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Sample records for monocyte-derived dc mddc

  1. Alcohol and cannabinoids differentially affect HIV infection and function of human monocyte-derived dendritic cells (MDDC

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    Marisela eAgudelo

    2015-12-01

    Full Text Available During human immunodeficiency virus (HIV infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC. However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%, THC (5 and 10 uM, or JWH-015 (5 and 10 uM for 4-7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR estimation. MDDC endocytosis assay and cytokine array profiles were measured to investigate the effects of HIV and substances of abuse on MDDC function. Our results show the HIV+EtOH treated MDDC had the highest levels of p24 production and expression when compared with the HIV positive controls and the cannabinoid treated cells. Although both cannabinoids, THC and JWH-015 had lower levels of p24 production and expression, the HIV+JWH-015 treated MDDC had the lowest levels of p24 when compared to the HIV+THC treated cells. In addition, MDDC endocytic function and cytokine production were also differentially altered after alcohol and cannabinoid treatments. Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection.

  2. Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide

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    Stojić-Vukanić Z.

    2011-01-01

    Full Text Available Leflunomide is an immunosuppressive drug effective in experimental models of transplantation and autoimmune diseases and in the treatment of active rheumatoid arthritis (RA. Having in mind that it has been shown that some other immunosuppressive drugs (glucocorticoids, mycophenolate mofetil, sirolimus etc. impair dendritic cell (DC phenotype and function, we investigated the effect of A77 1726, an active metabolite of leflunomide, on the differentiation and function of human monocyte-derived dendritic cells (MDDC in vitro. Immature MDDC were generated by cultivating monocytes in medium supplemented with GM-CSF and IL-4. To induce maturation, immature MDDC were cultured for 2 additional days with LPS. A77 1726 (100 μM was added at the beginning of cultivation. Flow cytometric analysis showed that MDDC differentiated in the presence of A77 1726 exhibited an altered phenotype, with a down-regulated surface expression of CD80, CD86, CD54 and CD40 molecules. Furthermore, the continuous presence of A77 1726 during differentiation and maturation prevented successful maturation, judging by the decreased expression of maturation marker CD83, costimulatory and adhesive molecules on A77 1726-treated mature MDDC. In addition, A77 1726-pretreated MDDC exhibited a poor stimulatory capacity of the allogeneic T cells and a low production of IL-10 and IL-18. These data suggest that leflunomide impairs the differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.

  3. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus.

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    Cyril Le Nouën

    2011-06-01

    Full Text Available Human respiratory syncytial virus (HRSV and, to a lesser extent, human metapneumovirus (HMPV and human parainfluenza virus type 3 (HPIV3, can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV-stimulated DC to

  4. Broad antiviral activity of carbohydrate-binding agents against the four serotypes of dengue virus in monocyte-derived dendritic cells.

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    Marijke M F Alen

    Full Text Available BACKGROUND: Dendritic cells (DC, present in the skin, are the first target cells of dengue virus (DENV. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN is present on DC and recognizes N-glycosylation sites on the E-glycoprotein of DENV. Thus, the DC-SIGN/E-glycoprotein interaction can be considered as an important target for inhibitors of viral replication. We evaluated various carbohydrate-binding agents (CBAs against all four described serotypes of DENV replication in Raji/DC-SIGN(+ cells and in monocyte-derived DC (MDDC. METHODOLOGY/PRINCIPAL FINDINGS: A dose-dependent anti-DENV activity of the CBAs Hippeastrum hybrid (HHA, Galanthus nivalis (GNA and Urtica dioica (UDA, but not actinohivin (AH was observed against all four DENV serotypes as analyzed by flow cytometry making use of anti-DENV antibodies. Remarkably, the potency of the CBAs against DENV in MDDC cultures was significantly higher (up to 100-fold than in Raji/DC-SIGN(+ cells. Pradimicin-S (PRM-S, a small-size non-peptidic CBA, exerted antiviral activity in MDDC but not in Raji/DC-SIGN(+ cells. The CBAs act at an early step of DENV infection as they bind to the viral envelope of DENV and subsequently prevent virus attachment. Only weak antiviral activity of the CBAs was detected when administered after the virus attachment step. The CBAs were also able to completely prevent the cellular activation and differentiation process of MDDC induced upon DENV infection. CONCLUSIONS/SIGNIFICANCE: The CBAs exerted broad spectrum antiviral activity against the four DENV serotypes, laboratory-adapted viruses and low passage clinical isolates, evaluated in Raji/DC-SIGN(+ cells and in primary MDDC.

  5. [Induction of monocyte-derived dendritic cell differentiation by asthmatic serum in a transendothelial trafficking model].

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    Zhou, Lin-fu; Wang, Wen-lu; Li, Hong-yan; Zhang, Ming-shun; Ji, Xiao-hui; He, Shao-heng; Huang, Mao; Yin, Kai-sheng

    2011-03-01

    To explore the effect of asthmatic and healthy serum on differentiation and function of monocyte-derived dendritic cells (MDDC) in a transendothelial trafficking model. The sera and peripheral blood mononuclear cells (PBMC) were separated from 12 asthmatic patients and 12 healthy volunteers, and monocytes were selected from PBMC using magnetic beads. The trypsin-digested human umbilical vein endothelial cells (HUVEC) at passage 2 from 5 healthy lying-in women were used to construct the transendothelial trafficking model under asthmatic or healthy serum, wherein MDDC were identified by silver nitrate staining and scanning electron microscopy. Nuclear factor κB (NF-κB) activity was determined by electrophoretic mobility shift assay. Flow cytometry, ELISA and mixed leukocyte reaction were relevantly utilized to detect the phenotype, cytokine and T cell proliferation. (1) Monocytes traversed through HUVEC monolayer after 2 h, and reverse-transmigrated to develop into DC 48 h later. (2) The healthy serum stimulated monocytes into immature MDDC with lower CD(14) [(20 ± 5)%] (F = 49.01, P 0.05), higher CD(80) and CD(83) [(49.7 ± 10.2)% and (30.2 ± 6.8)%] (F = 4.01 and 20.68, all P trafficking model, which provides a promising experimental platform for both investigation of immunological mechanisms in asthma and screening of novel anti-asthma drugs in vitro.

  6. Th1 disabled function in response to TLR4 stimulation of monocyte-derived DC from patients chronically-infected by hepatitis C virus.

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    Laure Perrin-Cocon

    Full Text Available BACKGROUND: Lack of protective antibodies and inefficient cytotoxic responses are characteristics of chronic hepatitis C infection. A defect in dendritic cell (DC function has thus been suspected, but this remains a controversial issue. METHODS AND FINDINGS: Here we show that monocyte-derived DC (MoDC from chronically-infected patients can mature in response to TLR1/2, TLR2/6 or TLR3 ligands. In contrast, when stimulated with the TLR4 ligand LPS, MoDC from patients show a profound defect in inducing IFNgamma secretion by allogeneic T cells. This defect is not due to defective phenotypic maturation or to the presence of HCV-RNA in DC or monocytes but is correlated to reduced IL-12 secretion by DC. Restoration of DC ability to stimulate IFNgamma secretion can be obtained by blocking MEK activation in DC, indicating that MEK/ERK pathway is involved in the Th1 defect of MoDC. Monocytes from HCV patients present increased spontaneous secretion of cytokines and chemokines, especially MIP-1beta. Addition of MIP-1beta on healthy monocytes during differentiation results in DC that have Th1 defect characteristic of MoDC from HCV patients, suggesting that MIP-1beta secretion by HCV monocytes participates in the Th1 defect of DC. CONCLUSIONS: Our data indicate that monocytes from HCV patients are activated in vivo. This interferes with their differentiation into DC, leading to deficient TLR4 signaling in these cells that are enable to induce a Th1 response. This specific defect is linked to the activation of the MEK/ERK pathway.

  7. Monocyte-derived dendritic cells in bipolar disorder

    NARCIS (Netherlands)

    Knijff, EM; Ruwhof, C; de Wit, HJ; Kupka, RW; Vonk, R; Akkerhuis, GW; Nolen, WA; Drexhage, HA

    2006-01-01

    Background: Dendritic cells (DC) are key regulators of the immune system, which is compromised in patients with bipolar disorder. We sought to study monocyte-derived DC in bipolar disorder. Methods: Monocytes purified from blood collected from DSM-IV bipolar disorder outpatients (n = 53, 12 without

  8. Monocyte-derived dendritic cells exposed to Der p 1 allergen enhance the recruitment of Th2 cells: major involvement of the chemokines TARC/CCL17 and MDC/CCL22.

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    Hammad, Hamida; Smits, Hermelijn H; Ratajczak, Céline; Nithiananthan, Asokananthan; Wierenga, Eddy A; Stewart, Geoffrey A; Jacquet, Alain; Tonnel, Andre-Bernard; Pestel, Joël

    2003-01-01

    Dendritic cells (DC) are potent antigen - presenting cells that can orientate the immune response towards a Th1 or a Th2 type. DC produce chemokines that are involved in the recruitment of either Th1 cells, such as IP10 (CXCL10), Th2 cells such as TARC (CCL17) and MDC (CCL22), or non-polarized T cells such as RANTES (CCL5) and MIP-lalpha (CCL3). We investigated whether monocyte-derived DC (MD-DC) generated from healthy donors or from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and exposed to the cysteine-protease Der p 1(allergen of Dpt), could upregulate the expression of chemokines involved in type 1 or type 2 T cell recruitment. MD-DC were pulsed with either Der p 1 or with LPS as the control and the chemokines produced were evaluated using ELISA and chemotaxis assays. Der p 1-pulsed DC from allergic patients showed increased TARC (CCL17) and MDC (CCL22) production without modifying IP-10 (CXCL10) release. Der p 1-pulsed DC from healthy donors showed only increased IP-10 (CXCL10) secretion. RANTES (CCL5) and MIP-lalpha (CCL3) production were similarly increased when DC were from healthy or allergic donors. The selective Th2 clone recruitment activity of supernatants from Der p 1-pulsed DC of allergic patients was inhibited by anti-TARC (CCL17) and anti-MDC (CCL22) neutralizing Abs. By using anti-IP10 (CXCL10) blocking Abs, supernatants of Der p 1-pulsed DC from healthy donors were shown to be involved in the recruitment of Th1 cells. These results suggest that in allergic patients exposed to house dust mites, DC may favour the exacerbation of the Th2 response via the increase in type 2 chemokine production. Copyright John Libbey Eurotext 2003.

  9. Role of DC-SIGN in Lassa virus entry into human dendritic cells.

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    Goncalves, Ana-Rita; Moraz, Marie-Laurence; Pasquato, Antonella; Helenius, Ari; Lozach, Pierre-Yves; Kunz, Stefan

    2013-11-01

    The arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with high mortality in humans. Antigen-presenting cells, in particular dendritic cells (DCs), are early and preferred targets of LASV, and their productive infection contributes to the virus-induced immunosuppression observed in fatal disease. Here, we characterized the role of the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in LASV entry into primary human DCs using a chimera of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) expressing the LASV glycoprotein (rLCMV-LASVGP). We found that differentiation of human primary monocytes into DCs enhanced virus attachment and entry, concomitant with the upregulation of DC-SIGN. LASV and rLCMV-LASVGP bound to DC-SIGN via mannose sugars located on the N-terminal GP1 subunit of LASVGP. We provide evidence that DC-SIGN serves as an attachment factor for rLCMV-LASVGP in monocyte-derived immature dendritic cells (MDDC) and can accelerate the capture of free virus. However, in contrast to the phlebovirus Uukuniemi virus (UUKV), which uses DC-SIGN as an authentic entry receptor, productive infection with rLCMV-LASVGP was less dependent on DC-SIGN. In contrast to the DC-SIGN-mediated cell entry of UUKV, entry of rLCMV-LASVGP in MDDC was remarkably slow and depended on actin, indicating the use of different endocytotic pathways. In sum, our data reveal that DC-SIGN can facilitate cell entry of LASV in human MDDC but that its role seems distinct from the function as an authentic entry receptor reported for phleboviruses.

  10. The effect of short-chain fatty acids on human monocyte-derived dendritic cells

    DEFF Research Database (Denmark)

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné

    2015-01-01

    negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly......The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood....... The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted...

  11. Sphingosylphosphorylcholine stimulates human monocyte-derived dendritic cell chemotaxis

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    Ha-young LEE; Eun-ha SHIN; Yoe-sik BAE

    2006-01-01

    Aim: To investigate the effects of Sphingosylphosphorylcholine (SPC) on human monocyte-derived dendritic cell (DC) chemotaxis. Methods: Human DC were generated from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4. The effect of SPC on the DC chemotactic migration was measured by chemotaxis assay. Intracellular signaling event involved in the SPC-induced DC chemotaxis was investigated with several inhibitors for specific kinase. The expression of the SPC receptors was examined by reverse transcription polymerase chain reaction. Results: We found that SPC induced chemotactic migration in immature DC (iDC) and mature DC (mDC). In terms of SPC-induced signaling events, mitogen activated protein kinase activation and Akt activation in iDC and mDC were stimulated. SPC-induced chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoino-sitide-3-kinase, but not by calcium in both iDC and mDC. Although mDC express ovarian cancer G protein-coupled receptor 1, but not G protein-coupled receptor 4, iDC do not express any of these receptors. To examine the involvement of sphin-gosine-1-phosphate (SIP) receptors, we checked the effect of an SIP receptor antagonist (VPC23019) on SPC-induced DC chemotaxis. VPC23019 did not affect SPC-induced DC chemotaxis. Conclusion: The results suggest that SPC may play a role in regulating DC trafficking during phagocytosis and the T cell-stimulating phase, and the unique SPC receptor, which is different from SIP receptors, is involved in SPC-induced chemotaxis.

  12. Monocyte-Derived Suppressor Cells in Transplantation.

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    Ochando, Jordi; Conde, Patricia; Bronte, Vincenzo

    Myeloid-derived suppressor cells (MDSC) are cells of myeloid origin with enhanced suppressive function. They are negative regulators of the immune responses and comprise a heterogeneous mixture of immunosuppressive cells of monocytic (M-MDSC) and granulocytic (G-MDSC) origin. A more recent nomenclature proposes the term "suppressive monocyte derived cells" (suppressive MCs) to define CSF1/CSF2-dependent mouse suppressor cells that develop from common monocyte progenitors (cMoPs) after birth. Here, we review the literature about monocytic-derived cells with demonstrated suppressor function in vitro and in vivo within the context of solid organ transplantation.

  13. Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity

    NARCIS (Netherlands)

    Bol, K.F.; Aarntzen, E.H.J.G.; Pots, J.M.; Olde Nordkamp, M.A.M.; Rakt, M.W.M.M. van de; Scharenborg, N.M.; Boer, A.J. de; Oorschot, T.G.M. van; Croockewit, S.; Blokx, W.A.M.; Oyen, W.J.G.; Boerman, O.C.; Mus, R.D.M.; Rossum, M.M. van; Graaf, C.A.A. van der; Punt, C.J.; Adema, G.J.; Figdor, C.G.; Vries, I.J. de; Schreibelt, G.

    2016-01-01

    Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that

  14. Establishing porcine monocyte-derived macrophage and dendritic cell systems for studying the interaction with PRRSV-1

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    Helen eSingleton

    2016-06-01

    Full Text Available Monocyte-derived macrophages (MoMØ and monocyte-derived dendritic cells (MoDC are two model systems well established in human and rodent systems that can be used to study the interaction of pathogens with host cells. Porcine reproductive and respiratory syndrome virus (PRRSV is known to infect myeloid cells, such as macrophages (MØ and dendritic cells (DC. Therefore, this study aimed to establish systems for the differentiation and characterization of MoMØ and MoDC for subsequent infection with PRRSV-1. M-CSF differentiated monocyte-derived macrophages (MoMØ were stimulated with activators for classical (M1 or alternative (M2 activation. GM-CSF and IL-4 generated monocyte-derived dendritic cells (MoDC were activated with the well established maturation cocktail containing PAMPs and cytokines. In addition, MoMØ and MoDC were treated with dexamethasone and IL-10, which are known immuno-suppressive reagents. Cells were characterized by morphology, phenotype and function and porcine MØ subsets highlighted some divergence from described human counterparts, while MoDC, appeared more similar to mouse and human DCs. The infection with PRRSV-1 strain Lena demonstrated different replication kinetics between MoMØ and MoDC and within subsets of each cell type. While MoMØ susceptibility was significantly increased by dexamethasone and IL-10 with an accompanying increase in CD163/CD169 expression, MoDC supported only a minimal replication of PRRSV These findings underline the high variability in the susceptibility of porcine myeloid cells towards PRRSV-1 infection.

  15. PGE2 confers survivin-dependent apoptosis resistance in human monocyte-derived dendritic cells.

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    Baratelli, Felicita; Krysan, Kostyantyn; Heuzé-Vourc'h, Nathalie; Zhu, Li; Escuadro, Brian; Sharma, Sherven; Reckamp, Karen; Dohadwala, Mariam; Dubinett, Steven M

    2005-08-01

    Control of apoptosis is fundamental for dendritic cell (DC) homeostasis. Numerous factors maintain DC viability throughout their lifespan, including inhibitor of apoptosis proteins. Among them, survivin is overexpressed in many human malignancies, but its physiological function in normal cells has not been fully delineated. Prostaglandin E2 (PGE2), also overproduced in several malignancies, has shown to induce proapoptotic and antiapoptotic effects in different cell types, including immune cells. In DC, PGE2 predominantly affects maturation and modulates immune functions. Here, we show that exposure of monocyte-derived DC to PGE2 (10(-5) M) for 72 h significantly increased DC survivin mRNA and protein expression. In contrast, DC, matured with lipopolysaccharide or tumor necrosis factor alpha, did not reveal survivin induction in response to PGE2. Following exposure to apoptotic stimuli, DC treated with PGE2 exhibited an overall increased viability compared with control DC, and this effect was correlated inversely with caspase-3 activation. Moreover, PGE2-treated, survivin-deficient DC demonstrated reduced viability in response to apoptotic stimuli. Further analysis indicated that PGE2 induced DC survivin expression in an E prostanoid (EP)2/EP4 receptor and phosphatidylinositol-3 kinase-dependent manner. These findings suggest that PGE2-dependent regulation of survivin is important in modulating apoptosis resistance in human DC.

  16. Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity

    OpenAIRE

    Bol, Kalijn F.; Aarntzen, Erik H. J. G.; Pots, Jeanette M.; Olde Nordkamp, Michel A. M.; van de Rakt, Mandy W. M. M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van Oorschot, Tom G. M.; Croockewit, Sandra A. J.; Blokx, Willeke A. M.; Oyen, Wim J. G.; Boerman, Otto C.; Mus, Roel D. M.; van Rossum, Michelle M.; van der Graaf, Chantal A. A.

    2016-01-01

    Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combi...

  17. cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells

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    Paijo, Jennifer; Döring, Marius; Spanier, Julia; Grabski, Elena; Nooruzzaman, Mohammed; Schmidt, Tobias; Witte, Gregor; Messerle, Martin; Hornung, Veit; Kaever, Volkhard; Kalinke, Ulrich

    2016-01-01

    Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages. PMID:27058035

  18. A novel in vitro human microglia model: characterization of human monocyte-derived microglia.

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    Etemad, Samar; Zamin, Rasheeda Mohd; Ruitenberg, Marc J; Filgueira, Luis

    2012-07-30

    Microglia are the innate immune cells of the central nervous system. They help maintaining physiological homeostasis and contribute significantly to inflammatory responses in the course of infection, injury and degenerative processes. To date, there is no standardized simple model available to investigate the biology of human microglia. The aim of this study was to establish a new human microglia model. For that purpose, human peripheral blood monocytes were cultured in serum free medium in the presence of M-CSF, GM-CSF, NGF and CCL2 to generate monocyte-derived microglia (M-MG). M-MG were clearly different in morphology, phenotype and function from freshly isolated monocytes, cultured monocytes in the absence of the cytokines and monocyte-derived dendritic cells (M-DC) cultured in the presence of GM-CSF and IL-4. M-MG acquired a ramified morphology with primary and secondary processes. M-MG displayed a comparable phenotype to the human microglia cell line HMC3, expressing very low levels of CD45, CD14 and HLA-DR, CD11b and CD11c; and undetectable levels of CD40, CD80 and CD83, and a distinct pattern of chemokine receptors (positive for CCR1, CCR2, CCR4, CCR5, CXCR1, CXCR3, CX3CR1; negative for CCR6 and CCR7). In comparison with M-DC, M-MG displayed lower T-lymphocyte stimulatory capacity, as well as lower phagocytosis activity. The described protocol for the generation of human monocyte-derived microglia is feasible, well standardized and reliable, as it uses well defined culture medium and recombinant cytokines, but no serum or conditioned medium. This protocol will certainly be very helpful for future studies investigating the biology and pathology of human microglia.

