Quantitative pharmacophore models with inductive logic programming

Three-dimensional models, or pharmacophores, describing Euclidean constraints on the location on small molecules of functional groups (like hydrophobic groups, hydrogen acceptors and donors, etc.), are often used in drug design to describe the medicinal activity of potential drugs (or ‘ligands’). This medicinal activity is produced by interaction of the functional groups on the ligand with a binding site on a target protein. In identifying structure-activity relations of this kind there are three principal issues: (1) It is often difficult to “align” the ligands in order to identify common structural properties that may be responsible for activity; (2) Ligands in solution can adopt different shapes (or `conformations’) arising from torsional rotations about bonds. The 3-D molecular substructure is typically sought on one or more low-energy conformers; and (3) Pharmacophore models must, ideally, predict medicinal activity on some quantitative scale. It has been shown that the logical representation adopted by Inductive Logic Programming (ILP) naturally resolves many of the difficulties associated with the alignment and multi-conformation issues. However, the predictions of models constructed by ILP have hitherto only been nominal, predicting medicinal activity to be present or absent. In this paper, we investigate the construction of two kinds of quantitative pharmacophoric models with ILP: (a) Models that predict the probability that a ligand is “active”; and (b) Models that predict the actual medicinal activity of a ligand. Quantitative predictions are obtained by the utilising the following statistical procedures as background knowledge: logistic regression and naive Bayes, for probability prediction; linear and kernel regression, for activity prediction. The multi-conformation issue and, more generally, the relational representation used by ILP results in some special difficulties in the use of any statistical procedure. We present the principal issues and some solutions. Specifically, using data on the inhibition of the protease Thermolysin, we demonstrate that it is possible for an ILP program to construct good quantitative structure-activity models. We also comment on the relationship of this work to other recent developments in statistical relational learning. Editors: Tamás Horváth and Akihiro Yamamoto     

Optimal Control of the Primary Drying Stage of Freeze Drying of Solutions in Vials Using Variational Calculus

The problem of operating freeze drying of pharmaceutical products in vials placed in trays of a freeze dryer to remove free water (in frozen state) at a minimum time was formulated as an optimal control problem. Two different types of freeze dryer designs were considered. In type I freeze dryer design, upper and lower plate temperatures were controlled together, while in type II freeze dryer design, upper and lower plate temperatures were controlled independently. The heat input to the material being dried and the drying chamber pressure were considered as control variables. Constraints were placed on the system state variables by the melting and scorch temperatures during primary drying stage. Necessary conditions of optimality for the primary drying stage of freeze drying process in vials are derived and presented. Furthermore, an approach for constructing the optimal control policies that would minimize the drying time for the primary drying stage was given. In order to analyze optimal control policy for the primary drying stage of the freeze-drying process in vials, a rigorous multi-dimensional unsteady state mathematical model was used. The theoretical approach presented in this work was applied in the freeze drying of skim milk. Significant reductions in the drying times of primary drying stage of freeze drying process in vials were obtained, as compared to the drying times obtained from conventional operational policies.     

A Relational Model of Workplace Victimization: Social Roles and Patterns of Victimization in Dyadic Relationships.

This article proposes a model of the ways in which dyadic interactions between employees who occupy 1 of 4 archetypal social roles in organizations can lead to either episodic or institutionalized patterns of victimization. The model shows how the occurrence of victimization involving these 4 role types is influenced by organizational variables such as power differences, culture, and access to social capital. The model integrates behavioral and social structural antecedents of victimization to develop a relational perspective on the dynamics of harmful behavior in the workplace. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The aditi deductive database system

Deductive databases generalize relational databases by providing support for recursive views and non-atomic data. Aditi is a deductive system based on the client-server model; it is inherently multi-user and capable of exploiting parallelism on shared-memory multiprocessors. The back-end uses relational technology for efficiency in the management of disk-based data and uses optimization algorithms especially developed for the bottom-up evaluation of logical queries involving recursion. The front-end interacts with the user in a logical language that has more expressive power than relational query languages. We present the structure of Aditi, discuss its components in some detail, and present performance figures.     

