Glycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo... Show moreGlycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo/polysaccharides, glycoproteins and glycolipids with tremendous efficiency. Abnormal glycosidase activity is intimately associated with a variety of human diseases. Overexpression of heparanase, for example, is implicated in almost all cancers examined, and correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. Specific inhibitors of glycosidases are of great value, not only because they can serve as useful biological tools to study the catalytic machinery, mechanism and itinerary of target enzymes by crystal structure analysis of (covalent) inhibitor-enzyme complexes, but also because they may act as starting points for the development of therapeutic drugs for the treatment of glycosidase-mediated diseases. Additionally, covalent mechanism-based inhibitors have been used as scaffolds for the development of activity-based probes (ABPs) which allow profiling of glycosidases in complex biological systems. The research described in this dissertation focus on the development and biochemical evaluation of covalent inhibitors and ABPs for retaining endo- and exo-glycosidases including starch-degrading enzymes and human lysosomal β-glucocerebrosidase (GBA), as well as the synthesis of a panel of uronic acid-type 1-N-iminosugars as potential competitive heparanase inhibitors. Show less
Plants produce an astonishing variety of secondary metabolites (SMs) which are thought to play vital roles in the fitness of plants through ecological interactions. The most characteristic features... Show morePlants produce an astonishing variety of secondary metabolites (SMs) which are thought to play vital roles in the fitness of plants through ecological interactions. The most characteristic features of SMs are their striking chemical diversity and inter- or intraspecific variation. Due to the large number, high structural diversity and multifunctionality of SMs, it is still an ongoing challenge to understand how this SM diversity comes about, and why such a large diversity is maintained in nature. In this thesis this question was studied using the pyrrolizidine alkaloids (PAs) of Jacobaea species as the study system from an evolutionary and biosynthetic perspective. PA variations were studied among and within Jacobaea species, and species-specific PA profiles were observed. In order to understand how PA diversity is related to species phylogeny, the evolutionary histories and phylogenetic signals of individual PAs were investigated under the phylogenetic context of Jacobaea species and no strong phylogenetic signals were found. To shed light on the mechanisms underlying PA diversity, a gene-to-metabolite approach targeting cytochrome P450 monooxygenases which play an important role in the evolution of chemical diversity was applied to study their involvement in PA biosynthesis and PA diversity. Show less
The main purpose of this article is to reveal the effect of self-archiving on the citation impact of preprints in Information Science & Library Science (LIS). The arXiv and WoS database are... Show moreThe main purpose of this article is to reveal the effect of self-archiving on the citation impact of preprints in Information Science & Library Science (LIS). The arXiv and WoS database are used and all citations from WoS are collected to address two key questions—one is the share of papers published in the core LIS journals that also deposited in arXiv and time lags in publication process, the other is the differences in aging characteristics and citation impact of journal articles deposited in arXiv compared to those not deposited—through statistical and bibliometric analysis. The results show that the proportion of journal articles deposited in arXiv is low but there is an overall increasing trend, nearly 80% of all arXiv papers are preprints and authors are more likely to post the paper to arXiv when it is received or accepted by a journal, the preprints enjoy a boost in early citations and the citation advantage decrease with the increasing author productivity, the citations to arXiv version papers indicate an OA effect of arXiv. Show less
The Second National Enterprise Innovation Survey was conducted in China in 2017, targeting industry, construction and service sectors. This survey used to a large extent the Oslo Manual as... Show moreThe Second National Enterprise Innovation Survey was conducted in China in 2017, targeting industry, construction and service sectors. This survey used to a large extent the Oslo Manual as reference in terms of norms and standards and drew on lessons and experiences from innovation survey practices in EU countries. However, there were additional contents to it, such as, survey of entrepreneurial groups. According to the results of the 2017 survey, approximately 40% of the enterprises surveyed had innovation activity and around 8% of them achieved 4 kinds of innovation; the innovation success rate of the manufacturing industry was relatively high and the innovation activeness of large-sized enterprises was the highest; cooperative innovation was conducive to enhancing market competitiveness; insufficient cognition of innovation, relatively high costs of innovation and lack of elements for innovation were believed to be the major obstacles to corporate innovation; and finally, the outcome of implementation of innovation policies was widely approved among the entrepreneurial groups. Show less
The present study applied functional partition to investigate disyllabic lexical tonal pattern categories in an underresourced Chinese dialect, Jinan Mandarin. A two-stage partitioning procedure... Show moreThe present study applied functional partition to investigate disyllabic lexical tonal pattern categories in an underresourced Chinese dialect, Jinan Mandarin. A two-stage partitioning procedure was introduced to process a multi-speaker corpus that contains irregular lexical variants in a semi automatic way In the first stage, a program provides suggestions for the phonetician to decide the lexical tonal variants for the recordings of each word, based on the result of a functional k-means partitioning algorithm and tonal information from an available pronunciation dictionary of a related Chinese dialect, i.e. Standard Chinese. The second stage iterates a functional version of k-means partitioning with silhouette-based criteria to abstract an optimal number of tonal patterns from the whole corpus, which also allows the phoneticians to adjust the results of the automatic procedure in a controlled way and so redo partitioning for a subset of clusters.The procedure yielded eleven disyllabic tonal patterns for Jinan Mandarin, representing the tonal system used by contemporary Jinan Mandarin speakers from a wide range of age groups. The procedure used in this paper is different from previous linguistic descriptions which were based on more elderly speakers' pronunciations . This method incorporates phoneticians' linguistic knowledge and preliminary linguistic resources into the procedure of partitioning. It can improve the efficiency and objectivity in the investigation of lexical tonal pattern categories when building pronunciation dictionaries for underresourced languages. Show less
Quality of the rice grain is determined mainly by starch and protein contents of the endosperm. In this thesis, the analyses of four genes involved in the regulation of development of rice grain... Show moreQuality of the rice grain is determined mainly by starch and protein contents of the endosperm. In this thesis, the analyses of four genes involved in the regulation of development of rice grain and floret are presented. Two CCCH type zinc finger proteins, OsGZF1 and OsGZF2, were identified as novel transcription factors for GluB-1, one of the major seed-storage protein genes. Both of them exhibited negative effects on the GluB-1 promoter in transient expression assays. In a collection of rice mutants, two Tos17 transposon lines were identified showing open-staying florets and abnormal seed development. The mutant gene was identified as OsJAR1 and was shown to encode a jasmonic acid-amino acid synthetase. Next, we identified the potassium antiporter OsCHX14 as one of the downstream genes of OsJAR1. Yeast complementation assays confirmed that OsCHX14 is capable of effluxing K+ outside of cells. Its potential role in regulating of floret closure in rice was discussed. Show less
