A novel hybrid method based on fuzzy cognitive maps and fuzzy clustering algorithms for grading celiac disease

This paper presents a new method based on fuzzy cognitive map (FCM) and possibilistic fuzzy c-means (PFCM) clustering algorithm for categorizing celiac disease (CD). CD is a complex disorder whose development is affected by genetics (HLA alleles) and gluten ingestion. The celiac patients who are not treated are at a high risk of cancer, malignant lymphoma, and small bowel neoplasia. Therefore, CD diagnosis and grading are of paramount importance. The proposed FCM models human thinking for the purpose of classifying patients suffering from CD. We used the latest grading method where three grades A, B1, and B2 are used. To improve FCM efficiency and classification capability, a nonlinear Hebbian learning algorithm is applied for adjusting the FCM weights. To this end, 89 cases are studied. Three experts extracted seven main determinant characteristics of CD which were considered as FCM concepts. The mutual effects of these concepts on one another and on the final concept were expressed in the form of fuzzy rules and linguistic variables. Using the center of gravity defuzzifier, we obtained the numerical values of these weights and obtained the total weight matrix. Ultimately, combining the FCM model with PFCM algorithm, we obtained the grades A, B1, and B2 accuracies as 88, 90, and 91%, respectively. The main advantage of the proposed FCM is the good transparency and interpretability in the decision-making procedure, which make it a suitable tool for daily usage in the clinical practice.

     

用于T细胞表位预测的分类器集成方法*

T细胞表位预测技术对于减少实验合成重叠肽,理解T细胞介导的免疫特异性和研制亚单位多肽及基因疫苗均有重要意义.为弥补已有基于机器学习方法的T细胞表位预测模型的可理解性的不足并进一步提高模型的预测精度,首先通过肽的预处理构建出了存储等长肽段的决策表,而后提出了基于粗糙集的分类器集成算法.该算法不但综合利用了基于信息熵的属性约简完备算法和其他属性约简算法的优势,而且将T细胞表位预测领域中的锚点知识融入到了属性值约简过程中.最后利用该算法来预测MHC Ⅱ类分子HLA-DR4(B1·0401)的结合肽,首次提取出了预测精度高且能帮助专家理解MHC分子与抗原肽的结合机理的产生式规则,为下一步的分子建模工作奠定了基础.     

Structure-based design of inhibitors of NS3 serine protease of hepatitis C virus

We have designed small focused combinatorial library of hexapeptide inhibitors of NS3 serine protease of the hepatitis C virus (HCV) by structure-based molecular design complemented by combinatorial optimisation of the individual residues. Rational residue substitutions were guided by the structure and properties of the binding pockets of the enzyme's active site. The inhibitors were derived from peptides known to inhibit the NS3 serine protease by using unusual amino acids and alpha-ketocysteine or difluoroaminobutyric acid, which are known to bind to the S1 pocket of the catalytic site. Inhibition constants (Ki) of the designed library of inhibitors were predicted from a QSAR model that correlated experimental Ki of known peptidic inhibitors of NS3 with the enthalpies of enzyme-inhibitor interaction computed via molecular mechanics and the solvent effect contribution to the binding affinity derived from the continuum model of solvation. The library of the optimised inhibitors contains promising drug candidates-water-soluble anionic hexapeptides with predicted Ki* in the picomolar range.     

Effective fragment potentials and the enzyme active site

Optimization of the binding conformation of a substrate in an enzyme active site using ab initio quantum chemistry methods are intractable since the active site comprises several hundred atoms. However, the active site can be decomposed into an active and spectator region where the spectator residues are represented by effective fragment potentials and reducing the number of all-electron atoms involved in the chemistry to a reasonable level. The effective fragment potentials for electrostatics and polarization are implemented in GAMESS but the repulsive and charge transfer potentials are fit to interaction energies of water with models of the residues. These repulsive/charge transfer potentials are generated for the protein residues and the EFP are then used to optimize binding of a transition state analogue to chorismate mutase (B. subtilis) and small dianions to ribonuclease A. For chorismate mutase the calculated binding conformation compares well to the comparable X-ray structure. The binding of the inhibitor to the glutamate/glutamine mutant active site is then predicted with the optimization including the glutamine residue constrained only at the C alpha atom. The binding conformations suggest important roles for tyr108 and arg63, which have not been noted earlier. The electrostatic stabilization of the transition state by the active site charge distribution has to be augmented by a specific electronic activation by glu78. In ribonuclease A, the protons are found to move to provide a clustering of the charges to bind the small dianions, phosphate, thiophosphate, and sulfate.     

