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.

Self-disclosure of HIV diagnosis to sexual partners by heterosexual and bisexual men: a challenge for HIV/AIDS care and prevention

This study investigated the disclosure of HIV-positive serostatus to sexual partners by heterosexual and bisexual men, selected in centers for HIV/AIDS care. In 250 interviews, we investigated disclosure of serostatus to partners, correlating disclosure to characteristics of relationships. The focus group further explored barriers to maintenance/establishment of partnerships and their association with disclosure and condom use. Fear of rejection led to isolation and distress, thus hindering disclosure to current and new partners. Disclosure requires trust and was more frequent to steady partners, to partners who were HIV-positive themselves, to female partners, and by heterosexuals, occurring less frequently with commercial sex workers. Most interviewees reported consistent condom use. Unprotected sex was more frequent with seropositive partners. Suggestions to enhance comprehensive care for HIV-positive men included stigma management, group activities, and human rights-based approaches involving professional education in care for sexual health, disclosure, and care of "persons living with HIV".

Validation of reference genes for gene expression studies in the honey bee, Apis mellifera, by quantitative real-time RT-PCR

For obtaining accurate and reliable gene expression results it is essential that quantitative real-time RT-PCR (qRT-PCR) data are normalized with appropriate reference genes. The current exponential increase in postgenomic studies on the honey bee, Apis mellifera, makes the standardization of qRT-PCR results an important task for ongoing community efforts. For this aim we selected four candidate reference genes (actin, ribosomal protein 49, elongation factor 1-alpha, tbp-association factor) and used three software-based approaches (geNorm, BestKeeper and NormFinder) to evaluate the suitability of these genes as endogenous controls. Their expression was examined during honey bee development, in different tissues, and after juvenile hormone exposure. Furthermore, the importance of choosing an appropriate reference gene was investigated for two developmentally regulated target genes. The results led us to consider all four candidate genes as suitable genes for normalization in A. mellifera. However, each condition evaluated in this study revealed a specific set of genes as the most appropriated ones.

Excitation energies from ground-state density-functionals by means of generator coordinates

The generator-coordinate method is a flexible and powerful reformulation of the variational principle. Here we show that by introducing a generator coordinate in the Kohn-Sham equation of density-functional theory, excitation energies can be obtained from ground-state density functionals. As a viability test, the method is applied to ground-state energies and various types of excited-state energies of atoms and ions from the He and the Li isoelectronic series. Results are compared to a variety of alternative DFT-based approaches to excited states, in particular time-dependent density-functional theory with exact and approximate potentials.

Improving the tracking capability of adaptive filters via convex combination

As is well known, Hessian-based adaptive filters (such as the recursive-least squares algorithm (RLS) for supervised adaptive filtering, or the Shalvi-Weinstein algorithm (SWA) for blind equalization) converge much faster than gradient-based algorithms [such as the least-mean-squares algorithm (LMS) or the constant-modulus algorithm (CMA)]. However, when the problem is tracking a time-variant filter, the issue is not so clear-cut: there are environments for which each family presents better performance. Given this, we propose the use of a convex combination of algorithms of different families to obtain an algorithm with superior tracking capability. We show the potential of this combination and provide a unified theoretical model for the steady-state excess mean-square error for convex combinations of gradient- and Hessian-based algorithms, assuming a random-walk model for the parameter variations. The proposed model is valid for algorithms of the same or different families, and for supervised (LMS and RLS) or blind (CMA and SWA) algorithms.

Modularity and robustness of bone networks

Cortical bones, essential for mechanical support and structure in many animals, involve a large number of canals organized in intricate fashion. By using state-of-the art image analysis and computer graphics, the 3D reconstruction of a whole bone (phalange) of a young chicken was obtained and represented in terms of a complex network where each canal was associated to an edge and every confluence of three or more canals yielded a respective node. The representation of the bone canal structure as a complex network has allowed several methods to be applied in order to characterize and analyze the canal system organization and the robustness. First, the distribution of the node degrees (i.e. the number of canals connected to each node) confirmed previous indications that bone canal networks follow a power law, and therefore present some highly connected nodes (hubs). The bone network was also found to be partitioned into communities or modules, i.e. groups of nodes which are more intensely connected to one another than with the rest of the network. We verified that each community exhibited distinct topological properties that are possibly linked with their specific function. In order to better understand the organization of the bone network, its resilience to two types of failures (random attack and cascaded failures) was also quantified comparatively to randomized and regular counterparts. The results indicate that the modular structure improves the robustness of the bone network when compared to a regular network with the same average degree and number of nodes. The effects of disease processes (e. g., osteoporosis) and mutations in genes (e.g., BMP4) that occur at the molecular level can now be investigated at the mesoscopic level by using network based approaches.

