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The immunogenicity of the pertussis vaccine can be significantly improved by adding Bordetella pertussis oligosaccharide with multiple trisaccharide units. The more trisaccharide units there are, the better the efficiency of the immune response induction. However, natural B. pertussis oligosaccharides usually contain only a single terminal trisaccharide unit. In addition, B. pertussis is pathogenic, and there are potential safety hazards when preparing oligosaccharides from B. pertussis. In this study, Escherichia coli MG1655 was engineered to produce B. pertussis oligosaccharides containing multiple trisaccharide units. Fifty-nine genes relevant to the biosynthesis of the O-antigen and core oligosaccharide of lipopolysaccharide, enterobacterial common antigen, and colanic acid were deleted in MG1655, resulting in strain MDCO020. Then, 25 genes relevant to the biosynthesis of the oligosaccharide antigen in B. pertussis and 3 genes relevant to the repeating trisaccharide unit in Pseudomonas aeruginosa PAO1 were overexpressed in MDCO020, resulting in the recombinant E. coli MDCO020/pWpBpD5. The production of B. pertussis oligosaccharide with multiple trisaccharide units by MDCO020/pWpBpD5 was confirmed by SDS-PAGE and 1H NMR analyses, and its immune response-stimulating activity was confirmed by using rabbit anti-pertussis serum.

Background FAM64A has been found to promote tumor cell proliferation in various tumors. However, the regulatory mechanism and clinical significance of FAM64A in gliomas still remain unclear. Methods FAM64A expression in gliomas with different grades was determined by TCGA database mining and immunoblotting assay. FAM64A silenced U87 cells were constructed with shRNA, and cell proliferation, migration, and cell cycle and were detected by CCK8 assay, scratch assay, and flow cytometry respectively. Intercellular crosstalk analysis and transcription factor prediction were performed to query the potential regulatory mechanisms. TGF-b and its downstream transcription factors were detected in glioma samples with different grades to validate the regulatory roles of TGF-b signaling. Results FAM64A was highly expressed in glioblastoma and associated with a poor prognosis. FAM64A silenced U87 cell lines displayed disrupted proliferation and migration ability. More cells would be stuck in the S phase. Expression profiles at the single-cell resolution further indicated that FAM64A could play a role in a cell-cycle-dependent way to promote the proliferation of glioma cells. FAM64A expression could be induced by TGF-β signal. And colocalization of SMAD4 and FAM64A could be observed in high-grade glioma tissues. Conclusions FAM64A could serve as a malignant biomarker in gliomas, and it could be induced via TGF-β pathway activation., which could explain the crosstalk between glioma cells and also the microenvironment.

Salt stress is one of the most severe adverse environments in rice production; increasing salinization is seriously endangering rice production around the world. In this study, a rice backcross inbred line (BIL) population derived from the cross of 9311 and wild rice Oryza longistaminata was employed to identify the favorable genetic loci of O. longistaminata for salt tolerance. A total of 27 quantitative trait loci (QTLs) related to salt tolerance were identified in 140 rice BILs, and 17 QTLs formed seven QTL clusters on different chromosomes, of which 18 QTLs were derived from O. longistaminata, and a QTL for salt injury score (SIS), water content of seedlings (WCS) under salt treatment, and relative water content of seedlings (RWCS) was repeatedly detected and colocalized at the same site on chromosome 2, and a cytochrome P450 86B1 (MH02t0466900) was suggested as the potential candidate gene responsible for the salt tolerance based on sequence and expression analysis. These findings laid the foundation for further improving rice salt tolerance through molecular breeding in the future.

