New Improvements in Automatic Structure Elucidation Using the LSD (Logic for Structure Determination) and the SISTEMAT Expert Systems

This article describes the integration of the LSD (Logic for Structure Determination) and SISTEMAT expert systems that were both designed for the computer-assisted structure elucidation of small organic molecules. A first step has been achieved towards the linking of the SISTEMAT database with the LSD structure generator. The skeletal descriptions found by the SISTEMAT programs are now easily transferred to LSD as substructural constraints. Examples of the synergy between these expert systems are given for recently reported natural products.

Structure-Based Approach for the Study of Estrogen Receptor Binding Affinity and Subtype Selectivity

Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpa (hER alpha) and beta (hER beta). Because the levels and relative proportion of hER alpha and hER beta differ significantly in different target cells, selective hER ligands could target specific tissues or pathways regulated by one receptor subtype without affecting the other. To understand the structural and chemical basis by which small molecule modulators are able to discriminate between the two subtypes, we have applied three-dimensional target-based approaches employing a series of potent hER-ligands. Comparative molecular field analysis (CoMFA) studies were applied to a data set of 81 hER modulators, for which binding affinity values were collected for both hER alpha and hER beta. Significant statistical coefficients were obtained (hER alpha, q(2) = 0.76; hER beta, q(2) = 0.70), indicating the internal consistency of the models. The generated models were validated using external test sets, and the predicted values were in good agreement with the experimental results. Five hER crystal structures were used in GRID/PCA investigations to generate molecular interaction fields (MIF) maps. hER alpha and hER beta were separated using one factor. The resulting 3D information was integrated with the aim of revealing the most relevant structural features involved in hER subtype selectivity. The final QSAR and GRID/PCA models and the information gathered from 3D contour maps should be useful for the design or novel hER modulators with improved selectivity.

PHA(MCL) biosynthesis systems in Pseudomonas aeruginosa and Pseudomonas putida strains show differences on monomer specificities

The production of PHA from plant oils by Pseudomonas species soil isolated from a sugarcane crop was evaluated. Out of 22 bacterial strains three were able to use efficiently plant oils to grow and to accumulate PHA. Pseudomonas putida and Pseudomonas aeruginosa strains produced PHA presenting differences on monomer composition compatible with variability on monomer specificity of their PHA biosynthesis system. The molar fraction of 3-hydroxydodecanoate detected in the PHA was linearly correlated to the oleic acid supplied. A non-linear relationship between the molar fractions of 3-hydroxy-6-dodecenoate (3HDd Delta(6)) detected in PHA and the linoleic acid supplied was observed, compatible with saturation in the biosynthesis system capability to channel intermediate of P-oxidation to PHA synthesis. Although P. putida showed a higher 3HDd Delta(6) yield from linoleic acid when compared to P. aeruginosa, in both species it was less than 10% of the maximum theoretical value. These results contribute to the knowledge about the biosynthesis of PHA with a controlled composition from plant oils allowing in the future establishing the production of these polyesters as tailor-made polymers. (C) 2009 Elsevier B.V. All rights reserved.

Formal validation of automated policy refinement in the management of network security systems

Policy hierarchies and automated policy refinement are powerful approaches to simplify administration of security services in complex network environments. A crucial issue for the practical use of these approaches is to ensure the validity of the policy hierarchy, i.e. since the policy sets for the lower levels are automatically derived from the abstract policies (defined by the modeller), we must be sure that the derived policies uphold the high-level ones. This paper builds upon previous work on Model-based Management, particularly on the Diagram of Abstract Subsystems approach, and goes further to propose a formal validation approach for the policy hierarchies yielded by the automated policy refinement process. We establish general validation conditions for a multi-layered policy model, i.e. necessary and sufficient conditions that a policy hierarchy must satisfy so that the lower-level policy sets are valid refinements of the higher-level policies according to the criteria of consistency and completeness. Relying upon the validation conditions and upon axioms about the model representativeness, two theorems are proved to ensure compliance between the resulting system behaviour and the abstract policies that are modelled.

