Molecular modeling and QSAR studies of a set of indole and benzimidazole derivatives as H(4) receptor antagonists

Histamine is an important biogenic amine, which acts with a group of four G-protein coupled receptors (GPCRs), namely H(1) to H(4) (H(1)R - H(4)R) receptors. The actions of histamine at H(4)R are related to immunological and inflammatory processes, particularly in pathophysiology of asthma, and H(4)R ligands having antagonistic properties could be helpful as antiinflammatory agents. In this work, molecular modeling and QSAR studies of a set of 30 compounds, indole and benzimidazole derivatives, as H(4)R antagonists were performed. The QSAR models were built and optimized using a genetic algorithm function and partial least squares regression (WOLF 5.5 program). The best QSAR model constructed with training set (N = 25) presented the following statistical measures: r (2) = 0.76, q (2) = 0.62, LOF = 0.15, and LSE = 0.07, and was validated using the LNO and y-randomization techniques. Four of five compounds of test set were well predicted by the selected QSAR model, which presented an external prediction power of 80%. These findings can be quite useful to aid the designing of new anti-H(4) compounds with improved biological response.

Generation and Analysis of Interaction Energy Maps of p-Substituted Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-Hydrazides Active against MRSA

In this preliminary study eighteen p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides with antimicrobial activity were evaluated against multidrug-resistant Staphylococcus aureus, correlating the three-dimensional characteristics of the ligands with their respective bioactivities. The computer programs Sybyl and CORINA were used, respectively, for the design and three-dimensional conversion of the ligands. Molecular interaction fields were calculated using GRID program. Calculations using Volsurf resulted in a statistically consistent model with 48 structural descriptors showing that hydrophobicity is a fundamental property in the analyzed biological response.

Multilabeled classification approach to find a plaint source for terpenoids

Recently, we have built a classification model that is capable of assigning a given sesquiterpene lactone (STL) into exactly one tribe of the plant family Asteraceae from which the STL has been isolated. Although many plant species are able to biosynthesize a set of peculiar compounds, the occurrence of the same secondary metabolites in more than one tribe of Asteraceae is frequent. Building on our previous work, in this paper, we explore the possibility of assigning an STL to more than one tribe (class) simultaneously. When an object may belong to more than one class simultaneously, it is called multilabeled. In this work, we present a general overview of the techniques available to examine multilabeled data. The problem of evaluating the performance of a multilabeled classifier is discussed. Two particular multilabeled classification methods-cross-training with support vector machines (ct-SVM) and multilabeled k-nearest neighbors (M-L-kNN)were applied to the classification of the STLs into seven tribes from the plant family Asteraceae. The results are compared to a single-label classification and are analyzed from a chemotaxonomic point of view. The multilabeled approach allowed us to (1) model the reality as closely as possible, (2) improve our understanding of the relationship between the secondary metabolite profiles of different Asteraceae tribes, and (3) significantly decrease the number of plant sources to be considered for finding a certain STL. The presented classification models are useful for the targeted collection of plants with the objective of finding plant sources of natural compounds that are biologically active or possess other specific properties of interest.

Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy

We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when Compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals. Two other proposals have been selected with virtual screening approaches and investigated by LIS, which suggest novel and alternatives scaffolds to design future potential FTase inhibitors. Such compounds can be explored as promising molecules to initiate a research protocol in order to discover novel anticancer drug candidates targeting farnesyltransferase, in the fight against cancer. (C) 2009 Elsevier Inc. All rights reserved.

Quantum-chemical, NMR and X-ray diffraction studies on (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane

Time-averaged conformations of (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane hydrochloride (MDMA, ""ecstasy"") in D(2)O, and of its free base and trifluoroacetate in CDCl(3), were deduced from their (1)H NMR spectra and used to calculate their conformer distribution. Their rotational potential energy surface (PES) was calculated at the RHF/6-31G(d,p), 133LYP/6-31G(d,p), B3LYP/cc-pVDZ and AM1 levels. Solvent effects were evaluated using the polarizable continuum model. The NMR and theoretical studies showed that, in the free base, the N-methyl group and the ring are preferentially trans. This preference is stronger in the salts and corresponds to the X-ray structure of the hydrochloride. However, the energy barriers separating these forms are very low. The X-ray diffraction crystal structures of the anhydrous salt and its monohydrate differed mainly in the trans or cis relationship of the N-methyl group to the a-methyl, although these two forms interconvert freely in solution. (C) 2007 Elsevier Inc. All rights reserved.