Background: Despite increased early diagnosis and improved treatment in breast cancer (BRCA) patients, prognosis prediction is still a challenging task due to the disease heterogeneity. This study was to identify a novel gene signature that can accurately evaluate BRCA patient survival. Methods: The gene expression and clinical data of BRCA patients were collected from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of BRCA International Consortium (METABRIC) databases. Genes associated with prognosis were determined by Kaplan–Meier survival analysis and multivariate Cox regression analysis. A prognostic 16-gene score was established with linear combination of 16 genes. The prognostic value of the signature was validated in the METABRIC dataset. Gene expression analysis was performed to investigate the diagnostic values of 16 genes. Results: The 16-gene score was associated with shortened overall survival in BRCA patients independently of clinicopathological characteristics. The signalling pathways of cell cycle, oocyte meiosis, RNA degradation, progesterone mediated oocyte maturation and DNA replication were the top five most enriched pathways in the high 16-gene score group. The 16-gene nomogram incorporating the survival‐related clinical factors showed improved prediction accuracies for 1-year, 3-year and 5‐year survival (area under curve [AUC] = 0.91, 0.79 and 0.77 respectively). MORN3, IGJ, DERL1 exhibited high accuracy in differentiating BRCA tissues from normal breast tissues (AUC > 0.80 for all cases). Conclusions: The 16-gene profile provides novel insights into the identification of BRCA with a high risk of death, which eventually guides treatment decision making.

BackgroundRice is the staple food feeding for more than half of the world's population. Breeding rice with high yield, superior quality and strong resistance is the goal of breeding to meet the needs of rapidly increased population. However, it is hard to achieve the aggregation of multiple complex traits based on traditional breeding methods. ResultsHere, we report the successful development of elite rice with high yield, superior quality and strong resistance to brown planthopper (BPH) by rational molecular design. According to the function of Gn8.1, APO1, Ghd7, Ghd8 and Gn1a for large panicle, Bph6 and Bph9 for brown planthopper, GW7, GS3 and qSW5 for grain appearance quality, and Wx, ALK, SBE3, SSIV2 and SSIII for cooking and eating quality of rice, we staked all of the favorable genes together by crossing five donor lines one another. There are obvious phenotypic differences between different groups of the favorable genes. After careful screening of genotype, phenotype and genetic background, three molecular design lines were bred. The newly bred line exhibited higher yield potential, better grain quality and stronger BPH-resistance than their parents. Conclusions The successful creation of elite rice with high yield, superior quality and strong resistance to BPH demonstrate that molecular design at the basis of characterized genes is an effective and powerful strategy to improve multiple complex traits, it will provide a reference for the future commercial rice improvement.

Breeding rice (Oryza sativa L.) with high yield, superior quality, desired grain shape and high resistance is the goal of breeding to meet the needs of current consumers. It is usually hard to combine multiple complex traits based on traditional breeding methods because they are frequently antagonistic to each other. However, molecular design breeding, as a novel breeding method, is an optional alternative to this challenge. To demonstrate molecular design breeding, 15 favorable genes from five parent lines were pyramided together to develop elite rice with high-yield, superior-quality, desired grain shape and high resistance to brown planthopper (BPH). The parental lines were 9311, the recurrent parent, carrying APO1, Ghd7, Ghd8 and Gn1a for high yield, GS3 and qSW5 for grain shape, and Wx and ALK for eating and cooking quality; 1880 with Gn8.1 for large panicles; Luo-Yu-Xiang carrying GW7 for grain shape and SBE3, SSIV2 and SSIII for eating and cooking quality; Luoyang6 with Bph6 and Luoyang9 with Bph9 for BPH resistance. After careful screening for the 15 targeted genes, desired phenotype and maximum genetic background from 9311, three molecular design lines with desired phenotypes, named as MD1 (Molecular design 1), MD2 and MD3 were developed. MD3 carried all 15 targeted genes, and MD1 and MD2 had 14 of the 15 targeted genes. Only SBE3 was not introgressed into MD1 and MD2 but this had minimal impact on the gel consistency and alkali spreading value. These newly bred lines exhibited higher yield potential, better grain quality with slender grains, low amylose content, high gel consistency and alkali spreading value, and higher BPH resistance compared to the parent 9311. In this study, we successfully created three novel rice lines with high yield, superior quality and improved BPH resistance by rational molecular design. Our results demonstrate molecular design is a powerful strategy to improve multiple complex traits and will provide a reference for the future commercial rice improvement.