  19. Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation.

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    Singh, Tej Pratap; Zhang, Howard H; Borek, Izabela; Wolf, Peter; Hedrick, Michael N; Singh, Satya P; Kelsall, Brian L; Clausen, Bjorn E; Farber, Joshua M

    2016-12-16

    Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6C(hi) blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.

  20. Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation

    Science.gov (United States)

    Singh, Tej Pratap; Zhang, Howard H.; Borek, Izabela; Wolf, Peter; Hedrick, Michael N.; Singh, Satya P.; Kelsall, Brian L.; Clausen, Bjorn E.; Farber, Joshua M.

    2016-01-01

    Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells. PMID:27982014

  1. Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis

    OpenAIRE

    Czibere Akos; Winter Meike; Diaz Blanco Elena; Papewalis Claudia; Schott Matthias; Maihöfer Dagmar; Kronenwett Ralf; Safaian Nancy; Korthals Mark; Haas Rainer; Kobbe Guido; Fenk Roland

    2007-01-01

    Abstract Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profil...

  2. Neutrophil extracellular traps downregulate lipopolysaccharide-induced activation of monocyte-derived dendritic cells.

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    Barrientos, Lorena; Bignon, Alexandre; Gueguen, Claire; de Chaisemartin, Luc; Gorges, Roseline; Sandré, Catherine; Mascarell, Laurent; Balabanian, Karl; Kerdine-Römer, Saadia; Pallardy, Marc; Marin-Esteban, Viviana; Chollet-Martin, Sylvie

    2014-12-01

    Polymorphonuclear neutrophils (PMN) play a central role in inflammation and participate in its control, notably by modulating dendritic cell (DC) functions via soluble mediators or cell-cell contacts. Neutrophil extracellular traps (NETs) released by PMN could play a role in this context. To evaluate NET effects on DC maturation, we developed a model based on monocyte-derived DC (moDC) and calibrated NETs isolated from fresh human PMN. We found that isolated NETs alone had no discernable effect on moDC. In contrast, they downregulated LPS-induced moDC maturation, as shown by decreased surface expression of HLA-DR, CD80, CD83, and CD86, and by downregulated cytokine production (TNF-α, IL-6, IL-12, IL-23), with no increase in the expression of tolerogenic DC genes. Moreover, the presence of NETs during moDC maturation diminished the capacity of these moDC to induce T lymphocyte proliferation in both autologous and allogeneic conditions, and modulated CD4(+) T lymphocyte polarization by promoting the production of Th2 cytokines (IL-5 and IL-13) and reducing that of Th1 and Th17 cytokines (IFN-γ and IL-17). Interestingly, the expression and activities of the lymphoid chemokine receptors CCR7 and CXCR4 on moDC were not altered when moDC matured in the presence of NETs. Together, these findings reveal a new role for NETs in adaptive immune responses, modulating some moDC functions and thereby participating in the control of inflammation.

  3. HIV infection of monocytes-derived dendritic cells inhibits Vγ9Vδ2 T cells functions.

    Directory of Open Access Journals (Sweden)

    Alessandra Sacchi

    Full Text Available DCs act as sentinel cells against incoming pathogens and represent the most potent antigen presenting cells, having the unique capability to prime naïve T cells. In addition to their role in induction of adaptive immune responses, DC are also able to activate innate cells as γδ T cells; in particular, a reciprocal crosstalk between DC and γδ T cells was demonstrated. However, whether HIV infection may alter DC-Vγ9Vδ2 T cells cross-talk was not yet described. To clarify this issue, we cultured activated Vγ9Vδ2 T cells with HIV infected monocyte derived DC (MoDC. After 5 days we evaluated MoDC phenotype, and Vγ9Vδ2 T cells activation and proliferation. In our model, Vγ9Vδ2 T cells were not able to proliferate in response to HIV-infected MoDC, although an up-regulation of CD69 was observed. Upon phosphoantigens stimulation, Vγ9Vδ2 T cells proliferation and cytokine production were inhibited when cultured with HIV-infected MoDC in a cell-contact dependent way. Moreover, HIV-infected MoDC are not able to up-regulate CD86 molecules when cultured with activated Vγ9Vδ2 T cells, compared with uninfected MoDC. Further, activated Vγ9Vδ2 T cells are not able to induce HLA DR up-regulation and CCR5 down-regulation on HIV-infected MoDC. These data indicate that HIV-infected DC alter the capacity of Vγ9Vδ2 T cells to respond to their antigens, pointing out a new mechanisms of induction of Vγ9Vδ2 T cells anergy carried out by HIV, that could contribute to immune evasion.

  4. HIV infection of monocytes-derived dendritic cells inhibits Vγ9Vδ2 T cells functions.

    Science.gov (United States)

    Sacchi, Alessandra; Rinaldi, Alessandra; Tumino, Nicola; Casetti, Rita; Agrati, Chiara; Turchi, Federica; Bordoni, Veronica; Cimini, Eleonora; Martini, Federico

    2014-01-01

    DCs act as sentinel cells against incoming pathogens and represent the most potent antigen presenting cells, having the unique capability to prime naïve T cells. In addition to their role in induction of adaptive immune responses, DC are also able to activate innate cells as γδ T cells; in particular, a reciprocal crosstalk between DC and γδ T cells was demonstrated. However, whether HIV infection may alter DC-Vγ9Vδ2 T cells cross-talk was not yet described. To clarify this issue, we cultured activated Vγ9Vδ2 T cells with HIV infected monocyte derived DC (MoDC). After 5 days we evaluated MoDC phenotype, and Vγ9Vδ2 T cells activation and proliferation. In our model, Vγ9Vδ2 T cells were not able to proliferate in response to HIV-infected MoDC, although an up-regulation of CD69 was observed. Upon phosphoantigens stimulation, Vγ9Vδ2 T cells proliferation and cytokine production were inhibited when cultured with HIV-infected MoDC in a cell-contact dependent way. Moreover, HIV-infected MoDC are not able to up-regulate CD86 molecules when cultured with activated Vγ9Vδ2 T cells, compared with uninfected MoDC. Further, activated Vγ9Vδ2 T cells are not able to induce HLA DR up-regulation and CCR5 down-regulation on HIV-infected MoDC. These data indicate that HIV-infected DC alter the capacity of Vγ9Vδ2 T cells to respond to their antigens, pointing out a new mechanisms of induction of Vγ9Vδ2 T cells anergy carried out by HIV, that could contribute to immune evasion.

  5. Induction of monocyte-derived dendritic cell differentiation by asthmatic serum in a transendothelial trafficking model%支气管哮喘患者血清对内皮穿越模型中单核细胞分化为树突状细胞的作用

    Institute of Scientific and Technical Information of China (English)

    周林福; 王文璐; 李红岩; 张明顺; 季晓辉; 何韶衡; 黄茂; 殷凯生

    2011-01-01

    新的体外实验平台.%Objective To explore the effect of asthmatic and healthy serum on differentiation and function of monocyte-derived dendritic cells (MDDC) in a transendothelial trafficking model. Methods The sera and peripheral blood mononuclear cells (PBMC) were separated from 12 asthmatic patients and 12 healthy volunteers, and monocytes were selected from PBMC using magnetic beads. The trypsin-digested human umbilical vein endothelial cells (HUVEC) at passage 2 from 5 healthy lying-in women were used to construct the transendothelial trafficking model under asthmatic or healthy serum, wherein MDDC were identified by silver nitrate staining and scanning electron microscopy. Nuclear factor κB (NF-κB) activity was determined by electrophoretic mobility shift assay. Flow cytometry, ELISA and mixed leukocyte reaction were relevantly utilized to detect the phenotype, cytokine and T cell proliferation. Results ( 1 ) Monocytes traversed through HUVEC monolayer after 2 h, and reverse-transmigrated to develop into DC 48 h later. ( 2 ) The healthy serum stimulated monocytes into immature MDDC with lower CD14 [ ( 20 ±5)%] (F=49.01, P<0.05), and higher HLA-DR, CD80, CD86 and CD83 [(43 ±4)%, (17.9 ±3.5)%, (43 ± 11)% and (6.7 ± 1.8)%, respectively] (F= 10.35 -40.17, all P<0.05) than monocytes did before transmigration at 0 h [ CD14(81 ±6)%, HLA-DR (24 ±5)%, CD80(2. 8 ±2. 0)%,CD86( 14 ±4)% and CD83(0. 9 ±0. 8)%, respectively]. (3) The asthmatic serum stimulated monocytes into mature MDDC, characteristic of dendrites, with similar HLA-DR and CD86 [ ( 55 ± 6 ) % and ( 59 ±12)%] (F=15.29 and 35.97, all P >0.05), higher CD80 and CD83 [(49.7 ± 10.2)% and (30.2 ±6. 8) % ] ( F = 4. 01 and 20. 68, all P < 0. 05), accompanied by increased levels of NF-κB activity, IL-12 p70 and T cell proliferation [ ( 100 ± 11 )%, (568 ±43) ng/L and (2033 ± 198) cpm, respectively] (F=49. 23 - 350. 84, all P < 0. 05 ) relative to the healthy serum-stimulated immature MDDC [ ( 12 ± 3 ) %,(220 ± 35) ng

  6. Human XCR1+ Dendritic Cells Derived In Vitro from CD34+ Progenitors Closely Resemble Blood Dendritic Cells, Including Their Adjuvant Responsiveness, Contrary to Monocyte-Derived Dendritic Cells

    OpenAIRE

    S. Balan; Ollion, V.; Colletti, N.; Chelbi, R.; Montanana-Sanchis, F.; LIU, H.; Vu Manh, T.-P.; Sanchez, C.; Savoret, J.; Perrot, I.; Doffin, A.-C.; Fossum, E.; Bechlian, D.; Chabannon, C.; Bogen, B

    2014-01-01

    Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1+ DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1+ human DC. Assessment of the immunoactivation potential of XCR1+ human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1+ and XCR1− human DC in CD3...

  7. Isolation of IL-12p70-competent human monocyte-derived dendritic cells

    DEFF Research Database (Denmark)

    Søndergaard, Jonas Nørskov; Pedersen, Susanne Brix

    2012-01-01

    that moDCs generated under standard conditions develop into two subsets based on CD1a-expression with the CD1a+ moDCs being the main IL-12p70 producers. This has however not been generally accepted, which we show here because the subset described as CD1a-negative does express CD1a, but at a lower level......Diverse methodologies ranging from experimental immunological studies to immunotherapy involve the application of human monocyte-derived dendritic cells (moDCs). Considerable donor-dependent variations in the moDC production of IL-12p70 affect the outcome of these methodologies. It has been shown...

  8. Gene expression profiling of human monocyte-derived dendritic cells - Searching for molecular regulators of tolerogenicity

    Directory of Open Access Journals (Sweden)

    Katina eSchinnerling

    2015-10-01

    Full Text Available The ability of dendritic cells (DCs to initiate and modulate antigen-specific immune responses has made them attractive targets for immunotherapy. Since DC research in humans is limited by the scarcity of DC populations in the blood circulation, most of our knowledge about DC biology and function has been obtained in vitro from monocyte-derived DCs (moDCs, which can be readily generated in sufficient numbers and are able to differentiate into distinct functional subsets depending on the nature of stimulus. In particular, moDCs with tolerogenic properties (tolDCs possess great therapeutic potential for the treatment of autoimmune diseases. Several protocols have been developed to generate tolDCs in vitro, able to reinstruct auto-reactive T cells and to promote regulatory cells. While ligands and soluble mediators, by which DCs shape immune responses, have been vastly studied, the intracellular pathways and transcriptional regulators that govern tolDC differentiation and function are poorly understood. Whole-genome microarrays and proteomics provide useful strategies to dissect the complex molecular processes that promote tolerogenicity. Only few attempts have been made to understand tolDC biology through a global view on ‘omics’ profiles. So far, the identification of a common regulator of tolerogenicity has been hampered by the fact that each protocol, used for tolDC generation, targets distinct signaling pathways. Here we review the progress in understanding the transcriptional regulation of moDC differentiation, with a special focus on tolDCs, and highlight candidate molecules that might be associated with DC tolerogenicity.

  9. Advanced glycation end products inhibit both infection and transmission in trans of HIV-1 from monocyte-derived dendritic cells to autologous T cells.

    Science.gov (United States)

    Nasreddine, Nadine; Borde, Chloé; Gozlan, Joël; Bélec, Laurent; Maréchal, Vincent; Hocini, Hakim

    2011-05-15

    Highly active antiretroviral therapy is associated with carbohydrate metabolic alterations that may lead to diabetes. One consequence of hyperglycemia is the formation of advanced glycation end products (AGEs) that are involved in diabetes complications. We investigated the impact of AGEs on the infection of monocyte-derived dendritic cells (MDDCs) by HIV-1 and the ability of MDDCs to transmit the virus to T cells. We showed that AGEs could inhibit infection of MDDCs with primary R5-tropic HIV-1(Ba-L) by up to 85 ± 9.2% and with primary X4-tropic HIV-1(VN44) by up to 60 ± 8.5%. This inhibitory effect of AGEs was not prevented by a neutralizing anti-receptor for advanced glycation end products (anti-RAGE) Ab, demonstrating a RAGE-independent mechanism. Moreover, AGEs inhibited by 70-80% the transmission in trans of the virus to CD4 T cells. Despite the inhibitory effect of AGEs on both MDDC infection and virus transmission in trans, no inhibition of virus attachment to cell membrane was observed, confirming that attachment and transmission of the virus involve independent mechanisms. The inhibitory effect of AGEs on infection was associated with a RAGE-independent downregulation of CD4 at the cell membrane and by a RAGE-dependent repression of the CXCR4 and CCR5 HIV-1 receptors. AGEs induce the secretion of proinflammatory cytokines IL-6, TNF-α, and IL-12, but not RANTES or MIP-1α, and did not lead to MDDC maturation as demonstrated by the lack of expression of the CD83 molecule. Taken together, our results suggest that AGEs can play an inhibiting role in HIV-1 infection in patients who accumulate circulating AGEs, including patients treated with protease inhibitors that developed diabetes.

  10. Salvianolic acid B suppresses maturation of human monocyte-derived dendritic cells by activating PPARγ

    Science.gov (United States)

    Sun, Aijun; Liu, Hongying; Wang, Shijun; Shi, Dazhuo; Xu, Lei; Cheng, Yong; Wang, Keqiang; Chen, Keji; Zou, Yunzeng; Ge, Junbo

    2011-01-01

    BACKGROUND AND PURPOSE Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a Chinese medicinal herb, is known to be effective in the prevention of atherosclerosis. Here, we tested the hypothesis that the anti-atherosclerotic effect of Sal B might be mediated by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). EXPERIMENTAL APPROACH h-monDC were derived by incubating purified human monocytes with GM-CSF and IL-4. h-monDC were pre-incubated with or without Sal B and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of PPARγ siRNA. Expression of h-monDC membrane molecules (CD40, CD86, CD1a, HLA-DR) were analysed by FACS, cytokines were measured by elisa and the TLR4-associated signalling pathway was determined by Western blotting. KEY RESULTS Ox-LDL promoted h-monDC maturation, stimulated CD40, CD86, CD1a, HLA-DR expression and IL-12, IL-10, TNF-α production; and up-regulated TLR4 signalling. These effects were inhibited by Sal B. Sal B also triggered PPARγ activation and promoted PPARγ nuclear translocation, attenuated ox-LDL-induced up-regulation of TLR4 and myeloid differentiation primary-response protein 88 and inhibited the downstream p38-MAPK signalling cascade. Knocking down PPARγ with the corresponding siRNA blocked these effects of Sal B. CONCLUSIONS AND IMPLICATIONS Our data suggested that Sal B effectively suppressed maturation of h-monDC induced by ox-LDL through PPARγ activation. PMID:21649636

  11. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

    Science.gov (United States)

    Bueso-Ramos, Carlos E.; Newberry, Kate J.; Knez, Liza; Post, Sean M.; Ahn, Jihae; Levine, Ross L.; Kantarjian, Hagop M.

    2016-01-01

    Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients’ BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process. PMID:27481130

  12. Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients

    DEFF Research Database (Denmark)

    Trepiakas, Redas; Pedersen, Anders Elm; Met, Ozcan

    2008-01-01

    polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC......The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1...... of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up...

  13. Human dendritic cell DC-SIGN and TLR-2 mediate complementary immune regulatory activities in response to Lactobacillus rhamnosus JB-1.

    Science.gov (United States)

    Konieczna, Patrycja; Schiavi, Elisa; Ziegler, Mario; Groeger, David; Healy, Selena; Grant, Ray; O'Mahony, Liam

    2015-01-01

    The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.

  14. Human dendritic cell DC-SIGN and TLR-2 mediate complementary immune regulatory activities in response to Lactobacillus rhamnosus JB-1.

    Directory of Open Access Journals (Sweden)

    Patrycja Konieczna

    Full Text Available The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1. Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.

  15. Indoor pollutant hexabromocyclododecane enhances house dust mite-induced activation of human monocyte-derived dendritic cells.

    Science.gov (United States)

    Canbaz, Derya; Lebre, M Cristina; Logiantara, Adrian; van Ree, Ronald; van Rijt, Leonie S

    2016-11-01

    The indoor pollutant hexabromocyclododecane (HBCD) has been added as flame retardant to many consumer products but detaches and accumulates in house dust. Inhalation of house dust leads to exposure to house dust mite (HDM) allergens in the presence of HBCD. Activation of dendritic cells is crucial in the sensitization to HDM allergens. The current study examined whether exposure to HBCD affected activation/maturation of HDM-exposed human dendritic cells (DC). Human monocyte-derived DC (moDC) were exposed simultaneously to HDM and a concentration range of HBCD (0.1-20 μM) in vitro. HDM exposure of moDC induced expression of co-stimulatory molecule CD80 and production of pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α. However, simultaneous exposure of moDC to HBCD and HDM enhanced the expression of antigen presenting molecule HLA-DR, co-stimulatory molecule CD86 and pro-inflammatory cytokine IL-8 depending on the dose of HBCD. Our results indicate that simultaneous exposure of HDM and HBCD can enhance the antigen presentation and maturation/activation of DC.

  16. Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

    Institute of Scientific and Technical Information of China (English)

    Houjun Xia; Hongliang Liu; Gaohong Zhang; Yongtang Zheng

    2009-01-01

    Dendritic cells (DCs) play a pivotal role in linking the innate immunity and acquired immunity in responses to pathogen. Non-human primates such as Chinese Rhesus Macaque (CRM) are the favorable models for preclinical study of potential therapeutic drugs, vaccines and mechanisms of human diseases. However, the phenotypicai characterization of monocyte-derived dendritic cells (MDDCs) from CRM has not been elucidated. Monocytes from CRM were cultured with GM-CSF and IL-4 in RPMI-1640. Six days later, these cells were differentiated with typical dendritical morphology. CDllc and DC-SIGN were highly expressed. The immature MDDCs expressed the low levels of CD25, CD80, CD83, moderate CD40, CD86, and high MHC. After stimulation, the mature MDDCs increased expression of mature molecules CD25 and CD83, co-stimulatory molecules such as CD80, CD86 and CD40, and kept a high level of MHC. The capacity of endocytosis decreased with maturation. The mature MDDCs have strong ability of inducing allogeneic T cell proliferation and producing IL-12. In conclusion, we have characterized the phenotype and ultimate function of MDDCs from CRM for the first time. Cellular & Molecular Immunology. 2009;6(3):159-165.

  17. CHI3L1 nuclear localization in monocyte derived dendritic cells.

    Science.gov (United States)

    Di Rosa, Michelino; Tibullo, Daniele; Saccone, Salvatore; Distefano, Gisella; Basile, Maria Sofia; Di Raimondo, Francesco; Malaguarnera, Lucia

    2016-02-01

    Chitinase-3-like-1 protein (CHI3L1) is a glycosyl hydrolase (GH) highly expressed in a variety of inflammatory diseases at infectious and non-infectious etiology. CHI3L1 is produced by a wide variety of cells including monocyte-derived macrophages cell lines such as polarized M1 and M2 type macrophages, osteoclasts and Kupffer cells. In this study we have examined the expression of CHI3L1 during the differentiation and maturation of dendritic cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) through a combination of factors and cytokines. Our result showed, for the first time, that CHI3L1 is expressed during the process of differentiation and maturation of dendritic cells in time dependent manner. Furthermore, the CHI3L1 is evenly distributed in cytoplasm and in the nucleus of both the iDCs and mDCs. These results suggest that CHI3L1 may play crucial role in the DCs immunoresponse.