多效精馏烷烃混合物的Aspen Plus模拟分离

精馏是石油化工能耗最大的单元操作之一,因此对其过程的节能研究非常重要。本文利用Aspen Plus化工模拟软件中的RADFRAC模块和PENG-ROB热力学计算模型,系统模拟了多效精馏顺流(DQF、IQF)、逆流(DQB、IQB)及常规精馏(DQ、IQ)的烃类混合物异丁烷/正丁烷/正己烷的分离。根据各组分的分离要求,通过灵敏度分析优化各工艺参数;同时比较了各精馏构造的有效能损失和热力学效率,并计算了它们的年度总费用(TAC)。结果表明:与间接精馏方案IQ相比,精馏方案IQF、DQB、DQ分别节能20.6%、16.0%、8.4%;热力学效率方面,多效精馏IQF为19.6%,DQB22.2%,普遍比常规精馏的DQ10.0%、IQ10.3%要高;至于年度总费用(TAC),相比于IQ,DQB多耗资12.1%,而IQF、DQ少耗资9.0%和8.7%。综合节能效果、热力学效率、年度总费用得知,IQF这种多效精馏方案最优。     

WEIGHTED AVERAGE OF DIRICHLET KERNELS FOR VILENKIN-LIKE SYSTEM

For Vilenkin-like system, the authors define a new operator H*f := supn |Hnf|, where Hnf is the weighted average for partial sums, and prove that H* is of type (Hp* (Gm), Lp(Gm)) for all 1/2 < p ≤∞. As a consequence, the authors prove the operator S*f := supn |Snf| is of type (p, p) for 1 < p < ∞, where Snf is the n-partial sum.     

Numerical and experimental LDL transport through arterial wall

Atherosclerosis develops from oxidized low-density lipoprotein molecules (LDL). When oxidized LDL evolves in plaque formations within an artery wall, a series of reactions occur to repair the damage to the artery wall caused by oxidized LDL. Aim of this study was to compare experimental data of LDL transport through isolated blood vessel with computational results of bounding of oxidized LDL receptor-1 (LOX-1) for endothelial cells with numerical discrete methods such as dissipative particle dynamics (DPD) and lattice Boltzmann (LB) method. Experiments of LDL transport were performed on the isolated rabbit common carotid arteries acquired from fifteen rabbits after 12 weeks of high-fat diet. Oxidative LDL molecule is built and used for docking with LOX-1 receptor. Energies that give the best binding are computed, and the energy with greatest probability of attachment for oxidative LDL molecule and glutamine acid is further used in numerical simulations. Simulations using DPD and LB method use the computed binding energy to calculate the force necessary for binding of LDL molecule to the endothelial blood vessel layer. Experimental results have shown large uptake for shear stress below 1 dyn/cm². Computational results for both discrete methods DPD and LB have shown good accuracy with experimental data. Calculation of the interactive molecule forces from computational chemistry open a new avenue for multiscale modeling methods, which will give better insight for the understanding and the prediction of LDL transport through the arterial wall for the medical community.     

Identification of novel allosteric modulator binding sites in NMDA receptors: A molecular modeling study

The dysfunction of N-methyl-d-Aspartate receptors (NMDARs), a subtype of glutamate receptors, is correlated with schizophrenia, stroke, and many other neuropathological disorders. However, not all NMDAR subtypes equally contribute towards these disorders. Since NMDARs composed of different GluN2 subunits (GluN2A-D) confer varied physiological properties and have different distributions in the brain, pharmacological agents that target NMDARs with specific GluN2 subunits have significant potential for therapeutic applications. In our previous research, we have identified a family of novel allosteric modulators that differentially potentiate and/or inhibit NMDARs of differing GluN2 subunit composition. To further elucidate their molecular mechanisms, in the present study, we have identified four potential binding sites for novel allosteric modulators by performing molecular modeling, docking, and in silico mutations. The molecular determinants of the modulator binding sites (MBS), analysis of particular MBS electrostatics, and the specific loss or gain of binding after mutations have revealed modulators that have strong potential affinities for specific MBS on given subunits and the role of key amino acids in either promoting or obstructing modulator binding. These findings will help design higher affinity GluN2 subunit-selective pharmaceuticals, which are currently unavailable to treat psychiatric and neurological disorders.     

