Physics Constrained Flow Neural Network for Short-Timescale Predictions in Data Communications Networks

Machine learning is gaining growing momentum in various recent models for the dynamic analysis of information flows in data communications networks. These preliminary models often rely on off-the-shelf learning models to predict from historical statistics while disregarding the physics governing the generating behaviors of these flows. This paper instead introduces Flow Neural Network (FlowNN) to improve the feature representation with learned physical bias. This is implemented by an induction layer, working upon the embedding layer, to impose the physics connected data correlations, and a self-supervised learning strategy with stop-gradient to make the learned physics universal. For the short-timescale network prediction tasks, FlowNN achieves 17% - 71% of loss decrease than the state-of-the-art baselines on both synthetic and real-world networking datasets, which shows the strength of this new approach. Code will be made available.Comment: re-organize the presentatio

Preparation and properties of the specific anti-influenza virus transfer factor

Specific anti-influenza virus and normal transfer factors prepared in an experimental animal model, the pig, have been tested for their components, characteristics, and activity of known specificity. Two transfer factors are small molecular mixture which consist entirely or partly of polypeptides and polynucleosides. Moreover, the biological activity of transfer factors could be approved by Rosettes test and specific skin test. The study would lay a foundation for the research and development of other specific transfer factor

Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction

Early growth response gene-1 (EGR1) is a multifunctional transcription factor that is implicated in viral infection. In this study, we observed that foot-and-mouth disease virus (FMDV) infection significantly triggered EGR1 expression. Overexpression of EGR1 suppressed FMDV replication in porcine cells, and knockdown of EGR1 considerably promoted FMDV replication. A previously reported FMDV mutant virus (with two amino acids mutations in SAP domain) that displays a strong type I interferon (IFN) induction activity was used in this study. We found that SAP mutant FMDV infection induced a higher expression of EGR1 than wildtype FMDV infection, and also triggered higher IFN-β and IFN-stimulated genes (ISGs) expression than wildtype FMDV infection. This implied a link between EGR1 and type I IFN signaling. Further study showed that overexpression of EGR1 resulted in Sendai virus (SeV)-induced IFN-stimulated response element (ISRE) and NF-κB promoter activation. In addition, the SeV-induced ISGs expression was impaired in EGR1 knockdown cells. EGR1 upregulation promoted type I IFN signaling activation and suppressed FMDV and Seneca Valley virus replication. Suppression of the transcriptional activity of EGR1 did not affect its antiviral effect against FMDV. This study reveals a new mechanism evolved by EGR1 to enhance type I IFN signaling and suppress FMDV replication

MicroRNA Expression Profile in Peripheral Blood Lymphocytes of Sheep Vaccinated with Nigeria 75/1 Peste Des Petits Ruminants Virus

Peste des petits ruminants (PPR) is one of the highly contagious transboundary viral diseases of small ruminants. Host microRNA (miRNA) expression patterns may change in response to virus infection, and it mainly works as a post-transcriptional moderator in gene expression and affects viral pathogenesis and replication. In this study, the change of miRNA expression profile in peripheral blood lymphocyte (PBMC) from sheep inoculated with PPR vaccine virus in vivo as well as primary sheep testicular (ST) cells inoculated with PPR vaccine virus in vitro were determined via deep sequencing technology. In PBMC cells, 373 and 115 differentially expressed miRNAs (DEmiRNAs) were identified 3 days and 5 days post inoculated (dpi), respectively. While, 575 DEmiRNAs were identified when comparing miRNA profiles on 5 dpi with 3 dpi. Some of the DEmiRNAs were found to change significantly via time-course during PPR vaccine virus inoculated. Similarly, in ST cells, 136 DEmiRNAs were identified at 3 dpi in comparison with mock-inoculation. A total of 12 DEmiRNAs were validated by real-time quantitative PCR (RT-qPCR). The oar-miR-150, oar-miR-370-3p and oar-miR-411b-3p were found common differentially expressed in both PPR vaccine virus-inoculated PBMC cells and ST cells. Targets prediction and functional analysis of the DEmiRNAs uncovered mainly gathering in antigen processing and presentation pathways, protein processing in endoplasmic reticulum pathways and cell adhesion molecules pathways. Our study supplies information about the DEmiRNAs in PPR vaccine virus-inoculated PBMC cells and ST cells, and provides clues for further understanding the function of miRNAs in PPR vaccine virus replication

Development of real-time and lateral flow dipstick recombinase polymerase amplification assays for rapid detection of goatpox virus and sheeppox virus

