2,036 research outputs found

    Evidence that platelet-derived microvesicles may transfer platelet-specific immunoreactive antigens to the surface of endothelial cells and CD34+ hematopoietic stem/ progenitor cells--implication for the pathogenesis of immune thrombocytopenias.

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    The pathogenesis and tissue damage that accompanies destruction of platelets in immune thrombocytopenias (IT) is still not understood very well and in addition to platelets, other cells (e.g. endothelial cells, CD34+ hematopoietic stem/progenitors) may also become affected. Based on our previous work that platelet antigens (e.g., CD41) may be transferred by platelet-derived microvesicles (PMV) to the surface of other cells, we asked if platelet derived-antigens, especially those that are involved in the formation of anti-platelet antibodies in IT (e.g., against antigen HPA 1 a) could be also transferred by similar mechanism. To address this issue normal human CD34+ cells, human umbilical vein-endothelial cells (HUVEC) and monocytic cell line THP-1 were incubated with PMV derived from HPA1a+ donors. We noticed that the HPA1a antigen is highly expressed on PMV-derived from the HPAla positive platelets and is transferred in PMV-dependent manner to the surface of CD34+ cells, HUVEC and monocytic THP-1 cells. These cells covered with HPA1a positive PMV but not by PMV derived from HPAla negative platelets reacted with anti-HPA1a antibodies derived from the alloimmunized pregnant women. More importantly, human hematopoietic cells that were preincubated with HPA1a+ PMV and subsequently exposed to anti-HPA 1 a serum and human NK cells, become subject to elimination by antibody dependent cell cytotoxicity ADCC. Thus, we postulate that PMV-dependent transfer of antigens may playing an important role in "expanding" the population of target cells that may be affected by anti-platelet antibodies and explain several pathologies that accompany IT (e.g. damage of endothelium, cytopenias)

    Evidence that platelet-derived microvesicles may transfer platelet-specific immunoreactive antigens to the surface of endothelial cells and CD34^+ hematopoietic stem/progenitor cells : implication for the pathogenesis of immune thrombocytopenias

    Get PDF
    The pathogenesis and tissue damage that accompanies destruction of platelets in immune thrombocytopenias (IT) is still not understood very well and in addition to platelets, other cells (e.g. endothelial cells, CD34+ hematopoietic stem/progenitors) may also become affected. Based on our previous work that platelet antigens (e.g., CD41) may be transferred by platelet-derived microvesicles (PMV) to the surface of other cells, we asked if platelet derived-antigens, especially those that are involved in the formation of anti-platelet antibodies in IT (e.g., against antigen HPA 1 a) could be also transferred by similar mechanism. To address this issue normal human CD34+ cells, human umbilical vein-endothelial cells (HUVEC) and monocytic cell line THP-1 were incubated with PMV derived from HPA1a+ donors. We noticed that the HPA1a antigen is highly expressed on PMV-derived from the HPAla positive platelets and is transferred in PMV-dependent manner to the surface of CD34+ cells, HUVEC and monocytic THP-1 cells. These cells covered with HPA1a positive PMV but not by PMV derived from HPAla negative platelets reacted with anti-HPA1a antibodies derived from the alloimmunized pregnant women. More importantly, human hematopoietic cells that were preincubated with HPA1a+ PMV and subsequently exposed to anti-HPA 1 a serum and human NK cells, become subject to elimination by antibody dependent cell cytotoxicity ADCC. Thus, we postulate that PMV-dependent transfer of antigens may playing an important role in "expanding" the population of target cells that may be affected by anti-platelet antibodies and explain several pathologies that accompany IT (e.g. damage of endothelium, cytopenias)

    SDF-1 alone and in co-operation with HGF regulates biology of human cervical carcinoma cells

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    Stromal Derived Factor-1 (SDF-1)-CXCR4 axis plays a pivotal role in biology and metastasis of several tumors. The aim of this study was to see if SDF-1 alone or in combination with Hepatocyte Growth Factor (HGF) affects biology of human cervical carcinoma (HCC) cells. We found that HCC cell lines investigated in our study highly express CXCR4 on their surface. CXCR4 was also expressed on tumor cells in tissue sections derived from cervical cancer patients. At the same time normal cervical epithelium was negative for CXCR4 expression what suggests a strong correlation between CXCR4 and malignant cell phenotype. Subsequently, we studied a potential role of the SDF-1-CXCR4 axis in HCC and noticed that SDF-1 (i) chemoattracted HCC cells, (ii) enhanced their scattering, (iii) stimulated nuclear localization of beta-catenins and upregulated their target gene cyclin D1 and (iv) at the molecular level induced calcium flux and activated RAS-MAPK, PI3-AKT and JAK-STAT pathways. SDF-1-mediated functions were additionally enhanced in the presence of HGF. Thus, our data show that the SDF-1-CXCR4 axis affects biology of HCC cells. Furthermore, we postulate that this axis might become a potential target to prevent progression of cervical cancer

    SDF-1 alone and in co-operation with HGF regulates biology of human cervical carcinoma cells.