On the localization of water-soluble porphyrins in micellar systems evaluated by static and time-resolved frequency-domain fluorescence techniques

Fluorescence quenching of meso-tetrakis-4-sulfonatophenyl (TPPS4) and meso-tetrakis-4-N-methylpyridil (TMPyP) porphyrins is studied in aqueous solution and upon addition of micelles of sodium dodecylsulfate (SDS), cetyltrimethylammonium chloride (CTAC), N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS) and t-octylphenoxypolyethoxyethanol (Triton X-100). Potassium iodide (KI) was used as quencher. Steady-state Stern-Volmer plots were best fitted by a quadratic equation, including dynamic (K-D) and static (K-s) quenching. Ks was significantly smaller than K-D. Frequency-domain fluorescence lifetimes allowed estimating bimolecular quenching constants, k(q). At 25 degrees C, in aqueous solution, TMPyP shows k(q), values a factor of 2-3 higher than the diffusional limit. TPPS4 shows collisional quenching with pH dependent k(q) values. For TMPyP quenching results are consistent with reported binding constants: a significant reduction of quenching takes place for SDS, a moderate reduction is observed for H PS and almost no change is seen for Triton X-100. Similar data were obtained at 50 C. For CTAC-TPPS4 system an enhancement of quenching was observed as compared to pure buffer. This is probably associated to accumulation of iodide at the cationic micellar interface. The attraction between CTAC headgroups and 1(-), and repulsion between SDS and 1(-), enhances and reduces the fluorescence quenching, respectively, of porphyrins located at the micellar interface. The small quenching of TPPS4 in Triton X-100 is consistent with strong binding as reported in the literature. (C) 2008 Elsevier B.V. All rights reserved.

Novel Application of 2D and 3D-Similarity Searches To Identify Substrates among Cytochrome P450 2C9, 2D6, and 3A4

Cytochrome P450 (CYP450) is a class of enzymes where the substrate identification is particularly important to know. It would help medicinal chemists to design drugs with lower side effects due to drug-drug interactions and to extensive genetic polymorphism. Herein, we discuss the application of the 2D and 3D-similarity searches in identifying reference Structures with higher capacity to retrieve Substrates of three important CYP enzymes (CYP2C9, CYP2D6, and CYP3A4). On the basis of the complementarities of multiple reference structures selected by different similarity search methods, we proposed the fusion of their individual Tanimoto scores into a consensus Tanimoto score (T(consensus)). Using this new score, true positive rates of 63% (CYP2C9) and 81% (CYP2D6) were achieved with false positive rates of 4% for the CYP2C9-CYP2D6 data Set. Extended similarity searches were carried out oil a validation data set, and the results showed that by using the T(consensus) score, not only the area of a ROC graph increased, but also more substrates were recovered at the beginning of a ranked list.

Prediction of dynamical, nonlinear, and unstable process behavior

Process scheduling techniques consider the current load situation to allocate computing resources. Those techniques make approximations such as the average of communication, processing, and memory access to improve the process scheduling, although processes may present different behaviors during their whole execution. They may start with high communication requirements and later just processing. By discovering how processes behave over time, we believe it is possible to improve the resource allocation. This has motivated this paper which adopts chaos theory concepts and nonlinear prediction techniques in order to model and predict process behavior. Results confirm the radial basis function technique which presents good predictions and also low processing demands show what is essential in a real distributed environment.

Document engineering approaches toward scalable and structured multimedia, web and printable documents

Document engineering is the computer science discipline that investigates systems for documents in any form and in all media. As with the relationship between software engineering and software, document engineering is concerned with principles, tools and processes that improve our ability to create, manage, and maintain documents (http://www.documentengineering.org). The ACM Symposium on Document Engineering is an annual meeting of researchers active in document engineering: it is sponsored by ACM by means of the ACM SIGWEB Special Interest Group. In this editorial, we first point to work carried out in the context of document engineering, which are directly related to multimedia tools and applications. We conclude with a summary of the papers presented in this special issue.

On modeling and evaluating multicomputer transcoding architectures for live-video streams

The pervasive and ubiquitous computing has motivated researches on multimedia adaptation which aims at matching the video quality to the user needs and device restrictions. This technique has a high computational cost which needs to be studied and estimated when designing architectures and applications. This paper presents an analytical model to quantify these video transcoding costs in a hardware independent way. The model was used to analyze the impact of transcoding delays in end-to-end live-video transmissions over LANs, MANs and WANs. Experiments confirm that the proposed model helps to define the best transcoding architecture for different scenarios.

