Engineering Kinases to Phosphorylate Nucleoside Analogs for Antiviral and Cancer Therapy

Enzyme engineering by directed evolution presents a powerful strategy for tailoring the function and physicochemical properties of biocatalysts to therapeutic and industrial applications. Our laboratory's research focuses on developing novel molecular tools for protein engineering, as well as on utilizing these methods to customize enzymes and to study fundamental aspects of their structure and function. Specifically, we are interested in nucleoside and nucleotide kinases which are responsible for the intracellular phosphorylation of nucleoside analog (NA) prodrugs to their biologically active triphosphates. The high substrate specificity of the cellular kinases often interferes with prodrug activation and consequently lowers the potency of NAs as antiviral and cancer therapeutics. A working solution to the problem is the co-adminstration of a promiscuous kinase from viruses, bacteria, and other mammals. However, further therapeutic enhancements of NAs depend on the selective and efficient prodrug phosphorylation. In the absence of true NA kinases in nature, we are pursuing laboratory evolution strategies to generate efficient phosphoryl-transfer catalysts. This review summarizes some of our recent work in the field and outlines future challenges

Microsatellites within genes and ESTs of the Pacific oyster Crassostrea gigas and their transferability in five other Crassostrea species

We developed 15 novel polymorphic microsatellites for the Pacific oyster Crassostrea gigas by screening genes and expressed sequence tags (ESTs) found in GenBank. The number of alleles per locus ranged from two to 24 with an average of 8.7, and the values of observed heterozygosity (Ho) and expected heterozygosity (He) ranged from 0.026 to 0.750 and from 0.120 to 0.947, respectively. No significant pairwise linkage disequilibrium was detected among loci and eight loci conformed to Hardy-Weinberg equilibrium. Transferability of the markers was examined on five other Crassostrea species and all the markers were amplified successfully in at least one species. These new microsatellites should be useful for population genetics, parentage analysis and genome mapping studies of C. gigas and closely related species. The nine markers identified from known genes are expected to be especially valuable for comparative mapping as type I markers

Study on the Formalized Development of the Street Stall Economybased on Domestic and International Experiences and Perspectives

The ground-floor economy has a long history as a significant part of the informal economy. Due to the dependence on its own social status and relationship to the government’s political and economic objectives, it has developed precariously in recent years. In the face of post-epidemic problems, a shortcut is to learn from international experience. This paper used the structural theory and drew from the secondary data, demonstrating the background of informal economy and exploring the rational ways to maintain and develop street vending. Spatialization, legalization and network digitization are proven international approaches, which display the empirical and theoretical implications to urban practice and studies

Sen2Pro: A Probabilistic Perspective to Sentence Embedding from Pre-trained Language Model

Sentence embedding is one of the most fundamental tasks in Natural Language Processing and plays an important role in various tasks. The recent breakthrough in sentence embedding is achieved by pre-trained language models (PLMs). Despite its success, an embedded vector (Sen2Vec) representing a point estimate does not naturally express uncertainty in a taskagnostic way. This paper thereby proposes an efficient framework on probabilistic sentence embedding (Sen2Pro) from PLMs, and it represents a sentence as a probability density distribution in an embedding space to reflect both model uncertainty and data uncertainty (i.e., many-to-one nature) in the sentence representation. The proposed framework performs in a plug-and-play way without retraining PLMs anymore, and it is easy to implement and generally applied on top of any PLM. The superiority of Sen2Pro over Sen2Vec has been theoretically verified and practically illustrated on different NLP tasks.Comment: Accepted to ACL2023 workshop Rep4NL

A novel machine-vision-based facility for the automatic evaluation of yield-related traits in rice

The evaluation of yield-related traits is an essential step in rice breeding, genetic research and functional genomics research. A new, automatic, and labor-free facility to automatically thresh rice panicles, evaluate rice yield traits, and subsequently pack filled spikelets is presented in this paper. Tests showed that the facility was capable of evaluating yield-related traits with a mean absolute percentage error of less than 5% and an efficiency of 1440 plants per continuous 24 h workday