Brazil

Brazil has led development of collective rights in Ibero-American states and has developed from consumer origins a general procedure on ""public civil actions"" largely brought by the attorney general. These have a two-stage process, involving a declaration on general liability followed by individuals bringing personal compensation claims.

RFID adoption: framework and survey in large Brazilian companies

Purpose - The purpose of this paper is to provide a framework for radio frequency identification (RFID) technology adoption considering company size and five dimensions of analysis: RFID applications, expected benefits business drivers or motivations barriers and inhibitors, and organizational factors. Design/methodology/approach - A framework for RFID adoption derived from literature and the practical experience on the subject is developed. This framework provides a conceptual basis for analyzing a survey conducted with 114 companies in Brazil. Findings - Many companies have been developing RFID initiatives in order to identify potential applications and map benefits associated with their implementation. The survey highlights the importance business drivers in the RFID implementation stage, and that companies implement RFID focusing on a few specific applications. However, there is a weak association between expected benefits and business challenges with the current level of RFID technology adoption in Brazil. Research limitations/implications - The paper is not exhaustive, since RFID adoption in Brazil is at early stages during the survey timeline. Originality/value - The main contribution of the paper is that it yields a framework for analyzing RFID technology adoption. The authors use this framework to analyze RFID adoption in Brazil, which proved to be a useful one for identifying key issues for technology adoption. The paper is useful to any researchers or practitioners who are focused on technology adoption, in particular, RFID technology.

A note on the multiple partners assignment game

In the assignment game of Shapley and Shubik [Shapley, L.S., Shubik, M., 1972. The assignment game. I. The core, International journal of Game Theory 1, 11-130] agents are allowed to form one partnership at most. That paper proves that, in the context of firms and workers, given two stable payoffs for the firms there is a stable payoff which gives each firm the larger of the two amounts and also one which gives each of them the smaller amount. Analogous result applies to the workers. Sotomayor [Sotomayor, M., 1992. The multiple partners game. In: Majumdar, M. (Ed.), Dynamics and Equilibrium: Essays in Honor to D. Gale. Mcmillian, pp. 322-336] extends this analysis to the case where both types of agents may form more than one partnership and an agent`s payoff is multi-dimensional. Instead, this note concentrates in the total payoff of the agents. It is then proved the rather unexpected result that again the maximum of any pair of stable payoffs for the firms is stable but the minimum need not be, even if we restrict the multiplicity of partnerships to one of the sides. (C) 2009 Elsevier B.V. All rights reserved.

Stability property of matchings is a natural solution concept in coalitional market games

Stability of matchings was proved to be a new cooperative equilibrium concept in Sotomayor (Dynamics and equilibrium: essays in honor to D. Gale, 1992). That paper introduces the innovation of treating as multi-dimensional the payoff of a player with a quota greater than one. This is done for the many-to-many matching model with additively separable utilities, for which the stability concept is defined. It is then proved, via linear programming, that the set of stable outcomes is nonempty and it may be strictly bigger than the set of dual solutions and strictly smaller than the core. The present paper defines a general concept of stability and shows that this concept is a natural solution concept, stronger than the core concept, for a much more general coalitional game than a matching game. Instead of mutual agreements inside partnerships, the players are allowed to make collective agreements inside coalitions of any size and to distribute his labor among them. A collective agreement determines the level of labor at which the coalition operates and the division, among its members, of the income generated by the coalition. An allocation specifies a set of collective agreements for each player.

Evaluating the efficiency of fractional integration parameter estimators

This article deals with the efficiency of fractional integration parameter estimators. This study was based on Monte Carlo experiments involving simulated stochastic processes with integration orders in the range]-1,1[. The evaluated estimation methods were classified into two groups: heuristics and semiparametric/maximum likelihood (ML). The study revealed that the comparative efficiency of the estimators, measured by the lesser mean squared error, depends on the stationary/non-stationary and persistency/anti-persistency conditions of the series. The ML estimator was shown to be superior for stationary persistent processes; the wavelet spectrum-based estimators were better for non-stationary mean reversible and invertible anti-persistent processes; the weighted periodogram-based estimator was shown to be superior for non-invertible anti-persistent processes.

