New approach for screening anti—tumor compounds

A new screening approach for anticancer active compounds is presented.In this method,a target enzyme is incubated with a mixture of compounds,and then the com-plex formed by the target and small molecules is separated from the rest of the mixture by ultra-filtration.The complex that is retained on the membrane is subsequently washed with acid and small molecules that are specifically bound to the target are released and collected,then analyzed by high-performance liquid chromatograph combined with electrospray ionization mass spectrometry (HPLC/ESI-MS) analysis.We have successfully applied this method to screen anti-cancer compounds.DNA topoisomerase Ⅱ is used as a target to capture anti-tumor candidates from a mixture of combinatorial compounds,such as doxorubicin,daunorubi-cin and pravastain.     

Approach to Weighted Geometric Evaluation Based on Projection Pursuit

Weighted geometric evaluation approach based on Projection pursuit （PP） model is presented in this paper to optimize the choice of schemes. By using PP model, the multi-dimension evaluation index values of schemes can be synthesized into projection value with one dimension. The scheme with a bigger projection value is much better, so the schemes sample can be an optimized choice according to the projection value of each scheme. The modeling of PP based on accelerating genetic algorithm can predigest the realized process of projection pursuit technique, can overcome the shortcomings of large computation amount and the difficulty of computer programming in traditional projection pursuit methods, and can give a new method for application of projection pursuit technique to optimize choice of schemes by using weighted geometric evaluation. The analysis of an applied sample shows that applying PP model driven directly by samples data to optimize choice of schemes is both simple and feasible, that its projection values are relatively decentralized and profit decision-making, that its applicability and maneuverability are high. It can avoid the shortcoming of subjective weighing method, and its results are scientific and objective.     

Recursive Algorithm Based Reliability Analysis of Multiphase Satellite Systems with Propagated Failures

Modern satellite systems are generally designed to fulfill multiphase-missions. Component /subsystem redundancies are commonly used to achieve high reliability and long life of modern satellite systems. These characteristics have leaded to a critical issue of reliability analysis of satellites that is how to deal with the reliability analysis with multiphase-missions and propagated failures of redundant components. Traditional methods based on the binary decision diagram( BDD) can hardly cope with these issues efficiently. Accordingly, a recursive algorithm method was introduced to facilitate the reliability analysis of satellites. This method was specified for the analysis of static fault tree and it was implemented by generating combination of component failures and carrying out a backward recursive algorithm. The effectiveness of the proposed method was demonstrated through the reliability analysis of a multiphase satellite system with propagated failures.The major advantage of the proposed method is that it does not need composition of BDD and its computational process is automated.     

Back-propagation network improved by conjugate gradient based on genetic algorithm in QSAR study on endocrine disrupting chemicals

Since the complexity and structural diversity of man-made compounds are considered, quantitative structure-activity relationships （QSARs）-based fast screening approaches are urgently needed for the assessment of the potential risk of endocrine disrupting chemicals （EDCs）. The artificial neural networks （ANN） are capable of recognizing highly nonlinear relationships, so it will have a bright application prospect in building high-quality QSAR models. As a popular supervised training algorithm in ANN, back-propagation （BP） converges slowly and immerses in vibration frequently. In this paper, a research strategy that BP neural network was improved by conjugate gradient （CG） algorithm with a variable selection method based on genetic algorithm was applied to investigate the QSAR of EDCs. This resulted in a robust and highly predictive ANN model with R2 of 0.845 for the training set, q^2 pred of 0.81 and root-mean-square error （RMSE） of 0.688 for the test set. The result shows that our method can provide a feasible and practical tool for the rapid screening of the estrogen activity of organic compounds.     

Modal extension rule

Modal logics are good candidates for a formal theory of agents. The efficiency of reasoning method in modal logics is very important, because it determines whether or not the reasoning method can be widely used in systems based on agent. In this paper, we modify the extension rule theorem proving method we presented before, and then apply it to P-logic that is translated from modal logic by functional transformation. At last, we give the proof of its soundness and completeness.     

Ranking Related Research Papers Based on Citation Graph

Research papers are of great importance for researchers to record and share their ideas, studies and results. Meanwhile, they are the bases for further research work. Finding related research papers is the preliminary of good research. A new method for ranking related research papers is introduced in this paper. Given a set of interested papers, the method proposed in this paper may rank related papers just based on a citation graph by constructing the minimal Steiner trees. The method can work with the existing keyword based methods. Intensive experiments on a specific research topic show that the proposed method provides a different ranking criterion to existing ones, and can effectively retrieve those highly related papers.     

