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

Effect of surface stone cover on sediment and solute transport on the slope of fallow land in the semi-arid loess region of northwestern China

In the semi-arid loess region of northwestern China, use of stone and gravel as mulch has been an indigenous farming technique for improving crop production for over 300 years. However, systematic studies on the effects of stone covers on soil and water conservation have been rarely conducted, except for a few investigations and documentations on the stone cover effects on erosion and solute transport in such a highly erodible loess region. Materials and methods We experimentally examined the effects of surface stone cover on sediment erosion and solute transport using the water-scouring method on sloping land in a semi-arid region in China, which had been left fallow with alfalfa (Medicago sativa) for 3 years. All covered stones rested on the soil surface, and none were partly or completely embedded in the soil surface layer. Stone cover percentages were classified into three groups: 0% (no stone cover, the control treatment), 5.1%, and 20.8%. Two sizes of stones, SCA (7.6 x 7.6 cm) and SCB (18.4 x 18.4 cm), were used in the treatment of 5.1% stone cover. A dye method was used to measure flow velocities in the experiments. Each stone treatment had one replicate. Results and discussion The surface cover by stones influenced soil erosion processes, runoff generation, and solute transport. Runoff rate and sediment yield decreased as stone cover percentages increased from zero (no stone cover) to 20.8%. The effect of stone sizes on the runoff was not significant, whereas stone size type SCA caused lower sediment yield than SCB at the same stone cover percentage of 5.1%. Likewise, water flow velocity and the Froude numbers also decreased with increasing stone cover percentage. The Manning roughness increased with increasing stone cover percentage, ranging from 0.0296 to 0.0579 m(-1/3) s. But the Reynolds numbers among different stone cover percentages and sizes remained nearly the same with a small variation from 483 to 486. Conclusions The study implied that stone cover percentage and size have important influences on sediment and solute concentration in runoff. Surface-covering stones reduced the velocity of runoff, increased surface roughness, decreased sediment yield in runoff, and consequently reduced the quantities of solute release from soil surface

Transfer of cadmium from soil to vegetable in the Pearl River Delta area, South China.

The purpose of this study was to investigate the regional Cadmium (Cd) concentration levels in soils and in leaf vegetables across the Pearl River Delta (PRD) area; and reveal the transfer characteristics of Cadmium (Cd) from soils to leaf vegetable species on a regional scale. 170 paired vegetables and corresponding surface soil samples in the study area were collected for calculating the transfer factors of Cadmium (Cd) from soils to vegetables. This investigation revealed that in the study area Cd concentration in soils was lower (mean value 0.158 mg kg(-1)) compared with other countries or regions. The Cd-contaminated areas are mainly located in west areas of the Pearl River Delta. Cd concentrations in all vegetables were lower than the national standard of Safe vegetables (0.2 mg kg(-1)). 88% of vegetable samples met the standard of No-Polluted vegetables (0.05 mg kg(-1)). The Cd concentration in vegetables was mainly influenced by the interactions of total Cd concentration in soils, soil pH and vegetable species. The fit lines of soil-to-plant transfer factors and total Cd concentration in soils for various vegetable species were best described by the exponential equation (y = ax(b)), and these fit lines can be divided into two parts, including the sharply decrease part with a large error range, and the slowly decrease part with a low error range, according to the gradual increasing of total Cd concentrations in soils

Sediment and solute transport on soil slope under simultaneous influence of rainfall impact and scouring flow

Soil erosion and nutrient losses with surface runoff in the loess plateau in China cause severe soil quality degradation and water pollution. It is driven by both rainfall impact and runoff flow that usually take place simultaneously during a rainfall event. However, the interactive effect of these two processes on soil erosion has received limited attention. The objectives of this study were to better understand the mechanism of soil erosion, solute transport in runoff, and hydraulic characteristics of flow under the simultaneous influence of rainfall and shallow clear-water flow scouring. Laboratory flume experiments with three rainfall intensities (0, 60, and 120 mm h(-1)) and four scouring inflow rates (10, 20, 30, and 40 l min(-1)) were conducted to evaluate their interactive effect on runoff. Results indicate that both rainfall intensity and scouring inflow rate play important roles on runoff formation, soil erosion, and solute transport in the surface runoff. A rainfall splash and water scouring interactive effect on the transport of sediment and solute in runoff were observed at the rainfall intensity of 60 mm h(-1) and scouring inflow rates of 20 l min(-1). Cumulative sediment mass loss (Ms) was found to be a linear function of cumulative runoff volume (Wr) for each treatment. Solute transport was also affected by both rainfall intensity and scouring inflow rate, and the decrease in bromide concentration in the runoff with time fitted to a power function well. Reynolds number (Re) was a key hydraulic parameter to determine erodability on loess slopes. The Darcy-Weisbach friction coefficients (f) decreased with the Reynolds numbers (Re), and the average soil and water loss rate (M(1)) increased with the Reynolds numbers (Re) on loess slope for both scenarios with or without rainfall impact. Copyright (C) 2010 John Wiley & Sons, Ltd

Thermal Cycles and Deformation Characters During High-Speed Micro Friction Stir Welding Process of AA7075-T6 Sheets

Thermal cycles and deformations during high-speed micro friction stir welding (μFSW) under different welding conditions were studied by experimental methods. The results show that the peak temperature and elevated-temperature exposure time (t150) increased with the increasing of rotational speed and decreased with the increasing of welding speed. Increasing rotational speed or welding speed led to an increase in both heating and cooling rates. The joint fabricated by the pinless tool experienced a lower peak temperature, a shorter elevated-temperature exposure time, and a larger temperature gradient than that by the pin tool. The welded sheet presented an anti-saddle deformation character, with convex bending in a longitudinal direction and concave angular bending in a transverse direction. In comparison to the pin tool, the longitudinal maximum bending deformation, Zmax, of the joint fabricated by the pinless tool was reduced by 12.35%, and the transverse angular deformation, α, was reduced by 6.67%. In comparison to the steel backing plate, the Zmax of the joint produced using a copper backing plate was reduced by 40.66%, but the α was increased by 53.27%