Application of high-throughput screening techniques to drug discovery

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Child and adolescent psychiatry training in Brazil, Argentina, Uruguay and Chile: current panorama and future challenges

Mental disorders affect approximately 10-15% of children and adolescents worldwide. In South America these numbers are probably higher due to poverty and adverse life events that frequently affect this region. The availability of qualified services and well-trained professionals to care for those children are by far insufficient. The aim of this study was to assess and describe child and adolescent psychiatry (CAP) training in Brazil, Argentina, Uruguay, and Chile, to support the development and strengthen training standards. The coordinators of CAP residency programs in Brazil, Argentina, Uruguay, and Chile were invited to answer an online questionnaire about the characteristics of their training programs. Twelve programs from Brazil, three programs from Chile, two from Argentina, and one from Uruguay completed the questionnaires. In the last three countries, CAP is recognized as an independent specialty, while in Brazil it is considered a subspecialty of psychiatry. None of the countries have a national guideline for CAP residency training. Recently, there has been an increase in the number of professionals interested in pursuing a formal CAP training. This is the first study aiming to evaluate the current scenario of CAP training in South America. The results point to a great potential in the evaluated programs, but also to the need for homogeneous criteria for CAP training and evaluation of residents. A more efficient communication among programs would be an enriching strategy for their development, which may be facilitated by the results of this study718

Combinatorial library design: using a multiobjective genetic algorithm

Early results from screening combinatorial libraries have been disappointing with libraries either failing to deliver the improved hit rates that were expected or resulting in hits with characteristics that make them undesirable as lead compounds. Consequently, the focus in library design has shifted toward designing libraries that are optimized on multiple properties simultaneously, for example, diversity and druglike physicochemical properties. Here we describe the program MoSELECT that is based on a multiobjective genetic algorithm and which is able to suggest a family of solutions to multiobjective library design where all the solutions are equally valid and each represents a different compromise between the objectives. MoSELECT also allows the relationships between the different objectives to be explored with competing objectives easily identified. The library designer can then make an informed choice on which solution(s) to explore. Various performance characteristics of MoSELECT are reported based on a number of different combinatorial libraries

Source partitioning of H₂O and CO₂ fluxes based on high-frequency eddy covariance data: a comparison between study sites

For an assessment of the roles of soil and vegetation in the climate system, a further understanding of the flux components of H2O and CO2 (e.g., transpiration, soil respiration) and their interaction with physical conditions and physiological functioning of plants and ecosystems is necessary. To obtain magnitudes of these flux components, we applied source partitioning approaches after Scanlon and Kustas (2010; SK10) and after Thomas et al. (2008; TH08) to high-frequency eddy covariance measurements of 12 study sites covering different ecosystems (croplands, grasslands, and forests) in different climatic regions. Both partitioning methods are based on higher-order statistics of the H2O and CO2 fluctuations, but proceed differently to estimate transpiration, evaporation, net primary production, and soil respiration. We compared and evaluated the partitioning results obtained with SK10 and TH08, including slight modifications of both approaches. Further, we analyzed the interrelations among the performance of the partitioning methods, turbulence characteristics, and site characteristics (such as plant cover type, canopy height, canopy density, and measurement height). We were able to identify characteristics of a data set that are prerequisites for adequate performance of the partitioning methods. SK10 had the tendency to overestimate and TH08 to underestimate soil flux components. For both methods, the partitioning of CO2 fluxes was less robust than for H2O fluxes. Results derived with SK10 showed relatively large dependencies on estimated water use efficiency (WUE) at the leaf level, which is a required input. Measurements of outgoing longwave radiation used for the estimation of foliage temperature (used in WUE) could slightly increase the quality of the partitioning results. A modification of the TH08 approach, by applying a cluster analysis for the conditional sampling of respiration–evaporation events, performed satisfactorily, but did not result in significant advantages compared to the original method versions developed by Thomas et al. (2008). The performance of each partitioning approach was dependent on meteorological conditions, plant development, canopy height, canopy density, and measurement height. Foremost, the performance of SK10 correlated negatively with the ratio between measurement height and canopy height. The performance of TH08 was more dependent on canopy height and leaf area index. In general, all site characteristics that increase dissimilarities between scalars appeared to enhance partitioning performance for SK10 and TH08.</p