Alpha(1) adrenoceptor subtype selectivity. 3D-QSAR models for a new class of alpha(1) adrenoceptor antagonists derived from the novel antipsychotic sertindole

Receptor-binding affinities for the alpha(1) adrenoceptor subtypes alpha(1a), alpha(1b) and alpha(1d) for a series of 39 alpha(1) adrenoceptor antagonists derived from the antipsychotic sertindole are reported. The SAR of the compounds with respect to affinity for the alpha(1a), alpha(1b) and alpha(1d) adrenoceptor subtypes as well as affinity obtained by an alpha(1) assay (rat brain membranes) were investigated using a 3D-QSAR approach based on the GRID/GOLPE methodology. Good statistics (r(2)=0.91-0.96; q(2)=0.65-0.73) were obtained with the combination of the water (OH2) and methyl (C3) probes. The combination of steric repulsion and electrostatic attractions explain the affinities of the included molecules. The adrenergic alpha(1a) receptor seems to be more tolerant to large substituents in the area between the indole 5- and 6-positions compared to the adrenergic alpha(1b) and alpha(1d) receptor subtypes. There seems to be minor differences in the position of areas in the alpha(1b) receptor compared to alpha(1a) and alpha(1d) receptors where electrostatic interaction between the molecules and the receptor (OH2 probe) contribute to increased affinity. These observations may be used in the design of new subtype selective compounds. In addition, the model based on biological data from an alpha(1) assay (rat brain membranes) resembles the model for the alpha(1b) adrenoceptor subtype.     

Structural determinants of the psychosocial work environment: introducing technology in the work stress framework

To extend current models of psychosocial work stress research into organizational structure, technology is introduced. An exploratory model is developed combining research from ergonomics, epidemiology, and organizational science. It is hypothesized that technology influences a worker's health by structuring the job, and the relationship between the job and a worker's health is mediated by attitudes at work. To test the model, data are used from a 1978 NIOSH survey of postal workers sorting mail (N = 4903). Path analysis shows technology is indirectly associated with job satisfaction and psychosomatic symptoms by how it structured the job. A machine-paced technological system of work is associated with greater job demands, less control in the job, and less co-worker support but not with supervisor support. The implications of this model for prevention strategies at the workplace are discussed suggesting that influencing supervisor support is the most effective way to affect a person's job satisfaction and level of psychosomatic symptomology.     

On the complexity of computing determinants

We present new baby steps/giant steps algorithms of asymptotically fast running time for dense matrix problems. Our algorithms compute the determinant, characteristic polynomial, Frobenius normal form and Smith normal form of a dense n × n matrix A with integer entries in and bit operations; here denotes the largest entry in absolute value and the exponent adjustment by +o(1) captures additional factors for positive real constants C₁, C₂, C₃. The bit complexity results from using the classical cubic matrix multiplication algorithm. Our algorithms are randomized, and we can certify that the output is the determinant of A in a Las Vegas fashion. The second category of problems deals with the setting where the matrix A has elements from an abstract commutative ring, that is, when no divisions in the domain of entries are possible. We present algorithms that deterministically compute the determinant, characteristic polynomial and adjoint of A with n^3.2+o(1) and O(n^2.697263) ring additions, subtractions and multiplications.To B. David Saunders on the occasion of his 60th birthday     

Modeling the determinants of Internet use

The purpose of the study is to build a model that predicts the level of Internet use by teachers of English as a foreign language in the northern Taiwanese higher education institutions. It examines interactional relationships among variables associated with barriers and issues of technology application as a means of analyzing the extent and the nature of Internet-integration instruction. A multivariate hypothesized model was tested using structural equation modeling to analyze statistically the variables examined in the study. The resulting model is found to have a good statistical fit. Teacher training, classroom pedagogy, and perceived capability have direct effect on Internet use, whereas institutional support, constructivist thinking, beliefs, and attitudes affect Internet use indirectly. These seven variables account for approximately 58.6% of the variance of Internet use. Teacher training appears to be the most dominant determinant of Internet use. More opportunities for professional development focused on technology applications in language instruction are crucial.     

