20 research outputs found
datasheet1_AVA: A Financial Service Chatbot Based on Deep Bidirectional Transformers.pdf
We develop a chatbot using deep bidirectional transformer (BERT) models to handle client questions in financial investment customer service. The bot can recognize 381 intents, decides when to say I don’t know, and escalate escalation/uncertain questions to human operators. Our main novel contribution is the discussion about the uncertainty measure for BERT, where three different approaches are systematically compared with real problems. We investigated two uncertainty metrics, information entropy and variance of dropout sampling, in BERT, followed by mixed-integer programming to optimize decision thresholds. Another novel contribution is the usage of BERT as a language model in automatic spelling correction. Inputs with accidental spelling errors can significantly decrease intent classification performance. The proposed approach combines probabilities from masked language model and word edit distances to find the best corrections for misspelled words. The chatbot and the entire conversational AI system are developed using open-source tools and deployed within our company’s intranet. The proposed approach can be useful for industries seeking similar in-house solutions in their specific business domains. We share all our code and a sample chatbot built on a public data set on GitHub.</p
Table_1_Comparative Secretome Analysis of Mesenchymal Stem Cells From Dental Apical Papilla and Bone Marrow During Early Odonto/Osteogenic Differentiation: Potential Role of Transforming Growth Factor-β2.DOCX
To understand the functions of secretory proteins in odontogenesis and to further the understanding of the different molecular events during odontogenesis and osteogenesis, we induced the odonto/osteogenic differentiation of stem cells from dental apical papilla (SCAPs) and bone marrow–derived stem cells (BMSCs) in vitro and compared the expression of secretory proteins during early odonto/osteogenic differentiation using high-performance liquid chromatography with tandem mass spectrometry. The results revealed significant changes by at least 50% in 139 SCAP proteins and 203 BMSC proteins during differentiation. Of these, 92 were significantly upregulated and 47 were significantly downregulated during the differentiation of SCAPs. Most of these proteins showed the same trend during the differentiation of BMSCs. Among the proteins that showed significantly changes during the differentiation of SCAPs and BMSCs, we found that transforming growth factor-β2 (TGFβ2) is a key protein in the network with powerful mediation ability. TGFβ2 was secreted more by SCAPs than BMSCs, was significantly upregulated during the differentiation of SCAPs and was significantly downregulated during the differentiation of BMSCs. Furthermore, the effects of recombinant human TGFβ2 and TGFβ1 on the odonto/osteogenic differentiation of SCAPs and BMSCs were investigated. Real-time reverse transcription polymerase chain reaction (RT-PCR) and western blotting data revealed that TGFβ2 enhanced the odontogenic-related markers [dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1)] and inhibited the osteogenic-related marker bone sialoprotein (BSP) in SCAPs, whereas TGFβ1 enhanced the BSP expression and inhibited the DSPP and DMP1 expression at early odonto/osteogenic differentiation of SCAPs. However, in BMSCs, TGFβ2 enhanced the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), DSPP, and DMP1, whereas TGFβ1 enhanced the expression of ALP and RUNX2, with no significant intergroup difference of DSPP at the early odonto/osteogenic differentiation of BMSCs. TGFβ2 is a potentially important molecule with a distinct function in the regulation of odontogenesis and osteogenesis.</p
Table_3_Comparative Secretome Analysis of Mesenchymal Stem Cells From Dental Apical Papilla and Bone Marrow During Early Odonto/Osteogenic Differentiation: Potential Role of Transforming Growth Factor-β2.xls
To understand the functions of secretory proteins in odontogenesis and to further the understanding of the different molecular events during odontogenesis and osteogenesis, we induced the odonto/osteogenic differentiation of stem cells from dental apical papilla (SCAPs) and bone marrow–derived stem cells (BMSCs) in vitro and compared the expression of secretory proteins during early odonto/osteogenic differentiation using high-performance liquid chromatography with tandem mass spectrometry. The results revealed significant changes by at least 50% in 139 SCAP proteins and 203 BMSC proteins during differentiation. Of these, 92 were significantly upregulated and 47 were significantly downregulated during the differentiation of SCAPs. Most of these proteins showed the same trend during the differentiation of BMSCs. Among the proteins that showed significantly changes during the differentiation of SCAPs and BMSCs, we found that transforming growth factor-β2 (TGFβ2) is a key protein in the network with powerful mediation ability. TGFβ2 was secreted more by SCAPs than BMSCs, was significantly upregulated during the differentiation of SCAPs and was significantly downregulated during the differentiation of BMSCs. Furthermore, the effects of recombinant human TGFβ2 and TGFβ1 on the odonto/osteogenic differentiation of SCAPs and BMSCs were