  18. Levamisole enhances immune response by affecting the activation and maturation of human monocyte-derived dendritic cells

    Science.gov (United States)

    Chen, L-Y; Lin, Y-L; Chiang, B-L

    2008-01-01

    Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent. Current studies have been focused upon its effect on immune response and on cancer treatment. We examined the molecular mechanisms of levamisole in the activation and maturation of human monocyte-derived dendritic cells (DC) and human T cells. Treatment of DC with levamisole increased the presentation of CD80, CD86, CD83 and human leucocyte antigen D-related (HLA-DR) molecules on the cell membrane, as well as the production of interleukin (IL)-12 p40 and IL-10. Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune response by inducing interferon-γ secretion. Neutralization with antibodies against Toll-like receptor (TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10, suggesting a vital role for TLR-2 in signalling DC upon incubation with levamisole. The inhibition of nuclear factor-κB, extracellular signal-regulated kinases 1/2 or c-Jun N-terminal kinases pathways also prevented the effects of levamisole on DC in producing IL-12 p40 or IL-10. Taken together, levamisole could enhance immune response towards T helper 1 development through the activation of dendritic cells or T cell aspects. PMID:18005262

  19. Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells.

    Science.gov (United States)

    Balan, Sreekumar; Ollion, Vincent; Colletti, Nicholas; Chelbi, Rabie; Montanana-Sanchis, Frédéric; Liu, Hong; Vu Manh, Thien-Phong; Sanchez, Cindy; Savoret, Juliette; Perrot, Ivan; Doffin, Anne-Claire; Fossum, Even; Bechlian, Didier; Chabannon, Christian; Bogen, Bjarne; Asselin-Paturel, Carine; Shaw, Michael; Soos, Timothy; Caux, Christophe; Valladeau-Guilemond, Jenny; Dalod, Marc

    2014-08-15

    Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1(+) DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1(+) human DC. Assessment of the immunoactivation potential of XCR1(+) human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1(+) and XCR1(-) human DC in CD34(+) progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1(-) CD34-DC are similar to canonical MoDC, whereas XCR1(+) CD34-DC resemble XCR1(+) blood DC (bDC). XCR1(+) DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1(+) DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1(+) CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1(+) bDC. Hence, it is feasible to generate high numbers of bona fide XCR1(+) human DC in vitro as a model to decipher the functions of XCR1(+) bDC and as a potential source of XCR1(+) DC for clinical use.

  20. Galectin-3 Binding Protein Secreted by Breast Cancer Cells Inhibits Monocyte-Derived Fibrocyte Differentiation.

    Science.gov (United States)

    White, Michael J V; Roife, David; Gomer, Richard H

    2015-08-15

    To metastasize, tumor cells often need to migrate through a layer of collagen-containing scar tissue which encapsulates the tumor. A key component of scar tissue and fibrosing diseases is the monocyte-derived fibrocyte, a collagen-secreting profibrotic cell. To test the hypothesis that invasive tumor cells may block the formation of the fibrous sheath, we determined whether tumor cells secrete factors that inhibit monocyte-derived fibrocyte differentiation. We found that the human metastatic breast cancer cell line MDA-MB-231 secretes activity that inhibits human monocyte-derived fibrocyte differentiation, whereas less aggressive breast cancer cell lines secrete less of this activity. Purification indicated that Galectin-3 binding protein (LGALS3BP) is the active factor. Recombinant LGALS3BP inhibits monocyte-derived fibrocyte differentiation, and immunodepletion of LGALS3BP from MDA-MB 231 conditioned media removes the monocyte-derived fibrocyte differentiation-inhibiting activity. LGALS3BP inhibits the differentiation of monocyte-derived fibrocytes from wild-type mouse spleen cells, but not from SIGN-R1(-/-) mouse spleen cells, suggesting that CD209/SIGN-R1 is required for the LGALS3BP effect. Galectin-3 and galectin-1, binding partners of LGALS3BP, potentiate monocyte-derived fibrocyte differentiation. In breast cancer biopsies, increased levels of tumor cell-associated LGALS3BP were observed in regions of the tumor that were invading the surrounding stroma. These findings suggest LGALS3BP and galectin-3 as new targets to treat metastatic cancer and fibrosing diseases.

  1. Lentiviral-mediated gene delivery in human monocyte-derived dendritic cells: optimized design and procedures for highly efficient transduction compatible with clinical constraints.

    Science.gov (United States)

    Rouas, Redouane; Uch, Rathviro; Cleuter, Yvette; Jordier, François; Bagnis, Claude; Mannoni, Patrice; Lewalle, Philippe; Martiat, Philippe; Van den Broeke, Anne

    2002-09-01

    Gene delivery to dendritic cells (DCs) could represent a powerful method of inducing potent, long-lasting immunity. Although recent studies underline the intense interest in lentiviral vector-mediated monocyte-derived DC transduction, efficient gene transfer methods currently require high multiplicities of infection and are not compatible with clinical constraints. We have designed a strategy to optimize the efficiency and clinical relevance of this approach. Initially, using a third generation lentiviral vector expressing green fluorescent protein, we found that modifying the vector design, the DC precursor cell type, and the DC differentiation stage for transduction results in sustained transgene expression in 75-85% of immature DCs (transduction at a multiplicity of infection of 8). This high efficiency was reproducible among different donors irrespective of whether DCs were expanded from fresh or cryopreserved CD14(+) precursors. We then developed procedures that bypass the need for highly concentrated lentiviral preparations and the addition of polybrene to achieve efficient transduction. DCs transduced under these conditions retain their immature phenotype and immunostimulatory potential in both autologous and allogeneic settings. Furthermore, genetically modified DCs maintain their ability to respond to maturation signals and secrete bioactive IL-12, indicating that they are fully functional. Finally, the level of transgene expression is preserved in the therapeutically relevant mature DCs, demonstrating that there is neither promoter-silencing nor loss of transduced cells during maturation. The novel approach described should advance lentiviral-mediated monocyte-derived DC transduction towards a clinical reality.

  2. PU.1 is essential for CD11c expression in CD8(+/CD8(- lymphoid and monocyte-derived dendritic cells during GM-CSF or FLT3L-induced differentiation.

    Directory of Open Access Journals (Sweden)

    Xue-Jun Zhu

    Full Text Available Dendritic cells (DCs regulate innate and acquired immunity through their roles as antigen-presenting cells. Specific subsets of mature DCs, including monocyte-derived and lymphoid-derived DCs, can be distinguished based on distinct immunophenotypes and functional properties. The leukocyte integrin, CD11c, is considered a specific marker for DCs and it is expressed by all DC subsets. We created a strain of mice in which DCs and their progenitors could be lineage traced based on activity of the CD11c proximal promoter. Surprisingly, we observed levels of CD11c promoter activity that were similar in DCs and in other mature leukocytes, including monocytes, granulocytes, and lymphocytes. We sought to identify DNA elements and transcription factors that regulate DC-associated expression of CD11c. The ets transcription factor, PU.1, is a key regulator of DC development, and expression of PU.1 varies in different DC subsets. GM-CSF increased monocyte-derived DCs in mice and from mouse bone marrow cultured in vitro, but it did not increase CD8(+ lymphoid-derived DCs or B220(+ plasmacytoid DCs. FLT3L increased both monocyte-derived DCs and lymphoid-derived DCs from mouse bone marrow cultured in vitro. GM-CSF increased the 5.3 Kb CD11c proximal promoter activity in monocyte-derived DCs and CD8(+ lymphoid-derived DCs, but not in B220(+ plasmacytoid DCs. In contrast, FLT3L increased the CD11c proximal promoter activity in both monocyte-derived DCs and B220(+ plasmacytoid DCs. We used shRNA gene knockdown and chromatin immunoprecipitation to demonstrate that PU.1 is required for the effects of GM-CSF or FLT3L on monocyte-derived DCs. We conclude that both GM-CSF and FLT3L act through PU.1 to activate the 5.3 Kb CD11c proximal promoter in DCs and to induce differentiation of monocyte-derived DCs. We also confirm that the CD11c proximal promoter is not sufficient to direct lineage specificity of CD11c expression, and that additional DNA elements are required

  3. Inducing Maturation of Monocyte-Derived Dendritic Cells on Human Epithelial Cell Feeder Layer

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    Delirezh N

    2012-02-01

    Full Text Available Background: Nowadays, dendritic cells (DCs have a special place in cancer treatment strategies and they have been used for tumor immunotherapy as they can induce immune response against tumor cells. Researchers have been trying to generate efficient dendritic cells in vitro; therefore, this research was done to generate them for use in research and tumor immunotherapy. Methods: This study took place at Urmia University in 2010-2011 years. In this study plastic adherent monocytes were incubated with granulocyte-macrophage colony stimulating factor (GM-CSF and interleukin-4 (IL-4 for five days. Finally, fully matured and stable DCs were generated by 48 hours of incubation in a monocyte conditioned medium (MCM containing tumor necrosis factor-α (TNF-α and epithelial cells. Phenotypic and functional analysis were carried out by using anti-CD14, anti-CD80, anti-CD86, and anti-CD83 monoclonal antibodies, and by determining their phagocytic activity, mixed lymphocyte reaction (MLR and cytokine production, respectively. Results: Dendritic cells were produced with high levels of surface molecule, i.e. of CD80, CD83, CD86, HLA-DR, expression and low levels of CD14 expression. Dendritic cells showed efficient phagocytosis and ability to stimulate T-lymphocytes. Moreover, dendritic cells could secrete high levels of interleukin-12 (IL-12 cytokine which was depictive of their full maturation. Measurement of the produced cytokines showed the generation of type-1 dendritic cells (DC1. Conclusion: Our study showed that skin epithelial cells could induce maturation of monocyte-derived dendritic cells (DCs. This feeder layer led to the production of efficient dendritic cells with the ability to be used for tumor immunotherapy.

  4. Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity.

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    Bol, Kalijn F; Aarntzen, Erik H J G; Pots, Jeanette M; Olde Nordkamp, Michel A M; van de Rakt, Mandy W M M; Scharenborg, Nicole M; de Boer, Annemiek J; van Oorschot, Tom G M; Croockewit, Sandra A J; Blokx, Willeke A M; Oyen, Wim J G; Boerman, Otto C; Mus, Roel D M; van Rossum, Michelle M; van der Graaf, Chantal A A; Punt, Cornelis J A; Adema, Gosse J; Figdor, Carl G; de Vries, I Jolanda M; Schreibelt, Gerty

    2016-03-01

    Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase. Tumor antigen-specific T cell responses were monitored in blood and skin-test infiltrating-lymphocyte cultures. Almost all patients mounted prophylactic vaccine- or KLH-specific immune responses. Both after intranodal injection and after intradermal/intravenous injection, tumor antigen-specific immune responses were detected, which coincide with longer overall survival in stage IV melanoma patients. VAC-DC induce local and systemic CTC grade 2 and 3 toxicity, which is most likely caused by BCG in the maturation cocktail. The side effects were self-limiting or resolved upon a short period of systemic steroid therapy. We conclude that VAC-DC can induce functional tumor-specific responses. Unfortunately, toxicity observed after vaccination precludes the general application of VAC-DC, since in DC maturated with prophylactic vaccines BCG appears to be essential in the maturation cocktail.

  5. Phenotypic, functional, and quantitative characterization of canine peripheral blood monocyte-derived macrophages

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    R Bueno

    2005-08-01

    Full Text Available The yield as well as phenotypic and functional parameters of canine peripheral blood monocyte-derived macrophages were analyzed. The cells that remained adherent to Teflon after 10 days of culture had high phagocytic activity when inoculated with Leishmania chagasi. Flow cytometric analysis demonstrated that more than 80% of cultured cells were positive for the monocyte/macrophage marker CD14.

  6. The TLR Expression Pattern on Monocyte-Derived Macrophages for Lipopolysaccharid Stimulation of Calves

    Institute of Scientific and Technical Information of China (English)

    GUO Yi-jie; ZHAO Guo-Qi; HUO Yong-jiu; Sachi Tana-ka; Hisashi Aso; Takahiro Yamaguchi

    2009-01-01

    In this paper, toll-like receptor expression pattern in monocytes-derived macrophages by lipopolysaccharid (LPS) stimulation was examined. Jugular venous blood samples from 4 Japanese calves were obtained and the peripheral blood mononuclear cells (PBMC) were isolated. The PBMC were cultured for 7 d so as to collect monocytes-derived macrophages in Repcell. The PBMC were stimulated by LPS for 24 h and the mRNA expression pattern of TLR and cytokines in monocytes-derived macrophages (Mod-Mφ) was analyzed. Results showed that LPS stimulation of Mod-Mφ could increase the mRNA levels of the genes of TNF-α, IL-6, and IL-8. In addition, the mRNA levels of the genes of TNF-α and IL-6 in the group of LPS stimulation were most significantly (P<0.01) higher than those in control group and the mRNA levels of TLR1, 3, 5, 8, and 10 were significantly (P<0.05) decreased after LPS stimulation. There was no difference in the mRNA expressions of TLR2, 4, 6, and 7 between the groups of the control and LPS stimulation. Besides, expression of TLR9 was not found. It suggested that monocytes-derived macrophages could respond to LPS and they might take an important role in the innate immunity. The important function of the cells might contribute to better disease treatment.

  7. Inhibition of the differentiation of monocyte-derived dendritic cells by human gingival fibroblasts.

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    Sylvie Séguier

    Full Text Available We investigated whether gingival fibroblasts (GFs can modulate the differentiation and/or maturation of monocyte-derived dendritic cells (DCs and analyzed soluble factors that may be involved in this immune modulation. Experiments were performed using human monocytes in co-culture with human GFs in Transwell® chambers or using monocyte cultures treated with conditioned media (CM from GFs of four donors. The four CM and supernatants from cell culture were assayed by ELISA for cytokines involved in the differentiation of dendritic cells, such as IL-6, VEGF, TGFβ1, IL-13 and IL-10. The maturation of monocyte-derived DCs induced by LPS in presence of CM was also studied. Cell surface phenotype markers were analyzed by flow cytometry. In co-cultures, GFs inhibited the differentiation of monocyte-derived DCs and the strength of this blockade correlated with the GF/monocyte ratio. Conditioned media from GFs showed similar effects, suggesting the involvement of soluble factors produced by GFs. This inhibition was associated with a lower stimulatory activity in MLR of DCs generated with GFs or its CM. Neutralizing antibodies against IL-6 and VEGF significantly (P<0.05 inhibited the inhibitory effect of CM on the differentiation of monocytes-derived DCs and in a dose dependent manner. Our data suggest that IL-6 is the main factor responsible for the inhibition of DCs differentiation mediated by GFs but that VEGF is also involved and constitutes an additional mechanism.

  8. Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells.

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    Chan, Ben Chung Lap; Li, Long Fei; Hu, Shui Qing; Wat, Elaine; Wong, Eric Chun Wai; Zhang, Vanilla Xin; Lau, Clara Bik San; Wong, Chun Kwok; Hon, Kam Lun Ellis; Hui, Patrick Chi Leung; Leung, Ping Chung

    2015-09-10

    Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

  9. Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells

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    Ben Chung Lap Chan

    2015-09-01

    Full Text Available Atopic dermatitis (AD is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC culture model coupled with the high-speed counter-current chromatography (HSCCC, high pressure liquid chromatography (HPLC and Liquid Chromatography-Mass Spectrometry (LCMS analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL-12 p40 and the functional cluster of differentiation (CD surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

  10. Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis

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    Czibere Akos

    2007-09-01

    Full Text Available Abstract Background Dendritic cell (DC vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC. Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01. Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006. Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In

  11. Human monocyte-derived dendritic cells expressing both chemotactic cytokines IL-8, MCP-1, RANTES and their receptors,and their selective migration to these chemokines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation,normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC- CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocyte derived dendritic cells (MoDCs).The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was alsso studied. Methods In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratoly ability was assessed by a micromultiwell chemotaxis chamber assay. Results IL-8, MCP-1, RANTES and their corres ponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable efter 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present. Conclusion Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses.

  12. Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells

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    Stefanie Hoyer

    2015-01-01

    Full Text Available For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs. However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs’ immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1, and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFα of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-κB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs.

  13. HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells.

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    Del Cornò, Manuela; Donninelli, Gloria; Varano, Barbara; Da Sacco, Letizia; Masotti, Andrea; Gessani, Sandra

    2014-10-01

    Dendritic cells (DCs) are fundamental for the initiation of immune responses and are important players in AIDS immunopathogenesis. The modulation of DC functional activities represents a strategic mechanism for HIV-1 to evade immune surveillance. Impairment of DC function may result from bystander effects of HIV-1 envelope proteins independently of direct HIV-1 infection. In this study, we report that exposure of immature monocyte-derived DCs (MDDCs) to HIV-1 R5 gp120 resulted in the CCR5-dependent production of interleukin-6 (IL-6) via mitogen-activated protein kinase (MAPK)/NF-κB pathways. IL-6 in turn activated STAT3 by an autocrine loop. Concomitantly, gp120 promoted an early activation of STAT3 that further contributed to IL-6 induction. This activation paralleled a concomitant upregulation of the STAT3 inhibitor PIAS3. Notably, STAT3/IL-6 pathway activation was not affected by the CCR5-specific ligand CCL4. These results identify STAT3 as a key signaling intermediate activated by gp120 in MDDCs and highlight the existence of a virus-induced dysregulation of the IL-6/STAT3 axis. HIV-1 gp120 signaling through STAT3 may provide an explanation for the impairment of DC function observed upon HIV exposure. This study provides new evidence for the molecular mechanisms and signaling pathways triggered by HIV-1 gp120 in human DCs in the absence of productive infection, emphasizing a role of aberrant signaling in early virus-host interaction, contributing to viral pathogenesis. We identified STAT3 as a key component in the gp120-mediated signaling cascade involving MAPK and NF-κB components and ultimately leading to IL-6 secretion. STAT3 now is recognized as a key regulator of DC functions. Thus, the identification of this transcription factor as a signaling molecule mediating some of gp120's biological effects unveils a new mechanism by which HIV-1 may deregulate DC functions and contribute to AIDS pathogenesis. Copyright © 2014, American Society for Microbiology

  14. In vitro interactions of Candida parapsilosis wild type and lipase deficient mutants with human monocyte derived dendritic cells

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    Vágvölgyi Csaba

    2011-05-01

    Full Text Available Abstract Background Candida parapsilosis typically is a commensal of human skin. However, when host immune defense is compromised or the normal microflora balance is disrupted, C. parapsilosis transforms itself into an opportunistic pathogen. Candida-derived lipase has been identified as potential virulence factor. Even though cellular components of the innate immune response, such as dendritic cells, represent the first line of defense against invading pathogens, little is known about the interaction of these cells with invading C. parapsilosis. Thus, the aim of our study was to assess the function of dendritic cells in fighting C. parapsilosis and to determine the role that C. parapsilosis-derived lipase plays in the interaction with dendritic cells. Results Monocyte-derived immature and mature dendritic cells (iDCs and mDCs, respectively co-cultured with live wild type or lipase deficient C. parapsilosis strains were studied to determine the phagocytic capacity and killing efficiency of host cells. We determined that both iDCs and mDCs efficiently phagocytosed and killed C. parapsilosis, furthermore our results show that the phagocytic and fungicidal activities of both iDCs and mDCs are more potent for lipase deficient compared to wild type yeast cells. In addition, the lipase deficient C. parapsilosis cells induce higher gene expression and protein secretion of proinflammatory cytokines and chemokines in both DC types relative to the effect of co-culture with wild type yeast cells. Conclusions Our results show that DCs are activated by exposure to C. parapsilosis, as shown by increased phagocytosis, killing and proinflammatory protein secretion. Moreover, these data strongly suggest that C. parapsilosis derived lipase has a protective role during yeast:DC interactions, since lipase production in wt yeast cells decreased the phagocytic capacity and killing efficiency of host cells and downregulated the expression of host effector molecules.

