DNA依赖蛋白激酶抑制剂的CoMFA研究

运用比较分子力场分析方法(CoMFA),以DNA依赖蛋白激酶(DNA-PK)抑制剂分子为研究对象,建立1组对DNA依赖蛋白激酶有抑制活性化合物的三维定量构效关系(3D-QSAR)模型,探索其活性数据和三维结构参数的关系,所建最佳模型交叉验证相关系数q2=0.670,非交叉验证相关系数R2=0.993,标准偏差SD=0.053,说明该模型预测能力较好.根据CoMFA模型的三维等势图可知,小体积、电负性大的取代基团,能提高该类化合物的活性,为新型DNA-PK抑制剂分子的设计提供了理论依据.     

基于遗传算法的黄酮类化合物对PTKs抑制性的QSAR研究

用文献设定的结构参数和本文设定的结构参数,分别与由HyperChem7.5Student Evaluation计算得到的量化参数作为自变量构成2组数据,以逐步回归,遗传算法-偏最小二乘法(GA-PLS)和遗传算法-支持向量机(GA-SVM)等算法就黄酮类化合物对PTKs抑制性进行QSAR研究。用各算法模型处理数据,由本文设定的结构参数构成的数据集获得的预测结果更好,表明采用取代基团类型和取代位置结合的编码参数包含的信息更为丰富,对物质性质的描述更加合理。在各种算法中, GA-SVM模型均具有最佳预测效果,该算法对2组数据作留一法预测处理得到的相关系数R和PTKs抑制性实验值与预测值的平均绝对误差MAE分别为0.7595,0.2871和0.7864,0.2883。研究还表明,GA-PLS和GA-SVM联用算法的预测效果远高于单独使用的PLS和SVM算法;由逐步回归建立的MLR模型对2组数据进行计算处理,尽管拟合时相关系数R分别达到0.8136和0.8250,但作留一法交互验证时却下降到0.7113和0.7354,明显低于GA-PLS和GA-SVM联用算法。     

非线性折射和反射平面场景的实时光线跟踪

该文利用光学映射虚对象的概念,提出了实时计算平面折射虚物体的新方法,给出了在不同情况下实时计算平面折射虚顶点的计算公式,实现了基于三维图形硬件（加速卡）加速的实时光线跟踪算法。该算法能够处理非线性平面折射和反射问题,极大地提高了真实感图形绘制和显示的速度。这对于建筑物实时漫游、实时动画和虚拟现实等领域具有非常广阔的应用前景。     

Reconfigurable systolic arrays with fixed size and structure degradation

Reconfiguration algorithms are proposed for VLSI systolic arrays constructed from identical self-testing processors. The properties of fault-tolerant arrays with fixed size and structure degradation are considered.Translated from Kibernetika i Sistemnyi Analiz, No. 4, pp. 153–162, July–August, 1992.     

Querying datalog with arrays: Design and implementation issues

This paper deals with the implementation of logic queries where array structures are manipulated. Both top-down and bottom-up implementations of the presented logic language, called Datalog ^A , are considered. Indeed, SLD-resolution is generalized to realize Datalog ^A top-down query answering. Further, a fixpoint based evaluation of Datalog ^A queries is introduced, which forms the basis for efficient bottom-up implementation of queries obtained by generalizing rewriting techniques such as magic set method to the case of Datalog ^A programs.Work partially supported by a European Union grant under the EC-US project DEUS EX MACHINA: nondeterminism for deductive databases and by a MURST grant (40% share) under the project Sistemi formali e strumenti per basi di dati evolute.     

Generation and validation of the first predictive pharmacophore model for cyclin-dependent kinase 9 inhibitors

A three-dimensional (3D) pharmacophore modelling approach was applied to a diverse data set of known cyclin-dependent kinase 9 (CDK9) inhibitors. Diversity sampling and principal components analysis (PCA) were employed to ensure the rational selection of representative training sets. Twelve statistically robust pharmacophore models were generated using the HypoGen algorithm. The resulting models showed high homology and indicated great convergence in ascertaining pharmacophoric features essential for CDK9 inhibitory activity. One of the best models (Hypo 6) was assessed further by external predictive capability, randomization test, as well as its performance in virtual screening. The capability of the resulting models to reliably predict the inhibitory activity of external data sets and discriminate active structures from general databases would assist the identification and optimization of novel CDK9 inhibitors.     