investigated. Real-time reverse transcription polymerase chain reaction (RT-PCR) and western blotting data revealed that TGFβ2 enhanced the odontogenic-related markers [dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1)] and inhibited the osteogenic-related marker bone sialoprotein (BSP) in SCAPs, whereas TGFβ1 enhanced the BSP expression and inhibited the DSPP and DMP1 expression at early odonto/osteogenic differentiation of SCAPs. However, in BMSCs, TGFβ2 enhanced the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), DSPP, and DMP1, whereas TGFβ1 enhanced the expression of ALP and RUNX2, with no significant intergroup difference of DSPP at the early odonto/osteogenic differentiation of BMSCs. TGFβ2 is a potentially important molecule with a distinct function in the regulation of odontogenesis and osteogenesis.</p
Exploring Different Patterns of Love Attitudes among Chinese College Students
<div><p>Individual differences in love attitudes and the relationship between love attitudes and other variables in Asian culture lack in-depth exploration. This study conducted cluster analysis with data regarding love attitudes obtained from 389 college students in mainland China. The result of cluster analysis based on love-attitude scales distinguished four types of students: game players, rational lovers, emotional lovers, and absence lovers. These four groups of students showed significant differences in sexual attitudes and personality traits of deliberation and dutifulness but not self-discipline. The study’s implications for future studies on love attitudes in certain cultural groups were also discussed.</p></div
Table_2_Comparative Secretome Analysis of Mesenchymal Stem Cells From Dental Apical Papilla and Bone Marrow During Early Odonto/Osteogenic Differentiation: Potential Role of Transforming Growth Factor-β2.xls
To understand the functions of secretory proteins in odontogenesis and to further the understanding of the different molecular events during odontogenesis and osteogenesis, we induced the odonto/osteogenic differentiation of stem cells from dental apical papilla (SCAPs) and bone marrow–derived stem cells (BMSCs) in vitro and compared the expression of secretory proteins during early odonto/osteogenic differentiation using high-performance liquid chromatography with tandem mass spectrometry. The results revealed significant changes by at least 50% in 139 SCAP proteins and 203 BMSC proteins during differentiation. Of these, 92 were significantly upregulated and 47 were significantly downregulated during the differentiation of SCAPs. Most of these proteins showed the same trend during the differentiation of BMSCs. Among the proteins that showed significantly changes during the differentiation of SCAPs and BMSCs, we found that transforming growth factor-β2 (TGFβ2) is a key protein in the network with powerful mediation ability. TGFβ2 was secreted more by SCAPs than BMSCs, was significantly upregulated during the differentiation of SCAPs and was significantly downregulated during the differentiation of BMSCs. Furthermore, the effects of recombinant human TGFβ2 and TGFβ1 on the odonto/osteogenic differentiation of SCAPs and BMSCs were investigated. Real-time reverse transcription polymerase chain reaction (RT-PCR) and western blotting data revealed that TGFβ2 enhanced the odontogenic-related markers [dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1)] and inhibited the osteogenic-related marker bone sialoprotein (BSP) in SCAPs, whereas TGFβ1 enhanced the BSP expression and inhibited the DSPP and DMP1 expression at early odonto/osteogenic differentiation of SCAPs. However, in BMSCs, TGFβ2 enhanced the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), DSPP, and DMP1, whereas TGFβ1 enhanced the expression of ALP and RUNX2, with no significant intergroup difference of DSPP at the early odonto/osteogenic differentiation of BMSCs. TGFβ2 is a potentially important molecule with a distinct function in the regulation of odontogenesis and osteogenesis.</p
Additional file 1 of Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis
Additional file 1: Fig. S1 a Schematic diagram of neutrophil isolation from the peripheral blood of mice. b Neutrophils were identified by using Giemsa staining. Fig. S2 a-c Comparison of protein concentration (a), cell membrane vesicle number (b) and average diameter (c) for three methods for separating neutrophil membrane vesicles. d The adhesion molecule LFA-1 on the neutrophils and neutrophil membrane vesicles were detected by western blot. Fig. S3 The polydispersity index (PDI) of NM@f127 and R4F-NM@F127. Fig. S4 Confocal imaging of the ability of DiR-BOA-labeled R4F-NM@F127 to target RAW264.7 cells at 37 °C or 4 °C in vitro. Fig. S5 Quantitative analysis of the radiant efficiency in organs. Fig. S6 a Ex vivo imaging of the serum at 24 h after intravenous injection. b Quantitative analysis of the radiant efficiency with DiR-BOA-loaded R4F-NM@F127, NM@F127, F127 and free DiR-BOA in serum. Fig. S7 a Average size of NM@F127-Cel and R4F-NM@F127-Cel. b Zeta potential of NM@F127-Cel and R4F-NM@F127-Cel. Fig. S8 White light image and UV-Vis absorption spectrum of R4F-NM@F127, free Cel and R4F-NM@F127-Cel. Fig. S9 RT-qPCR analysis of mRNA expression of M1 and M2 macrophage markers in LPS-induced RAW264.7 cells after different treatments. Fig. S10 Quantitative analysis of iNOS and Arg-1 protein levels in LPS-induced RAW264.7 cells after different treatments. Fig. S11 Quantitative analysis the protein levels of p65 in the nucleus and cytoplasm in LPS-induced RAW264.7 cells after different treatments. Fig. S12 The dates of clinical scores (a), and ankle diameter (mm) of the left hind paw (b) and the right hind paw (c) of mice were counted on days 45. Fig. S13 Representative ankle histopathology pictures of H&E staining and S&O staining. Fig. S14 H&E staining of heart, liver, spleen, lung, kidney and brain extracted at 45st day after the first immunization. Fig. S15 Levels of ALT (a) and AST (b) in serum. Table S1. Primer sequences for the amplification