Shallow Linear Action Graphs and their Embeddings

Action calculi, which generalise process calculi such as Petri nets, π-calculusand ambient calculus, have been presented in terms of action graphs. We here offer linear action graphs as a primitive basis for action calculi. This paper presents the category of embeddings of undirected linear action graphs without nesting, using a novel form of graphical reasoning which simplifies some otherwise complex manipulations in regular algebra. The results are adapted in a few lines to directed graphs. This work is part of a long-term search for a uniform behavioural theory for process calculi. Received October 2000 / Accepted in revised form April 2001     

Contextualizing is not nullifying: Reply to Mills (2005).

In omitting crucial words and sentencees, neglecting relevant citations, and overlooking important distinctions, Jon Mills' (see record 2005-04819-001) critique of relational psychoanalysis significantly misrepresents the authors' viewpoint. This viewpoint seeks to contextualize, but not to nullify, individual worlds of experience and their limiting horizons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multiplicative cases from additive cases: Extension of Kolmogorov–Feller equation to parametric Poisson white noise processes

In this paper the response of nonlinear systems driven by parametric Poissonian white noise is examined.As is well known, the response sample function or the response statistics of a system driven by external white noise processes is completely defined. Starting from the system driven by external white noise processes, when an invertible nonlinear transformation is applied, the transformed system in the new state variable is driven by a parametric type excitation. So this latter artificial system may be used as a tool to find out the proper solution to solve systems driven by parametric white noises. In fact, solving this new system, being the nonlinear transformation invertible, we must pass from the solution of the artificial system (driven by parametric noise) to that of the original one (driven by external noise, that is known). Moreover, introducing this invertible nonlinear transformation into the Itô’s rule for the original system driven by external input, one can derive the Itô’s rule for systems driven by a parametric type excitation, directly. In this latter case one can see how natural is the presence of the Wong–Zakai correction term or the presence of the hierarchy of correction terms in the case of normal and Poissonian white noise, respectively. Direct transformation on the Fokker–Planck and on the Kolmogorov–Feller equation for the case of parametric input are found.     

HiSQL: A Front-end Query System for Historical Relational Databases

The paper describes a prototype system called HiSQL (Historical SQL) which extends the functionality of SQL in manipulating historical data, by providing functions for spatial and temporal processing. Conceptually the paper is divided into three parts: the first part deals with the design and architecture of the system; the second part introduces a case study (the defters); and the third part describes specific functions for spatial and temporal processing of serial documents. The paper concludes with a comparison between HiSQL and SQL and suggestions for further work. This revised version was published online in August 2006 with corrections to the Cover Date.     

灰色关联分析在腐蚀非晶态镍基合金中的应用

用灰色关联分析方法取代传统的数理统计方法,对非晶态镍基合金在FeCl_3溶液中的腐蚀速率与影响因素之间的相互关系进行处理,确定各影响因子之间的主次关系。结果表明溶液流速是最关键因子,次关键因子为溶液pH值,其次为溶液温度和溶液浓度,并根据分析结果提出实际应用时的相应对策。     

A Refinement Calculus for Shared-Variable Parallel and Distributed Programming

Parallel computers have not yet had the expected impact on mainstream computing. Parallelism adds a level of complexity to the programming task that makes it very error-prone. Moreover, a large variety of very different parallel architectures exists. Porting an implementation from one machine to another may require substantial changes. This paper addresses some of these problems by developing a formal basis for the design of parallel programs in the form of a refinement calculus. The calculus allows the stepwise formal derivation of an abstract, low-level implementation from a trusted, high-level specification. The calculus thus helps structuring and documenting the development process. Portability is increased, because the introduction of a machine-dependent feature can be located in the refinement tree. Development efforts above this point in the tree are independent of that feature and are thus reusable. Moreover, the discovery of new, possibly more efficient solutions is facilitated. Last but not least, programs are correct by construction, which obviates the need for difficult debugging. Our programming/specification notation supports fair parallelism, shared-variable and message-passing concurrency, local variables and channels. The calculus rests on a compositional trace semantics that treats shared-variable and message-passing concurrency uniformly. The refinement relation combines a context-sensitive notion of trace inclusion and assumption-commitment reasoning to achieve compositionality. The calculus straddles both concurrency paradigms, that is, a shared-variable program can be refined into a distributed, message-passing program and vice versa. Received July 2001 / Accepted in revised form May 2002