Watch-and-Comment as a Paradigm toward Ubiquitous Interactive Video Editing

The literature reports research efforts allowing the editing of interactive TV multimedia documents by end-users. In this article we propose complementary contributions relative to end-user generated interactive video, video tagging, and collaboration. In earlier work we proposed the watch-and-comment (WaC) paradigm as the seamless capture of an individual`s comments so that corresponding annotated interactive videos be automatically generated. As a proof of concept, we implemented a prototype application, the WACTOOL, that supports the capture of digital ink and voice comments over individual frames and segments of the video, producing a declarative document that specifies both: different media stream structure and synchronization. In this article, we extend the WaC paradigm in two ways. First, user-video interactions are associated with edit commands and digital ink operations. Second, focusing on collaboration and distribution issues, we employ annotations as simple containers for context information by using them as tags in order to organize, store and distribute information in a P2P-based multimedia capture platform. We highlight the design principles of the watch-and-comment paradigm, and demonstrate related results including the current version of the WACTOOL and its architecture. We also illustrate how an interactive video produced by the WACTOOL can be rendered in an interactive video environment, the Ginga-NCL player, and include results from a preliminary evaluation.

FAST, PARALLEL AND SECURE CRYPTOGRAPHY ALGORITHM USING LORENZ`S ATTRACTOR

A novel cryptography method based on the Lorenz`s attractor chaotic system is presented. The proposed algorithm is secure and fast, making it practical for general use. We introduce the chaotic operation mode, which provides an interaction among the password, message and a chaotic system. It ensures that the algorithm yields a secure codification, even if the nature of the chaotic system is known. The algorithm has been implemented in two versions: one sequential and slow and the other, parallel and fast. Our algorithm assures the integrity of the ciphertext (we know if it has been altered, which is not assured by traditional algorithms) and consequently its authenticity. Numerical experiments are presented, discussed and show the behavior of the method in terms of security and performance. The fast version of the algorithm has a performance comparable to AES, a popular cryptography program used commercially nowadays, but it is more secure, which makes it immediately suitable for general purpose cryptography applications. An internet page has been set up, which enables the readers to test the algorithm and also to try to break into the cipher.

Structural basis for selective inhibition of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase: Molecular docking and 3D QSAR studies

The glycolytic enzyme glyceraldehyde-3 -phosphate dehydrogenase (GAPDH) is as an attractive target for the development of novel antitrypanosomatid agents. In the present work, comparative molecular field analysis and comparative molecular similarity index analysis were conducted on a large series of selective inhibitors of trypanosomatid GAPDH. Four statistically significant models were obtained (r(2) > 0.90 and q(2) > 0.70), indicating their predictive ability for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results. Molecular modeling studies provided further insight into the structural basis for selective inhibition of trypanosomatid GAPDH.

THERMAL BEHAVIOR STUDY AND DECOMPOSITION KINETICS OF SALBUTAMOL UNDER ISOTHERMAL AND NON-ISOTHERMAL CONDITIONS

The thermal decomposition of salbutamol (beta(2) - selective adrenoreceptor) was studied using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG). It was observed that the commercial sample showed a different thermal profile than the standard sample caused by the presence of excipients. These compounds increase the thermal stability of the drug. Moreover, higher activation energy was calculated for the pharmaceutical sample, which was estimated by isothermal and non-isothermal methods for the first stage of the thermal decomposition process. For isothermal experiments the average values were E(act) = 130 kJ mol(-1) (for standard sample) and E(act) = 252 kJ mol(-1) (for pharmaceutical sample) in a dynamic nitrogen atmosphere (50 mL min(-1)). For non-isothermal method, activation energy was obtained from the plot of log heating rates vs. 1/T in dynamic air atmosphere (50 mL min(-1)). The calculated values were E(act) = 134 kJ mol(-1) (for standard sample) and E(act) (=) 139 kJ mol(-1) (for pharmaceutical sample).