In decades of hybrid rice breeding, the combining ability has been successfully used to evaluate excellent parental lines and predict heterosis. However, previous studies for the combining ability mainly focused on cultivated rice and rarely involved wild rice. In this study, for the first time, we identified 20 new quantitative trait loci (QTLs) for the combining ability in wild rice using a North Carolina II mating design. Among them, qGCA1, one of the major QTLs that can significantly improve the general combining ability of the plant height, spikelet number, and yield per plant, was delimited to an interval of about 72 kb on chromosome 1. qSCA8, another major QTL, which can significantly improve the specific combining ability of the seed-setting rate and yield per plant, was located in an interval of about 90 kb on chromosome 8. These QTLs discovered from wild rice will provide new ideas to explain the genetic mechanism of the combining ability and establish the basis for breeding of high-combining-ability rice.

Plant-specific GROWTH-REGULATING FACTORs (GRFs) participate in central developmental processes, including leaf and root development; inflorescence, flower, and seed formation; senescence; and tolerance to stresses. In rice (Oryza sativa), there are 12 GRFs, but the role of the miR396-OsGRF7 regulatory module remains unknown. Here, we report that OsGRF7 shapes plant architecture via the regulation of auxin and GA metabolism in rice. OsGRF7 is mainly expressed in lamina joints, nodes, internodes, axillary buds, and young inflorescences. Overexpression of OsGRF7 causes a semidwarf and compact plant architecture with an increased culm wall thickness and narrowed leaf angles mediated by shortened cell length, altered cell arrangement, and increased parenchymal cell layers in the culm and adaxial side of the lamina joints. Knockout and knockdown lines of OsGRF7 exhibit contrasting phenotypes with severe degradation of parenchymal cells in the culm and lamina joints at maturity. Further analysis indicated that OsGRF7 binds the ACRGDA motif in the promoters of a cytochrome P450 gene and AUXIN RESPONSE FACTOR12, which are involved in the GA synthesis and auxin signaling pathways, respectively. Correspondingly, OsGRF7 alters the contents of endogenous GAs and auxins and sensitivity to exogenous phytohormones. These findings establish OsGRF7 as a crucial component in the OsmiR396-OsGRF-plant hormone regulatory network that controls rice plant architecture.

Rice false smut (RFS), caused by Ustilaginoidea virens, is one of the most destructive grain diseases in rice production worldwide. Hence, to increase the ability of rice resistance to U. virens is a major breeding goal of rice breeders. However, it is difficult to evaluate rice resistance to U. virens. Hence, to clarify the RFS-resistance genetic mechanism is of great significance. In this study, a diversity panel landrace comprising of 315 accessions was identified for resistance against U. virens at reproductive stage in 2017 and 2018. Totally, 58 significant SNPs were distributed on the rice whole genome except chromosome 7, and 3 SNPs associated with three RFS-related traits were identified in 2 years. Haplotype block structure analysis predicted that a total of 15 candidate genes for U. virens resistance were screened based on significant SNPs with minimum P value (− log10P = 13.86). Of which, LOC_Os01g15580, a plant NBS-LRR protein coding gene near the significant SNP chr01_8738751 (12.3 kb), was considered a candidate for key resistance factor in the disease. These findings might provide a new insight into the genetic basis of resistance to rice false smut.

Missing attribute values are prevalent in real relational data, especially the data extracted from the Web. Their accurate imputation is important for ensuring high quality of data analytics. Even though many techniques have been proposed for this task, none of them provides a flexible mechanism for quality control. The lack of quality guarantee may result in many missing data being filled with wrong values, which can easily result in biased data analysis. In this paper, we first propose a novel probabilistic framework based on the concept of Generalized Feature Dependency (GFD). By exploiting the monotonicity between imputation precision and match probability, it enables a flexible mechanism for quality control. We then present the imputation model with precision guarantee and the techniques to maximize recall while meeting a user-specified precision requirement. Finally, we evaluate the performance of the proposed approach on real data. Our extensive experiments show that it has performance advantage over the state-of-the-art alternatives and most importantly, its quality control mechanism is effective.

In relational data, identifying the distinct attribute values that refer to the same real-world entities is an essential task for many data cleaning and mining applications (e.g., duplicate record detection and functional dependency mining). The state-of-the-art approaches for attribute value matching are mainly based on string similarity among attribute values. However, these approaches may not perform well in the cases where the specified string similarity metric is not a reliable indicator for attribute value equivalence. To alleviate such limitations, we propose a new framework for attribute value matching in relational data. Firstly, we propose a novel probabilistic approach to reason about attribute value equivalence by value correlation analysis. We also propose effective methods for probabilistic equivalence reasoning with multiple attributes. Next, we present a unified framework, which incorporates both string similarity measurement and value correlation analysis by evidential reasoning. Finally, we demonstrate the effectiveness of our framework empirically on real-world datasets. Through extensive experiments, we show that our framework outperforms the string-based approaches by considerable margins on matching accuracy and achieves the desired efficiency.