Abstract Background Goatpox virus (GTPV) and sheeppox virus (SPPV), which belong to the Capripoxvirus (CaPV), are economically important pathogens of small ruminants. Therefore, a sensitive, specific and rapid diagnostic assay for detection of GTPV and SPPV is necessary to accurately and promptly control these diseases. Methods Recombinase polymerase amplification (RPA) assays combined with a real-time fluorescent detection (real-time RPA assay) and lateral flow dipstick (RPA LFD assay) were developed targeting the CaPV G-protein-coupled chemokine receptor (GPCR) gene, respectively. Results The sensitivity of both CaPV real-time RPA assay and CaPV RPA LFD assay were 3 × 102 copies per reaction within 20 min at 38 °C. Both assays were highly specific for CaPV, with no cross-reactions with peste des petits ruminants virus, foot-and-mouth disease virus and Orf virus. The evaluation of the performance of these two assays with clinical sample (n = 107) showed that the CaPV real-time RPA assay and CaPV RPA LFD assay were able to specially detect SPPV or GTPV present in samples of ovine in liver, lung, kidney, spleen, skin and blood. Conclusions This study provided a highly time-efficient and simple alternative for rapid detection of GTPV and SPPV

RIG-I is responsible for activation of type I interferon pathway in Seneca Valley virus-infected porcine cells to suppress viral replication

Abstract Background Retinoic acid-inducible gene I (RIG-I) is a key cytosolic receptor of the innate immune system. Seneca valley virus (SVV) is a newly emerging RNA virus that infects pigs causing significant economic losses in pig industry. RIG-I plays different roles during different viruses infections. The role of RIG-I in SVV-infected cells remains unknown. Understanding of the role of RIG-I during SVV infection will help to clarify the infection process of SVV in the infected cells. Methods In this study, we generated a RIG-I knockout (KO) porcine kidney PK-15 cell line using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) genome editing tool. The RIG-I gene sequence of RIG-I KO cells were determined by Sanger sequencing method, and the expression of RIG-I protein in the RIG-I KO cells were detected by Western bloting. The activation status of type I interferon pathway in Sendai virus (SeV)- or SVV-infected RIG-I KO cells was investigated by measuring the mRNA expression levels of interferon (IFN)-β and IFN-stimulated genes (ISGs). The replicative state of SVV in the RIG-I KO cells was evaluated by qPCR, Western bloting, TCID50 assay and indirect immunofluorescence assay. Results Gene editing of RIG-I in PK-15 cells successfully resulted in the destruction of RIG-I expression. RIG-I KO PK-15 cells had a lower expression of IFN-β and ISGs compared with wildtype (WT) PK-15 cells when stimulated by the model RNA virus SeV. The amounts of viral RNA and viral protein as well as viral yields in SVV-infected RIG-I WT and KO cells were determined and compared, which showed that knockout of RIG-I significantly increased SVV replication and propagation. Meanwhile, the expression of IFN-β and ISGs were considerably decreased in RIG-I KO cells compared with that in RIG-I WT cells during SVV infection. Conclusion Altogether, this study indicated that RIG-I showed an antiviral role against SVV and was essential for activation of type I IFN signaling during SVV infection. In addition, this study suggested that the CRISPR/Cas9 system can be used as an effective tool to modify cell lines to increase viral yields during SVV vaccine development

Clinical and laboratory profiles of refractory Mycoplasma pneumoniae pneumonia in children

Objectives: The purpose of this study was to explore the clinical and laboratory characteristics of children with refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods: Seventy-six children with RMPP and 26 children with non-refractory M. pneumoniae pneumonia (NRMPP), confirmed by both serology and fluorescent quantitation PCR in bronchoalveolar lavage fluid (BALF), were evaluated retrospectively. Results: Compared to those with NRMPP, children with RMPP were older (66.6 ± 39.0 vs. 48.4 ± 35.4 months, p = 0.038) and had a longer duration of fever (12.7 ± 2.6 vs. 7.5 ± 1.8 days) and hospital stay (12.1 ± 3.2 vs. 7.4 ± 2.9 days). Children with RMPP presented neutrophil infiltration both in serum and BALF, as well as severe pulmonary lesions with pleural effusion. Children with RMPP had a significantly higher M. pneumoniae DNA load in BALF compared to NRMPP patients, and the M. pneumoniae load in BALF was significantly correlated with neutrophils and inversely correlated with macrophages for both the NRMPP and RMPP groups. The serum concentrations of tumor necrosis factor alpha (median 114.5 pg/ml, range 49.1–897.9 pg/ml) and interferon gamma (median 376.9 pg/ml, range 221.4–1997.6 pg/ml) were significantly higher in children with RMPP compared to children with NRMPP. Conclusions: This study indicates that a direct microbe effect and the subsequent induced excessive host immune response contribute in part to the progression of RMPP