Exploring the selectivity of inhibitor complexes with Bcl-2 and Bcl-XL: A molecular dynamics simulation approach

B-cell lymphoma 2 (Bcl-2) family proteins are potential drug targets in cancer and have a relatively flat and flexible binding site. ABT-199 is one of the most promising selective Bcl-2 inhibitors, and A-1155463 selectively inhibits Bcl-XL. Although the amino acid sequences of the binding sites of these two inhibitors are similar, the inhibitors selectively bind the target protein. In order to determine the origin of the selectivity of these inhibitors, we conducted molecular dynamics simulations using protein-inhibitor modeling. We confirmed that ASP103 of Bcl-2 is a key residue and that hydrogen bonding between ASP103 and ABT-199 confers the Bcl-2 selectivity of this inhibitor. For Bcl-XL selectivity, the secondary structure of α-helix 3 is a key factor. PHE105, SER106, and LEU108 in the loose α-helix 3 interact with A-1155463 to confer Bcl-XL selectivity. These findings provide important insights into the molecular mechanisms of selective inhibitors of Bcl-2 family proteins.     

线结构光视觉传感器结构参数优化分

为实现线结构光视觉传感器的优化设计,建立了线结构光视觉传感器的像面点与被测空间物体上对应点之间的数学模型,该模型反映了空间被测点与传感器结构参数之间的相互关系.然后基于此模型对线结构光视觉传感器的测量误差进行了分析,得出了线结构光传感器各参数与测量精度之间的关系.在对各设计参数综合分析的基础上,提出了线结构光传感器最优结构参数判据,并给出了优化线结构光传感器结构参数的实例.     

Designers as the determinants of design innovations

Design innovations have become increasingly important appropriation mechanisms for firms. Since 2003, the number of applications for design rights (protecting design innovations) has tripled compared to a doubling in the numbers of both patent and trademark applications. However, despite the growing interest of firms in design innovations, knowledge of the determinants of design innovations is limited. Prior work on labour mobility within the innovation studies literature has focused primarily on the discussion of scientists as being crucial for the creation of technological innovations. The present paper expands on this discussion by drawing parallels with the relation between scientists and technological innovation and the relation between designers and design innovation. We explore whether a similar positive relationship exists between the labour mobility of designers and the generation of design innovations and which determinants influence this relation. We employ a unique Danish dataset containing information on firms, their hiring of designers, and their design innovation activity measured by design rights. Our findings show that hiring a designer does increase the likelihood of producing a design innovation. Hence, designers are a determinant of design innovations. However, in order for the firm to benefit fully from hiring a designer, prior experience in design innovation is required.     

Structural equation model (SEM)-neural network (NN) model for predicting quality determinants of e-learning management systems

The success of e-learning management systems (e-LMSs) such as MOODLE depends on the usage of students as well as instructor acceptance in a virtual learning environment. E-Learning enables instructors to access educational resources to support traditional classroom teaching. This paper attempts to develop a model to understand and predict the effect of individual characteristics (technology experience [TE] and personal innovativeness [PI]) and e-LMS quality determinants (system quality [SYS-Q], information quality, and service quality) on the continuous use of e-LMS by instructors, which is critical to its success. A total of 219 instructors using MOODLE responded to the survey. The structural equation model (SEM) was employed to test the proposed research model. The SEM results showed that SYS-Q, PI, service quality, and TE have a statistically significant influence on continuous usage of e-LMS by instructors. Furthermore, all determinants of the research model were given as input to an NN model to overcome the simplistic nature of the SEM model. The NN model results showed that service quality is the most important predictor of e-learning acceptance followed by SYS-Q, PI, information quality, and TE. This paper attempts to develop a causal and predictive statistical model for predicting instructor e-LMS acceptance.     