Spatial portability of numerical models of leaf wetness duration based on empirical approaches

Leaf wetness duration (LWD) models based on empirical approaches offer practical advantages over physically based models in agricultural applications, but their spatial portability is questionable because they may be biased to the climatic conditions under which they were developed. In our study, spatial portability of three LWD models with empirical characteristics - a RH threshold model, a decision tree model with wind speed correction, and a fuzzy logic model - was evaluated using weather data collected in Brazil, Canada, Costa Rica, Italy and the USA. The fuzzy logic model was more accurate than the other models in estimating LWD measured by painted leaf wetness sensors. The fraction of correct estimates for the fuzzy logic model was greater (0.87) than for the other models (0.85-0.86) across 28 sites where painted sensors were installed, and the degree of agreement k statistic between the model and painted sensors was greater for the fuzzy logic model (0.71) than that for the other models (0.64-0.66). Values of the k statistic for the fuzzy logic model were also less variable across sites than those of the other models. When model estimates were compared with measurements from unpainted leaf wetness sensors, the fuzzy logic model had less mean absolute error (2.5 h day(-1)) than other models (2.6-2.7 h day(-1)) after the model was calibrated for the unpainted sensors. The results suggest that the fuzzy logic model has greater spatial portability than the other models evaluated and merits further validation in comparison with physical models under a wider range of climate conditions. (C) 2010 Elsevier B.V. All rights reserved.

A contribution to the phytogeography of Brazilian campos: an analysis based on Poaceae

Twenty areas from eight Brazilian states were compared according to a list of 224 species of Poaceae. In order to determinate affinity patterns between the areas, a binary matrix was submitted to cluster and ordination analysis. The patterns found were then faced to climate and geographic position. The scores corresponding to the areas obtained from the cluster analysis showed a strong correlation to temperature. The scores corresponding to the species suggest a gradient that associates distribution patterns to the photosynthetic pathway (C3 or C4). The current results suggest that the traditional classification of the Southern American grasslands might require some modification in order to be broadly applicable in the Brazilian context.

Merluccius hubbsi (Teleostei: Merlucciidae): stock identification based on reproductive biology in the south-southeast brazilian region

The Argentine hake, Merluccius hubbsi, a demersal-pelagic species found from Rio de Janeiro, Brazil to the Tierra del Fuego, Argentina, has become an important target of the Brazilian bottom-trawler fleet since 2001. Earlier studies focusing on the species have suggested that more than one stock might occur off the Brazilian coast, in accordance with environmental features. In order to evaluate this hypothesis, fish were collected from four different areas in the Brazilian waters in which the hake is distributed, during the summers and winters of 1996-2001 and 2004, the females being used to analyze and compare spatial-temporal variations in ovarian maturation. Gonad indexes were also applied for the same purpose. Results indicate a north-south spawning gradient occurring as from summer at around 21°S to winter near 34°S, leading to the identification of two distinct stocks: one located between 21°S and 29°S (Southeastern stock) and the other between 29°S and 34°S (Southern stock), this latter shared with Uruguay and Argentina. Brazilian stocks present clear signs of overexploitation, the situation calling for an urgent solution.

Sequential injections as an alternative to gradient exploitation for implementing differential kinetic analysis in a flow injection system

A novel flow-based strategy for implementing simultaneous determinations of different chemical species reacting with the same reagent(s) at different rates is proposed and applied to the spectrophotometric catalytic determination of iron and vanadium in Fe-V alloys. The method relies on the influence of Fe(II) and V(IV) on the rate of the iodide oxidation by Cr(VI) under acidic conditions, the Jones reducing agent is then needed Three different plugs of the sample are sequentially inserted into an acidic KI reagent carrier stream, and a confluent Cr(VI) solution is added downstream Overlap between the inserted plugs leads to a complex sample zone with several regions of maximal and minimal absorbance values. Measurements performed on these regions reveal the different degrees of reaction development and tend to be more precise Data are treated by multivariate calibration involving the PLS algorithm The proposed system is very simple and rugged Two latent variables carried out ca 95% of the analytical information and the results are in agreement with ICP-OES. (C) 2010 Elsevier B V. All rights reserved.

