AFFINE INTERVAL EXCHANGE TRANSFORMATIONS WITH FLIPS AND WANDERING INTERVALS

There exist uniquely ergodic affine interval exchange transformations of [0,1] with flips which have wandering intervals and are such that the support of the invariant measure is a Cantor set.

Systematic Management of Variability in UML-based Software Product Lines

This paper presents SMarty, a variability management approach for UML-based software product lines (PL). SMarty is supported by a UML profile, the SMartyProfile, and a process for managing variabilities, the SMartyProcess. SMartyProfile aims at representing variabilities, variation points, and variants in UML models by applying a set of stereotypes. SMartyProcess consists of a set of activities that is systematically executed to trace, identify, and control variabilities in a PL based on SMarty. It also identifies variability implementation mechanisms and analyzes specific product configurations. In addition, a more comprehensive application of SMarty is presented using SEI's Arcade Game Maker PL. An evaluation of SMarty and related work are discussed.

Determination of post-mortem interval using in situ tissue optical fluorescence

In this study we have used fluorescence spectroscopy to determine the post-mortem interval. Conventional methods in forensic medicine involve tissue or body fluids sampling and laboratory tests, which are often time demanding and may depend on expensive analysis. The presented method consists in using time-dependent variations on the fluorescence spectrum and its correlation with the time elapsed after regular metabolic activity cessation. This new approach addresses unmet needs for post-mortem interval determination in forensic medicine, by providing rapid and in situ measurements that shows improved time resolution relative to existing methods. (C) 2009 Optical Society of America

Atratividade de projetos de software livre: importância teórica e estratégias para administração

Thousands of Free and Open Source Software Projects (FSP) were, and continually are, created on the Internet. This scenario increases the number of opportunities to collaborate to the same extent that it promotes competition for users and contributors, who can guide projects to superior levels, unachievable by founders alone. Thus, given that the main goal of FSP founders is to improve their projects by means of collaboration, the importance to understand and manage the capacity of attracting users and contributors to the project is established. To support researchers and founders in this challenge, the concept of attractiveness is introduced in this paper, which develops a theoretical-managerial toolkit about the causes, indicators and consequences of attractiveness, enabling its strategic management.

Evaluation of three brands of drug interaction software for use in intensive care units

Objective To evaluate drug interaction software programs and determine their accuracy in identifying drug-drug interactions that may occur in intensive care units. Setting The study was developed in Brazil. Method Drug interaction software programs were identified through a bibliographic search in PUBMED and in LILACS (database related to the health sciences published in Latin American and Caribbean countries). The programs` sensitivity, specificity, and positive and negative predictive values were determined to assess their accuracy in detecting drug-drug interactions. The accuracy of the software programs identified was determined using 100 clinically important interactions and 100 clinically unimportant ones. Stockley`s Drug Interactions 8th edition was employed as the gold standard in the identification of drug-drug interaction. Main outcome Sensitivity, specificity, positive and negative predictive values. Results The programs studied were: Drug Interaction Checker (DIC), Drug-Reax (DR), and Lexi-Interact (LI). DR displayed the highest sensitivity (0.88) and DIC showed the lowest (0.69). A close similarity was observed among the programs regarding specificity (0.88-0.92) and positive predictive values (0.88-0.89). The DIC had the lowest negative predictive value (0.75) and DR the highest (0.91). Conclusion The DR and LI programs displayed appropriate sensitivity and specificity for identifying drug-drug interactions of interest in intensive care units. Drug interaction software programs help pharmacists and health care teams in the prevention and recognition of drug-drug interactions and optimize safety and quality of care delivered in intensive care units.