Plant fertility and resistance to stress environments are antagonistic to each other. At booting stage, fertility is often sacrificed for survive in rice under abiotic stress. However, the relationship between fertility and resistance at molecular level remains elusive. Here, we identified a transcription factor, OsAlfin like 5, which regulates the OsTMS5 and links both the drought stress response and thermosensitive genic male sterility. The OsAL5 overexpression plants (OE-OsAL5) became sensitive to temperature owning to the OsTMS5 that the OE-OsAL5 plants were fertile under low temperature (23 °C) and sterile under high temperature (28 °C). Significantly, the survival rate of OE-OsAL5 lines was higher than that of the wide-type (WT) under drought stress. Further experiments confirmed that the OsAL5 regulated both of the OsTMS5 and the down-stream drought-related genes by binding to the ‘GTGGAG’ element in vivo, revealing that the OsAL5 participated both in the drought stress response and thermosensitive genic male sterility in rice. These findings open up the possibility of breeding elite TGMS lines with strong drought tolerance by manipulating the expression of OsAL5.

A molecular marker is a valuable tool in genetic research. Insertions–deletions (InDels) are commonly used polymorphisms in gene mapping, analysing genetic diversity, marker-assisted breeding, and phylogenetics. The 3000 Rice Genome Project, a re-sequencing project, discovered millions of genome-wide InDels. We found that the proportion of &gt, 50-bp long InDels (699,475) of the total (1,248,503) is 56.02%. The number of InDels on each chromosome was consistent with the corresponding chromosome length. The maximum InDels were on chromosome 1 (78,935), and the minimum InDels were on chromosome 9 (41,752), with an average density of 1.87 InDels/kb (range: 1.50–2.36 InDels/kb). Furthermore, 96 InDels of about 3.98 Mb/InDel were selected to detect the polymorphism. The results exhibited ideal performance in 2% agarose gel electrophoresis. Phylogenetic analysis exhibited that InDel markers had excellent polymorphisms between rice varieties of japonica and indica, and varieties could be classified based on the statistical results of their polymorphisms. The InDel markers could be applied to identify the recombinant inbred lines in a population. These results reveal that the high-density long InDel markers could help us examine the functional diversity, species variation, and map-based cloning.

In decades of hybrid rice breeding, the combining ability has been successfully used to evaluate excellent parental lines and predict heterosis. However, previous studies for the combining ability mainly focused on cultivated rice and rarely involved wild rice. In this study, for the first time, we identified 20 new quantitative trait loci (QTLs) for the combining ability in wild rice using a North Carolina II mating design. Among them

In a typical GPGPU, the on-chip storage is critical to the massive parallelism and is desired to be large. However, the fast increasing size of the on-chip storage based on traditional SRAM cells, such as register file (RF), shared memory and first level data (L1D) cache, makes the area cost and energy consumption unsustainable for future GPGPUs. In this paper, we first propose to use the embedded-DRAM (eDRAM) as an alternative for the on-chip storage. Compared to the conventional SRAM, eDRAM enables higher density and lower leakage power, but suffers from limited data retention time. Periodic refresh operation is a viable approach to maintain data integrity but aggravates the performance and energy consumption with the scaling of eDRAM cells into deep sub-micron technology nodes. To recover the performance loss, we exploit the features in the GPGPU architecture and propose various novel refresh schemes to mitigate the refresh penalty. To improve the energy efficiency, we apply lightweight compiler techniques and runtime monitoring for selective refreshing that intelligently eliminate the unnecessary refreshes. The evaluation on our proposed refresh schemes demonstrates that, comparing to the conventional SRAM-based designs, our eDRAM-based on-chip storage exhibits comparable performance but less energy consumption and smaller silicon area, enabling the sustainable on-chip storage scaling for even higher parallelism in future GPGPUs.