    Get PDF
    Stromal Derived Factor-1 (SDF-1)-CXCR4 axis plays a pivotal role in biology and metastasis of several tumors. The aim of this study was to see if SDF-1 alone or in combination with Hepatocyte Growth Factor (HGF) affects biology of human cervical carcinoma (HCC) cells. We found that HCC cell lines investigated in our study highly express CXCR4 on their surface. CXCR4 was also expressed on tumor cells in tissue sections derived from cervical cancer patients. At the same time normal cervical epithelium was negative for CXCR4 expression what suggests a strong correlation between CXCR4 and malignant cell phenotype. Subsequently, we studied a potential role of the SDF-1-CXCR4 axis in HCC and noticed that SDF-1 (i) chemoattracted HCC cells, (ii) enhanced their scattering, (iii) stimulated nuclear localization of beta-catenins and upregulated their target gene cyclin D1 and (iv) at the molecular level induced calcium flux and activated RAS-MAPK, PI3-AKT and JAK-STAT pathways. SDF-1-mediated functions were additionally enhanced in the presence of HGF. Thus, our data show that the SDF-1-CXCR4 axis affects biology of HCC cells. Furthermore, we postulate that this axis might become a potential target to prevent progression of cervical cancer

    Sybil tolerance and probabilistic databases to compute web services trust

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    © Springer International Publishing Switzerland 2015. This paper discusses how Sybil attacks can undermine trust management systems and how to respond to these attacks using advanced techniques such as credibility and probabilistic databases. In such attacks end-users have purposely different identities and hence, can provide inconsistent ratings over the same Web Services. Many existing approaches rely on arbitrary choices to filter out Sybil users and reduce their attack capabilities. However this turns out inefficient. Our approach relies on non-Sybil credible users who provide consistent ratings over Web services and hence, can be trusted. To establish these ratings and debunk Sybil users techniques such as fuzzy-clustering, graph search, and probabilistic databases are adopted. A series of experiments are carried out to demonstrate robustness of our trust approach in presence of Sybil attacks

    Highly deformed 40^{40}Ca configurations in 28^{28}Si + 12^{12}C

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    The possible occurrence of highly deformed configurations in the 40^{40}Ca di-nuclear system formed in the 28^{28}Si + 12^{12}C reaction is investigated by analyzing the spectra of emitted light charged particles. Both inclusive and exclusive measurements of the heavy fragments (A \geq 10) and their associated light charged particles (protons and α\alpha particles) have been made at the IReS Strasbourg {\sc VIVITRON} Tandem facility at bombarding energies of Elab(28E_{lab} (^{28}Si) = 112 MeV and 180 MeV by using the {\sc ICARE} charged particle multidetector array. The energy spectra, velocity distributions, and both in-plane and out-of-plane angular correlations of light charged particles are compared to statistical-model calculations using a consistent set of parameters with spin-dependent level densities. The analysis suggests the onset of large nuclear deformation in 40^{40}Ca at high spin.Comment: 33 pages, 11 figure

    First Results from KamLAND: Evidence for Reactor Anti-Neutrino Disappearance

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    KamLAND has been used to measure the flux of νˉe\bar{\nu}_e's from distant nuclear reactors. In an exposure of 162 ton\cdotyr (145.1 days) the ratio of the number of observed inverse β\beta-decay events to the expected number of events without disappearance is 0.611±0.085(stat)±0.041(syst)0.611\pm 0.085 {\rm (stat)} \pm 0.041 {\rm (syst)} for νˉe\bar{\nu}_e energies >> 3.4 MeV. The deficit of events is inconsistent with the expected rate for standard νˉe\bar{\nu}_e propagation at the 99.95% confidence level. In the context of two-flavor neutrino oscillations with CPT invariance, these results exclude all oscillation solutions but the `Large Mixing Angle' solution to the solar neutrino problem using reactor νˉe\bar{\nu}_e sources.Comment: 6 pages, 6 figure

    Search for the Invisible Decay of Neutrons with KamLAND

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    The Kamioka Liquid scintillator Anti-Neutrino Detector (KamLAND) is used in a search for single neutron or two neutron intra-nuclear disappearance that would produce holes in the s\it{s}-shell energy level of 12^{12}C nuclei. Such holes could be created as a result of nucleon decay into invisible modes (invinv), e.g. n3νn \to 3\nu or nn2νnn \to 2\nu. The de-excitation of the corresponding daughter nucleus results in a sequence of space and time correlated events observable in the liquid scintillator detector. We report on new limits for one- and two-neutron disappearance: τ(ninv)>5.8×1029\tau(n\to inv)> 5.8\times 10^{29} years and τ(nninv)>1.4×1030\tau (nn \to inv)> 1.4 \times 10^{30} years at 90% CL. These results represent an improvement of factors of \sim3 and >104>10^4 over previous experiments.Comment: 5 pages, 3 figure
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