Developing and implementing an open and non-proprietary device description for FOUNDATION fieldbus based on software standards

Support for interoperability and interchangeability of software components which are part of a fieldbus automation system relies on the definition of open architectures, most of them involving proprietary technologies. Concurrently, standard, open and non-proprietary technologies, such as XML, SOAP, Web Services and the like, have greatly evolved and been diffused in the computing area. This article presents a FOUNDATION fieldbus (TM) device description technology named Open-EDD, based on XML and other related technologies (XLST, DOM using Xerces implementation, OO, XMIL Schema), proposing an open and nonproprietary alternative to the EDD (Electronic Device Description). This initial proposal includes defining Open-EDDML as the programming language of the technology in the FOUNDATION fieldbus (TM) protocol, implementing a compiler and a parser, and finally, integrating and testing the new technology using field devices and a commercial fieldbus configurator. This study attests that this new technology is feasible and can be applied to other configurators or HMI applications used in fieldbus automation systems. (c) 2008 Elsevier B.V. All rights reserved.

A Referential Model for Small Companies of Development Software

This paper presents the proposal for a reference model for developing software aimed at small companies. Despite the importance of that represent the small software companies in Latin America, the fact of not having its own standards, and able to meet their specific, has created serious difficulties in improving their process and also in quality certification. In this sense and as a contribution to better understanding of the subject they propose a reference model and as a means to validate the proposal, presents a report of its application in a small Brazilian company, committed to certification of the quality model MPS.BR.

Hybrid fault diagnosis scheme implementation for power distribution systems automation

Power distribution automation and control are import-ant tools in the current restructured electricity markets. Unfortunately, due to its stochastic nature, distribution systems faults are hardly avoidable. This paper proposes a novel fault diagnosis scheme for power distribution systems, composed by three different processes: fault detection and classification, fault location, and fault section determination. The fault detection and classification technique is wavelet based. The fault-location technique is impedance based and uses local voltage and current fundamental phasors. The fault section determination method is artificial neural network based and uses the local current and voltage signals to estimate the faulted section. The proposed hybrid scheme was validated through Alternate Transient Program/Electromagentic Transients Program simulations and was implemented as embedded software. It is currently used as a fault diagnosis tool in a Southern Brazilian power distribution company.

Quantitative Trait Loci Mapping and The Genetic Basis of Heterosis in Maize and Rice

Despite its importance to agriculture, the genetic basis of heterosis is still not well understood. The main competing hypotheses include dominance, overdominance, and epistasis. NC design III is an experimental design that. has been used for estimating the average degree of dominance of quantitative trait 106 (QTL) and also for studying heterosis. In this study, we first develop a multiple-interval mapping (MIM) model for design III that provides a platform to estimate the number, genomic positions, augmented additive and dominance effects, and epistatic interactions of QTL. The model can be used for parents with any generation of selling. We apply the method to two data sets, one for maize and one for rice. Our results show that heterosis in maize is mainly due to dominant gene action, although overdominance of individual QTL could not completely be ruled out due to the mapping resolution and limitations of NC design III. For rice, the estimated QTL dominant effects could not explain the observed heterosis. There is evidence that additive X additive epistatic effects of QTL could be the main cause for the heterosis in rice. The difference in the genetic basis of heterosis seems to be related to open or self pollination of the two species. The MIM model for NC design III is implemented in Windows QTL Cartographer, a freely distributed software.

Validated method for the quantification of artepillin-C in Brazilian propolis

Brazilian propolis contains several phenolic compounds among which 5 diprenyl-4-hydroxycinnamic acid (artepillin-C) is commonly found in areas where flora is rich in Baccharis species. The quantification of artepillin-C has become an important factor as an indicator of Brazilian propolis quality and the compound may be used as a chemical marker for quality control in exportating green propolis. This work was to validate the method and evaluate the content of artepillin-C from 33 samples collected in different Brazilian regions. The method used was HPLC with UV-vis detection and a reversed-phase C-18 Column. The validation parameters studied were: linearity, accuracy, precision, quantification and detection limits. The results obtained were: detection limit = 0.0036 mu g/mL, quantification limit = 0.012 mu g/mL, accuracy = 0.0064 and 0.078, recovery 98-102%. Artepillin-C content varied from 0 to 11% depending on the geographical origin. Propolis from the southeast region presented the highest level of artepillin-C (5.0-11.0%). Whist that from the northeast region did not show any artepillin-C. Copyright (C) 2008 John Wiley & Sons, Ltd.

