) photo, energy dispersive spectroscopy (EDS) analysis on the Mn-contained intermediate phase and differential scanning calorimetry (DSC) results indicate that Mn element plays an important role in the heterogeneous nucleation of ??-Mg grain. In the early stage of solidification, Al-Mn-C compound particles formed on the surface of Al₄C₃ nano-particles should be the potential nuclei for primary ??-Mg and probably responsible for the grain refinement achieved in the carbon inoculation process.     

Research on Nonlinear Dynamic Simulation and Fatigue Reliability Life Prediction for Synthesis Transmission System of Self-Propelled Gun

Aiming to the puzzle that the inner load of nonlinear synthesis transmission system is difficult to obtain, a new kind of virtual prototype establishment and simulation method is put forward. The influence on nonlinear vibration with flexible rotor, bearing backlash is analyzed based on a virtual prototype. To validate the virtual prototype of nonlinear gear transmission system, the corresponding test platform is established. The consistency between simulation results and test results proves that the simulation results of the virtual prototype can be used to calculate the fatigue reliability life of key components. A new kind of fatigue reliability life prediction method of gear system considering multi-random parameter distribution is put forward based on the fatiguestatistic theory. Considering the periodicity of gear meshing, linear interpolation method is adopted to obtain the stress-time course of random load spectrum based on the gear’s complicated torque provided by virtual prototype. The gear’s P-S_a-S_m-N curved cluster can be simulated based on material’s P-S-N curve. The simulation process considers the parameter distributions of stress concentration coefficients, dimension coefficients and surface quality treatment coefficients, and settles the puzzle that traditional test methods cannot acquire the gear’s fatigue life of all reliability levels. This method can provide the distribution function and the interval of fatigue reliability life of gear’s danger region, and has a guide meaning for the gear maintenance periods determination and reliability evaluation.     

THE LA ANTIGEN INHIBITS THE ACTIVATION OF THE INTERFERON－INDUCIBLE PROTEIN KINASE PKR BY SEQUESTERING AND UNWINDING DOUBLE－ST

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Recognition of red cell and megakaryocyte based L-shaped envelope function

In order to explore the cell composition and its metabolism, it is important to let computer recognize the cells and get the counts of different cells for a sample. This paper proposes an L-shaped envelop function and the related fuzzy clustering method as a way to identify the megakaryocyte and the red cell from the sliced marrow image. This method is useful when the staining is insufficient and the color cannot be used as the identifying factor. This method uses the experimental histogram data to fit the L-shaped function and then use it as the envelop for the match test. The fuzzy c-means (FCM) performance index is used to test the adjacent area and get the minimum and finally secure the identification. The new method is not limited to megakaryocyte or red cell and can be used for general purposes of cell recognition. Tests show that this envelop function can ensure the recognition rate with different staining batches and can reach satisfied counting under similar illumination condition.     

重组毒素DT389-IL13的复性与纯化工艺

为了获得有较高生物活性的靶向重组毒素DT389-IL13,在大肠杆菌中高效表达DT389-IL13,并采用凝胶过滤的方法对DT389-IL13进行柱上复性及初步纯化,然后使用离子交换色谱方法进一步纯化,最后应用CCK-8细胞活力检测试剂盒检测DT389-IL13对肿瘤细胞的抑制作用.实验结果显示,经柱上复性和纯化后,DT389-IL13的纯度可达90%以上,且对脑胶质瘤细胞U251有明显的抑制作用,存在明确的剂量依赖关系,48h的半数抑制浓度为8.87×10-10mol/L.表明联合应用凝胶过滤和离子交换两种色谱方法可获得高纯度的复性蛋白,是可行的复性及纯化方案.     

基于有限元-神经网络-Monte-Carlo的结构可靠度计算方法

针对以往结构可靠度计算方法的不足,根据结构可靠度理论,引入神经网络理论和Monte-Carlo理论,结合结构有限元分析方法,提出基于有限元-神经网络-Monte-Carlo的结构可靠度计算方法;首先,建立结构有限元法分析模型,进行结构分析得到相应的结构响应量;然后,用得到的作用效应和结构响应量作为神经网络的训练样本和检验样本对神经网络进行训练,得到高度非线性映射关系的结构作用效应-结构响应模型;利用神经网络随机产生足够多的结构响应值;最后,用Monte-Carlo法计算结构的可靠度。该方法充分发挥了各方法的优点,相互弥补了不足,大大提高了计算效率,为结构可靠度计算提供了新的思路。     

碳纤维箱形梁的剪力滞效应试验研究

近几年来,利用各向异性层合复合材料作为结构元件有了显著的增长．这种增长是利用了复合材料重量轻、强度高和各向异性材料等性质,这些性质都可以通过改变纤维取向和铺层顺序而加以调整,从而可以有效地使用层合复合材料．复合材料的正确和有效使用,要求进行更复杂的分析,以便能准确地预报这些材料对外栽荷的弹性响应．通过试验的方法来研究碳纤维层合箱梁在集中荷载作用下的剪力滞效应．     

基于有限元-神经网络-Monte-Carlo的结构可靠度计算方法

针对以往结构可靠度计算方法的不足,根据结构可靠度理论,引入神经网络理论和Monte-Carlo理论,结合结构有限元分析方法,提出基于有限元-神经网络-Monte-Carlo的结构可靠度计算方法;首先,建立结构有限元法分析模型,进行结构分析得到相应的结构响应量;然后,用得到的作用效应和结构响应量作为神经网络的训练样本和检验样本对神经网络进行训练,得到高度非线性映射关系的结构作用效应-结构响应模型;利用神经网络随机产生足够多的结构响应值;最后,用Monte-Carlo法计算结构的可靠度。该方法充分发挥了各方法的优点,相互弥补了不足,大大提高了计算效率,为结构可靠度计算提供了新的思路。     

H ∞ parameter identification and H 2 feedback control synthesizing for inflight aircraft icing

Aircraft icing accident happens frequently. Researchers try to find new ways to solve this problem. The study is facing the direction of intelligent inspection and control system. Previous studies focused on the principle of aircraft icing and its effects on flight performance. The onboard icing detection equipment can only give the qualitative icing information, but cannot effectively describe how serious the consequences would be. If the icing detection equipment fails, it will cause a serious threat to flight safety. This paper reviews the smart icing system and its fundamental principle. Then based on H∞ theory, an aircraft icing parameter identification method is introduced, and its feasibility is verified by simulation results. Moreover, this method can work normally under noise interference and measurement error. Icing parameter identification method can also test part of aircraft’s stability or control derivatives which would be changed obviously after aircraft icing. Classified by neural networks, the stability or control derivatives’ variation can be mapped to ice parameters’ variation that reflects the severity of aircraft icing. Then H2 state feedback control is designed originally to suppress the impact of noise interference, so aircraft can keep steady after it is iced. Seeing from simulation result of the whole system, it is clear that the system can effectively detect icing parameters and by using feedback control system, it can ensure the safety of aircraft in the flight envelope.     

REVERSAL OF THE DOUBLE－STRANDED－RNA－INDUCED INHIBITION OF PROTEIN SYNTHESIS BY A CATALYTICALLY INACTIVE MUTANT OF THE PROTEIN

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