AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Pollination And Breeding System Of Couepia Uiti (mart. And Zucc.) Benth (chrysobalanaceae) In The Pantanal Da Nhecolândia.

The pollination biology and breeding system of Couepia uiti was studied. In this species, flowers opened at 06:00 AM anthesis, and nectar production began at around 0800 h, reached a maximum volume from 09:30 AM to 10:30 AM, and decreased thereafter. The nectar sugar concentration increased continuously, but showed an abrupt increase from 10:00 AM to 12:00 AM. Pollen release occurred at about 09:30 AM and was quickly collected. The stigmas became receptive at around 12:00 AM. The pollinators of C. uiti included the bees Apis mellifera, Xylocopa sp. and Bombus sp., and three species of wasps. This conclusion was based on the observation that these hymenopterans had C. uiti pollen on their bodies, visited the receptive flowers, and touched the anthers and stigmas, thereby promoting pollination. Of these floral visitors, A. mellifera was considered to be the most efficient pollinator. However, mixed pollination also occurred. The number of C. uiti flowers visited in the morning (n = 52) was three times smaller than in the afternoon (n = 62), and the species richness of floral visitors was also bigger in the afternoon (eight in the afternoon versus five in the morning). This finding indicated that these floral visitors preferred to exploit nectar rather than pollen. Controlled pollination experiments showed that C. uiti was a self-incompatible species that produced fruits only by cross-pollination. Treatments such as agamospermy and spontaneous and self-pollinations did not produce fruits.67715-

Modelos agrometeorológicos para estimação do número de frutos por planta em laranjeira 'pêra' na Região de Limeira-SP, Brasil.

O estabelecimento de modelos que permitam previsões de tendências de produtividade apontando se as colheitas serão menores ou maiores é de grande importância para todos os elos da cadeia citrícola. Buscou-se avaliar a influência de variáveis agrometeorológicas em diferentes fases do ciclo das plantas e propor modelos empíricos para estimação do número de frutos por planta em laranja 'Pêra', na região de Limeira-SP. Foram utilizados dados amostrais de número de frutos por planta, em três classes de idade, referentes à estimativa anual de produção da indústria de suco paulista, no total de 15 safras (1990/91 a 2004/05), e dados meteorológicos (temperatura máxima e mínima e precipitação) para o município de Limeira (22°32'S, 47°27'W, 639 metros). Foram determinados os coeficientes de correlação linear entre número de frutos por planta e variáveis agrometeorológicas componentes do balanço hídrico e temperatura, em diferentes períodos. Foram desenvolvidos modelos de regressão linear múltipla, mediante procedimento 'stepwise', para os subconjuntos de variáveis agrometeorológicas que apresentaram as maiores correlações significativas com o número de frutos por planta em diferentes fases do ciclo da cultura. As condições meteorológicas durante as fases de crescimento vegetativo de verão, pré-florescimento, florescimento e início de crescimento dos frutos, influenciaram a produção de frutos por planta. Os modelos obtidos apresentaram ajustes satisfatórios entre valores observados e estimados, com coeficiente de determinação variando de 0,75 a 0,88.Made available in DSpace on 2015-08-18T05:53:16Z (GMT). No. of bitstreams: 1 2006AP027.pdf: 4971889 bytes, checksum: d4601f6935e241ed783ac2660a6ae500 (MD5) Previous issue date: 2015-08-14200

Agrometeorological models for 'Valencia' and 'Hamlin' sweet oranges to estimate the number of fruits per plant.

The development of models that allow forecasting yield tendencies is important to all sectors of the citrus industry. This work evaluated the influence of meteorological variables in different phases of the crop cycle in order to propose empirical models to estimate the number of fruits per plant (NFP) of 'Valencia' and 'Hamlin' sweet oranges. NFP sampling data from the citrus juice industry of the State of São Paulo, on the total of 15 harvests (1990/91 to 2004/05), classified into three age classes, and meteorological data of maximum and minimum air temperature and rainfall of Limeira, SP, Brazil, were utilized. Correlation coefficients were initially computed between the number of fruits per plant and each meteorological variable used for water balance and variables related to air temperature, in different periods. Linear multiple regression models were fit to describe the empirical relationship between NFP and the subsets of agrometeorological predictors that presented higher correlations in different phases of the crop cycle. The meteorological conditions during the phases of vegetative summer flush, pre-flowering, flowering and beginning of fruit growth influenced the number of fruits per plant. The proposed models presented adequate goodness-of-fit with determination coefficients varying from 0.72 to 0.87

Características biométricas de mudas de Tabebula chrysotricha(standl.) formadas em diferentes substratos e soluções de fertirrigação, quando plantadas em campo Biometric characterizations of Tabebula chrysotricha (standl.) seedlings formed in different substrates and fertirrigation solutions, when planted in fields