Bioequivalence Evaluation of Single Doses of Two Tramadol Formulations: A Randomized, Open-Label, Two-Period Crossover Study in Healthy Brazilian Volunteers

Background: Tramadol is a well tolerated and effective analgesic used to treat moderate to severe pain. Several generic formulations of tramadol are available in Brazil; however, published information regarding their bioequivalence in the Brazilian population is not available. A study was designed for Brazilian regulatory authorities to allow marketing of a generic formulation. Objective: The purpose of this study was to compare the bioequivalence of 2 commercial tablet preparations containing tramadol 100 mg marketed for use in Brazil. Methods: A randomized, open-label, 2 x 2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a washout period of 12 days. Two tablet formulations of tramadol 100 mg (test and reference formulations) were administered as a single oral dose, and blood samples were collected over 24 hours. Tramadol plasma concentrations were quantified using a validated HPLC method. A plasma concentration time profile was generated for each volunteer and then mean values were determined, from which C(max), T(max), AUC(0-t), AUC(0-infinity), k(e), and t(1/2) were calculated using a noncompartmental model. Bioequivalence between the products was determined by calculating 90% CIs for the ratios of C(max), AUC(0-t), and AUC(0-infinity) values for the test and reference products using log-transformed data. Tolerability was assessed by monitoring vital signs (temperature, blood pressure, heart rate), laboratory tests (hematology, blood biochemistry, hepatic function, urinalysis), and interviews with the volunteers before medication administration and every 2 hours during the study. Results: Twenty-six healthy volunteers (13 men, 13 women) were enrolled in and completed the study. Mean (SD) age was 30 (6.8) years (range, 21-44 years), mean weight was 64 (8.3) kg (range, 53-79 kg), and mean height was 166 (6.4) cm (range, 155-178 cm). The 90% CIs for the ratios of C(max) (1.01-1.17), AUC(0-t) (1.00-1.13), and AUC(0-infinity) (1.00-1.14) values for the test and reference products fell within the interval of 0.80 to 1.25 proposed by most regulatory agencies, including the Brazilian regulatory body. No clinically important adverse effects were reported; only mild somnolence was reported by 4 volunteers and mild headaches by 5 volunteers, and there was no need to use medication to treat these symptoms. Conclusion: Pharmacokinetic analysis in these healthy Brazilian volunteers suggested that the test and reference formulations of tramadol 100-mg tablets met the regulatory requirements to assume bio-equivalence based on the Brazilian regulatory definition. (Clin Ther 2010;32:758-765) (C) 2010 Excerpta Medica Inc.

Bioequivalence assay between orally disintegrating and conventional tablet formulations in healthy volunteers

The purpose of this study was to evaluate bioequivalence of two commercial 8 mg tablet formulations of ondansetrona available ill the Brazilian market. In this study, a simple, rapid, sensitive and selective liquid chromarography-tandem mass spectrometry method is described for the determination of ondansetron in human plasma samples. The method was validated over a concentration range of 2.5-60 ng/ml and used in a bioequivalence trial between orally disintegrating and conventional tablet ondansetron formulations, to assess its usefulness in this kind of Study. Vonau flash (R) (Biolab Sanus Farmaceutica, Brazil, as test formulations) and Zofran (R) (GlaxoSmithKline, Brazil, as reference formulation) were evaluated following a single 8 mg close to 23 healthy volunteers of both genders. The dose was administered after an overnight fast according to a two-way crossover design. Bioequivalence between the products was determinated by Calculating 90% confidence interval (90% CI) for the ratio of C(max), AUC(0-t) and AUC(0-(sic)) values for the test and reference products, using logarithmically transformed data. The 90% confidence interval for the ratio of C(max) (87.5-103.8%), AUC(0-t) (89.3-107.2%) and AUC(0--(sic)) (89.7-106.0%) values for the test and reference products is Within the 80-125% interval, proposed by FDA, EMEA and ANVISA. It was concluded that two ondansetron formulations are bioequivalent ill their rate and extent of absorption. (C) 2008 Elsevier B.V. All rights reserved.

Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability study

In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether-dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5 mm NH(4)OH on a Gemini Phenomenex C(8) 5 mu m column (50 x 4.6 mm i.d.) in 5.0 min/run. The method fitted to a linear calibration curve (0.05-10 ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0 mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine (R), Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for C(max) and AUC ratios were all within the 80-125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption. Copyright (C) 2009 John Wiley & Sons, Ltd.

Bioequivalence and pharmacokinetics of two zidovudine formulations in healthy Brazilian volunteers: An open-label, randomized, single-dose, two-way crossover study

Background: Zidovudine is a thymidine nucleoside reverse transcriptase inhibitor with activity against HIV type 1. Some (similar to 8) generic formulations of zidovudine are available in Brazil; however, based on a literature search, information concerning their bioavailability and pharmacokinetic properties in the Brazilian population has not been reported. Objective: The aim of this study was to compare the bioavailability and pharmacokinetic properties of 2 capsule formulations of zidovudine 100 mg in healthy Brazilian volunteers. Methods: This open-label, randomized, 2-way crossover study utilized a 1-week washout period between doses. Blood samples were collected for 8 hours after a single dose of zidovudine 100-mg test (Zidovudina, Fundaqdo para o Remedio Popular, Sao Paulo, Brazil) or reference formulation (Retrovir (R), GlaxoSmithKline, Philadelphia, Pennsylvania). Plasma zidovudine concentrations were determined using a validated high-performance liquid chromatography method with ultraviolet detection at 265 nm. C-max, T-max, AUC(0-t), AUC(0-infinity), t(1/2), and the elimination constant (k(e)) were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIS for C-max, AUC(0-t), and AUC(0-infinity) fell within the interval of 80 % to 125 %, the regulatory definition set by the US Food and Drug Administration (FDA). Results: Twenty-four healthy volunteers (12 males, 12 females; mean age, 27 years; weight, 60 kg; height, 167 cm) were enrolled and completed the study. The 90% CIs of the treatment ratios for the logarithmic-transformed values of C-max, AUC(0-t), and AUC(0-infinity) were 80.0% to 113.6%, 93.9% to 109.7%, and 93.6% to 110.1 %, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition intervals of 80% to 125%. Conclusions: In this small study in healthy subjects, no statistically significant differences in C-max, AUC(0-t), and AUC(0-)infinity were found between the test and reference formulations of zidovudine 100-mg capsules. The 90% CIs for the mean ratio values for the test and reference formulations of AUC(0-t), AUC(0-infinity), and C-max indicated that the reported data were entirely within the bioequivalence acceptance range proposed by the FDA of 80% to 125% (using log-transformed data).

Online identification of chlorogenic acids, sesquiterpene lactones, and flavonoids in the Brazilian arnica Lychnophora ericoides Mart. (Asteraceae) leaves by HPLC-DAD-MS and HPLC-DAD-MS/MS and a validated HPLC-DAD method for their simultaneous analysis

Lychnophora ericoides Mart. (Asteraceae, Vernonieae) is a plant, endemic to Brazil, with occurrence restricted to the ""cerrado"" biome. Traditional medicine employs alcoholic and aqueous-alcoholic preparations of leaves from this species for the treatment of wounds, inflammation, and pain. Furthermore, leaves of L. ericoides are also widely used as flavorings for the Brazilian traditional spirit ""cachaca"". A method has been developed for the extraction and HPLC-DAD analysis of the secondary metabolites of L. ericoides leaves. This analytical method was validated with 11 secondary metabolites chosen to represent the different classes and polarities of secondary metabolites occurring in L. ericoides leaves, and good responses were obtained for each validation parameter analyzed. The same HPLC analytical method was also employed for online secondary metabolite identification by HPLC-DAD-MS and HPLC-DAD-MS/MS, leading to the identification of di-C-glucosylflavones, coumaroylglucosylflavonols, flavone, flavanones, flavonols, chalcones, goyazensolide, and eremantholide-type sesquiterpene lactones and positional isomeric series of chlorogenic acids possessing caffeic and/or ferulic moieties. Among the 52 chromatographic peaks observed, 36 were fully identified and 8 were attributed to compounds belonging to series of caffeoylferuloylquinic and diferuloylquinic acids that could not be individualized from each other.