18 research outputs found

    Non-orthogonal joint block diagonalization based on the LU or QR factorizations for convolutive blind source separation

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    This article addresses the problem of blind source separation, in which the source signals are most often of the convolutive mixtures, and moreover, the source signals cannot satisfy independent identical distribution generally. One kind of prevailing and representative approaches for overcoming these difficulties is joint block diagonalization (JBD) method. To improve present JBD methods, we present a class of simple Jacobi-type JBD algorithms based on the LU or QR factorizations. Using Jacobi-type matrices we can replace high dimensional minimization problems with a sequence of simple one-dimensional problems. The novel methods are more general i.e. the orthogonal, positive definite or symmetric matrices and a preliminary whitening stage is no more compulsorily required, and further, the convergence is also guaranteed. The performance of the proposed algorithms, compared with the existing state-of-the-art JBD algorithms, is evaluated with computer simulations and vibration experimental. The results of numerical examples demonstrate that the robustness and effectiveness of the two novel algorithms provide a significant improvement i.e., yield less convergence time, higher precision of convergence, better success rate of block diagonalization. And the proposed algorithms are effective in separating the vibration signals of convolutive mixtures

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Polysaccharide of Atractylodes macrocephala Koidz alleviate lipopolysaccharide-induced liver injury in goslings via the p53 and FOXO pathways

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    ABSTRACT: Lipopolysaccharide (LPS) can affect the immune system of geese by inducing liver injury. The polysaccharide of Atractylodes macrocephala Koidz (PAMK) have obvious immune-enhancing effects. Accordingly, this experiment investigated the effect of PAMK on LPS-induced liver injury in goslings. Two hundred 1-day-old goslings were randomly divided into the control group, LPS group, PAMK group, and PAMK+ LPS group, and the PAMK and PAMK+ LPS groups were fed the basal diet with 400 mg/kg PAMK, while the control and LPS groups were fed the basal diet. On D 21, 23, and 25 of the formal trial, the goslings in the LPS and PAMK+LPS groups were injected intraperitoneally with 2 mg/kg LPS, and goslings in the control and PAMK groups were injected intraperitoneally with the same amount of saline. Livers were collected on D 25. HE-stained sections showed that PAMK could effectively alleviate the LPS-induced indistinct hepatic cord structure, loss of cytoplasmic contents of hepatocytes, and dilatation of hepatic sinusoids. The biochemical parameters of liver tissues showed that PAMK could alleviate the LPS-induced upregulation of alanine aminotransferase and aspartate aminotransferase. To further investigate the mechanism of the mitigating effect of PAMK on LPS-induced injury, livers from the LPS and PAMK+LPS groups were selected for transcriptome sequencing. The sequencing results showed that there were 406 differentially expressed genes (DEGs) in the livers of LPS and PAMK+LPS goslings, of which 242 upregulated and 164 downregulated. The Kyoto Encyclopedia of Genes and Genome (KEGG) analysis showed that DEGs were significantly enriched in immune signal transduction, cell cycle, and cell metabolism. Besides, protein‒protein interaction analysis showed that 129 DEGs were associated with each other, including 7 DEGs enriched in the p53 and FOXO signaling pathway. In conclusion, PAMK may alleviate LPS-induced liver injury in gosling through the p53 and FOXO signaling pathway. These results provide a basis for further development of PAMK as an immunomodulator

    Electrochemiluminescent Immune-Modified Electrodes Based on Ag<sub>2</sub>Se@CdSe Nanoneedles Loaded with Polypyrrole Intercalated Graphene for Detection of CA72‑4

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    This work described a new electrochemiluminescence (ECL) immunosensor based on polypyrrole intercalated graphene and Ag<sub>2</sub>Se@CdSe nanoneedles. The novel nanomaterial Ag<sub>2</sub>Se@CdSe, with needle-like morphology, was synthesized for the first time. The prepared Ag<sub>2</sub>Se@CdSe nanoneedles exhibited good luminous performance in the presence of K<sub>2</sub>S<sub>2</sub>O<sub>8</sub>. Polypyrrole intercalated amination graphene with high specific binding sites and excellent electrochemical performance was used as the platform for the sensor. The developed ECL immunosensor was used for the detection of CA72-4 with good linear relation in the range from 10<sup>–4</sup> to 20 U/mL and low detection limit of 2.1 × 10<sup>–5</sup> U/mL (S/N = 3). The developed ECL immunosensor with high sensitivity and spectral selectivity can be used for detection of real samples. Ag<sub>2</sub>Se@CdSe nanoneedles could be promising candidate emitter for ECL biosensors in the future
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