Este trabalho objetivou estudar as características biométricas de plantas de ipê-amarelo (Tabebuia chrysotricha Standl.) formadas, na fase de viveiro, em função de quatro substratos, variando as soluções de fertirrigação. Para compor os substratos, foram utilizadas fibras de coco fibrosa e granulada, formando os tratamentos 100% fibrosa, 60% fibrosa e 40% granulada, 40% fibrosa e 60% granulada e 100% granulada. A adubação de base foi igual em todos os tratamentos, e as soluções de adubação variaram, a fim de se obterem soluções completas com condutividades elétricas de 1,06 dS m-1; 2,12 dS m-1; 3,2 dS m-1; e 4,24 dS m¹. As sementes foram colocadas diretamente nos tubetes (120 mL) contendo os respectivos substratos e receberam as fertirrigações por subsuperfície uma vez por semana, respeitando-se os tratamentos de adubação. Quando as mudas atingiram aproximadamente 20 cm de altura, elas foram realocadas sob tela de 9% de sombreamento, onde permaneceram até o plantio, em Taubaté, SP. Mudas produzidas em fibra de coco 100% granulada alcançaram, em campo, maiores alturas, diâmetros de coleto e número de folhas. Apesar das diferentes soluções de fertirrigação aplicadas, as alturas de parte aérea se igualaram a partir dos 167 dias após o plantio em campo. Recomendase a produção de mudas de ipê-amarelo (T. chrysotricha) em substratos contendo fibra de coco granulada e soluções de fertirrigação com condutividade elétrica de 1,06 dS m-1.<br>The work aimed to study the formation of Tabebuia chrysotricha Standl. seedlings in function of four substrates, varying the fertirrigation solutions. To compose the substrate, fibrous and granulated coconut fiber was used, obtaining the following treatments: 100% fibrous, 60% fibrous and 40% granulated, 40% fibrous and 60% granulated and 100% granulated. The base fertilization was the same for all treatments and the solutions of fertilization varied in order to obtain complete solutions with electric conductivities of 1.06 dS m-1, 2.12 dS m-1, 3.2 dS m-1 and 4.25 dS m-1. The propagative material was sowed directly into plastic containers (120mL) with the respective substrates. The fertilization was received through sub irrigation once a week, respecting the treatments of fertilizations. When the seedlings reached 20cm of height, approximately, they were replaced under black screens (9% of shading), where they remained until planting in Taubaté-SP. Seedlings produced in coconut fiber 100% granulate reached, in the field, higher heights, stem diameters and number of leaves. In function of applied solutions, heights of the aerial part were homogeneous starting from 167 days after planting. The production of T. chrysotricha seedlings is recommended in granulated coconut fiber substrate and fertilizer solutions with electric conductivity of 1.06 dS m-1

Protective Effect of <i>Cimicifuga racemosa</i> (L.) Nutt Extract on Oocyte and Follicle Toxicity Induced by Doxorubicin during In Vitro Culture of Mice Ovaries

This study evaluated the potential of Cimicifuga racemosa (L.) Nutt extract (CIMI) to reduce the deleterious effects of doxorubicin (DOXO) in oocytes, follicles and stromal cells in mice ovaries cultured in vitro. In experiment 1, mice ovaries were cultured in DMEM+ alone or supplemented with 5, 50 or 500 ng/mL CIMI, while in experiment 2, mice ovaries were cultured in DMEM+ alone or supplemented with 5 ng/mL CIMI (better concentration), 0.3 μg/mL DOXO or both. Thereafter, the ovaries were processed for histological (morphology, growth, activation, extracellular matrix configuration and stromal cell density), immunohistochemical (caspase-3) analyses. Follicle viability was evaluated by fluorescence microscopy (ethidium homodimer-1 and calcein) while real-time PCR was performed to analyses the levels of (mRNA for SOD, CAT and nuclear factor erythroid 2–related factor 2 (NRF2) analyses. The results showed that DOXO reduces the percentage of normal follicles and the density of stromal cells in cultured ovaries, but these harmful effects were blocked by CIMI. The DOXO reduced the percentage of primordial follicles, while the presence of CIMI alone did not influence percentage of primordial follicles. A higher staining for caspase-3 was seen in ovaries cultured in control medium alone or with DOXO when compared with those cultured with CIMI alone or both CIMI and DOXO. In addition, follicles from ovaries cultured with both CIMI and DOXO were stained by calcein, while those follicles cultured with only DOXO were stained with ethidium homodimer-1. Furthermore, ovaries cultured with CIMI or both CIMI and DOXO had higher levels of mRNA for SOD and CAT, respectively, than those cultured with only DOXO. In conclusion, the extract of CIMI protects the ovaries against deleterious effects of DOXO on follicular survival and ovarian stromal cells