Structural basis for ligand recognition at the benzodiazepine binding site of GABAA alpha 3 receptor, and pharmacophore-based virtual screening approach

Given the heterogeneity of GABA(A) receptor, the pharmacological significance of identifying subtype selective modulators is increasingly being recognized. Thus, drugs selective for GABA(A) alpha(3) receptors are expected to display fewer side effects than the drugs presently in clinical use. Hence we carried out 3D QSAR (three-dimensional quantitative structure-activity relationship) studies on a series of novel GABA(A) alpha(3) subtype selective modulators to gain more insight into subtype affinity. To identify the 3D functional attributes required for subtype selectivity, a chemical feature-based pharmacophore, primarily based on selective ligands representing diverse structural classes was generated. The obtained pseudo receptor model of the benzodiazepine binding site revealed a binding mode akin to "Message-Address" concept. Scaffold hopping was carried out across multi-conformational May Bridge database for the identification of novel chemotypes. Further a focused data reduction approach was employed to choose a subset of enriched compounds based on "Drug likeness" and "Similarity-based" methods. These results taken together could provide impetus for rational design and optimization of more selective and high affinity leads with a potential to have decreased adverse effects.     

Structural indexing: efficient 2D object recognition

The problem of recognition of multiple flat objects in a cluttered environment from an arbitrary viewpoint is addressed. The models are acquired automatically and approximated by polygons with multiple line tolerances for robustness. Groups of consecutive segments (super segments) are then encoded and entered into a table. This provides the essential mechanism for indexing and fast retrieval. Once the database of all models is built, the recognition proceeds by segmenting the scene into a polygonal approximation; the code for each super segment retrieves model hypotheses from the table. Hypotheses are clustered if they are mutually consistent and represent the instance of a model. Finally, the estimate of the transformation is refined. This methodology makes it possible to recognize models despite noise, occlusion, scale rotation translation, and a restricted range of weak perspective. A complexity bound is obtained     

F2＋uF2上奇偶长循环码的结构特性

码长为2n（n为奇数）的循环码被称为奇偶长的循环码。本文证明了F2＋uF2上奇偶长循环码具有形如（a1（x^2）a3（x^2）a4（x^2）a5（x）a6（x），ua1（x^2）a2（x^2）a4（x）a5（x^2））的结构，其中ai（x），i=1，2，…，6，满足Пi=1^6ai（x）=x^n-1，而且a5^ ～（x）≡a5（x）（modu），并给出了奇偶长循环码之对偶码的生成元表达。     

Enhanced studies on the mechanism of gas selectivity and electronic interactions of SnO2/Na-ionic conductors

The selectivity of metal oxide gas sensors (MOG) can be improved significantly by forming composites with solid ionic conductor additives. First investigations were done using model composites of SnO₂/Natrium Super Ionic Conductor (NASICON) with the result of a huge sensitivity enhancement to substances ending with R–OH, R–HO or R–COOH groups and a reduction of sensitivity to other gas components. This selectivity of the new composite to those functional groups could be confirmed by catalytic conversion measurements with FTIR-spectroscopy at three gas components, respectively. The specific conductivity of the NASICON containing composites is significantly lower than that of pure SnO₂. Advanced studies show that the activation energy of the bulk-conductivity increases by approximately 30% in the presence of NASICON. In spite of high volume parts of NASICON (20%), no polarization effects were found (a complete Ohmic current–voltage behavior) and mainly the resistive part of the electrical impedance is influenced.     

Structural sensitivity analysis and optimization in the RIPAK system. Part 2

An approach to structural optimization within the framework of the RIPAK FEM package is presented. Part 2 is devoted to information technologies realized in the RIPAK package for user-system interface improvement. The data base scheme offered integrates design information and allows us to describe structure in a natural way. The expert system helps to tune the algorithm and to reach efficient results in the best way. Numerical tests of aviation structural optimization with aeroelastic constraints are presented.     

Multi-way spatial join selectivity for the ring join graph

Efficient spatial query processing is very important since the applications of the spatial DBMS (e.g. GIS, CAD/CAM, LBS) handle massive amount of data and consume much time. Many spatial queries contain the multi-way spatial join due to the fact that they compute the relationships (e.g. intersect) among the spatial data. Thus, accurate estimation of the spatial join selectivity is essential to generate an efficient spatial query execution plan that takes advantages of spatial access methods efficiently. For the multi-way spatial joins, the selectivity estimation formulae only for the two kinds of query types, tree and clique, have been developed. However, the selectivity estimation for the general query graph which contains cycles has not been developed yet. To fill this gap, we devise a formula for the multi-way spatial ring join selectivity. This is an indispensable step to compute the selectivity of the general multi-way spatial join whose join graph contains cycles. Our experiment shows that the estimated sizes of query results using our formula are close to the sizes of actual query results.     