  15. Dysfunctional HDL from HIV+ individuals promotes monocyte-derived foam cell formation in vitro.

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    Angelovich, Thomas A; Hearps, Anna C; Oda, Michael N; Borja, Mark S; Huynh, Diana; Homann, Stefanie; Jaworowski, Anthony; Kelesidis, Theodoros

    2017-09-18

    The role of HDL function in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. HDLs isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals (HDL) were assessed for HDL function and ability to promote monocyte-derived foam cell formation (MDFCF) (a key event in HIV-related CVD) ex vivo. Using an established in vitro model of atherogenesis and plasma samples from an established cross-sectional study of virologically-suppressed HIV+ males on stable effective antiretroviral therapy (ART) and with low CVD risk (median age: 42 years; n = 10), we explored the impact of native HDL [HIV(+)HDL] on MDFCF. In this exploratory study we selected HIV-HDL known to be dysfunctional based on two independent measures of impaired HDL function: a) antioxidant (high HDLox) b) ability of HDL to release apoA-I [low HDL-apoA-I exchange (HAE %)]. Five healthy males matched by age and race to the HIV+ group were included. Given that oxidation of HDL leads to abnormal HDL function, we also compared proatherogenic effects of HIV-HDL versus chemically-derived HDLox. The ex vivo atherogenesis assay was performed using lipoproteins (purchased or isolated from plasma using ultracentrifugation) and monocytes purified via negative selection from healthy donors. HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoAI exchange promoted MDFCF to a greater extent than HDL (33.0% vs 26.2% foam cells; p = 0.015). HDL oxidized in vitro also enhanced foam cell formation as compared to non-oxidized HDL (p HDL in virologically suppressed HIV+ individuals may potentiate atherosclerosis in HIV infection by promoting monocyte-derived foam cell formation.The role of HDL function in HIV-related atherosclerotic cardiovascular disease is unclear. HDL isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals [HIV(-)HDL] were assessed for HDL function and ability to promote foam cell formation ex vivo. HIV(+)HDL known to have reduced antioxidant function and

  16. Leishmania mexicana promastigotes down regulate JNK and p-38 MAPK activation: Role in the inhibition of camptothecin-induced apoptosis of monocyte-derived dendritic cells.

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    Rodríguez-González, Jorge; Wilkins-Rodríguez, Arturo; Argueta-Donohué, Jesús; Aguirre-García, Magdalena; Gutiérrez-Kobeh, Laila

    2016-04-01

    Dendritic cells (DC) are one of the principal host cells of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. We have previously shown that the infection of monocyte-derived dendritic cells (moDC) with Leishmania mexicana inhibits campthotecin-induced apoptosis. Nevertheless, the mechanisms involved in the inhibition of apoptosis of dendritic cells by Leishmania have not been established. Mitogen-activated protein kinases (MAPK) are key participants in the process of apoptosis and different species of Leishmania have been shown to regulate these kinases. In the present study, we analyzed the effect of L. mexicana promastigotes in the activation of JNK and p38 MAP kinase and their participation in the inhibition of apoptosis. The infection of moDC with L. mexicana promastigotes diminished significantly the phosphorylation of the MAP kinases JNK and p38. The inhibition of both kinases diminished DNA fragmentation, but in a major extent was the reduction of DNA fragmentation when JNK was inhibited. The capacity of L. mexicana promastigotes to diminish MAP kinases activation is probably one of the strategies employed to delay apoptosis induction in the infected moDC and may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.

  17. Human Monocyte-Derived Osteoclasts Are Targeted by Staphylococcal Pore-Forming Toxins and Superantigens.

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    Sacha Flammier

    Full Text Available Staphylococcus aureus is the leading cause of bone and joint infections (BJIs. Staphylococcal pathogenesis involves numerous virulence factors including secreted toxins such as pore-forming toxins (PFTs and superantigens. The role of these toxins on BJI outcome is largely unknown. In particular, few studies have examined how osteoclasts, the bone-resorbing cells, respond to exposure to staphylococcal PFTs and superantigens. We investigated the direct impact of recombinant staphylococcal toxins on human primary mature monocyte-derived osteoclasts, in terms of cytotoxicity and cell activation with cell death and bone resorption assays, using macrophages of the corresponding donors as a reference. Monocyte-derived osteoclasts displayed similar toxin susceptibility profiles compared to macrophages. Specifically, we demonstrated that the Panton-Valentine leukocidin, known as one of the most powerful PFT which lyses myeloid cells after binding to the C5a receptor, was able to induce the death of osteoclasts. The archetypal superantigen TSST-1 was not cytotoxic but enhanced the bone resorption activity of osteoclasts, suggesting a novel mechanism by which superantigen-producing S. aureus can accelerate the destruction of bone tissue during BJI. Altogether, our data indicate that the diverse clinical presentations of BJIs could be related, at least partly, to the toxin profiles of S. aureus isolates involved in these severe infections.

  18. Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells.

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    Wang, C; Ye, Z; Kijlstra, A; Zhou, Y; Yang, P

    2014-08-01

    Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.

  19. SLAM/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte-derived dendritic cells.

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    Réthi, Bence; Gogolák, Péter; Szatmari, Istvan; Veres, Agota; Erdôs, Erika; Nagy, Laszlo; Rajnavölgyi, Eva; Terhorst, Cox; Lányi, Arpád

    2006-04-01

    Signaling lymphocyte activation molecule (SLAM, CD150, or SLAMF1) is a self-ligand receptor on the surface of activated T- and B-lymphocytes, macrophages, and dendritic cells (DCs). Here we examine the effect of SLAM/SLAM interactions on CD40L-induced CD40 signaling pathways in human DCs. CD40L-expressing L929 cells induced DCs to produce interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and IL-12, which was strongly inhibited by coexpression of SLAM on the surface of the L929 cells. Similarly, transfection of DCs with SLAM strongly reduced CD40L-induced IL-12 production. Furthermore, the negative effect of SLAM/SLAM interactions on CD40L-induced DC activation was also detected in the presence of lipopolysaccharide (LPS). LPS-induced IL-12 secretion, however, was not inhibited by SLAM engagement. CD40L-activated DCs affected by exposure to SLAM/SLAM engagement were impaired in their ability to induce differentiation of naive T lymphocytes into interferon-gamma (IFN-gamma)-producing T-helper 1 (Th1) effector cells. These inhibitory effects were not the result of a general unresponsiveness of DCs to CD40L, as SLAM/SLAM interactions did not prevent CD40L-induced up-regulation of CD83, CD86, or human leukocyte antigen (HLA)-DQ on the surface of DCs. Taken together, the results indicate that SLAM/SLAM interactions inhibit CD40-induced signal transduction in monocyte-derived dendritic cells, an effect that was not detectable in earlier studies using anti-SLAM monoclonal antibodies.

  20. Human monocyte-derived dendritic cells from leukoreduction system chambers after plateletpheresis are functional in an in vitro co-culture assay with intestinal epithelial cells.

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    Tiscornia, Inés; Sánchez-Martins, Viviana; Hernández, Ana; Bollati-Fogolín, Mariela

    2012-10-31

    PP as an alternative source of PBMC, to be used in co-culture systems with IEC. The novelty of this protocol is the combination of the blood monocyte source with a simple and fast differentiation method to obtain DC, and their use in a combined culture with IEC and LAB to model microbial-host interaction. Since the initial PP volume is ten times lower than that of BC, the use of PP minimizes biological residue generation and reagent consumption. In addition, monocyte-derived DC from PP were suitable for use in co-culture assays as a first screening step to study the immunomodulatory properties of LAB.

  1. PGE2 differentially regulates monocyte-derived dendritic cell cytokine responses depending on receptor usage (EP2/EP4).

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    Poloso, Neil J; Urquhart, Paula; Nicolaou, Anna; Wang, Jenny; Woodward, David F

    2013-07-01

    Dendritic cells (DCs) are central players in coordinating immune responses, both innate and adaptive. While the role of lipid mediators in the immune response has been the subject of many investigations, the precise role of prostaglandins has often been plagued by contradictory studies. In this study, we examined the role of PGE(2) on human DC function. Although studies have suggested that PGE(2) specifically plays a role in DC motility and cytokine release profile, the precise receptor usage and signaling pathways involved remain unclear. In this report we found that irrespective of the human donor, monocyte-derived dendritic cells (MoDCs) express three of the four PGE(2) receptor subtypes (EP(2-4)), although only EP(2) and EP(4) were active with respect to cytokine production. Using selective EP receptor antagonists and agonists, we demonstrate that PGE(2) coordinates control of IL-23 release (a promoter of Th17, an autoimmune associated T cell subset) in a dose-dependent manner by differential use of EP(2) and EP(4) receptors in LPS-activated MoDCs. This is in contrast to IL-12, which is dose dependently inhibited by PGE(2) through both receptor subtypes. Low concentrations (∼1-10nM) of PGE(2) promoted IL-23 production via EP(4) receptors, while at higher (>50 nM), but still physiologically relevant concentrations, IL-23 is suppressed by an EP(2) dependent mechanism. These results can be explained by differential regulation of the common subunit, IL-12p40, and IL-23p19, by EP(2) and EP(4). By these means, PGE(2) can act as a regulatory switch of immune responses depending on its concentration in the microenvironment. In addition, we believe these results may also explain why seemingly conflicting biological functions assigned to PGE(2) have been reported in the literature, as the concentration of ligand (PGE(2)) fundamentally alters the nature of the response. This finding also highlights the potential of designing therapeutics which differentially target

  2. TNF and PGE2 in human monocyte-derived macrophages infected with Chlamydia trachomatis

    Directory of Open Access Journals (Sweden)

    E. Manor

    1993-01-01

    Full Text Available In this study levels of prostaglandin E2 (PGE2, tumour necrosis factor (TNF and interleukin-1 (IL-1 alpha in medium from monocyte derived macrophages (MdM infected with Chlamydia trachomatis (L2/434/Bu or K biovars. TNF and PGE2 were found in both cases while IL-1 alpha was not detected. Both TNF and PGE2 levels were higher in the medium of the MdM infected with K biovars. TNF reached maximum levels 24 h postinfection, and then declined, while PGE2 levels increased continuously during the infection time up to 96 h post-infection. Addition of dexamethasone inhibited production of TNF and PGE2. Inhibition of PGE2 production by indomethacin resulted in increased production of TNF, while addition of PGE2 caused partial inhibition of TNF production from infected MdM.

  3. In vitro interaction of Stenotrophomonas maltophilia with human monocyte-derived dendritic cells

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    Emanuela eRoscetto

    2015-07-01

    Full Text Available Stenotrophomonas maltophilia is increasingly identified as an opportunistic pathogen in immunocompromised, cancer and cystic fibrosis (CF patients. Knowledge on innate immune responses to S. maltophilia and its potential modulation is poor. The present work investigated the ability of 12 clinical S. maltophilia strains (5 from CF patients, 7 from non-CF patients and one environmental strain to survive inside human monocyte-derived dendritic cells (DCs. The effects of the bacteria on maturation of and cytokine secretion by DCs were also measured. S. maltophilia strains presented a high degree of heterogeneity in internalization and intracellular replication efficiencies as well as in the ability of S. maltophilia to interfere with normal DCs maturation. By contrast, all S. maltophilia strains were able to activate DCs, as measured by increase in the expression of surface maturation markers and proinflammatory cytokines secretion.

  4. HCMV Displays a Unique Transcriptome of Immunomodulatory Genes in Primary Monocyte-Derived Cell Types

    Science.gov (United States)

    Van Damme, Ellen; Thys, Kim; Tuefferd, Marianne; Van Hove, Carl; Aerssens, Jeroen; Van Loock, Marnix

    2016-01-01

    Human cytomegalovirus (HCMV) is a betaherpesvirus which rarely presents problems in healthy individuals, yet may result in severe morbidity in immunocompromised patients and in immune-naïve neonates. HCMV has a large 235 kb genome with a coding capacity of at least 165 open reading frames (ORFs). This large genome allows complex gene regulation resulting in different sets of transcripts during lytic and latent infection. While latent virus mainly resides within monocytes and CD34+ progenitor cells, reactivation to lytic infection is driven by differentiation towards terminally differentiated myeloid dendritic cells and macrophages. Consequently, it has been suggested that macrophages and dendritic cells contribute to viral spread in vivo. Thus far only limited knowledge is available on the expression of HCMV genes in terminally differentiated myeloid primary cells and whether or not the virus exhibits a different set of lytic genes in primary cells compared with lytic infection in NHDF fibroblasts. To address these questions, we used Illumina next generation sequencing to determine the HCMV transcriptome in macrophages and dendritic cells during lytic infection and compared it to the transcriptome in NHDF fibroblasts. Here, we demonstrate unique expression profiles in macrophages and dendritic cells which significantly differ from the transcriptome in fibroblasts mainly by modulating the expression of viral transcripts involved in immune modulation, cell tropism and viral spread. In a head to head comparison between macrophages and dendritic cells, we observed that factors involved in viral spread and virion composition are differentially regulated suggesting that the plasticity of the virion facilitates the infection of surrounding cells. Taken together, this study provides the full transcript expression analysis of lytic HCMV genes in monocyte-derived type 1 and type 2 macrophages as well as in monocyte-derived dendritic cells. Thereby underlining the potential

  5. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques.

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    Paul F Bradfield

    Full Text Available Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies.

  6. Characterization of canine monocyte-derived dendritic cells with phenotypic and functional differentiation.

    Science.gov (United States)

    Wang, Yu-Shan; Chi, Kwan-Hwa; Liao, Kuang-Wen; Liu, Cheng-Chi; Cheng, Chiao-Lei; Lin, Yi-Chun; Cheng, Chiung-Hsiang; Chu, Rea-Min

    2007-07-01

    For therapeutic purposes, large numbers of dendritic cells (DCs) are essential. In this study, we used 2% autologous canine plasma, granulocyte/macrophage colony-stimulating factor (GM-CSF), fms-like tyrosine kinase 3 ligand (Flt3L), and interleukin 4 (IL-4) in generating monocyte-derived DCs from peripheral blood mononuclear cells of dogs. The plasma enriched the population of CD14-positive monocytes by greatly enhancing the efficiency of monocyte adherence, the proportion of adherent cells increasing from 6.6% with 10% fetal bovine serum to 15.3% with 2% autologous canine plasma. Culturing the adherent monocytes for 6 d with human GM-CSF, canine IL-4, and human Flt3L significantly increased the yield of DCs, more than 90% of which were CD14-negative. Because, in the presence of lipopolysaccharide (LPS), monocytes that were CD14-positive expressed tumor necrosis factor ac much more than DCs with low levels of CD14, it is important to decrease the numbers of CD14-positive cells in generating monocyte-derived DCs. With flow cytometry and real-time reverse-transcriptase-mediated polymerase chain reaction assays, we found that in canine immature DCs (iDCs) the expression of DLA class II molecules, CD1a, CD11c, CD40, and CD86 was high and the expression of CD80, CD83, and CD14 either low or negative. During maturation (stimulated by LPS), the expression of CDla, CD40, CD83, and CD80 was upregulated. However, the expression of DLA class II molecules, CD11c, and CD86 was not increased in mature DCs. Incubating the iDCs with LPS decreased antigen uptake and increased the cells' immunostimulatory capacity (assessed by the allogeneic mixed-lymphocyte reaction), indicating that LPS accelerates the functional maturation of DCs. This protocol may facilitate the use of DCs in cellular immunotherapy.

  7. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques.

    Science.gov (United States)

    Bradfield, Paul F; Menon, Arjun; Miljkovic-Licina, Marijana; Lee, Boris P; Fischer, Nicolas; Fish, Richard J; Kwak, Brenda; Fisher, Edward A; Imhof, Beat A

    2016-01-01

    Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C) expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies.

  8. Nogo-B is associated with cytoskeletal structures in human monocyte-derived macrophages

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    Gredler Viktoria

    2011-01-01

    Full Text Available Abstract Background The reticulon Nogo-B participates in cellular and immunological processes in murine macrophages. Since leukocytes are an essential part of the immune system in health and disease, we decided to investigate the expression of Nogo-A, Nogo-B and Nogo-C in different human immune cell subpopulations. Furthermore, we analyzed the localization of Nogo-B in human monocyte-derived macrophages by indirect immunofluorescence stainings to gain further insight into its possible function. Findings We describe an association of Nogo-B with cytoskeletal structures and the base of filopodia, but not with focal or podosomal adhesion sites of monocyte-derived macrophages. Nogo-B positive structures are partially co-localized with RhoA staining and Rac1 positive membrane ruffles. Furthermore, Nogo-B is associated with the tubulin network, but not accumulated in the Golgi region. Although Nogo-B is present in the endoplasmic reticulum, it can also be translocated to large cell protrusions or the trailing end of migratory cells, where it is homogenously distributed. Conclusions Two different Nogo-B staining patterns can be distinguished in macrophages: firstly we observed ER-independent Nogo-B localization in cell protrusions and at the trailing end of migrating cells. Secondly, the localization of Nogo-B in actin/RhoA/Rac1 positive regions supports an influence on cytoskeletal organization. To our knowledge this is the first report on Nogo-B expression at the base of filopodia, thus providing further insight into the distribution of this protein.

  9. Induction of Th17 Lymphocytes and Treg Cells by Monocyte-Derived Dendritic Cells in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus

    Science.gov (United States)

    Estrada-Capetillo, Lizbeth; Hernández-Castro, Berenice; Monsiváis-Urenda, Adriana; Alvarez-Quiroga, Crisol; Layseca-Espinosa, Esther; Abud-Mendoza, Carlos; Baranda, Lourdes; Urzainqui, Ana; Sánchez-Madrid, Francisco; González-Amaro, Roberto

    2013-01-01

    Dendritic cells (DCs) have a key role in the regulation of immune response. We herein explored, in patients with inflammatory diseases, the role of monocyte derived DC's (mo-DCs) on the generation of Th17 and T regulatory (Treg) lymphocytes. Peripheral blood was obtained from thirty-five patients with rheumatoid arthritis (RA), twelve with systemic lupus erythematosus (SLE), and twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF) or tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10) conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs from SLE patients also released high levels of IL-6/IL-23, it did not show an increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients with RA and SLE generated under the engagement of PSGL-1, showed a defective capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE, when DC's cells were generated under PDL-1 engagement. Our data indicate that DCs from patients with rheumatic inflammatory disease show an aberrant function that may have an important role in the pathogenesis of these conditions. PMID:24288552

  10. Mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs induce immune modulatory profile in monocyte-derived dendritic cells.

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    Fernando de Sá Silva

    Full Text Available BACKGROUND: Mesenchymal stem cells have prominent immune modulatory properties, which may have clinical applications; however their major source, bone marrow, is of limited availability. On the other hand, mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs are readily accessible, but their immune regulatory properties have not been completely investigated. This study was designed, therefore, to evaluate the SHEDs influence on DCs differentiation, maturation, ability to activate T cells and to expand CD4(+Foxp3(+ T cells. METHODOLOGY/PRINCIPAL FINDINGS: The experiments were based in cellular co-culture during differentiation and maturation of monocyte derived-DCs (moDCs, with, or not, presence of SHEDs. After co-culture with SHEDs, (moDCs presented lower expression of BDCA-1 and CD11c, in comparison to DC cultivated without SHEDs. CD40, CD80, CD83 and CD86 levels were also decreased in mature DCs (mDCs after co-cultivation with SHEDs. To assess the ability of SHEDs-exposed moDCs to modulate T cell responses, the former were separated from SHEDs, and co-cultured with peripheral blood lymphocytes. After 5 days, the proliferation of CD4(+ and CD8(+ T cells was evaluated and found to be lower than that induced by moDCs cultivated without SHEDs. In addition, an increase in the proportion of CD4(+Foxp3(+IL-10(+ T cells was observed among cells stimulated by mature moDCs that were previously cultivated with SHEDs. Soluble factors released during co-cultures also showed a reduction in the pro-inflammatory cytokines (IL-2, TNF-α and IFN-γ, and an increase in the anti-inflammatory molecule IL-10. CONCLUSION/SIGNIFICANCE: This study shows that SHEDs induce an immune regulatory phenotype in moDCs cells, evidenced by changes in maturation and differentiation rates, inhibition of lymphocyte stimulation and ability to expand CD4(+Foxp3(+ T cells. Further characterization and validation of this phenomenon could support the use of SHEDs

  11. Transcriptional analysis of diverse strains Mycobacterium avium subspecies paratuberculosis in primary bovine monocyte derived macrophages.

    Science.gov (United States)

    Zhu, Xiaochun; Tu, Zheng J; Coussens, Paul M; Kapur, Vivek; Janagama, Harish; Naser, Saleh; Sreevatsan, Srinand

    2008-10-01

    In this study we analyzed the macrophage-induced gene expression of three diverse genotypes of Mycobacterium avium subsp. paratuberculosis (MAP). Using selective capture of transcribed sequences (SCOTS) on three genotypically diverse MAP isolates from cattle, human, and sheep exposed to primary bovine monocyte derived macrophages for 48 h and 120 h we created and sequenced six cDNA libraries. Sequence annotations revealed that the cattle isolate up-regulated 27 and 241 genes; the human isolate up-regulated 22 and 53 genes, and the sheep isolate up-regulated 35 and 358 genes, at the two time points respectively. Thirteen to thirty-three percent of the genes identified did not have any annotated function. Despite variations in the genes identified, the patterns of expression fell into overlapping cellular functions as inferred by pathway analysis. For example, 10-12% of the genes expressed by all three strains at each time point were associated with cell-wall biosynthesis. All three strains of MAP studied up-regulated genes in pathways that combat oxidative stress, metabolic and nutritional starvation, and cell survival. Taken together, this comparative transcriptional analysis suggests that diverse MAP genotypes respond with similar modus operandi for survival in the host.