Fast Ray Tracing of Arbitrary Implicit Surfaces with Interval and Affine Arithmetic

Existing techniques for rendering arbitrary-form implicit surfaces are limited, either in performance, correctness or flexibility. Ray tracing algorithms employing interval arithmetic (IA) or affine arithmetic (AA) for root-funding are robust and general in the class of surfaces they support, but traditionally slow. Nonetheless, implemented efficiently using a stack-driven iterative algorithm and SIMD vector instructions, these methods can achieve interactive performance for common algebraic surfaces on the CPU. A similar algorithm can also be implemented stacklessly, allowing for efficient ray tracing on the GPU. This paper presents these algorithms, as well as an inclusion-preserving reduced affine arithmetic (RAA) for faster ray-surface intersection. Shader metaprogramming allows for immediate and automatic generation of symbolic expressions and their interval or affine extensions. Moreover, we are able to render even complex forms robustly, in real-time at high resolution .     

酪氨酸激酶抑制剂的虚拟受体模型方法研究

利用柔性原子受体模型(FLARM)方法对一系列的异黄酮和喹诺酮衍生物表皮生长因子受体酪氨酸激酶抑制剂进行了三维定量构效关系研究,得到了合理的构效关系模型。FLARM方法的计算结果还给出了虚拟的受体模型,该模型说明了抑制剂与受体之间可能的相互作用。这些相互作用包括两个氢键和一个硫-芳香相互作用,以上结果仅仅是由7个化合物得到的。     

Detection and discrimination of coliform bacteria with gas sensor arrays

Electronic noses, which are used for characterizing complex vapors and aromas, may be useful for detection of bacterial contamination or diagnosis of infections, if minimal standards of selectivity and sensitivity can be met. A culture of Enterobacter aerogenes is readily discriminated from an Escherichia coli strain using principal components analysis (PCA) of data generated by an array of eight quartz microbalance (QMB), eight metal oxide semiconductor (MOX), and four electrochemical gas sensors. Two strains of E. coli were not discriminated under identical conditions. Retaining headspace air in a sealed vial containing growing bacteria results in an enhancement of sensitivity, so that a concentration of bacteria of about 5×10⁸/ml may be both detected and distinguished from other species. Improvements in sensitivity to levels useful for practical applications will require enhancement of sensors, sampling system, and pattern classification.     

Asset management with reverse product flows and environmental considerations

Today many business enterprises employ capital assets in the form of electronic equipment, such as personal computers, workstations and peripherals, in large quantities. Due to rapid technological progress (leading to a short life cycle for these products), and hazardous material content in electronic products (which is an environmental problem and a disposal challenge), leasing or procurement contracts with take-back considerations can be attractive. For a large electronic equipment leasing company, optimal management of assets supported by good logistics and end-of-life processing decisions is crucial, and may provide a significant competitive advantage. There is currently no analytic approach for making these decisions in an integrated fashion.     

Chk2抑制剂2-芳香基苯并咪唑类化合物活性的CoMFA研究

利用比较分子力场分析(CoMFA)法,研究训练集中的37个Chk2抑制剂2-芳香基苯并咪唑类化合物的生物活性,考察了互变异构对抑制剂活性的影响,建立了主成分为4的三维定量结构-活性关系模型.模型的交叉和非交叉验证回归系数(q2、r2)分别为0.660和0.908,是稳定性较高和预测能力较好的模型,立体场对活性的影响比静电场大.模型可用于指导设计新的Chk2抑制剂.     