H9N2亚型禽流感病毒HA基因氨基酸位点分析

通过系统进化分析,分离自我国的56条全长序列H9N2亚型禽流感病毒株HA基因的氨基酸残基序列,结果表明我国病毒株在早期具有散在发生性,同属于欧亚种系,进化方向与香港人源病毒株明显不同。采用codeml程序检测到HA基因,共有5个阳性选择位点(2T,3T,197T,233Q,380R),除380R外,均位于HA1肽链上,阳性选择位点位于主要的受体结合位点附近,对此需密切监测H9N2亚型禽流感,以防其关键位点的突变。分析蛋白质基序,也发现H9N2禽流感突破种间屏障感染人,可能与病毒株糖基化位点的突变有关。     

基于J2EE的结构设计规范验算系统

设计规范是结构设计的重要依据，全面掌握规范的设计思想，合理运用规范的设计条文可以帮助工程师准确、高效地完成设计任务。将设计规范与计算机技术相结合，融入到CAD系统，实现“规范程序化”是工程师的愿望。该文基于协同设计的思想，采用面向对象技术设计了基于J2EE平台的结构设计规范验算系统模型，实践证明该系统在一定程度上降低了结构设计数据处理的工作量，提高了设计效率，改善了设计质量。     

Structural matching of 2D electrophoresis gels using deformed graphs

2D electrophoresis is a well-known method for protein separation which is extremely useful in the field of proteomics. Each spot in the image represents a protein accumulation and the goal is to perform a differential analysis between pairs of images to study changes in protein content. It is thus necessary to register two images by finding spot correspondences. Although it may seem a simple task, generally, the manual processing of this kind of images is very cumbersome, especially when strong variations between corresponding sets of spots are expected (e.g. strong non-linear deformations and outliers). In order to solve this problem, this paper proposes a new quadratic assignment formulation together with a correspondence estimation algorithm based on graph matching which takes into account the structural information between the detected spots. Each image is represented by a graph and the task is to find a maximum common subgraph. Successful experimental results using real data are presented, including an extensive comparative performance evaluation with ground-truth data.     

Development of CoMFA models of affinity and selectivity to angiotensin II type-1 and type-2 receptors

The renin-angiotensin system (RAS) is of major importance in cardiovascular and renal regulation and has been an attractive target in drug discovery for a long time. The main receptors involved in the RAS are the Angiotensin type-1 (AT(1)) and type-2 (AT(2)) receptors, which are both activated by the endogenous octapeptide angiotensin II (AngII). This study describes the development of 3D-QSAR models for AT(1) and AT(2) receptor affinity and AT(1)/AT(2) receptor selectivity using CoMFA. A data set of 244 compounds, based on the triazolinone and quinazolinone structural classes was compiled from the literature. Before CoMFA could be performed, an alignment rule for the two structural classes was defined using the pharmacophore-searching program DISCOtech. Models were validated using a test set obtained by dividing the data set into a training set and test set using hierarchical clustering, based on the CoMFA fields, AT(1)-, AT(2)-receptor affinities, and AT(1)/AT(2) selectivity values. Predictive models with good statistics could be developed both for AT(1) and AT(2) receptor affinity as well as selectivity towards these receptors.     

An empirical examination of the determinants of mobile purchase

As en emerging service, mobile purchase has not received wide adoption among users. Drawing on the trust and flow theory, this research identified the factors affecting user adoption of mobile purchase. We conducted data analysis with structural equation modeling (SEM). The results indicated that contextual offering has strong effects on trust, flow, and perceived usefulness. In addition, structural assurance affects trust. Trust affects flow, which further affects perceived usefulness. These three factors determine mobile purchase intention.