  12. Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats.

    Science.gov (United States)

    Hattori, Hidenori; Suzuki, Shigeaki; Okazaki, Yuka; Suzuki, Norihiro; Kuwana, Masataka

    2012-02-01

    Cell transplantation has emerged as a potential therapy to reduce the neurological deficits caused by ischemic stroke. We previously reported a primitive cell population, monocyte-derived multipotential cells (MOMCs), which can differentiate into mesenchymal, neuronal, and endothelial lineages. In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC-transplanted rats than in macrophage-transplanted or mock-treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC-transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31(+) cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating MOMC-derived endothelial cells expressing a mature endothelial marker RECA-1 were detected at 4 weeks after transplantation. In addition, MOMCs expressed a series of angiogenic factors, including vascular endothelial growth factor, angiopoetin-1, and placenta growth factor (PlGF). These findings provide evidence that the intracranial delivery of MOMCs enhances functional recovery by promoting neovascularization in a rat model for ischemic stroke.

  13. Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation

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    Marincola Francesco M

    2005-12-01

    Full Text Available Abstract We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs, produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLPAs. The HIV-VLPAs induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells. In the present manuscript, the effects of the baculovirus-expressed HIV-VLPAs on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLPA stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLPAs at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers.

  14. HIV-1 Vpr induces interferon-stimulated genes in human monocyte-derived macrophages.

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    Muhammad Atif Zahoor

    Full Text Available Macrophages act as reservoirs of human immunodeficiency virus type 1 (HIV-1 and play an important role in its transmission to other cells. HIV-1 Vpr is a multi-functional protein involved in HIV-1 replication and pathogenesis; however, its exact role in HIV-1-infected human macrophages remains poorly understood. In this study, we used a microarray approach to explore the effects of HIV-1 Vpr on the transcriptional profile of human monocyte-derived macrophages (MDMs. More than 500 genes, mainly those involved in the innate immune response, the type I interferon pathway, cytokine production, and signal transduction, were differentially regulated (fold change >2.0 after infection with a recombinant adenovirus expressing HIV-1 Vpr protein. The differential expression profiles of select interferon-stimulated genes (ISGs and genes involved in the innate immune response, including STAT1, IRF7, MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, APOBEC3A, DDX58 (RIG-I, TNFSF10 (TRAIL, and RSAD2 (viperin were confirmed by real-time quantitative PCR and were consistent with the microarray data. In addition, at the post-translational level, HIV-1 Vpr induced the phosphorylation of STAT1 at tyrosine 701 in human MDMs. These results demonstrate that HIV-1 Vpr leads to the induction of ISGs and expand the current understanding of the function of Vpr and its role in HIV-1 immune pathogenesis.

  15. The transcriptome of Legionella pneumophila-infected human monocyte-derived macrophages.

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    Christopher T D Price

    Full Text Available Legionella pneumophila is an intracellular bacterial pathogen that invades and replicates within alveolar macrophages through injection of ∼ 300 effector proteins by its Dot/Icm type IV translocation apparatus. The bona fide F-box protein, AnkB, is a nutritional virulence effector that triggers macrophages to generate a surplus of amino acids, which is essential for intravacuolar proliferation. Therefore, the ankB mutant represents a novel genetic tool to determine the transcriptional response of human monocyte-derived macrophages (hMDMs to actively replicating L. pneumophila.Here, we utilized total human gene microarrays to determine the global transcriptional response of hMDMs to infection by wild type or the ankB mutant of L. pneumophila. The transcriptomes of hMDMs infected with either actively proliferating wild type or non-replicative ankB mutant bacteria were remarkably similar. The transcriptome of infected hMDMs was predominated by up-regulation of inflammatory pathways (IL-10 anti-inflammatory, interferon signaling and amphoterin signaling, anti-apoptosis, and down-regulation of protein synthesis pathways. In addition, L. pneumophila modulated diverse metabolic pathways, particularly those associated with bio-active lipid metabolism, and SLC amino acid transporters expression.Taken together, the hMDM transcriptional response to L. pneumophila is independent of intra-vacuolar replication of the bacteria and primarily involves modulation of the immune response and metabolic as well as nutritional pathways.

  16. Environmentally relevant dose of arsenic interferes in functions of human monocytes derived dendritic cells.

    Science.gov (United States)

    Bahari, Abbas; Salmani, Vahid

    2017-06-05

    Arsenic is a major environmental pollutant and highly hazardous toxin to human health, which well established as carcinogen and immune deregulatory properties. Dendritic cells (DCs) have a pivotal role in cell-mediated immunity for T-cell activation and antigen presentation. In this study, T cell activation, some key functional genes expression, cell stability and phagocytosis capacity of human monocytes derived DCs (MDDCs) were analyzed after in vitro exposure to very low dose of arsenic for 12 and 24h. Arsenic decreased continually phagocytosis capacity of MDDCs. Furthermore, down-regulation of the cell-surface expression of the co-stimulatory molecule CD40 after 24h post treatment with arsenic, confirmed arsenic interferers in the phagocytosis process. Pro inflammatory cytokines, IL1β and TNFα were more expressed in arsenic-treated MDDCs while IL6 transiently was down regulated. In general, our novel findings here strongly suggest that low level of arsenic dysregulates four fundamental immune processes of DCs. Mechanistically; this could explain the observed immunodeficiency activity of Arsenic, and give direction for comprehension the pathogenesis of Arsenic-induced diseases. Copyright © 2017. Published by Elsevier B.V.

  17. Evaluating the Effects of Cytomegalovirus Glycoprotein B on the Maturation and Function of Monocyte-derived dendritic cells

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    Afsson shariat

    2015-11-01

    Full Text Available Background & Objectives: Interaction of cytomegalovirus glycoprotein B with toll-like receptors of dendritic cells leads to early signaling and innate immune responses. The aim of this study is to evaluate the effects of cytomegalovirus glycoprotein B on the maturation and function of monocyte-derived dendritic cells in treated groups in comparison with control groups. Materials & Methods: Blood samples were taken from 5 healthy volunteers. Following the generation of monocyte-derived dendritic cells on the fifth day of cell culture, half of the immature dendritic cells were treated with cytomegalovirus glycoprotein B, and the rest of them were induced to mature dendritic untreated cells and were used as the control group. The maturation and function of dendritic cells were evaluated in these two groups. Results: The gene expression level of toll-like receptor-4 significantly increased in the group treated with glycoprotein B (p < 0.05, whereas there were no significant differences in the expression rates of CD83, CD86, CD1a, and HLA-DR and the secretion of IL-23 from monocyte-derived dendritic cells between the treated groups and the controls. Conclusion: The increase in the gene expression of toll-like receptor-4 in monocyte-derived dendritic cells treated with cytomegalovirus glycoprotein B showed that cell contact is required to elicit cellular antiviral response and toll-like receptor activation. Thus, it is critical to recognize the viral and cellular determinants of the immune system in order to develop new therapeutic strategies against cytomegalovirus.

  18. Effect of size of man-made and natural mineral fibers on chemiluminescent response in human monocyte-derived macrophages.

    OpenAIRE

    2001-01-01

    Fiber size is an important factor in the tumorigenicity of various mineral fibers and asbestos fibers in animal experiments. We examined the time course of the ability to induce lucigenin-dependent chemiluminescence (CL) from human monocyte-derived macrophages exposed to Japan Fibrous Material standard reference samples (glass wool, rock wool, micro glass fiber, two types of refractory ceramic fiber, refractory mullite fiber, potassium titanium whisker, silicon carbide whisker, titanium oxide...

  19. HIV-1-infected monocytes and monocyte-derived macrophages are impaired in their ability to produce superoxide radicals.

    Science.gov (United States)

    Howell, A L; Groveman, D S; Wallace, P K; Fanger, M W

    1997-01-01

    Monocytes and monocyte-derived macrophages play a key role in immune defense against pathogenic organisms. Superoxide anion production is a key mechanism by which phagocytes kill pathogens. We sought to determine whether human immunodeficiency virus-infected monocytes and monocyte-derived macrophages are compromised in their ability to produce the superoxide anion following stimulation with phorbol myristate acetate (PMA) or after cross-linking the type I Fc receptor for IgG (Fc gamma RI). Fc gamma RI was cross-linked by the binding of monoclonal antibody 197, which reacts with an epitope of Fc gamma RI via its Fc region. Monocytes and monocyte-derived macrophages obtained from seronegative donors were infected in vitro with human immunodeficiency virus-1JR-FL and used in effector assays that measured superoxide anion production by the reduction of nitroblue tetrazolium. Reduced nitroblue tetrazolium was measured spectrophotometrically and by microscopy in which the percentage of cells containing intracellular deposits of the dye was assessed. By spectrophotometric measurement, we found that human immunodeficiency virus-infected monocytes and monocyte-derived macrophages produced less superoxide anion following either phorbol myristate acetate stimulation or Fc gamma RI cross-linking than uninfected cells from the same donor. Using microscopy we saw no difference in the percentage of infected and uninfected macrophages containing intracellular deposits of nitroblue tetrazolium suggesting that human immunodeficiency virus-infected macrophages produce less superoxide anion on a per cell basis than uninfected macrophages. Activation of human immunodeficiency virus-infected monocytes with interferon-gamma for 72 h prior to stimulation with phorbol myristate acetate or monoclonal antibody 197 increased their ability to reduce nitroblue tetrazolium. These findings suggest that impairment in the production of reactive oxygen intermediates may, in some cases, contribute to

  20. Characterization of monocyte-derived dendritic cells maturated with IFN-alpha

    DEFF Research Database (Denmark)

    Svane, I M; Nikolajsen, K; Walter, M R;

    2006-01-01

    Dendritic cells (DC) are promising candidates for cancer immunotherapy. These cells can be generated from peripheral blood monocytes cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). In order to obtain full functional capacity, maturation is required......, maturation with IFN-alpha has only a small effect on induction of autologous T-cell stimulatory capacity of the DC. However, an increase in DC allogeneic T-cell stimulatory capacity was observed. These data suggest that IFN-alpha has a potential as a maturation agent used in DC-based cancer vaccine trials...

  1. Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina.

    Science.gov (United States)

    O'Koren, E G; Mathew, R; Saban, D R

    2016-02-09

    The recent paradigm shift that microglia are yolk sac-derived, not hematopoietic-derived, is reshaping our knowledge about the isolated role of microglia in CNS diseases, including degenerative conditions of the retina. However, unraveling microglial-specific functions has been hindered by phenotypic overlap of microglia with monocyte-derived macrophages. The latter are differentiated from recruited monocytes in neuroinflammation, including retina. Here we demonstrate the use of fate mapping wherein microglia and monocyte-derived cells are endogenously labeled with different fluorescent reporters. Combining this method with 12-color flow cytometry, we show that these two populations are definitively distinguishable by phenotype in retina. We prove that retinal microglia have a unique CD45(lo) CD11c(lo) F4/80(lo) I-A/I-E(-) signature, conserved in the steady state and during retinal injury. The latter was observed in the widely used light-induced retinal degeneration model and corroborated in other models, including whole-body irradiation/bone-marrow transplantation. The literature contains conflicting observations about whether microglia, including in the retina, increase expression of these markers in neuroinflammation. We show that monocyte-derived macrophages have elevated expression of these surface markers, not microglia. Our resolution of such phenotypic differences may serve as a robust way to help characterize isolated roles of these cells in retinal neuroinflammation and possibly elsewhere in CNS.

  2. Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells

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    Bertin Jonathan

    2012-03-01

    Full Text Available Abstract Background Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS. Leukotriene B4 (LTB4 and cysteinyl-leukotrienes such as LTC4 are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs in HIV-1 infection of microglial cells. Methods To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2 or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR. Results We report in this study that virus replication is reduced upon treatment of MDMis with LTB4 and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5 surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C. Conclusions These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.

  3. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

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    Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A. (Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT (USA))

    1990-05-15

    Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons.

  4. Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells.

    Science.gov (United States)

    Bertin, Jonathan; Barat, Corinne; Bélanger, Dave; Tremblay, Michel J

    2012-03-16

    Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B4 (LTB4) and cysteinyl-leukotrienes such as LTC4 are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells. To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR). We report in this study that virus replication is reduced upon treatment of MDMis with LTB4 and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C. These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.

  5. Proteomic alteration of equine monocyte-derived macrophages infected with equine infectious anemia virus.

    Science.gov (United States)

    Du, Cheng; Liu, Hai-Fang; Lin, Yue-Zhi; Wang, Xue-Feng; Ma, Jian; Li, Yi-Jing; Wang, Xiaojun; Zhou, Jian-Hua

    2015-06-01

    Similar to the well-studied viruses human immunodeficiency virus (HIV)-1 and simian immunodeficiency virus (SIV), equine infectious anemia virus (EIAV) is another member of the Lentivirus genus in the family Retroviridae. Previous studies revealed that interactions between EIAV and the host resulted in viral evolution in pathogenicity and immunogenicity, as well as adaptation to the host. Proteomic analysis has been performed to examine changes in protein expression and/or modification in host cells infected with viruses and has revealed useful information for virus-host interactions. In this study, altered protein expression in equine monocyte-derived macrophages (eMDMs, the principle target cell of EIAV in vivo) infected with the EIAV pathogenic strain EIAV(DLV34) (DLV34) was examined using 2D-LC-MS/MS coupled with the iTRAQ labeling technique. The expression levels of 210 cellular proteins were identified to be significantly upregulated or downregulated by infection with DLV34. Alterations in protein expression were confirmed by examining the mRNA levels of eight selected proteins using quantitative real-time reverse-transcription PCR, and by verifying the levels of ten selected proteins using parallel reaction monitoring (PRM). Further analysis of GO and Kyoto Encyclopedia of Genes and Genomes (KEGG)-Pathway enrichment demonstrated that these differentially expressed proteins are primarily related to the biological processes of oxidative phosphorylation, protein folding, RNA splicing, and ubiquitylation. Our results can facilitate a better understanding of the host response to EIAV infection and the cellular processes required for EIAV replication and pathogenesis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Staphylococcus aureus from atopic dermatitis skin alters cytokine production triggered by monocyte-derived Langerhans cell.

    Science.gov (United States)

    Iwamoto, Kazumasa; Moriwaki, Masaya; Niitsu, Yoshie; Saino, Masachika; Takahagi, Shunsuke; Hisatsune, Junzo; Sugai, Motoyuki; Hide, Michihiro

    2017-08-05

    Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The skin of patients with AD presents as a disbalance of the microbiome with a strong colonization by Staphylococcus aureus, which positively correlates with the severity of the disease. However, the effect of colonized S. aureus on the skin immune system has not been fully elucidated. The aim of this study is to explore whether S. aureus isolated from AD skin is able to skew T cell responses via Langerhans cells (LC) as compared to a standard strain of S. aureus and S. epidermidis. We prepared monocyte-derived LC (MoLC) from healthy controls and patients with AD, and stimulated MoLC with a standard strain of S. aureus NCTC8325, S. aureus TF3378 isolated from AD skin, or S. epidermidis. Stimulated MoLC were co-cultured with autologous CD4(pos) T cells and then T cell responses were analyzed by T cell polarization assays, cytokine analysis and real-time PCR. MoLC stimulated by S. aureus TF3378 induced significantly high and rapid proliferation of T cells as compared to those by S. aureus NCTC8325 and S. epidermidis. Cytokine productions from T cells cultured with S. aureus TF3378-stimulated MoLC showed significantly high amounts of IL-2 and less IFN-γ production with imbalanced Th1/Th2 (decreased TBX21/GATA3 ratio) mRNA expression. The T cell proliferation with increased IL-2 production via S. aureus TF3378-stimulated MoLC was diminished by treatment of proteinase K. S. aureus TF3378 on AD skin can skew T cell responses via LC toward imbalanced Th1/Th2 skin immunity. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  7. A novel method to generate monocyte-derived dendritic cells during coculture with HaCaT facilitates detection of weak contact allergens in cosmetics.

    Science.gov (United States)

    Frombach, Janna; Sonnenburg, Anna; Krapohl, Björn-Dirk; Zuberbier, Torsten; Stahlmann, Ralf; Schreiner, Maximilian

    2017-01-01

    The in vitro sensitization assay LCSA (Loose-fit Coculture-based Sensitization Assay) has proved reliable for the detection of contact sensitizers in the past. However, the coculture of human monocyte-derived dendritic cells (DCs) with primary human keratinocytes (KCs) in serum-free medium is relatively complex compared to other sensitization assays which use continuous cell lines. To facilitate high-throughput screening of chemicals, we replaced KCs with the HaCaT cell line under various culture conditions. Coculture of HaCaT with peripheral blood mononuclear cells in serum-supplemented medium leads to generation of CD1a(+)/CD1c(+) DCs after addition of GM-CSF, IL-4, and TGF-β1 (as opposed to CD1a(-)/CD1c(-) DCs which arise in the "classic" LCSA coculture). These cells resemble monocyte-derived DCs generated in monoculture, but, unlike those, they show a marked upregulation CD86 after treatment with contact allergens. All of the nine sensitizers in this study were correctly identified by CD1a(+)/CD1c(+) DCs in coculture with HaCaT. Among the substances were weak contact allergens such as propylparaben (which is false negative in the local lymph node assay in mice) and resorcinol (which was not detected by CD1a(-)/CD1c(-) DCs in the "classic" LCSA). The level of CD86 upregulation on CD1a(+)/CD1c(+) DCs was higher for most allergens compared to CD1a(-)/CD1c(-) DCs, thus improving the assay's discriminatory power. Three out of four non-sensitizers were also correctly assessed by the coculture assay. A false-positive reaction to caprylic (octanoic) acid confirms earlier results that some fatty acids are able to induce CD86 on DC in vitro. In conclusion, change of the LCSA protocol led to reduction of time and cost while even increasing the assay's sensitivity and discriminatory power.

  8. Monocyte-derived dendritic cells from late gestation cows have an impaired ability to mature in response to E. coli stimulation in a receptor and cytokine-mediated fashion.

    Science.gov (United States)

    Pomeroy, Brianna; Sipka, Anja; Klaessig, Suzanne; Schukken, Ynte

    2015-09-15

    During late gestation the bovine immune system is less capable of eliciting inflammatory responses and eliminating invading pathogens. The maternal immune system is directed toward tolerance in order to prevent fetal rejection due to recognition of paternal antigens. In humans and mice, dendritic cell (DC) populations maintain a tolerogenic phenotype essential in the generation and preservation of maternal immune tolerance throughout pregnancy. However, the primary mechanisms which facilitate maternal immune tolerance involved in bovine gestation remain poorly understood. In order to determine if DC phenotype and function were regulated toward tolerance during bovine gestation, we compared in vitro generated monocyte-derived DC (mo-DC) from monocytes isolated from cows in late gestation (LG) to those from non-pregnant (NP) cows in their ability to mature following stimulation with UV irradiated Escherichia coli. Our results show mo-DC from LG cows have an impaired ability to mature in response to E. coli stimulation in a receptor and cytokine-mediated fashion in comparison to those from NP cows. Specifically, mo-DC from LG cows were unable to upregulate MHC II and maintained high expression of CD14, both indicative of an immature phenotype following E. coli-stimulation. Only mo-DC from LG showed significant increase in IL-10 production and had a significantly lower ratio of production of the Th1-polarizing cytokine IL-12 to regulatory cytokine IL-10 following E. coli stimulation compared to mo-DC from NP cows. Our findings demonstrate mo-DC from LG cows have a stifled capacity to develop a mature phenotype and drive pro-inflammatory Th1-type responses to E. coli stimulation. Results from this study provide insight into DC immune modulation in bovine pregnancy and elucidate host factors which may contribute to the heightened susceptibility to infection in late gestation. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The impact of telmisartan on angiotensin converting enzyme 2 mRNA expression in monocyte-derived macrophages of diabetic hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    李永勤

    2013-01-01

    Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2(ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. Methods 62 essential hypertensive patients accompanied with

  10. Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Mervi Alanne-Kinnunen

    Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

  11. iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation

    Science.gov (United States)

    Thanabalasuriar, A; Neupane, A.S; Wang, J; Krummel, M.F; Kubes, P

    2017-01-01

    iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against a variety of bacterial infections including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the potent iNKT cell ligand α-galactosylceramide or during S. pneumoniae infection. In untreated mice the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae, induced CD1d dependent rapid recruitment of neutrophils out of the vasculature. This neutrophil exodus paved the way for extravasation of iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell migration out of the lung vasculature by blocking CCL17 greatly increased susceptibility to S. pneumoniae infection, suggesting a critical role for the secondary wave of iNKT cells in host defense. PMID:27653688

  12. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte-derived dendritic cells.

