Activity

Machine learning is widely used in drug development to predict activity in biological assays based on chemical structure. read more However, the process of transitioning from one experimental setup to another for the same biological endpoint has not been extensively studied. In a retrospective study, we here explore different modeling strategies of how to combine data from the old and new assays when training conformal prediction models using data from hERG and NaV assays. We suggest to continuously monitor the validity and efficiency of models as more data is accumulated from the new assay and select a modeling strategy based on these metrics. In order to maximize the utility of data from the old assay, we propose a strategy that augments the proper training set of an inductive conformal predictor by adding data from the old assay but only having data from the new assay in the calibration set, which results in valid (well-calibrated) models with improved efficiency compared to other strategies. We study the results for varying sizes of new and old assays, allowing for discussion of different practical scenarios. We also conclude that our proposed assay transition strategy is more beneficial, and the value of data from the new assay is higher, for the harder case of regression compared to classification problems.Six CuO/ZnO nanorod (CuO/ZnONR)-based microfluidic reactors were constructed for different UV irradiation durations, with which an aqueous methylene blue (MB) solution was photodegraded at varied volume flow rate Q. Via numerical and experimental routes, the effects of the Q on the kinetic adsorption rate constant Ka and the initial rate constant KA of the CuO/ZnONR-based microfluidic reactors were discussed. Moreover, a reverse contacting angle (CA) trend of CuO/ZnONRs to the reaction constant K curve of corresponding CuO/ZnONR-based microfluidic reactor suggested that the CA of CuO/ZnONRs was another key influencing factor that affected greatly the photodegradation performance of the microfluidic reactors. The Q of the aqueous MB solution and the UV irradiation duration for the photodeposition of CuO/ZnONRs were optimized to be 125 μL/min and 1.0 h, the K of the CuO/ZnONR-based microfluidic reactors reached 4.84 min-1, and the related ΔKA/K was less than 6%. Similarly, these methods and results can be employed not only to enhance the mass transport and adsorption of specific species within other nanostructured matrix material-coated microchannels but also to enlarge the actual contacting surface areas between these microchannels and the related solution, which further improve the performance of other nanostructured catalyst-based microfluidic reactors, rGO microfluidic voltage generation, and a GOx/AuNW enzymatic glucose microfluidic sensor.Studies have shown that when insulator surfaces become electrostatically charged, complex spatial distributions of charge are produced, which are made up of micrometer-scale regions of both charge polarities. The origin of these charge patterns, often called “charge mosaics”, is not understood. Here, we carried out controlled Kelvin force microscopy experiments on microfabricated interdigitated electrode systems to show that the process of wetting a surface by a liquid followed by evaporation of the liquid in an electric field can lead to neighboring micrometer-scale regions of positive and negative charge, which remain stable long after the electric field is removed. We thus suggest that local electric fields, perhaps due to the existing charge on the surface, can act in concert with liquid evaporation to contribute to the creation of charge mosaics.The stereoselective construction of all-carbon quaternary stereocenters, especially acyclic ones, represents an important challenge in organic synthesis. In particular, homopropargyl amides with a quaternary stereocenter β to a nitrogen atom are valuable synthetic intermediates, which could be transformed to diverse chiral structures through alkyne transformations. However, highly enantioselective synthetic methods for homopropargyl amides with a β quaternary stereocenter are extremely rare. We report here unprecedented substrate-directed, iridium-catalyzed enantioselective hydroalkynylations of trisubstituted alkenes to form an acyclic all-carbon quaternary stereocenter β to a nitrogen atom. The hydroalkynylation of enamide occurred with unconventional selectivity, favoring the more hindered reaction site. Homopropargyl amides with β-stereocenters were prepared in high regio- and enantioselectivities. Combined experimental and computational studies revealed the origin of the regio- and enantioselectivities.Microplastics (MPs) exposed to the natural environment provide an ideal surface for biofilm formation, which potentially acts as a reactive phase facilitating the sorption of hazardous contaminants. Until now, changes in the contaminant sorption capacity of MPs due to biofilm formation have not been quantified. This is the first study that compared the capacity of naturally aged, biofilm-covered microplastic fibers (BMFs) to adsorb perfluorooctane sulfonate (PFOS) and lead (Pb) at environmentally relevant concentrations. Changes in the surface properties and morphology of aged microplastic fibers (MF) were studied by surface area analysis, infrared spectroscopy, and scanning electron microscopy. Results revealed that aged MFs exhibited higher surface areas because of biomass accumulation compared to virgin samples and followed the order polypropylene>polyethylene>nylon>polyester. The concentrations of adsorbed Pb and PFOS were 4-25% and 20-85% higher in aged MFs and varied among the polymer types. The increased contaminant adsorption was linked with the altered surface area and the hydrophobic/hydrophilic characteristics of the samples. Overall, the present study demonstrates that biofilms play a decisive role in contaminant-plastic interactions and significantly enhance the vector potential of MFs for toxic environmental contaminants. We anticipate that knowledge generated from this study will help refine the planetary risk assessment of MPs.