Dispersion and deposition of nanoparticles in microchannels with arrays of obstacles

Air pollutants are among the hazardous materials for human health. Therefore, many scientists are interested in removing particles from the carrier gas. In this study, flow of air and airborne particles through the virtual multi-fibrous filters that consist of different fiber cross-sectional shapes and arrangements is simulated where particle deposition and filtration performance are studied. Regular and irregular arrangements of fibers with the circular, elliptical, and equilateral triangular cross sections have been considered. Effects of important parameters such as solid volume fraction, internal structure, and filter thickness on particle collection efficiency and pressure drop are investigated, and the best internal structure of the multi-fiber filters for the collection of particles is obtained. Results indicate that an increase in the ratio of the vertical distances between fibers to fiber diameter and the solid volume fraction would result in a dramatic reduction of filtration. Collection efficiency of multi-fiber filters is validated with the available numerical studies.     

Performance of RAID5 disk arrays with read and write caching

In this paper, we develop analytical models and evaluate the performance of RAID5 disk arrays in normal mode (all disks operational), in degraded mode (one disk broken, rebuild not started) and in rebuild mode (one disk broken, rebuild started but not finished). Models for estimating rebuild time under the assumption that user requests get priority over rebuild activity have also been developed. Separate models were developed for cached and uncached disk controllers. Particular emphasis is on the performance of cached arrays, where the caches are built of Non-Volatile memory and support write caching in addition to read caching. Using these models, we evaluate the performance of arrayed and unarrayed disk subsystems when driven by a database workload such as those seen on systems running any of several popular database managers. In particular, we assume single-block accesses, flat device skew and little seek affinity.With the above assumptions, we find six significant results. First, in normal mode, we find there is no difference in performance between subsystems built out of either small arrays or large arrays as long as the total number of disks used is the same. Second, we find that if our goal is to minimize the average response time of a subsystem in degraded and rebuild modes, it is better to use small arrays rather than large arrays in the subsystem. Third, we find the counter-intuitive result that if our goal is to minimize the average response time of requests to any one array in the subsystem, it is better to use large arrays than small arrays in the subsystem. We call this the best worst-case phenomenon.Fourth, we find that when no caching is used in the disk controller, subsystems built out of arrays have a normal mode performance that is significantly worse than an equivalent unarrayed subsystem built of the same drives. For the specific drive, controller, workload and system parameters we used for our calculations, we find that, without a cache in the controller and operating at typical I/O rates, the normal mode response time of a subsystem built out of arrays is 50% higher than that of an unarrayed subsystem. In rebuild mode, we find that a subsystem built out of arrays can have anywhere from 100% to 200% higher average response time than an equivalent unarrayed subsystem.Out fifth result is that, with cached controllers, the performance differences between arrayed and equivalent unarrayed subsystems shrink considerably. We find that the normal mode response time in a subsystem built out of arrays is only 4.1% higher than that of an equivalent unarrayed system. In degraded (rebuild) mode, a subsystem built out of small arrays has a response time 11% (13%) higher and a subsystem built out of large arrays has a response time 15% (19%) higher than an unarrayed subsystem.Our sixth and last result is that cached arrays have significantly better response times and throughputs than equivalent uncached arrays. For one workload, a cached array with good hit ratios had 5 times the throughout and 10 to 40 times lower response times than the equivalent uncached array. With poor hit ratios, the cached array is still a factor of 2 better in throughput and a factor of 4 to 10 better in response time for this same workload.We conclude that 3 design decisions are important when designing disk subsystems built out of RAID level 5 arrays. First, it is important that disk subsystems built out of arrays have disk controllers with caches, in particular Non-Volatile caches that cache writes in addition to reads. Second, if one were trying to minimize the worst response time seen by any user, one would choose disk array subsystems built out of large RAID level 5 arrays because of the best worst-case phenomenon. Third, if average subsystem response time is the most important design metric, the subsystem should be built out of small RAID level 5 arrays.     