    Science.gov (United States)

    Sebastian, Katrin; Ott, Hagen; Zwadlo-Klarwasser, Gabriele; Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F; Baron, Jens Malte

    2012-08-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides - which are the most frequent cause of adverse drug reactions - were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines.

  13. Engineering monocyte-derived dendritic cells to secrete interferon-α enhances their ability to promote adaptive and innate anti-tumor immune effector functions.

    Science.gov (United States)

    Willemen, Yannick; Van den Bergh, Johan M J; Lion, Eva; Anguille, Sébastien; Roelandts, Vicky A E; Van Acker, Heleen H; Heynderickx, Steven D I; Stein, Barbara M H; Peeters, Marc; Figdor, Carl G; Van Tendeloo, Viggo F I; de Vries, I Jolanda; Adema, Gosse J; Berneman, Zwi N; Smits, Evelien L J

    2015-07-01

    Dendritic cell (DC) vaccination has demonstrated potential in clinical trials as a new effective cancer treatment, but objective and durable clinical responses are confined to a minority of patients. Interferon (IFN)-α, a type-I IFN, can bolster anti-tumor immunity by restoring or increasing the function of DCs, T cells and natural killer (NK) cells. Moreover, type-I IFN signaling on DCs was found to be essential in mice for tumor rejection by the innate and adaptive immune system. Targeted delivery of IFN-α by DCs to immune cells could boost the generation of anti-tumor immunity, while avoiding the side effects frequently associated with systemic administration. Naturally circulating plasmacytoid DCs, major producers of type-I IFN, were already shown capable of inducing tumor antigen-specific T cell responses in cancer patients without severe toxicity, but their limited number complicates their use in cancer vaccination. In the present work, we hypothesized that engineering easily generated human monocyte-derived mature DCs to secrete IFN-α using mRNA electroporation enhances their ability to promote adaptive and innate anti-tumor immunity. Our results show that IFN-α mRNA electroporation of DCs significantly increases the stimulation of tumor antigen-specific cytotoxic T cell as well as anti-tumor NK cell effector functions in vitro through high levels of IFN-α secretion. Altogether, our findings mark IFN-α mRNA-electroporated DCs as potent inducers of both adaptive and innate anti-tumor immunity and pave the way for clinical trial evaluation in cancer patients.

  14. Th2 polarization by Der p 1--pulsed monocyte-derived dendritic cells is due to the allergic status of the donors.

    Science.gov (United States)

    Hammad, H; Charbonnier, A S; Duez, C; Jacquet, A; Stewart, G A; Tonnel, A B; Pestel, J

    2001-08-15

    The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC--T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive to Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite--sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor--alpha and interleukin (IL)-1 beta, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite-sensitive patients stimulated by autologous Der p 1--pulsed DCs preferentially produced IL-4 rather than interferon-gamma. These effects were abolished in the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite--sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure. (Blood. 2001;98:1135-1141)

  15. Effects of titanium(iv) ions on human monocyte-derived dendritic cells.

    Science.gov (United States)

    Chan, Erwin Ph; Mhawi, Amir; Clode, Peta; Saunders, Martin; Filgueira, Luis

    2009-03-01

    Orthopaedic metal implants composed of titanium are routinely used in bone fracture repair and for joint replacement therapies. A considerable fraction of implant recipients are unable to benefit due to implant failure resulting from aseptic loosening, while others may experience cutaneous sensitivity to titanium after implantation. An adaptive immune reactivity towards titanium ions, originating from the biocorrosion of the implants, could play a role. As an initiator of the adaptive immune response, dendritic cells (DC) were studied for uptake and characteristics after titanium exposure. Energy filtered transmission electron microscopy showed uptake of titanium(iv) (Ti(iv)) ions by DCs in vitro and co-localisation with phosphorus-rich cell structures of the DC membranes (phospholipids), cytoplasm (ribosomes and phosphorylated proteins) and the nucleus (DNA). DC maturation and function were investigated by measuring cell surface marker expression by flow cytometry. After exposure, DCs showed a decrease in MHC class II (HLA-DR), co-stimulatory molecules (CD40, CD80 & CD86) and chemokine receptors (CCR) 6 and CCR7 but an increase in CCR4 after Ti(iv) treatment. However, Ti(iv) treated DCs had an increased stimulatory capacity towards allogenic lymphocytes. A Ti(iv) concentration dependant increase of IL-12p70 was observed amidst decrease of the other measured cytokines (TGF-β1 and TGF-β2). Hence, Ti(iv) alters DC properties, resulting in an enhanced T lymphocyte reactivity and deviation towards a Th1 type immune response. This effect may be responsible for the inflammatory side effects of titanium implants seen in patients.

  16. High density lipoprotein suppresses lipoprotein associated phospholipase A2 in human monocytes-derived macrophages through peroxisome proliferator-activated receptor-γ pathway

    Institute of Scientific and Technical Information of China (English)

    HAN Guan-ping; REN Jing-yi; QIN Li; SONG Jun-xian; WANG Lan; CHEN Hong

    2012-01-01

    Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages,serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects.It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors,however,the relationship between HDL and Lp-PLA2 remains elusive.Methods In this study,reverse transcription-polymerase chain reaction (RT-PCR),Western blotting,and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level,protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations.To investigate the underlying mechanism of HDL-induced Lp-PLA2 action,pioglitazone,a peroxisome proliferator-activated receptor-y (PPARy) ligand,was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2,as well as its activity,were determined.Results Lp-PLA2 mRNA levels,protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages.Pioglitazone treatment (1-10 ng/ml) upregulated the Lp-PLA2 mRNA level,protein expression and activity in human monocyte-derived macrophages,while the effects were markedly reversed by HDL.In addition,pioglitazone resulted in a significant increase in PPARY phosphorylation in human monocyte-derived macrophages,which could be inhibited by HDL.Conclusion These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages,and the underlying mechanisms may be mediated through the PPARY pathway.

  17. Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region.

    Science.gov (United States)

    Jobe, Ousman; Trinh, Hung V; Kim, Jiae; Alsalmi, Wadad; Tovanabutra, Sodsai; Ehrenberg, Philip K; Peachman, Kristina K; Gao, Guofen; Thomas, Rasmi; Kim, Jerome H; Michael, Nelson L; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

    2016-06-01

    Monocytes and monocyte-derived macrophages express relatively low levels of CD4. Despite this, macrophages can be effectively infected with human immunodeficiency virus type 1. Macrophages have a critical role in human immunodeficiency virus type 1 transmission; however, the mechanism or mechanisms of virus infection are poorly understood. We report that growth factors, such as granulocyte macrophage colony-stimulating factor and macrophage colony-stimulating factor affect the phenotypic profile and permissiveness of macrophages to human immunodeficiency virus type 1. Human immunodeficiency virus type 1 infection of monocyte-derived macrophages derived from granulocyte macrophage and macrophage colony-stimulating factors was predominantly facilitated by the sialic acid-binding immunoglobulin-like lectin-1. The number of sialic acid-binding immunoglobulin-like lectin receptors on macrophage colony-stimulating factor-derived monocyte-derived macrophages was significantly greater than on granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages, and correspondingly, human immunodeficiency virus type 1 infection was greater in the macrophage colony-stimulating factor-derived monocyte-derived macrophages. Single-genome analysis and quantitative reverse transcriptase-polymerase chain reaction revealed that the differences in infectivity was not due to differences in viral fitness or in viral variants with differential infectivity but was due to reduced viral entry into the granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages. Anti-sialic acid-binding immunoglobulin-like lectin, trimeric glycoprotein 145, and scaffolded V1V2 proteins were bound to sialic acid-binding immunoglobulin-like lectin and significantly reduced human immunodeficiency virus type 1 entry and infection. Furthermore, sialic acid residues present in the V1V2 region of the envelope protein mediated human immunodeficiency virus type 1

  18. HIV-1 inhibits phagocytosis and inflammatory cytokine responses of human monocyte-derived macrophages to P. falciparum infected erythrocytes.

    Directory of Open Access Journals (Sweden)

    Louise E Ludlow

    Full Text Available HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1(Ba-L infection of monocyte-derived macrophages (MDM on phagocytosis of opsonised P. falciparum infected erythrocytes (IE and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR (10 (0-28 versus (34 (27-108; IE internalised/100 MDM; p = 0.001 and decreased secretion of IL-6 (1,116 (352-3,387 versus 1,552 (889-6,331; pg/mL; p = 0.0078 and IL-1β (16 (7-21 versus 33 (27-65; pg/mL; p = 0.0078. Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals.

  19. The effect of low oxygen with and without steady-state hydrogen peroxide on cytokine gene and protein expression of monocyte-derived macrophages - biomed 2011

    NARCIS (Netherlands)

    Owegi, H.; Bouwens, M.; Egot-Lemaire, S.; Mueller, S.; Geib, R.W.; Waite, G.N.

    2011-01-01

    An early event during inflammation and infection is the migration of monocytes into tissues where they differentiate into macrophages. Such monocyte-derived macrophages face an unfavorable environment characterized by extremely low oxygen tension and accumulation of reactive oxygen species such as h

  20. Chemoresistance of human monocyte-derived dendritic cells is regulated by IL-17A.

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    Full Text Available Dendritic cells initiate adaptive immune responses, leading either to control cancer by effector T cells or to exacerbate cancer by regulatory T cells that inhibit IFN-γ-mediated Th1-type response. Dendritic cells can also induce Th17-type immunity, mediated by IL-17A. However, the controversial role of this cytokine in cancer requires further investigations. We generated dendritic cells from peripheral blood monocytes to investigate lifespan, phenotype and chemoresistance of dendritic cells, treated with IL-17A with or without IFN-γ. Studying the expression of Bcl-2 family members, we demonstrated that dendritic cells constitutively express one pro-survival Bcl-2 member: MCL1. Immature dendritic cells were CD40(lowHLADR(low CD1a(+ MCL1(+, did not express CD14, CD68 or BCL2A1, and displayed a short 2-day lifespan. IL-17A-treated DC exhibited a semi-mature (CD40(high HLADR(low pre-M2 (CCL22(+ CD206(+ CD163(+ IL1RN(+ IL-10(- CXCL10(- IL-12(- mixed (CD1a(+ CD14+ CD68(+ macrophage-dendritic cell phenotype. They efficiently exerted mannose receptor-mediated endocytosis and did not produce superoxide anions, in the absence of TLR engagement. Interestingly, IL-17A promoted a long-term survival of dendritic cells, beyond 12 days, that correlated to BCL2A1 induction, a pro-survival Bcl-2 family member. BCL2A1 transcription was activated by NF-κB, downstream of IL-17A transduction. Thus, immature dendritic cells only express MCL1, whereas IL-17A-treated dendritic cells concomitantly expressed two pro-survival Bcl-2 family members: MCL1 and BCL2A1. These latter developed chemoresistance to 11 of the 17 chemotherapy agents tested. However, high doses of either vinblastine or cytarabine decreased MCL1 expression and induced dendritic cell death. When IL-17A is produced in vivo, administration of anti-IL-17A biotherapy may impair dendritic cell survival by targeting BCL2A1 expression. Consequently, depending on the effector or regulatory role of dendritic

  1. Development of a standardized protocol for reproducible generation of matured monocyte-derived dendritic cells suitable for clinical application

    OpenAIRE

    Bohnenkamp, H.R.; Noll, T.

    2003-01-01

    There is increasing interest in the generation of dendritic cells (DC) for cancer immunotherapy. In order to utilize DC in clinical trials it is necessary to have standardized, reproducible and easy to use protocols. We describe here the process development for the generation of DC as the result of investigation of culture conditions as well as consumption rates of medium and cytokines. Our studies demonstrate that highly viable DC (93 ± 2%) can be produced from CD14+ enriched monocytes via i...

  2. Comparative nitric oxide production by LPS-stimulated monocyte-derived macrophages from Ovis canadensis and Ovis aries.

    Science.gov (United States)

    Sacco, R E; Waters, W R; Rudolph, K M; Drew, M L

    2006-01-01

    Bighorn sheep are more susceptible to respiratory infection by Mannheimia haemolytica than are domestic sheep. In response to bacterial challenge, macrophages produce a number of molecules that play key roles in the inflammatory response, including highly reactive nitrogen intermediates such as nitric oxide (NO). Supernatants from monocyte-derived macrophages cultured with M. haemolytica LPS were assayed for nitric oxide activity via measurement of the NO metabolite, nitrite. In response to LPS stimulation, bighorn sheep macrophages secreted significantly higher levels of NO compared to levels for non-stimulated macrophages. In contrast, levels of NO produced by domestic sheep macrophages in response to M. haemolytica LPS did not differ from levels detected in non-stimulated cell cultures. Nitrite levels detected in supernatants of LPS-stimulated bighorn macrophage cultures treated with an inducible nitric oxide synthase (INOS) inhibitor, N(G)-monomethyl-L-arginine, were similar to that observed in non-stimulated cultures indicating a role for the iNOS pathway.

  3. In vitro detection of contact allergens: development of an optimized protocol using human peripheral blood monocyte-derived dendritic cells.

    Science.gov (United States)

    Reuter, Hendrik; Spieker, Jochem; Gerlach, Silke; Engels, Ursula; Pape, Wolfgang; Kolbe, Ludger; Schmucker, Robert; Wenck, Horst; Diembeck, Walter; Wittern, Klaus-Peter; Reisinger, Kerstin; Schepky, Andreas G

    2011-02-01

    Allergic contact dermatitis is a delayed T-cell mediated allergic response associated with relevant social and economic impacts. Animal experiments (e.g. the local lymph node assay) are still supplying most of the data used to assess the sensitization potential of new chemicals. However, the 7th amendment to the EU Cosmetic Directive will introduce a testing ban for cosmetic ingredients after 2013. In vitro alternative methods are thus being actively developed. Although promising results have been obtained with cell lines, their reduced functionality and inherent genomic instability led us to reinvestigate the use of peripheral blood monocyte-derived dendritic cells (PBMDCs) for the establishment of a reliable in vitro sensitization test. To solve the issues associated with the use of primary cells, the culture and exposure conditions (cytokine concentrations, incubation time, readout, pooled vs. single donors and cytotoxicity) were re-assessed and optimized. Here we propose a stable and reproducible protocol based on PBMDCs. This should allow a wider acceptance of PBMDCs as a reliable test system for the detection of human skin sensitizers and the inclusion of this protocol in an integrated testing strategy.

  4. Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages

    Directory of Open Access Journals (Sweden)

    Elisabeth A. Diget

    2013-01-01

    Full Text Available Macrophages play an important role in human immunodeficiency virus (HIV pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived macrophages (MDMs generated through different differentiation protocols and evaluated different cellular, immunological, and virological properties. We found that elevated and persistent HIV-1 pWT/BaL replication could be obtained only in MDMs grown in RPMI containing macrophage colony-stimulating factor (M-CSF. Interestingly, this MDM type was also most responsive to toll-like receptor stimulation. By contrast, all MDM types were activated to a comparable extent by intracellular DNA, and the macrophage serum-free medium-(Mac-SFM-differentiated MDMs responded strongly to membrane fusion through expression of CXCL10. Finally, we found that HIV infection of RPMI/M-CSF-differentiated MDMs induced low-grade expression of two interferon-stimulated genes in some donors. In conclusion, our study demonstrates that the differentiation protocol used greatly influences the ability of MDMs to activate innate immune reactions and support HIV-1 replication. Paradoxically, the data show that the MDMs with the strongest innate immune response were also the most permissive for HIV-1 replication.

  5. Screening of Mycobacterium avium subsp. paratuberculosis Mutants for Attenuation in a Bovine Monocyte-Derived Macrophage Model

    Directory of Open Access Journals (Sweden)

    Elise A Lamont

    2014-06-01

    Full Text Available Vaccination remains a major tool for prevention and progression of Johne’s disease, a chronic enteritis of ruminants worldwide. Currently there is only one licensed vaccine within the United States and two vaccines licensed internationally against Johne’s disease. All licensed vaccines reduce fecal shedding of Mycobacterium avium subsp. paratuberculosis (MAP and delay disease progression. However, there are no available vaccines that prevent disease onset. A joint effort by the Johne’s Disease Integrated Program (JDIP, a USDA-funded consortium, and USDA- APHIS/VS sought to identify transposon insertion mutant strains as vaccine candidates in part of a three phase study. The focus of the Phase I study was to evaluate MAP mutant attenuation in a well-defined in vitro bovine monocyte-derived macrophage (MDM model. Attenuation was determined by colony forming unit (CFUs counts and slope estimates. Based on CFU counts alone, the MDM model did not identify any mutant that significantly differed from the wild-type control, MAP K-10. Slope estimates using mixed models approach identified six mutants as being attenuated. These were enrolled in protection studies involving murine and baby goat vaccination-challenge models. MDM based approach identified trends in attenuation but this did not correlate with protection in a natural host model. These results suggest the need for alternative strategies for Johne’s disease vaccine candidate screening and evaluation.

  6. Immunomodulatory effects of adult Haemonchus contortus excretory/secretory products on human monocyte-derived dendritic cells.

    Science.gov (United States)

    Rehman, Z U; Knight, J S; Koolaard, J; Simpson, H V; Pernthaner, A

    2015-12-01

    The levels of expression of surface molecules and release of cytokines and chemokines of human monocyte-derived dendritic cells were determined after their exposure to adult H. contortus excretory/secretory (ES) products or a combination of ES products and bacterial lipopolysaccharide (LPS). Worm products provoked a weak response and only partial maturation of the dendritic cells, consistent with the hyporesponsiveness and more tolerogenic immune environment present in parasitized animals and humans. Co-stimulation with LPS demonstrated that H. contortus secretions, like those of other helminths, contain immunomodulators capable of reducing some aspects of the strong T(H)1/T(H)2 response evoked by bacterial LPS. There were significant reductions in the release of some cytokine/chemokines by LPS-stimulated mdDCs and a trend (although not significant at P < 0.05) for reduced expression levels of CD40, CD80 and HLA-DR. A prominent feature was the variability in responses of dendritic cells from the four donors, even on different days in repeat experiments, suggesting that generalized conclusions may be difficult to make, except in genetically related animals. Such observations may therefore be applicable only to restricted populations. In addition, previous exposure to parasites in a target population for immunomodulatory therapy may be an important factor in assessing the likelihood of adverse reactions or failures in the treatment to worm therapy.

  7. The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells

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    Wu Wen-Mein

    2009-07-01

    Full Text Available Abstract Background Propolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE, the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs was investigated. Results CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IκBα phosphorylation and NF-κB activation but not mitogen-activated protein kinase (MAPK family phosphorylation in human MoDCs. Conclusion These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-κB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.

  8. Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells.

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    Szabo, Attila; Kovacs, Attila; Frecska, Ede; Rajnavolgyi, Eva

    2014-01-01

    The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.

  9. Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells.

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    Attila Szabo

    Full Text Available The orphan receptor sigma-1 (sigmar-1 is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT, its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.

  10. Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy

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    André Flores Braga

    2015-08-01

    Full Text Available Dendritic cells (DCs play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL-12p70 by MO-DCs from lepromatous (LL leprosy patients after in vitro stimulation with M. lepraewas lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy.

  11. Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy

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    Braga, André Flores; Moretto, Daniela Ferraz; Gigliotti, Patrícia; Peruchi, Mariela; Vilani-Moreno, Fátima Regina; Campanelli, Ana Paula; Latini, Ana Carla Pereira; Iyer, Anand; Das, Pranab Kumar; de Souza, Vânia Nieto Brito

    2015-01-01

    Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy. PMID:26222022

  12. A protocol for generation of clinical grade mRNA-transfected monocyte-derived dendritic cells for cancer vaccines.

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    Mu, L J; Gaudernack, G; Saebøe-Larssen, S; Hammerstad, H; Tierens, A; Kvalheim, G

    2003-11-01

    With the aim of producing large quantities of mRNA-transfected monocyte-derived dendritic cells (DCs) to be used as cancer vaccines, a new clinical grade procedure has been developed. Peripheral blood mononuclear cells (PBMCs) obtained by leukapheresis were enriched for monocytes by immunomagnetic depletion of CD19+ B cells and CD2+ T cells employing the ISOLEX 300i device. After 5 days of culture of enriched monocytes in gas permeable Teflon bags, using serum-free medium supplemented with granulocyte/macrophage-colony stimulating factor and interleukin-4 (IL-4), immature DCs were generated. Following transfection with mRNA from three human prostate cancer cell lines (DU145, LNCaP and PC-3), employing a newly developed square wave electroporation procedure, the immature DCs were immediately transferred to Teflon bags and matured for 48 h, using serum-free medium supplemented with IL-1alpha, IL-6, tumour necrosis factor-alpha and PGE2. The electroporation procedure efficiently transferred mRNA into the DCs with minor effect on the viability of the cells. The generated matured transfected DCs show high expression of the antigens CD83, CD80, CD86 and human leucocyte antigen-DR. Freezing and thawing of the transfected matured DCs had minor effect on cell viability and the phenotype. From 4 x 109 PBMCs, about 1 x 108 transfected matured DCs are produced. The thawed transfected DCs were able to elicit primary T-cell responses in vitro against antigens encoded by the prostate cancer mRNA as shown by enzyme-linked immunospot assay using mock-transfected DCs as control. Based on these results, clinical trials in cancer patients have been initiated.