EH＊p： 一种使用奇偶编码的高可用可扩展分布式数据结构

EH＊p是一种使用奇偶编码对数据进行备份的高可用可扩展分布式数据结构.EH＊p文件可以随着记录的插入而逐渐扩展到多台服务器上,并可在单服务器故障时自动对丢失的数据进行恢复.EH＊p采用数据桶满后立即分裂的扩展方法,直接把记录关键字映射到服务器地址,并且把数据桶的分裂和恢复操作分配给系统中的各服务器,克服了LH＊类数据结
构的不足之处.实验显示,该结构的备份数据的存储消耗较小,而且单次查询所花费的消息数接近理论最小值2.     

Quantitative prediction of MHC-II peptide binding affinity using relevance vector machine

Peptide-MHC binding is an important prerequisite event and has immediate consequences to immune response. Those peptides binding to MHC molecules can activate the T-cell immunity, and they are useful for understanding the immune mechanism and developing vaccines for diseases. Accurate prediction of the binding between peptides and MHC-II molecules has long been a challenge in bioinformatics. Recently, instead of differentiating peptides as binder or non-binder, researchers are more interested in making predictions directly on peptide binding affinities. In this paper, we investigate the use of relevance vector machine to quantitatively predict the binding affinities between MHC-II molecules and peptides. In our scheme, a new encoding scheme is used to generate the input vectors, and then by using relevance vector machine we develop the prediction models on the basis of binding cores, which are recognized in an iterative self-consistent way. When applied to three MHC-II molecules DRB1*0101, DRB1*0401 and DRB1*1501, our method produces consistently better performance than several popular quantitative methods, in terms of cross-validated squared error, cross-validated correlation coefficient, and area under ROC curve. All evidences indicate that our method is an effective tool for MHC-II binding affinity prediction.     

Binding research on flavones as ligands of β-amyloid aggregates by fluorescence and their 3D-QSAR, docking studies

The K(d)s (dissociation constants) of 21 flavone derivatives have been obtained by fluorescence in vitro when binding with Aβ(1-40) (β-amyloid(1-40)) aggregates protein. Extensive 3D-QSAR (quantitative structure-activity relationship) studies were performed on the fluorescent flavones, which are excellent ligands of Aβ(1-40) aggregates protein. Comparative molecular similarity indices analysis (CoMSIA) technique was used to relate the binding affinities with the ligand structures, and the QSAR model was obtained using the CoMFA technique. The QSAR model was proved to statistically significant and have high predictive power: the CoMSIA model yielded the cross-validated q2 = 0.512 and the non-cross-validated r2 = 0.911. This model showed that electrostatic (22.5%) and H-bond interaction (acceptor 15.3%; donor 45.1%) properties played major roles in ligand binding process. The QSAR model was further graphically interpreted in terms of field contribution maps. In order to further investigate the specific binding site of the flavones in the Aβ(1-40) aggregates, preliminary docking studies were performed. According to the 3D-QSAR results, the possible binding site in the protein was proposed in order to direct the molecular docking studies. A good correlation (R2: 0.846) between the calculated binding energies and the experimental binding affinities (pK(d)s) suggests that the identified binding site is reliable. The 3D-QSAR model and the information of the ligand-protein interaction will be helpful in the selection of flavones to be structurally modified and labeled by a radio nuclide for imaging Aβ(1-40) aggregates in the AD (Alzheimer's disease) brain.     