蛋白激酶活性及抑制性检测研究进展

蛋白激酶催化蛋白磷酸化是一种非常重要的蛋白质翻译后修饰方式,能够调节细胞内大多数蛋白的功能,在众多生理过程中发挥着至关重要的作用。磷酸化过程的异常以及激酶的过度表达往往与许多疾病密切相关,如癌症、糖尿病和老年痴呆症。因而,测定蛋白激酶的活性及筛选蛋白激酶抑制剂对基础生物医学研究和酶靶药物的开发是非常重要的。近年来,研究工作者们采用电化学法、比色法以及荧光检测法等方法研究了对蛋白激酶活性及抑制性的检测。该文回顾了蛋白激酶活性测定及抑制性检测的研究进展,主要关注了荧光检测法的应用,并对其未来的发展进行展望。     

Interconnection and addressing methods for LCD arrays with fewer leads than a matrix

An unconventional interconnection of liquid crystal display elements and a non-mulpilexed addressing scheme produce saturation contrast in a pseudo-analogue pointer display with nearly twice the resolution of a conventional matrix and the same of leads. A bar-graph presentation on the same array can be accomplished with a root mean square voltage selection ratio of 2.0. General patterns can be displayed on rectangular arrays with similarly reduced lead count, but electro-optic effects with sharp threshold or intrinsic memory are required.     

Flow rate-insensitive microparticle separation and filtration using a microchannel with arc-shaped groove arrays

Inertial microfluidics can separate microparticles in a continuous and high-throughput manner, and is very promising for a wide range of industrial, biomedical and clinical applications. However, most of the proposed inertial microfluidic devices only work effectively at a limited and narrow flow rate range because the performance of inertial particle focusing and separation is normally very sensitive to the flow rate (Reynolds number). In this work, an innovative particle separation method is proposed and developed by taking advantage of the secondary flow and particle inertial lift force in a straight channel (AR = 0.2) with arc-shaped groove arrays patterned on the channel top surface. Through the simulation results achieved, it can be found that a secondary flow is induced within the cross section of the microchannel and guides different-size particles to the corresponding equilibrium positions. On the other hand, the effects of the particle size, flow rate and particle concentration on particle focusing and separation quality were experimentally investigated. In the experiments, the performance of particle focusing, however, was found relatively insensitive to the variation of flow rate. According to this, a separation of 4.8 and 13 µm particle suspensions was designed and successfully achieved in the proposed microchannel, and the results show that a qualified particle separation can be achieved at a wide range of flow rate. This flow rate-insensitive microfluidic separation (filtration) method is able to potentially serve as a reliable biosample preparation processing step for downstream bioassays.     

Unrelated parallel-machine scheduling with aging effects and multi-maintenance activities

Machine maintenance is often performed in manufacturing to prevent premature machine failures with a view to sustaining production efficiency. In this paper we study the parallel-machine scheduling problem with aging effects and multi-maintenance activities simultaneously. We assume that each machine may be subject to several maintenance activities over the scheduling horizon. A machine reverts to its initial condition after maintenance and the aging effects start anew. The objective is to find jointly the optimal maintenance frequencies, the optimal positions of the maintenance activities, and the optimal job sequences such that the total machine load is minimized. We apply the group balance principle to obtain the optimal positions of the maintenance activities and the number of jobs in each group in the scheduling sequence on each machine. We provide an efficient algorithm to solve the problem when the maintenance frequencies on the machines are given.     

Scheduling with job-dependent learning effects and multiple rate-modifying activities

We consider a scheduling problem with job-dependent learning effects and multiple rate-modifying activities. The learning effects manifest such that the processing time of a job is a decreasing function of its position in a sequence. By job-dependent learning effects, we mean that the learning of the jobs is different. A rate-modifying activity is an activity that changes the production rate of a machine. So the actual processing time of a job in our problem is a variable, which depends not only on its position in a sequence but also on whether it is scheduled before or after a rate-modifying activity. We assume that each machine may have multiple rate-modifying activities. The objective is to minimize the total completion time. We show that all the cases of the problem are polynomially solvable.     

On a differential game with integral and phase constraints

Consideration is given to a differential game on the plane when the moves of a pursuer and a running away are described by equations of the simple move, and integral constraints are imposed on control functions. In the process of the game the pursuer moves within the prescribed closed convex subset of the plane and the running away moves along its boundary. In the case when the running away has an advantage of resources, the development is made of the runaway strategy that affords the lower bound for the distance between the players. In the case when the pursuer has an advantage of resources, for any initial positions of the players the optimal time of pursuit is found and optimal strategies of the players are set up.