Rapid Screening for Insecticidal Compounds Using [3H] EBOB Binding Assay

Binding assay is a convenient, simple, inexpensive, and rapid method that can be used for rapid screening insecticidal compounds. The present study examines 6 compounds for their inhibition of [^3H] EBOB bound to housefly-head membranes, of which 3 compounds have potency for housefly-head membranes.     

A Robust Pedestrian Detection Approach Based on Shapelet Feature and Haar Detector Ensembles

Detection of pedestrians in images and video sequences is important for many applications but is very challenging due to the various silhouettes of pedestrians and partial occlusions. This paper describes a two-stage robust pedestrian detection approach. The first stage uses a full body detector applied to a single image to generate pedestrian candidates. In the second stage, each pedestrian candidate is verified with a detector ensemble consisting of part detectors. The full body detector is trained based on improved shapelet features, while the part detectors make use of Haar-like wavelets as features. All the detectors are trained by a boosting method. The responses of the part detectors are then combined using a detector ensemble. The verification process is formulated as a combinatorial optimization problem with a genetic algorithm for optimization. Then, the detection results are regarded as equivalent classes so that multiple detections of the same pedestrian are quickly merged together. Tests show that this approach has a detection rate of over 95% for 0.1% FPPW on the INRIA dataset, which is significantly better than that of the original shapelet feature based approach and the existing detector ensemble approach. This approach can robustly detect pedestrians in different situations.     

A Steady-State Errors Correction Method for Eliminating Measurement Errors

This paper proposes a steady-state errors correction （SSEC） method for eliminating measurement errors.This method is based on the detections of error signal E（s） and output C（s） which generate an expected output R （s）.In comparison with the conventional solutions which are based on detecting the expected output R （s） and output C （s） to obtain error signal E （s）,the measurement errors are eliminated even the error might be at a significant level.Moreover,it is possible that the individual debugging by regulating the coefficient K for every member of the multiple objectives achieves the optimization of the open loop gain.Therefore,this simple method can be applied to the weak coupling and multiple objectives system,which is usually controlled by complex controller.The principle of eliminating measurement errors is derived analytically,and the advantages comparing with the conventional solutions are depicted.Based on the SSEC method analysis,an application of this method for an active power filter （APF） is investigated and the effectiveness and viability of the scheme are demonstrated through the simulation and experimental verifications.     

A wireframe model-based method for automated internal design

This paper proposes a wireframe model-based method for automated internal design. The method is used to extract geometric structure of an internal wireframe model and find out all loop structures of furniture models. The wireframe models are classified as the multiple independent sub-models according to the geometric structure by statistical analysis. The corresponding models are selected from a 3D model database to build an internal scene based on characteristic points of furniture wireframe models. In the experiments 3D database via manually selected 268 3D furniture models from Google 3D warehouse is built up. The experiments show that the method can construct 3D scenes in 1.1×103 ms. This method costs less time compared with traditional hierarchical method and depth-sensing camera method in the same experimental conditions. The method can be also used for 3D visualization either with complex backgrounds.     

Effect of antisense oligonucleotides targeting telomerase catalytic subunit on tumor cell proliferationin vitro

To screen specific antitumor drugs targeting telomerase catalytic subunit (hEST2), 12 different hEST2 antisense oligonucleotides were designed based on hEST2 mRNA second structure and transfected into tumor cell lines by the lipofectin-mediated method. Cell growth activity was evaluated by MTT assay. hEST212 was picked out and its specificity, antitumor tree and continuous effect were analyzed. The results showed that hEST212 had promising antitumor activity in vitro, hEST2 can be used as a pratical target and an antisense drug candidate for cancer.     

海洋木栖真菌抗肿瘤活性及其营养条件的影响

对从厦门海沧及漳州浮宫的红树林生态区分离到的177株海洋木栖真菌用MTT法进行抗肿瘤活性的测定，获得具有抗肿瘤活性的菌株共44株，占总受试菌株的24．9％，其中对KB瘸株有抑制作用的有12株．对Raji瘤株有抑制作用的菌株有43株，对这两种肿瘤细胞均有抑制作用的菌株有11株．并且考察了其中6株海洋木栖真菌在纤维素、羧甲基纤维素钠、淀粉和蔗糖为碳源的生物量和抗肿瘤活性。结果表明海洋木栖真菌在不同营养条件下的菌体生物量及代谢产物的抗肿瘤活性均存在差异，部分菌株在纤维素为碳源时，有最高的生物量和抗肿瘤活性，PDB培养基不宜作为抗肿瘤活性测定或生产发酵的基质．     