Even though many machine algorithms have been proposed for entity resolution, it remains very challenging to find a solution with quality guarantees. In this paper, we propose a novel HUman and Machine cOoperation (HUMO) framework for entity resolution (ER), which divides an ER workload between the machine and the human. HUMO enables a mechanism for quality control that can flexibly enforce both precision and recall levels. We introduce the optimization problem of HUMO, minimizing human cost given a quality requirement, and then present three optimization approaches: a conservative baseline one purely based on the monotonicity assumption of precision, a more aggressive one based on sampling and a hybrid one that can take advantage of the strengths of both previous approaches. Finally, we demonstrate by extensive experiments on real and synthetic datasets that HUMO can achieve high-quality results with reasonable return on investment (ROI) in terms of human cost, and it performs considerably better than the state-of-the-art alternatives in quality control., Comment: 12 pages, 11 figures. Camera-ready version of the paper submitted to ICDE 2018, In Proceedings of the 34th IEEE International Conference on Data Engineering (ICDE 2018)

We present POOLSIDE, an online PrObabilistic knOwLedge base for ShoppIng DEcision support, that provides with the on-target recommendation service based on explicit user requirement. With a natural language interface, POOLSIDE can answer question in real-time. We present how to construct the knowledge base and how to enable real-time response in POOLSIDE. Finally, we demonstrate that Poolside can give high-quality product recommendations with high efficiency.(The demo video can be accessed via the link:https://www.youtube.com/watch?v=D8ALi11CUcc)

In relational data, identifying the distinct attribute values that refer to the same real-world entities is an essential task for many data cleaning and mining applications (e.g., duplicate record detection and functional dependency mining). Existing approaches for attribute value matching include string-based approaches and rule-based approaches. However, the effectiveness of string similarity based approaches may severely rely on the choice of string similarity metric, proper threshold and even domain knowledge, while rule-based approaches suffer from the neighbour sparsity problem. To address such limitations, a cohesion-based metric is proposed to improve the matching performance between distinct attribute values. Additionally both string similarity and cohesion-based measurement are combined into a unified ranking by an evidential reasoning approach. Experimental evaluations show that our approach can improve the performance of matching attribute values greatly.

To fabricate molecularly imprinted polymer nanospheres via click reaction, five different clickable compounds were synthesized and two types of click reactions (azide-alkyne and thiol-yne) were explored. It was found that molecularly imprinted polymer nanospheres could be successfully synthesized via thiol-yne click reaction using 3,5-diethynyl-pyridine (1) as the monomer, tris(3-mercaptopropionate) (tri-thiol, 5) as the crosslinker, and hypericin as the template (MIP–NSHs). The click polymerization completed in merely 4 h to produce the desired MIP–NSHs, which were characterized by FTIR, SEM, DLS, and BET, respectively. The reaction conditions for adsorption capacity and selectivity towards hypericin were optimized, and the MIP–NSHs synthesized under the optimized conditions showed a high adsorption capacity (Q = 6.03 μmol•g−1) towards hypericin. The imprinting factors of MIP–NSHs towards hypericin, protohypericin, and emodin were 2.44, 2.88, and 2.10, respectively.

Hybrid rice has contributed significantly to the world food security. Breeding of elite high-yield, strong-resistant broad-spectrum restorer line is an important strategy for hybrid rice in commercial breeding programs. Here, we developed three elite brown planthopper (BPH)-resistant wide-spectrum restorer lines by pyramiding big-panicle gene Gn8.1, BPH-resistant genes Bph6 and Bph9, fertility restorer genes Rf3, Rf4, Rf5, and Rf6 through molecular marker assisted selection. Resistance analysis revealed that the newly developed restorer lines showed stronger BPH-resistance than any of the single-gene donor parent Luoyang-6 and Luoyang-9. Moreover, the three new restorer lines had broad spectrum recovery capabilities for Honglian CMS, Wild abortive CMS and two-line GMS sterile lines, and higher grain yields than that of the recurrent parent 9,311 under nature field conditions. Importantly, the hybrid crosses also showed good performance for grain yield and BPH-resistance. Thus, the development of elite BPH-resistant wide-spectrum restorer lines has a promising future for breeding of broad spectrum BPH-resistant high-yield varieties.