The pareto-stability concept is a natural solution concept for discrete matching markets with indifferences

In a decentralized setting the game-theoretical predictions are that only strong blockings are allowed to rupture the structure of a matching. This paper argues that, under indifferences, also weak blockings should be considered when these blockings come from the grand coalition. This solution concept requires stability plus Pareto optimality. A characterization of the set of Pareto-stable matchings for the roommate and the marriage models is provided in terms of individually rational matchings whose blocking pairs, if any, are formed with unmatched agents. These matchings always exist and give an economic intuition on how blocking can be done by non-trading agents, so that the transactions need not be undone as agents reach the set of stable matchings. Some properties of the Pareto-stable matchings shared by the Marriage and Roommate models are obtained.

Adjusting prices in the multiple-partners assignment game

Starting with an initial price vector, prices are adjusted in order to eliminate the excess demand and at the same time to keep the transfers to the sellers as low as possible. In each step of the auction, to which set of sellers should those transfers be made is the key issue in the description of the algorithm. We assume additively separable utilities and introduce a novel distinction by considering multiple sellers owing multiple identical objects and multiple buyers with an exogenously defined quota, consuming more than one object but at most one unit of a seller`s good and having multi-dimensional payoffs. This distinction induces a necessarily more complicated construction of the over-demanded sets than the constructions of these sets for the other assignment games. For this approach, our mechanism yields the buyer-optimal competitive equilibrium payoff, which equals the buyer-optimal stable payoff. The symmetry of the model allows to getting the seller-optimal stable payoff and the seller-optimal competitive equilibrium payoff can then be also derived.

The stability of the equilibrium outcomes in the admission games induced by stable matching rules

A stable matching rule is used as the outcome function for the Admission game where colleges behave straightforwardly and the students` strategies are given by their preferences over the colleges. We show that the college-optimal stable matching rule implements the set of stable matchings via the Nash equilibrium (NE) concept. For any other stable matching rule the strategic behavior of the students may lead to outcomes that are not stable under the true preferences. We then introduce uncertainty about the matching selected and prove that the natural solution concept is that of NE in the strong sense. A general result shows that the random stable matching rule, as well as any stable matching rule, implements the set of stable matchings via NE in the strong sense. Precise answers are given to the strategic questions raised.

Are supplier selection criteria going green? Case studies of companies in Brazil

Purpose - The purpose of this paper is to verify if Brazilian companies are adopting environmental requirements in the supplier selection process. Further, this paper intends to analyze whether there is a relation between the level of environmental management maturity and the inclusion of environmental criteria in the companies` selection of suppliers. Design/methodology/approach - A review of mainstream literature on environmental management, traditional criteria in the supplier selection process and the incorporation of environmental requirements in this context. The empirical study`s strategy is based on five Brazilian case studies with industrial companies. Face-to-face interviews and informal conversations are to be held, explanations made by e-mail with representatives from the purchasing, environmental management, logistics and other areas, and observation and the collection of company documents are also employed. Findings - Based on the cases, it is concluded that companies still use traditional criteria to select suppliers, such as quality and cost, and do not adopt environmental requirements in the supplier selection process in a uniform manner. Evidence found shows that the level of environmental management maturity influences the depth with which companies adopt environmental criteria when selecting suppliers. Thus, a company with more advanced environmental management adopts more formal procedures for selecting environmentally appropriate suppliers than others. Originality/value - This is the first known study to verify if Brazilian companies are adopting environmental requirements in the supplier selection process.

Barriers faced by MSEs: evidence from Mozambique

Purpose - The purpose of this research is to shed light on the main barriers faced by Mozambican micro and small enterprises (MSEs) and their implications in respect to the support policies available for these enterprises. Design/methodology/approach - A literature review was made on those barriers faced by the MSEs and on the policies and governmental instruments of assistance available for MSEs. Then, a two-step research was conducted. The first phase consisted of collecting data from 21 MSEs in Mozambique, mainly by means of interviews where the main barriers faced by those interviewed were identified and hence, this led to the second phase, which was interviewing governmental/support entities in order to know what they had done to minimize those barriers which had been identified by the entrepreneurs. Findings - The results show that financial and competitive barriers are the main barriers faced by the analyzed MSEs. These barriers vary according to the field of activity of the enterprises. Originality/value - This study serves to enrich the state of the art on the subject of smaller enterprises in Africa and will specially. help to fill the lack of academic research available about Mozambique.