  13. The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages.

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    Marc Daigneault

    Full Text Available Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the composite of environmental and differentiation-dependent imprinting. Phorbol-12-myristate-13-acetate (PMA and 1,25-dihydroxyvitamin D3 (VD(3 are stimuli commonly used to induce macrophage differentiation in monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear. We have compared the phenotype of the promonocytic THP-1 cell line after various protocols of differentiation utilising VD(3 and PMA in comparison to primary human monocytes or monocyte-derived macrophages (MDM. Both stimuli induced changes in cell morphology indicative of differentiation but neither showed differentiation comparable to MDM. In contrast, PMA treatment followed by 5 days resting in culture without PMA (PMAr increased cytoplasmic to nuclear ratio, increased mitochondrial and lysosomal numbers and altered differentiation-dependent cell surface markers in a pattern similar to MDM. Moreover, PMAr cells showed relative resistance to apoptotic stimuli and maintained levels of the differentiation-dependent anti-apoptotic protein Mcl-1 similar to MDM. PMAr cells retained a high phagocytic capacity for latex beads, and expressed a cytokine profile that resembled MDM in response to TLR ligands, in particular with marked TLR2 responses. Moreover, both MDM and PMAr retained marked plasticity to stimulus-directed polarization. These findings suggest a modified PMA differentiation protocol can enhance macrophage differentiation of THP-1 cells and identify increased numbers of mitochondria and lysosomes, resistance to apoptosis and the potency of TLR2 responses as important discriminators of the level of macrophage differentiation for transformed cells.

  14. Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells▿

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    Silva, Maria Carlan; Guerrero-Plata, Antonieta; Gilfoy, Felicia D.; Garofalo, Roberto P.; Mason, Peter W.

    2007-01-01

    Dendritic cells (DCs) play a central role in innate immunity and antiviral responses. In this study, we investigated the production of alpha interferon (IFN-α) and inducible chemokines by human monocyte-derived dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) infected with West Nile virus (WNV), an emergent pathogen whose infection can lead to severe cases of encephalitis in the elderly, children, and immunocompromised individuals. Our experiments demonstrated that WNV grown in mammalian cells (WNVVero) was a potent inducer of IFN-α secretion in pDCs and, to a lesser degree, in mDCs. The ability of WNVVero to induce IFN-α in pDCs did not require viral replication and was prevented by the treatment of cells with bafilomycin A1 and chloroquine, suggesting that it was dependent on endosomal Toll-like receptor recognition. On the other hand, IFN-α production in mDCs required viral replication and was associated with the nuclear translocation of IRF3 and viral antigen expression. Strikingly, pDCs failed to produce IFN-α when stimulated with WNV grown in mosquito cells (WNVC7/10), while mDCs responded similarly to WNVVero or WNVC7/10. Moreover, the IFN-dependent chemokine IP-10 was produced in substantial amounts by pDCs in response to WNVVero but not WNVC7/10, while interleukin-8 was produced in greater amounts by mDCs infected with WNVC7/10 than in those infected with WNVVero. These findings suggest that cell-specific mechanisms of WNV recognition leading to the production of type I IFN and inflammatory chemokines by DCs may contribute to both the innate immune response and disease pathogenesis in human infections. PMID:17913823

  15. Leukoreduction system chambers are an efficient, valid, and economic source of functional monocyte-derived dendritic cells and lymphocytes.

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    Pfeiffer, Isabell A; Zinser, Elisabeth; Strasser, Erwin; Stein, Marcello F; Dörrie, Jan; Schaft, Niels; Steinkasserer, Alexander; Knippertz, Ilka

    2013-11-01

    The demand for human monocyte-derived dendritic cells (moDCs), as well as for primary human B and T lymphocytes for immunological research purposes has been increased in recent years. Classically, these monocytes are isolated from blood, leukapheresis products or buffy coats of healthy donors by plastic adherence of peripheral blood mononuclear cells (PBMCs), followed by stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, while lymphocytes are usually isolated from the non-adherent fraction (NAF) by magnetic cell sorting. However, donor-blood is a limited resource and not every blood bank offers leukapheresis products or buffy coats for laboratory use. Additionally, a leukapheresis is very expensive and also the generation/isolation of cells is time- and cost-intensive. To overcome some of these obstacles, we evaluated if low-cost leukoreduction system chambers (LRSCs), which arise after routine donor plateletpheresis procedures, and are usually discarded, would be an alternative and appropriate source of PBMCs to generate moDCs and to isolate lymphocytes. By analyzing the number and phenotype of immature and mature dendritic cells (DCs), as well as of B and T lymphocytes derived from LRSCs, we found all cells to be of high quantity and quality. Further investigations on DCs comprising transwell migration assays, allogeneic mixed lymphocyte reactions (MLR), cytokine secretion assays, and cytotoxic T cell induction assays revealed high migratory, as well as stimulatory capacity of these cells. In addition, DCs and T cells were efficiently electroporated with mRNA and showed characteristic cytokine production after co-culture, demonstrating LRSCs as an efficient, valid, and economic source for generation of moDCs and lymphocytes for research purposes.

  16. ALV-J strain SCAU-HN06 induces innate immune responses in chicken primary monocyte-derived macrophages.

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    Feng, Min; Dai, Manman; Cao, Weisheng; Tan, Yan; Li, Zhenhui; Shi, Meiqing; Zhang, Xiquan

    2017-01-01

    Avian leucosis virus subgroup J (ALV-J) can cause lifelong infection and can escape from the host immune defenses in chickens. Since macrophages act as the important defense line against invading pathogens in host innate immunity, we investigated the function and innate immune responses of chicken primary monocyte-derived macrophages (MDM) after ALV-J infection in this study. Our results indicated that ALV-J was stably maintained in MDM cells but that the viral growth rate was significantly lower than that in DF-1 cells. We also found that ALV-J infection significantly increased nitric oxide (NO) production, but had no effect on MDM phagocytic capacity. Interestingly, infection with ALV-J rapidly promoted the expression levels of Myxovirus resistance 1 (Mx) (3 h, 6 h), ISG12 (6 h), and interleukin-1β (IL-1β) (3 h, 12 h) at an early infection stage, whereas it sharply decreased the expression of Mx (24 h, 36 h), ISG12 (36 h), and made little change on IL-1β (24 h, 36 h) production at a late infection stage in MDM cells. Moreover, the protein levels of interferon-β (IFN-β) and interleukin-6 (IL-6) had sharply increased in infected MDM cells from 3 to 36 h post infection (hpi) of ALV-J. And, the protein level of interleukin-10 (IL-10) was dramatically decreased at 36 hpi in MDM cells infected with ALV-J. These results demonstrate that ALV-J can induce host innate immune responses and we hypothesize that macrophages play an important role in host innate immune attack and ALV-J immune escape.

  17. In vitro generation of monocyte-derived macrophages under serum-free conditions improves their tumor promoting functions.

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    Flora Rey-Giraud

    Full Text Available The tumor promoting role of M2 macrophages has been described in in vivo models and the presence of macrophages in certain tumor types has been linked to a poor clinical outcome. In light of burgeoning activities to clinically develop new therapies targeting tumor-associated macrophages (TAMs, reliable in vitro models faithfully mimicking the tumor promoting functions of TAMs are required. Generation and activation of human monocyte-derived macrophages (MDM in vitro, described as M1 or M2 macrophages attributed with tumoricidal or tumor-promoting functions, respectively, has been widely reported using mainly serum containing culture methods. In this study, we compared the properties of macrophages originating from monocytes cultured either in media containing serum together with M-CSF for M2 and GM-CSF for M1 macrophages or in serum-free media supplemented with M-CSF or GM-CSF and cytokines such as IL-4, IL-10 to induce activated M2 or LPS together with IFN-γ to generate activated M1 phenotype. We observed differences in cell morphology as well as increased surface receptor expression levels in serum-containing culture whereas similar or higher cytokine production levels were detected under serum-free culture conditions. More importantly, MDM differentiated under serum-free conditions displayed enhanced tumoricidal activity for M1 and tumor promoting property for M2 macrophages in contrast to MDM differentiated in the presence of serum. Moreover, evaluation of MDM phagocytic activity in serum free condition resulted in greater phagocytic properties of M2 compared to M1. Our data therefore confirm the tumor promoting properties of M2 macrophages in vitro and encourage the targeting of TAMs for cancer therapy.

  18. Analysis of the bovine monocyte-derived macrophage response to Mycobacterium avium subspecies paratuberculosis infection using RNA-seq

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    Maura E Casey

    2015-02-01

    Full Text Available Johne’s disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, (MAP, is a chronic intestinal disease of ruminants with serious economic consequences for cattle production in the United States and elsewhere. During infection, MAP bacilli are phagocytosed and subvert host macrophage processes, resulting in subclinical infections that can lead to immunopathology and dissemination of disease. Analysis of the host macrophage transcriptome during infection can therefore shed light on the molecular mechanisms and host-pathogen interplay associated with Johne’s disease. Here we describe results of an in vitro study of the bovine monocyte-derived macrophage (MDM transcriptome response during MAP infection using RNA-seq. MDM were obtained from seven age- and sex-matched Holstein-Friesian cattle and were infected with MAP across a six-hour infection time course with non-infected controls. We observed 245 and 574 differentially expressed genes in MAP-infected versus non-infected control samples (adjusted P value ≤ 0.05 at 2 and 6 hours post-infection, respectively. Functional analyses of these differentially expressed genes, including biological pathway enrichment, highlighted potential functional roles for genes that have not been previously described in the host response to infection with MAP bacilli. In addition, differential expression of pro- and anti-inflammatory cytokine genes, such as those associated with the IL-10 signaling pathway, and other immune-related genes that encode proteins involved in the bovine macrophage response to MAP infection emphasize the balance between protective host immunity and bacilli survival and proliferation. Systematic comparisons of RNA-seq gene expression results with Affymetrix® microarray data generated from the same experimental samples also demonstrated that RNA-seq represents a superior technology for studying host transcriptional responses to intracellular infection.

  19. Δ(9)-Tetrahydrocannabinol (THC) enhances lipopolysaccharide-stimulated tissue factor in human monocytes and monocyte-derived microvesicles.

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    Williams, Julie C; Klein, Thomas W; Goldberger, Bruce A; Sleasman, John W; Mackman, Nigel; Goodenow, Maureen M

    2015-01-01

    Immunomodulatory effects in humans of Δ(9-)Tetrahydrocannabinol (THC), the psychoactive component of marijuana are controversial. Tissue factor (TF), the activator of the extrinsic coagulation cascade, is increased on circulating activated monocytes and is expressed on microvesicles released from activated monocytes during inflammatory conditions, which perpetuate coagulopathies in a number of diseases. In view of the increased medicinal use of marijuana, effects of THC on human monocytes and monocyte-derived microvesicles activated by lipopolysaccharide (LPS) were investigated. Peak levels of TF procoagulant activity developed in monocytes or microvesicles 6 h following LPS treatment and were unaltered by THC. After 24 h of LPS stimulation, TF activity declined in control-treated or untreated cells and microvesicles, but persisted with THC treatment. Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC. Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3-24 h with THC treatment. Activation of MAPK or NF-κB pathways was unaltered by THC treatment and inflammatory cytokine IL-6 levels were unchanged. In contrast, TNF and IL-8 levels were enhanced by 20-50 %. THC enhances TF expression in activated monocytes resulting in elevated procoagulant activity. Marijuana use could potentiate coagulopathies in individuals with chronic immune activation such as HIV-1 infection or inflammatory bowel disease.

  20. Mycobacterium tuberculosis ESAT6 and CPF10 Induce Adenosine Deaminase 2 mRNA Expression in Monocyte-Derived Macrophages

    Science.gov (United States)

    Bae, Mi Jung; Ryu, Suyeon; Kim, Ha-Jeong; Cha, Seung Ick

    2017-01-01

    Background Delayed hypersensitivity plays a large role in the pathogenesis of tuberculous pleural effusion (TPE). Macrophages infected with live Mycobacterium tuberculosis (MTB) increase the levels of adenosine deaminase2 (ADA2) in the pleural fluid of TPE patients. However, it is as yet unclear whether ADA2 can be produced by macrophages when challenged with MTB antigens alone. This study therefore evaluated the levels of ADA2 mRNA expression, using monocyte-derived macrophages (MDMs) stimulated with MTB antigens. Methods Purified monocytes from the peripheral blood mononuclear cells of healthy volunteers were differentiated into macrophages using granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). The MDMs were stimulated with early secretory antigenic target protein 6 (ESAT6) and culture filtrate protein 10 (CFP10). The mRNA expression levels for the cat eye syndrome chromosome region, candidate 1 (CECR1) gene encoding ADA2 were then measured. Results CECR1 mRNA expression levels were significantly higher in MDMs stimulated with ESAT6 and CFP10, than in the unstimulated MDMs. When stimulated with ESAT6, M-CSF-treated MDMs showed more pronounced CECR1 mRNA expression than GM-CSF-treated MDMs. Interferon-γ decreased the ESAT6- and CFP10-induced CECR1 mRNA expression in MDMs. CECR1 mRNA expression levels were positively correlated with mRNA expression of tumor necrosis factor α and interleukin 10, respectively. Conclusion ADA2 mRNA expression increased when MDMs were stimulated with MTB antigens alone. This partly indicates that pleural fluid ADA levels could increase in patients with culture-negative TPE. Our results may be helpful in improving the understanding of TPE pathogenesis.

  1. Evaluation of the cytotoxicity of organic dust components on THP1 monocytes-derived macrophages using high content analysis.

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    Ramery, Eve; O'Brien, Peter J

    2014-03-01

    Organic dust contains pathogen-associated molecular patterns (PAMPs) which can induce significant airway diseases following chronic exposure. Mononuclear phagocytes are key protecting cells of the respiratory tract. Several studies have investigated the effects of PAMPs and mainly endotoxins, on cytokine production. However the sublethal cytotoxicity of organic dust components on macrophages has not been tested yet. The novel technology of high content analysis (HCA) is already used to assess subclinical drug-induced toxicity. It combines the capabilities of flow cytometry, intracellular fluorescence probes, and image analysis and enables rapid multiple analyses in large numbers of samples. In this study, HCA was used to investigate the cytotoxicity of the three major PAMPs contained in organic dust, i.e., endotoxin (LPS), peptidoglycan (PGN) and β-glucans (zymosan) on THP-1 monocyte-derived macrophages. LPS was used at concentrations of 0.005, 0.01, 0.02, 0.05, 0.1, and 1 μg/mL; PGN and zymosan were used at concentrations of 1, 5, 10, 50, 100, and 500 μg/mL. Cells were exposed to PAMPs for 24 h. In addition, the oxidative burst and the phagocytic capabilities of the cells were tested. An overlap between PGN intrinsic fluorescence and red/far-red fluorescent dyes occurred, rendering the evaluation of some parameters impossible for PGN. LPS induced sublethal cytotoxicity at the lowest dose (from 50 ng/mL). However, the greatest cytotoxic changes occurred with zymosan. In addition, zymosan, but not LPS, induced phagosome maturation and oxidative burst. Given the fact that β-glucans can be up to 100-fold more concentrated in organic dust than LPS, these results suggest that β-glucans could play a major role in macrophage impairment following heavy dust exposure and will merit further investigation in the near future.

  2. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen.

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    Andrew S Brown

    2016-06-01

    Full Text Available Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC, which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

  3. Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

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    Ulrike Kuebler

    Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

  4. Expression and regulation of Schlafen (SLFN family members in primary human monocytes, monocyte-derived dendritic cells and T cells

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    Alexander Puck

    2015-01-01

    Full Text Available Schlafen (SLFN/Slfn family members have been investigated for their involvement in fundamental cellular processes including growth regulation, differentiation and control of viral replication. However, most research has been focused on the characterization of Slfns within the murine system or in human cell lines. Since little is known about SLFNs in primary human immune cells, we set out to analyze the expression and regulation of the six human SLFN genes in monocytes, monocyte-derived dendritic cells (moDCs and T cells. Comparison of SLFN gene expression across these three cell types showed high mRNA expression of SLFN11 in monocytes and moDCs and high SLFN5 expression in T cells, indicating functional importance within these cell types. Differentiation of monocytes to moDCs leads to the gradual upregulation of SLFN12L and SLFN13 while SLFN12 levels were decreased by differentiation stimuli. Stimulation of moDCs via human rhinovirus, lipopolysaccharide, or IFN-α lead to strong upregulation of SLFN gene expression, while peptidoglycan poorly stimulated regulation of both SLFNs and the classical interferon-stimulated gene MxA. T cell activation was found to downregulate the expression of SLFN5, SLFN12 and SLFN12L, which was reversible upon addition of exogenous IFN-α. In conclusion, we demonstrate, that SLFN gene upregulation is mainly dependent on autocrine type I interferon signaling in primary human immune cells. Rapid decrease of SLFN expression levels following T cell receptor stimulation indicates a role of SLFNs in the regulation of human T cell quiescence.

  5. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen.

    Science.gov (United States)

    Brown, Andrew S; Yang, Chao; Fung, Ka Yee; Bachem, Annabell; Bourges, Dorothée; Bedoui, Sammy; Hartland, Elizabeth L; van Driel, Ian R

    2016-06-01

    Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC), which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

  6. Increased immunopotency of monocyte derived dendritic cells from patients with optic neuritis is inhibited in vitro by simvastatin

    DEFF Research Database (Denmark)

    Tsakiri, Anna; Tsiantoulas, Dimitris; Frederiksen, Jette;

    2010-01-01

    properties of simvastatin influence the function of both T cells and APCs and could thus be a potential therapy for MS. The phenotype of myeloid DC in untreated patients with monosymptomatic optic neuritis (ON) was determined by flow cytometry and the impact of simvastatin on the function of myeloid DC...

  7. Development of a standardized protocol for reproducible generation of matured monocyte-derived dendritic cells suitable for clinical application.

    Science.gov (United States)

    Bohnenkamp, H R; Noll, T

    2003-09-01

    There is increasing interest in the generation of dendritic cells (DC) for cancer immunotherapy. In order to utilize DC in clinical trials it is necessary to have standardized, reproducible and easy to use protocols. We describe here the process development for the generation of DC as the result of investigation of culture conditions as well as consumption rates of medium and cytokines. Our studies demonstrate that highly viable DC (93 +/- 2%) can be produced from CD14(+) enriched monocytes via immunomagnetic beads in a high yield (31 +/- 6%) with X-VIVO 15, 400 U ml(-1) GM-CSF and 2000 U ml(-1) IL-4 without serum and feeding. For the maturation of DC different cocktails (TNF-alpha, IL-1beta, IL-6, PGE(2) and TNF-alpha, PGE(2)) were compared. In both cases cells expressed typical surface molecules of mature DC and induced high proliferative responses in mixed lymphocyte reactions which led to IFN-gamma producing T-lymphocytes. The data suggest that the use of this optimized, easy to use protocol results in highly mature DC.

  8. Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection.