DataSheet_1_Priming Is Dispensable for NLRP3 Inflammasome Activation in Human Monocytes In Vitro.pdf
Interleukin (IL)-18 and IL-1β are potent pro-inflammatory cytokines that contribute to inflammatory conditions such as rheumatoid arthritis and Alzheimer’s disease. They are produced as inactive precursors that are activated by large macromolecular complexes called inflammasomes upon sensing damage or pathogenic signals. NLRP3 inflammasome activation is regarded to require a priming step that causes NLRP3 and IL-1β gene upregulation, and also NLRP3 post-translational licencing. A subsequent activation step leads to the assembly of the complex and the cleavage of pro-IL-18 and pro-IL-1β by caspase-1 into their mature forms, allowing their release. Here we show that human monocytes, but not monocyte derived macrophages, are able to form canonical NLRP3 inflammasomes in the absence of priming. NLRP3 activator nigericin caused the processing and release of constitutively expressed IL-18 in an unprimed setting. This was mediated by the canonical NLRP3 inflammasome that was dependent on K+ and Cl− efflux and led to ASC oligomerization, caspase-1 and Gasdermin-D (GSDMD) cleavage. IL-18 release was impaired by the NLRP3 inhibitor MCC950 and by the absence of NLRP3, but also by deficiency of GSDMD, suggesting that pyroptosis is the mechanism of release. This work highlights the readiness of the NLRP3 inflammasome to assemble in the absence of priming in human monocytes and hence contribute to the very early stages of the inflammatory response when IL-1β has not yet been produced. It is important to consider the unprimed setting when researching the mechanisms of NLRP3 activation, as to not overshadow the pathways that occur in the absence of priming stimuli, which might only enhance this response.</p
CB6-induced SARS-CoV-2 cell-cell transmission in Vero E6-TMPRSS2 cells.
(A) Immunofluorescent images showing morphology of 2 MOI SARS-CoV-2 infected Vero E6-TMPRSS2 cells, without or with 1 μg/mL Anti-ACE2 blocking antibody, treated without or with 12.5 nM CB6 antibody 48 hours post infection (hpi). Anti-SARS-CoV-2 N and Anti-human IgG (H+L chains) were stained with Alexa fluor 488 and 555 respectively. Scale bars are indicative of 50 μm; (B) Immunoblots of SARS-CoV-2 full-length S, S2, S2’ and N, collected from Vero E6-TMPRSS2 lysates described in (A), blots are representative of two individual repeats. (TIF)</p
Protease-induced cleavage at S1/S2 bridge site promotes antibody evasion.
(A) Amino acid sequence alignment of the SARS-CoV-2 WT, R685A and ΔRRAR spike mutants at S1/S2 cleavage site. Polybasic and trypsin-cleavable arginine residues are labeled in bold; (B) Immunoblots showing full-length spike and S1, collected from supernatant and lysate fractions of HEK293T cells expressing WT, R685A and ΔRRAR spike mutants treated without or with 5 μg/mL TPCK-trypsin for 6 hours. Blots are representative of two independent experiments; (C) Luciferase activity (RLU) measured from HEK293T cells co-expressing Cre and R685A spike mutants, stimulated with 12.5 nM CB6 without or with 1 μg/mL TPCK-trypsin for 16 hours (top); and immunoblots showing shedded S1 subunits, hIgG Hc and full-length spike, S1, S2 and cleaved S2’ collected from co-cultured cell supernatants and lysates (bottom). Data and blots are representative of four independent experiments; (D) Luciferase activity (RLU) measured from HEK293T cells co-expressing Cre with R685A spike mutant, pretreated with 100 nM CB6 for 1 hour in the absence (Red bars) or presence (Gray bars) of 1 μg/mL trypsin, then co-cultured with Stop-Luc-expressing cells carrying control or ACE2 for further 6 hours (top); and immunoblots showing shedded S1 subunits, human hIgG Hc and full-length spike, S1, S2, S2’and ACE2 collected from co-cultured cell supernatants and lysates (bottom). Data are representative of nine individual repeats, blots are representative of six independent experiments; (E) Luciferase activity (RLU) measured from HEK293T cells co-expressing Cre with ΔRRAR spike mutant, pretreated with 100 nM CB6 for 1 hour in the absence (Blue bars) or presence (Gray bars) of 1 μg/mL trypsin, then co-cultured with Stop-Luc-expressing cells carrying control or ACE2 for further 6 hours (top); and immunoblots showing shedded S1 subunits, human hIgG Hc and full-length spike, S1, S2, S2’and ACE2 collected from co-cultured cell supernatants and lysates (bottom). Data are representative of six individual repeats, blots are representative of two independent experiments. P values were obtained by one-way ANOVA with Sidak’s post hoc test and are indicated on the figure.</p