Capturing data quality requirements for web applications by means of DQ_WebRE

The number of Web applications which are part of Business Intelligence (BI) applications has grown exponentially in recent years, as has their complexity. Consequently, the amount of data used by these applications has also increased. The larger the number of data used, the greater the chance to make errors is. That being the case, managing data with an acceptable level of quality is paramount to success in any organizational business process. In order to raise and maintain adequate levels of Data Quality (DQ), it is indispensable for Web applications to be able to satisfy specific DQ requirements. To do so, DQ requirements should be captured and introduced into the development process of the Web Application, together with the other software requirements needed in the applications. In the field of Web application development, however, there appears to us to exist a lack of proposals aimed at managing specific DQ software requirements. This paper considers the MDA (Model Driven Architecture) approach and, principally, the benefits provided by Model Driven Web Engineering (MDWE), putting forward a proposal for two artifacts. These consist of a metamodel and a UML profile for the management of Data Quality Software Requirements for Web Applications (DQ_WebRE).     

A multidimensional analysis of data quality for credit risk management: New insights and challenges

Recent studies have indicated that companies are increasingly experiencing Data Quality (DQ) related problems as more complex data are being collected. To address such problems, the literature suggests the implementation of a Total Data Quality Management Program (TDQM) that should consist of the following phases: DQ definition, measurement, analysis and improvement. As such, this paper performs an empirical study using a questionnaire that was distributed to financial institutions worldwide to identify the most important DQ dimensions, to assess the DQ level of credit risk databases using the identified DQ dimensions, to analyze DQ issues and to suggest improvement actions in a credit risk assessment context. This questionnaire is structured according to the framework of Wang and Strong and incorporates three additional DQ dimensions that were found to be important to the current context (i.e., actionable, alignment and traceable). Additionally, this paper contributes to the literature by developing a scorecard index to assess the DQ level of credit risk databases using the DQ dimensions that were identified as most important. Finally, this study explores the key DQ challenges and causes of DQ problems and suggests improvement actions. The findings from the statistical analysis of the empirical study delineate the nine most important DQ dimensions, which include accuracy and security for assessing the DQ level.     

一种基于DQ变换的解耦滞环控制

针对传统滞环控制方法无法对有功与无功功率进行解耦的缺点进行了研究.提出了一种基于DQ变换的解耦滞环控制方法,并将其应用于单相并网逆变器中.该方法对采样的电流信号进行DQ变换后,分别对DQ轴的信号进行控制.最后将这两个控制量进行DQ反变换后送入滞环比较器中,由此获得开关信号.系统整体结构上采用电压外环电流内环的双闭环控制,内环在完成功率解耦的同时还加入了对电网的无功功率补偿.在保持了滞环控制的快速性与抗干扰性的同时还完成了对有功与无功功率的解耦控制.Matlab的仿真和实验结果验证了所提出控制方法的有效性.     

Explicit substitutions and higher-order syntax

Recently there has been a great deal of interest in higher-order syntax which seeks to extend standard initial algebra semantics to cover languages with variable binding. The canonical example studied in the literature is that of the untyped λ-calculus which is handled as an instance of the general theory of binding algebras, cf. Fiore et al. [13]. Another important syntactic construction is that of explicit substitutions which are used to model local definitions and to implement reduction in the λ-calculus. The syntax of a language with explicit substitutions does not form a binding algebra as an explicit substitution may bind an arbitrary number of variables. Thus explicit substitutions are a natural test case for the further development of the theory and applications of syntax with variable binding. This paper shows that a language containing explicit substitutions and a first-order signature Σ is naturally modelled as the initial algebra of the Id + F _{Σ∘_} +_{_ ∘ _} endofunctor. We derive a similar formula for adding explicit substitutions to the untyped λ-calculus and then show these initial algebras provide useful datatypes for manipulating abstract syntax by implementing two reduction machines. We also comment on the apparent lack of modularity in syntax with variable binding as compared to first-order languages.     

