DNA-encoded library (DEL) technology is a powerful tool for small molecule identification in drug discovery, yet the reported DEL selection strategies were applied primarily on protein targets in either purified form or in cellular context. To expand the application of this technology, we employed DEL selection on an RNA target HIV-1 TAR (trans-acting responsive region), but found that the majority of signals were resulted from false positive DNA–RNA binding. We thus developed an optimized selection strategy utilizing RNA patches and competitive elution to minimize unwanted DNA binding, followed by k-mer analysis and motif search to differentiate false positive signal. This optimized strategy resulted in a very clean background in a DEL selection against Escherichia coli FMN Riboswitch, and the enriched compounds were determined with double digit nanomolar binding affinity, as well as similar potency in functional FMN competition assay. These results demonstrated the feasibility of small molecule identification against RNA targets using DEL selection. The developed experimental and computational strategy provided a promising opportunity for RNA ligand screening and expanded the application of DEL selection to a much wider context in drug discovery.
Previous user experience research emphasizes meaning in interaction design beyond conventional interactive gestures. However, existing exemplars that successfully reify abstract meanings through interactions are usually case-specific, and it is currently unclear how to systematically create or extend meanings for general gesture-based interactions. We present Metaphoraction, a creativity support tool that formulates design ideas for gesture-based interactions to show metaphorical meanings with four interconnected components: gesture , action , object , and meaning . To represent the interaction design ideas with these four components, Metaphoraction links interactive gestures to actions based on the similarity of appearances, movements, and experiences; relates actions to objects by applying the immediate association; bridges objects and meanings by leveraging the metaphor TARGET-SOURCE mappings. We build a dataset containing 588,770 unique design idea candidates through surveying related research and conducting two crowdsourced studies to support meaningful gesture-based interaction design ideation. Five design experts validate that Metaphoraction can effectively support creativity and productivity during the ideation process. The paper concludes by presenting insights into meaningful gesture-based interaction design and discussing potential future uses of the tool.
Wheat is a very important food crop for mankind. Many new varieties are bred every year. The accurate judgment of wheat varieties can promote the development of the wheat industry and the protection of breeding property rights. Although gene analysis technology can be used to accurately determine wheat varieties, it is costly, time-consuming, and inconvenient. Traditional machine learning methods can significantly reduce the cost and time of wheat cultivars identification, but the accuracy is not high. In recent years, the relatively popular deep learning methods have further improved the accuracy on the basis of traditional machine learning, whereas it is quite difficult to continue to improve the identification accuracy after the convergence of the deep learning model. Based on the ResNet and SENet models, this paper draws on the idea of the bagging-based ensemble estimator algorithm, and proposes a deep learning model for wheat classification, CMPNet, which is coupled with the tillering period, flowering period, and seed image. This convolutional neural network (CNN) model has a symmetrical structure along the direction of the tensor flow. The model uses collected images of different types of wheat in multiple growth periods. First, it uses the transfer learning method of the ResNet-50, SE-ResNet, and SE-ResNeXt models, and then trains the collected images of 30 kinds of wheat in different growth periods. It then uses the concat layer to connect the output layers of the three models, and finally obtains the wheat classification results through the softmax function. The accuracy of wheat variety identification increased from 92.07% at the seed stage, 95.16% at the tillering stage, and 97.38% at the flowering stage to 99.51%. The model’s single inference time was only 0.0212 s. The model not only significantly improves the classification accuracy of wheat varieties, but also achieves low cost and high efficiency, which makes it a novel and important technology reference for wheat producers, managers, and law enforcement supervisors in the practice of wheat production.
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