Political Systems and the Perspective on Nursing Education during the Spanish Transition (from the Franco Regime to Democracy). A Contribution based on Nursing History

The aim of this study is to describe the changes in nursing education during the process prior to and after the establishment of democracy in Spain. It begins with the hypothesis that differences in social and political organization influenced the way the system of nursing education evolved, keeping it in line with neopositivistic schemes and exclusively technical approaches up until the advent of democracy. The evolution of a specific profile for nursing within the educational system has been shaped by the relationship between the systems of social and political organization in Spain. To examine the insertion of subjects such as the anthropology of healthcare into education programs for Spanish nursing, one must consider the cultural, intercultural and transcultural factors that are key to understanding the changes in nursing education that allowed for the adoption of a holistic approach in the curricula. Until the arrival of democracy in 1977, Spanish nursing education was solely technical in nature and the role of nurses was limited to the tasks and procedures defined by the bureaucratic thinking characteristic of the rational-technological paradigm. Consequently, during the long period prior to democracy, nursing in Spain was under the influence of neopositivistic and technical thinking, which had its effect on educational curricula. The addition of humanities and anthropology to the curricula, which facilitated a holistic approach, occurred once nursing became a field of study at the university level in 1977, a period that coincided with the beginnings of democracy in Spain.

Three-phase harmonic distortion state estimation algorithm based on evolutionary strategies

This paper presents a new methodology to estimate unbalanced harmonic distortions in a power system, based on measurements of a limited number of given sites. The algorithm utilizes evolutionary strategies (ES), a development branch of evolutionary algorithms. The problem solving algorithm herein proposed makes use of data from various power quality meters, which can either be synchronized by high technology GPS devices or by using information from a fundamental frequency load flow, what makes the overall power quality monitoring system much less costly. The ES based harmonic estimation model is applied to a 14 bus network to compare its performance to a conventional Monte Carlo approach. It is also applied to a 50 bus subtransmission network in order to compare the three-phase and single-phase approaches as well as the robustness of the proposed method. (C) 2010 Elsevier B.V. All rights reserved.

Toward Optimal Design of Piezoelectric Transducers Based on Multifunctional and Smoothly Graded Hybrid Material Systems

This work explores the design of piezoelectric transducers based on functional material gradation, here named functionally graded piezoelectric transducer (FGPT). Depending on the applications, FGPTs must achieve several goals, which are essentially related to the transducer resonance frequency, vibration modes, and excitation strength at specific resonance frequencies. Several approaches can be used to achieve these goals; however, this work focuses on finding the optimal material gradation of FGPTs by means of topology optimization. Three objective functions are proposed: (i) to obtain the FGPT optimal material gradation for maximizing specified resonance frequencies; (ii) to design piezoelectric resonators, thus, the optimal material gradation is found for achieving desirable eigenvalues and eigenmodes; and (iii) to find the optimal material distribution of FGPTs, which maximizes specified excitation strength. To track the desirable vibration mode, a mode-tracking method utilizing the `modal assurance criterion` is applied. The continuous change of piezoelectric, dielectric, and elastic properties is achieved by using the graded finite element concept. The optimization algorithm is constructed based on sequential linear programming, and the concept of continuum approximation of material distribution. To illustrate the method, 2D FGPTs are designed for each objective function. In addition, the FGPT performance is compared with the non-FGPT one.

Directional Wave Spectrum Estimation Based on Vessel`s 1st-order Motions: Field Results

In this paper, 2 different approaches for estimating the directional wave spectrum based on a vessel`s 1st-order motions are discussed, and their predictions are compared to those provided by a wave buoy. The real-scale data were obtained in an extensive monitoring campaign based on an FPSO unit operating at Campos Basin, Brazil. Data included vessel motions, heading and tank loadings. Wave field information was obtained by means of a heave-pitch-roll buoy installed in the vicinity of the unit. `two of the methods most widely used for this kind of analysis are considered, one based on Bayesian statistical inference, the other consisting of a parametrical representation of the wave spectrum. The performance of both methods is compared, and their sensitivity to input parameters is discussed. This analysis complements a set of previous validations based on numerical and towing-tank results and allows for a preliminary evaluation of reliability when applying the methodology at full scale.

S/MIMO MC-CDMA Heuristic Multiuser Detectors Based on Single-Objective Optimization

This paper analyzes the complexity-performance trade-off of several heuristic near-optimum multiuser detection (MuD) approaches applied to the uplink of synchronous single/multiple-input multiple-output multicarrier code division multiple access (S/MIMO MC-CDMA) systems. Genetic algorithm (GA), short term tabu search (STTS) and reactive tabu search (RTS), simulated annealing (SA), particle swarm optimization (PSO), and 1-opt local search (1-LS) heuristic multiuser detection algorithms (Heur-MuDs) are analyzed in details, using a single-objective antenna-diversity-aided optimization approach. Monte- Carlo simulations show that, after convergence, the performances reached by all near-optimum Heur-MuDs are similar. However, the computational complexities may differ substantially, depending on the system operation conditions. Their complexities are carefully analyzed in order to obtain a general complexity-performance framework comparison and to show that unitary Hamming distance search MuD (uH-ds) approaches (1-LS, SA, RTS and STTS) reach the best convergence rates, and among them, the 1-LS-MuD provides the best trade-off between implementation complexity and bit error rate (BER) performance.