蛋白酪氨酸磷酸酶SHP2抑制剂高通量筛选模型的建立和应用

 为了建立体外蛋白酪氨酸磷酸酶SHP2抑制剂的高通量筛选模型,筛选潜在的SHP2抑制剂,通过应用大肠杆菌系统克隆表达GST-SHP2 融合蛋白,经过GST-Sepharose 亲和层析分离得到纯化的GST-SHP2 蛋白,建立384 孔板的高通量筛选模型,对48000个有明确结构的小分子化合物进行体外筛选,筛选出75个活性化合物对SHP2的抑制作用大于50%,确定3个化合物具有较高的抑制活性。该筛选模型灵敏、稳定,对SHP2抑制剂药物研发打下了基础。     

抗肿瘤喹唑啉衍生物的定量构效关系

用量子化学密度泛函(DFT)及分子力学(MM )方法,计算了一系列抗肿瘤喹唑啉衍生物分子的电子结构、几何结构及分子性质(广义结构参数),并通过回归分析,筛选出主要因素,建立定量构效关系(QSAR)方程.发现该类化合物分子的抗肿瘤活性与一些广义结构参数有密切关系,特别是苯环18位碳上取代基(R)的体积与表面积的比值r18,嘧啶环与苯环(C环)间的距离d,以及次低未占据分子轨道(NLUMO)的能量NL与抗肿瘤活性显著相关,可通过取代基的选择与计算来筛选药效最佳的先导物.QSAR方程的拟合相关系数(R2)及交叉验证相关系数(q2)分别为0.851 6和0.714 6,表明所得模型具有可信的预报能力,可用以精确预测该系列化合物活性,并为设计抗肿瘤活性更高的喹唑啉衍生物及作用机理分析提供理论指导.     

叠氮法合成谷氨酰胺类化合物及其抗肿瘤活性

研究发现抗癌酮（Antineoplaston A10）降解物中谷氨酰胺与异谷氨酰胺类衍生物显示出抗肿瘤少性。为此，设计并合成了一系列苯乙酰谷氨酰胺类化合物供抗肿瘤活性筛选，采用合成酰基叠氮化合物，再与胺类于低湿下反应生成酰胺类目标化合物，该方法反应条件温和，收率好，而且手性中心不发生消旋化，所合成化合物结构经IR、^1HNMR、MS及元素分析方法鉴定。对所合成目标化合物做抗肿瘤活性评价，采用MTT法对L1210细胞进行了测试，初步结果显示有一定的抑制肿瘤细胞存活的作用。     

主成份分析和交叉相关的红移测量

提出了一种新的红移测量方法.首先进行谱线提取,并利用谱线信息确定红移候选;然后,根据红移候选对目标光谱和模板光谱进行交叉相关计算,最大相关值对应的红移候选为目标光谱的红移.采用的静止模板是利用主成份分析构造的.与已有的基于交叉相关的方法相比,本文方法可测量的红移范围大,受谱线提取效果的影响较小.实验结果表明:该方法优于基于谱线匹配的方法,正确率达到95%以上.     

Effect of antisense oligonucleotides targeting telomerase catalytic subunit on tumor cell proliferationin vitro

To screen specific antitumor drugs targeting telomerase catalytic subunit (hEST2), 12 differenthEST2 antisense oligonucleotides were designed based on hEST2 mRNA second structure and transfected into tumor cell lines by the lipofectin-mediated method. Cell growth activity was evaluated by MTT assay.hEST212 was picked out and its specificity, antitumor tree and continuous effect were analyzed. The results showed thathEST212 had promising antitumor activityin vitro, hEST2 can be used as a pratical target and an antisense drug candidate for cancer.     

A kinetic proofreading mechanism for disentanglement of DNA by topoisomerases.

Cells must remove all entanglements between their replicated chromosomal DNAs to segregate them during cell division. Entanglement removal is done by ATP-driven enzymes that pass DNA strands through one another, called type II topoisomerases. In vitro, some type II topoisomerases can reduce entanglements much more than expected, given the assumption that they pass DNA segments through one another in a random way. These type II topoisomerases (of less than 10 nm in diameter) thus use ATP hydrolysis to sense and remove entanglements spread along flexible DNA strands of up to 3,000 nm long. Here we propose a mechanism for this, based on the higher rate of collisions along entangled DNA strands, relative to collision rates on disentangled DNA strands. We show theoretically that if a type II topoisomerase requires an initial 'activating' collision before a second strand-passing collision, the probability of entanglement may be reduced to experimentally observed levels. This proposed two-collision reaction is similar to 'kinetic proofreading' models of molecular recognition.