The effect of electrostatics on factor H function and related pathologies

Factor H (FH) contributes to the regulation of the complement system by binding to polyanionic surfaces and the proteins C3b/C3c/C3d. This implicates charge and electrostatic interactions in recognition and binding of FH. Despite the large amount of experimental and pathology data the exact mechanism at molecular level is not yet known. We have implemented a computational framework for comparative analysis of the charge and electrostatic diversity of FH modules and C3b domains to identify electrostatic hotspots and predict potential binding sites. Our electrostatic potential clustering analysis shows that charge distributions and electrostatic potential distributions are more useful in understanding C3b-FH interactions than net charges alone. We present a model of non-specific electrostatic interactions of FH with polyanion-rich surfaces and specific interactions with C3b, using our computational data and existing experimental data. We discuss the electrostatic contributions to the formation of the C3b-FH complex and the competition between FH and Factor Bb (Bb) for binding to C3b. We also discuss the significance of mutations of charged amino acids in the pathobiology of FH-mediated disease, such as age-related macular degeneration, atypical hemolytic uremic syndrome, and dense deposit disease. Our data can be used to guide future experimental studies.     

DIS/HLA转换器的研究与开发

分布交互仿真的发展经历了从最早的SimNet到DIS以及目前的HLA等多种体系结构,采用HLA结构是日前分布交互仿真发展的趋势。但是目前还存在许多基于DIS的仿真系统,为了能够利用这些已有的仿真资源,有必要使这些DIS系统能够与基于HLA的分布交互仿真系统相连接。因此需要研究DIS／HLA之间的转换和互联技术。该文分析了几种常用的DIS／HLA转换技术方案,指出对于一个具体的DIS与HLA互联问胚,采用转换器的方案是比较容易实现的,给出了相关的开发思路和程序实现,并对所开发的转换器的延时特性进行了测试。开发和应用表明采用转换器不需要对原有的DIS系统进行修改,具有使用方便且容易实现的特点。     

微分求积法分析二维亚音速壁板的失稳问题

采用微分求积方法(简称DQ方法)研究了亚音速气流中二维壁板的失稳问题.运用特征值方法分析了壁板在不同边界条件下的失稳特性.结果表明:本方法可有效确定系统的失稳;两端简支和两端固支的壁板出现了发散失稳而未出现颤振失稳;固支—弹性支承的壁板系统出现了颤振失稳,颤振失稳动压与系统参数相关.     

基于节点优化的改进全局路径规划A*算法

目前越来越多的领域使用移动机器人代替人工工作。路径规划就是移动机器人正常工作的保障之一,A*算法就是一种路径规划算法。针对A*算法生成路径拐点多、路径较长的问题,提出了一种基于将搜索邻域扩大至5×5的随机数去除节点的改进A*算法。首先,将3×3的搜索邻域扩大至5×5,从而减少拐点个数,改善转折角度,去除冗余点;其次,引入一种随机数去除冗余节点的方法,该方法是通过随机连接节点判定其是否穿过障碍物来去除冗余节点,从而进一步去除A*算法路径列表的冗余点;最后,将改进的算法与A*算法在30×30的栅格地图中进行仿真比较,实验结果表明,改进的算法在多组路径中都有很好的优化效果,路径长度、运行时长和访问节点数分别平均减少了4.46%、24.83%和39.93%,从而有效改善A*算法生成拐点多、路径较长的问题。     

Constant-time hough transform on the processor arrays with reconfigurable bus systems

We develop constant-time algorithms to compute the Hough transform on a processor array with a reconfigurable bus system (abbreviated to PARBS). The PARBS is a comptuation model which consists of a processor array and a reconfigurable bus system. It is a very powerful computation model in that many problems can be solved efficiently. In this paper, we introduce the concept of iterative-PARBS which is similar to the FOR-loop construct in sequential programming languages. The iterative-PARBS is a building block in which the processing data can be routed through it several times. We can think it as a “hardware subroutine”. Based on this scheme, we are able to explore constant-time Hough transform algorithms on PARBS. The following new results are derived in this study:

1. The sum ofn bits can be computed in O(1) times on a PARBS with O(n ^1+?) processors for any fixed ?>0.
2. The weights of each simple path of ann*n image can be computed in O(1) time on a 3-D PARBS with O(n ^2+?) processors for any fixed ?>0.
3. Thep angle Hough transform of ann*n image can be computed in O(1) time on a PARBS with O(p*n ^2+?) processors for any fixed ?>0 withp copies of the image pretiled.
4. Thep angle Hough transform of ann*n image can be computed in O(1) time on a PARBS with O(p*n ³) processors.