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    Jutta Sharbati

    Full Text Available BACKGROUND: Many efforts have been made to understand basal mechanisms of mycobacterial infections. Macrophages are the first line of host immune defence to encounter and eradicate mycobacteria. Pathogenic species have evolved different mechanisms to evade host response, e.g. by influencing macrophage apoptotic pathways. However, the underlying molecular regulation is not fully understood. A new layer of eukaryotic regulation of gene expression is constituted by microRNAs. Therefore, we present a comprehensive study for identification of these key regulators and their targets in the context of host macrophage response to mycobacterial infections. METHODOLOGY/PRINCIPAL FINDINGS: We performed microRNA as well as mRNA expression analysis of human monocyte derived macrophages infected with several Mycobacterium avium hominissuis strains by means of microarrays as well as quantitative reverse transcription PCR (qRT-PCR. The data revealed the ability of all strains to inhibit apoptosis by transcriptional regulation of BCL2 family members. Accordingly, at 48 h after infection macrophages infected with all M. avium strains showed significantly decreased caspase 3 and 7 activities compared to the controls. Expression of let-7e, miR-29a and miR-886-5p were increased in response to mycobacterial infection at 48 h. The integrated analysis of microRNA and mRNA expression as well as target prediction pointed out regulative networks identifying caspase 3 and 7 as potential targets of let-7e and miR-29a, respectively. Consecutive reporter assays verified the regulation of caspase 3 and 7 by these microRNAs. CONCLUSIONS/SIGNIFICANCE: We show for the first time that mycobacterial infection of human macrophages causes a specific microRNA response. We furthermore outlined a regulatory network of potential interactions between microRNAs and mRNAs. This study provides a theoretical concept for unveiling how distinct mycobacteria could manipulate host cell response

  9. Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells.

    NARCIS (Netherlands)

    Schreibelt, G.; Benitez-Ribas, D.; Schuurhuis, D.; Lambeck, A.J.A.; Hout-Kuijer, M.A. van; Schaft, N.; Punt, C.J.A.; Figdor, C.G.; Adema, G.J.; Vries, I.J.M. de

    2010-01-01

    Currently dendritic cell (DC)-based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limite

  10. Treatment with dexamethasone and monophosphoryl lipid A removes disease-associated transcriptional signatures in monocyte-derived dendritic cells from rheumatoid arthritis patients and confers tolerogenic features

    Directory of Open Access Journals (Sweden)

    Paulina Andrea García-González

    2016-10-01

    Full Text Available Tolerogenic dendritic cells (TolDCs are promising tools for therapy of autoimmune diseases such as rheumatoid arthritis (RA. Here we characterise monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA, referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties and T cell-stimulatory capacity, in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of costimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating towards the lymphoid chemokines CXCL12 and CCL19. These MPLA-tDCs induced hyporesponsiveness of autologous CD4+ T cells specific for synovial antigens in vitro. Global transcriptome analysis confirmed a unique transcriptional profile of MPLA-tDCs and revealed that RA-associated genes, which were upregulated in untreated DCs from RA patients, returned to expression levels of healthy donor-derived DCs after treatment with dexamethasone and MPLA. Thus, monocyte-derived DCs from RA patients have the capacity to develop tolerogenic features at transcriptional as well as at translational level, when modulated with dexamethasone and MPLA, overcoming disease-related effects. Furthermore, the ability of MPLA-tDCs to impair T cell responses to synovial antigens validates their potential as cellular treatment for RA.

  11. Novel characterization of monocyte-derived cell populations in the meninges and choroid plexus and their rates of replenishment in bone marrow chimeric mice.

    Science.gov (United States)

    Chinnery, Holly R; Ruitenberg, Marc J; McMenamin, Paul G

    2010-09-01

    The mouse dura mater, pia mater, and choroid plexus contain resident macrophages and dendritic cells (DCs). These cells participate in immune surveillance, phagocytosis of cellular debris, uptake of antigens from the surrounding cerebrospinal fluid and immune regulation in many pathologic processes. We used Cx3cr1 knock-in, CD11c-eYFP transgenic and bone marrow chimeric mice to characterize the phenotype, density and replenishment rate of monocyte-derived cells in the meninges and choroid plexus and to assess the role of the chemokine receptor CX3CR1 on their number and tissue distribution. Iba-1 major histocompatibility complex (MHC) Class II CD169 CD68 macrophages and CD11c putative DCs were identified in meningeal and choroid plexus whole mounts. Comparison of homozygous and heterozygous Cx3cr1 mice did not reveal CX3CR1-dependancy on density, distribution or phenotype of monocyte-derived cells. In turnover studies, wild type lethally irradiated mice were reconstituted with Cx3cr1/-positive bone marrow and were analyzed at 3 days, 1, 2, 4 and 8 weeks after transplantation. There was a rapid replenishment of CX3CR1-positive cells in the dura mater (at 4 weeks) and the choroid plexus was fully reconstituted by 8 weeks. These data provide the foundation for future studies on the role of resident macrophages and DCs in conditions such as meningitis, autoimmune inflammatory disease and in therapies involving irradiation and hematopoietic or stem cell transplantation.

  12. Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells.

    Science.gov (United States)

    Schreibelt, Gerty; Benitez-Ribas, Daniel; Schuurhuis, Danita; Lambeck, Annechien J A; van Hout-Kuijer, Maaike; Schaft, Niels; Punt, Cornelis J A; Figdor, Carl G; Adema, Gosse J; de Vries, I Jolanda M

    2010-07-29

    Currently dendritic cell (DC)-based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limited availability of clinical-grade TLR ligands significantly hampers the translation of these findings into DC-based vaccines. Therefore, we explored 15 commonly used preventive vaccines as a possible source of TLR ligands. We have identified a cocktail of the vaccines BCG-SSI, Influvac, and Typhim that contains TLR ligands and is capable of optimally maturing DCs. These DCs (vaccine DCs) showed high expression of CD80, CD86, and CD83 and secreted interleukin-12. Although vaccine DCs exhibited an impaired migratory capacity, this could be restored by addition of prostaglandin E(2) (PGE(2); vaccine PGE(2) DCs). Vaccine PGE(2) DCs are potent inducers of T-cell proliferation and induce Th1 polarization. In addition, vaccine PGE(2) DCs are potent inducers of tumor antigen-specific CD8(+) effector T cells. Finally, vaccine PGE(2)-induced DC maturation is compatible with different antigen-loading strategies, including RNA electroporation. These data thus identify a new clinical application for a mixture of commonly used preventive vaccines in the generation of Th1-inducing clinical-grade mature DCs.

  13. Design of tumour-specific immunotherapies using dendritic cells – analyses of IL15-DC

    OpenAIRE

    Al-Mahdi, Rania Ali Muhsen

    2009-01-01

    Immunotherapy of malignancies aims at activating the patient’s own immune system to fight the tumour affecting the patient. Even though the use of dendritic cells (DC) has shown promising results, the DC vaccination strategy needs improvement, as only few relevant clinical responses could be documented so far. Aim: In this study, the standard protocol to generate monocyte derived DC using GM-CSF and IL-4 was compared to the use of GM-CSF and IL-15. Methods: Monocytes were isolated by plastic ...

  14. Potentially probiotic bacteria induce efficient maturation but differential cytokine production in human monocyte-derived dendritic cells

    Institute of Scientific and Technical Information of China (English)

    Sinikka Latvala; Taija E Pietil(a); Ville Veckman; Riina A Kekkonen; Soile Tynkkynen; Riitta Korpela; Ilkka Julkunen

    2008-01-01

    MM: To analyze the ability of nine different potentially probiotic bacteria to induce maturation and cytokine production in human monocyLe-derived dendritic cells (moDCs).METHODS: Cytokine production and maturation of moDCs in response to bacterial stimulation was analyzed with enzyme-linked immunosorbent assay (ELISA) and flow cytometric analysis (FACS),respectively.The kinetics of mRNA expression of cytokine genes was determined by Northern blotting.The involvement of different signaling pathways in cytokine gene expression was studied using specific pharmacological signaling inhibitors.RESULTS: All studied bacteria induced the maturation of moDCs in a dose-dependent manner.More detailed analysis with S.thermophilus THS,B.breve Bb99,and L.lactis subsp,cremoris ARH74 indicated that these bacteria induced the expression of moDC maturation markers HLA class II and CD86 as efficiently as pathogenic bacteria.However,these bacteria differed in their ability to induce moDC cytokine gene expression.S.therrnophilus induced the expression of pro-inflammatory (TNF-a,IL-12,IL-6,and CCL20)and Th1 type (IL-12 and IFN-y) cytokines,while B.breve and L.lactis were also potent inducers of antiinflammatory IL-10.Mitogen-activated protein kinase (MAPK) p38,phosphatidylinositol 3 (PI3) kinase,and nuclear factor-kappa B (NF-κB) signaling pathways were shown to be involved in bacteria-induced cytokine production.CONCLUSION: Our results indicate that potentially probiotic bacteria are able to induce moDC maturation,but their ability to induce cytokine gene expression varies significantly from one bacterial strain to another.

  15. Genome-wide association study identifies single nucleotide polymorphism in DYRK1A associated with replication of HIV-1 in monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Sebastiaan M Bol

    Full Text Available BACKGROUND: HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART, macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96 or high (n = 96 p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16 × 10(-5. While the association was not genome-wide significant (p<1 × 10(-7, we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034. Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84 × 10(-6. In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the kinase

  16. In vitro evidence for the protective role of Sida rhomboidea. Roxb extract against LDL oxidation and oxidized LDL-induced apoptosis in human monocyte-derived macrophages.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjisinh V; Ramachandran, A V

    2011-06-01

    The present study was undertaken to evaluate protective role of S. rhomboidea. Roxb (SR) leaf extract against in vitro low-density lipoprotein (LDL) oxidation and oxidized LDL (Ox-LDL) induced macrophage apoptosis. Copper and cell-mediated LDL oxidation, Ox-LDL-induced peroxyl radical generation, mitochondrial activity, and apoptosis in human monocyte-derived macrophages (HMDMs) were assessed in presence of SR extract. Results clearly indicated that SR was capable of reducing LDL oxidation and formation of intermediary oxidation products. Also, SR successfully attenuated peroxyl radical formation, mitochondrial dysfunction, nuclear condensation, and apoptosis in Ox-LDL-exposed HMDMs. This scientific report is the first detailed investigation that establishes anti-atherosclerotic potential of SR extract.

  17. Surface modification of biomaterials based on high-molecular polylactic acid and their effect on inflammatory reactions of primary human monocyte-derived macrophages: perspective for personalized therapy.

    Science.gov (United States)

    Stankevich, Ksenia S; Gudima, Alexandru; Filimonov, Victor D; Klüter, Harald; Mamontova, Evgeniya M; Tverdokhlebov, Sergei I; Kzhyshkowska, Julia

    2015-06-01

    Polylactic acid (PLA) based implants can cause inflammatory complications. Macrophages are key innate immune cells that control inflammation. To provide higher biocompatibility of PLA-based implants with local innate immune cells their surface properties have to be improved. In our study surface modification technique for high-molecular PLA (MW=1,646,600g/mol) based biomaterials was originally developed and successfully applied. Optimal modification conditions were determined. Treatment of PLA films with toluene/ethanol=3/7 mixture for 10min with subsequent exposure in 0.001M brilliant green dye (BGD) solution allows to entrap approximately 10(-9)mol/cm(2) model biomolecules. The modified PLA film surface was characterized by optical microscopy, SERS, FT-IR, UV and TG/DTA/DSC analysis. Tensile strain of modified films was determined as well. The effect of PLA films modified with BGD on the inflammatory reactions of primary human monocyte-derived macrophages was investigated. We developed in vitro test-system by differentiating primary monocyte-derived macrophages on a coating material. Type 1 and type 2 inflammatory cytokines (TNFα, CCL18) secretion and histological biomarkers (CD206, stabilin-1) expression were analyzed by ELISA and confocal microscopy respectively. BGD-modified materials have improved thermal stability and good mechanical properties. However, BGD modifications induced additional donor-specific inflammatory reactions and suppressed tolerogenic phenotype of macrophages. Therefore, our test-system successfully demonstrated specific immunomodulatory effects of original and modified PLA-based biomaterials, and can be further applied for the examination of improved coatings for implants and identification of patient-specific reactions to implants.

  18. Monocytes-derived macrophages mediated stable expression of human brain-derived neurotrophic factor, a novel therapeutic strategy for neuroAIDS.

    Directory of Open Access Journals (Sweden)

    Jing Tong

    Full Text Available HIV-1 associated dementia remains a significant public health burden. Clinical and experimental research has shown that reduced levels of brain-derived neurotrophic factor (BDNF may be a risk factor for neurological complications associated with HIV-1 infection. We are actively testing genetically modified macrophages for their possible use as the cell-based gene delivery vehicle for the central nervous system (CNS. It can be an advantage to use the natural homing/migratory properties of monocyte-derived macrophages to deliver potentially neuroprotective BDNF into the CNS, as a non-invasive manner. Lentiviral-mediated gene transfer of human (hBDNF plasmid was constructed and characterized. Defective lentiviral stocks were generated by transient transfection of 293T cells with lentiviral transfer plasmid together with packaging and envelope plasmids. High titer lentiviral vector stocks were harvested and used to transduce human neuronal cell lines, primary cultures of human peripheral mononocyte-derived macrophages (hMDM and murine myeloid monocyte-derived macrophages (mMDM. These transduced cells were tested for hBDNF expression, stability, and neuroprotective activity. The GenomeLab GeXP Genetic Analysis System was used to evaluate transduced cells for any adverse effects by assessing gene profiles of 24 reference genes. High titer vectors were prepared for efficient transduction of neuronal cell lines, hMDM, and mMDM. Stable secretion of high levels of hBDNF was detected in supernatants of transduced cells using western blot and ELISA. The conditioned media containing hBDNF were shown to be protective to neuronal and monocytic cell lines from TNF-α and HIV-1 Tat mediated cytotoxicity. Lentiviral vector-mediated gene transduction of hMDM and mMDM resulted in high-level, stable expression of the neuroprotective factorBDNF in vitro. These findings form the basis for future research on the potential use of BDNF as a novel therapy for neuroAIDS.

  19. Monocytes-derived macrophages mediated stable expression of human brain-derived neurotrophic factor, a novel therapeutic strategy for neuroAIDS.

    Science.gov (United States)

    Tong, Jing; Buch, Shilpa; Yao, Honghong; Wu, Chengxiang; Tong, Hsin-I; Wang, Youwei; Lu, Yuanan

    2014-01-01

    HIV-1 associated dementia remains a significant public health burden. Clinical and experimental research has shown that reduced levels of brain-derived neurotrophic factor (BDNF) may be a risk factor for neurological complications associated with HIV-1 infection. We are actively testing genetically modified macrophages for their possible use as the cell-based gene delivery vehicle for the central nervous system (CNS). It can be an advantage to use the natural homing/migratory properties of monocyte-derived macrophages to deliver potentially neuroprotective BDNF into the CNS, as a non-invasive manner. Lentiviral-mediated gene transfer of human (h)BDNF plasmid was constructed and characterized. Defective lentiviral stocks were generated by transient transfection of 293T cells with lentiviral transfer plasmid together with packaging and envelope plasmids. High titer lentiviral vector stocks were harvested and used to transduce human neuronal cell lines, primary cultures of human peripheral mononocyte-derived macrophages (hMDM) and murine myeloid monocyte-derived macrophages (mMDM). These transduced cells were tested for hBDNF expression, stability, and neuroprotective activity. The GenomeLab GeXP Genetic Analysis System was used to evaluate transduced cells for any adverse effects by assessing gene profiles of 24 reference genes. High titer vectors were prepared for efficient transduction of neuronal cell lines, hMDM, and mMDM. Stable secretion of high levels of hBDNF was detected in supernatants of transduced cells using western blot and ELISA. The conditioned media containing hBDNF were shown to be protective to neuronal and monocytic cell lines from TNF-α and HIV-1 Tat mediated cytotoxicity. Lentiviral vector-mediated gene transduction of hMDM and mMDM resulted in high-level, stable expression of the neuroprotective factorBDNF in vitro. These findings form the basis for future research on the potential use of BDNF as a novel therapy for neuroAIDS.

  20. Different Transcriptional Profiles of Human Monocyte-Derived Dendritic Cells Infected with Distinct Strains of Mycobacterium tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin

    Directory of Open Access Journals (Sweden)

    Nunzia Sanarico

    2011-01-01

    Full Text Available In order to analyze dendritic cells (DCs activation following infection with different mycobacterial strains, we studied the expression profiles of 165 genes of human monocyte-derived DCs infected with H37Rv, a virulent Mycobacterium tuberculosis (MTB laboratory strain, CMT97, a clinical MTB isolate, Mycobacterium bovis bacillus Calmette-Guérin (BCG, Aventis Pasteur, and BCG Japan, both employed as vaccine against tuberculosis. The analysis of the gene expression reveals that, despite a set of genes similarly modulated, DCs response resulted strain dependent. In particular, H37Rv significantly upregulated EBI3 expression compared with BCG Japan, while it was the only strain that failed to release a significant IL-10 amount. Of note, BCG Japan showed a marked increase in CCR7 and TNF-α expression regarding both MTB strains and it resulted the only strain failing in exponential intracellular growth. Our results suggest that DCs display the ability to elicit a tailored strain-specific immune response.

  1. High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages In Vitro.

    Science.gov (United States)

    Farowski, Fedja; Cornely, Oliver A; Hartmann, Pia

    2016-06-01

    Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function in vitro In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of Aspergillus fumigatus conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of Aspergillus species infection warrants control of the pathogen and preservation of tissue integrity at the same time.

  2. Pathogenic prion protein fragment (PrP106–126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages

    Science.gov (United States)

    Bacot, Silvia M.; Feldman, Gerald M.; Yamada, Kenneth M.; Dhawan, Subhash

    2017-01-01

    Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prpsc, thought to be the causative agent of variant a Creutzfeldt–Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106–126, a synthetic domain of PrPsc that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106–126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106–126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106–126-mediated host cell response in promoting HIV-1 pathogenesis. PMID:25589240

  3. Wear particles from studded tires and granite pavement induce pro-inflammatory alterations in human monocyte-derived macrophages: a proteomic study.

    Science.gov (United States)

    Karlsson, Helen; Lindbom, John; Ghafouri, Bijar; Lindahl, Mats; Tagesson, Christer; Gustafsson, Mats; Ljungman, Anders G

    2011-01-14

    Airborne particulate matter is considered to be one of the environmental contributors to the mortality in cancer, respiratory, and cardiovascular diseases. For future preventive actions, it is of major concern to investigate the toxicity of defined groups of airborne particles and to clarify their pathways in biological tissues. To expand the knowledge beyond general inflammatory markers, this study examined the toxicoproteomic effects on human monocyte derived macrophages after exposure to wear particles generated from the interface of studded tires and a granite-containing pavement. As comparison, the effect of endotoxin was also investigated. The macrophage proteome was separated using two-dimensional gel electrophoresis. Detected proteins were quantified, and selected proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Among analyzed proteins, seven were significantly decreased and three were increased by exposure to wear particles as compared to unexposed control cells. Endotoxin exposure resulted in significant changes in the expression of six proteins: four decreased and two increased. For example, macrophage capping protein was significantly increased after wear particle exposure only, whereas calgizzarin and galectin-3 were increased by both wear particle and endotoxin exposure. Overall, proteins associated with inflammatory response were increased and proteins involved in cellular functions such as redox balance, anti-inflammatory response, and glycolysis were decreased. Investigating the effects of characterized wear particles on human macrophages with a toxicoproteomic approach has shown to be useful in the search for more detailed information about specific pathways and possible biological markers.

  4. Monocyte-derived dendritic cells induce a house dust mite-specific Th2 allergic inflammation in the lung of humanized SCID mice: involvement of CCR7.

    Science.gov (United States)

    Hammad, Hamida; Lambrecht, Bart N; Pochard, Pierre; Gosset, Philippe; Marquillies, Philippe; Tonnel, André-Bernard; Pestel, Joël

    2002-08-01

    In rodents, airway dendritic cells (DCs) capture inhaled Ag, undergo maturation, and migrate to the draining mediastinal lymph nodes (MLN) to initiate the Ag-specific T cell response. However, the role of human DCs in the pathogenesis of the Th2 cell-mediated disease asthma remains to be clarified. Here, by using SCID mice engrafted with T cells from either house dust mite (HDM)-allergic patients or healthy donors, we show that DCs pulsed with Der p 1, one of the major allergens of HDM, and injected intratracheally into naive animals migrated into the MLN. In the MLN, Der p 1-pulsed DCs from allergic patients induced the proliferation of IL-4-producing CD4(+) T cells, whereas those from healthy donors induced IFN-gamma-secreting cells. In reconstituted human PBMC-reconstituted SCID mice primed with pulsed DCs from allergic patients, repeated exposure to aerosols of HDM induced 1) a strong pulmonary inflammatory reaction rich in T cells and eosinophils, 2) an increase in IL-4 and IL-5 production in the lung lavage fluid, and 3) increased IgE production compared with that in mice primed with unpulsed DCs. All these effects were reduced following in vivo neutralization of the CCR7 ligand secondary lymphoid tissue chemokine. These data in human PBMC-reconstituted SCID mice show that monocyte-derived DCs might play a key role in the pathogenesis of the pulmonary allergic response by inducing Th2 effector function following migration to the MLN.

  5. Human monocyte-derived insulin-like growth factor-2 enhances the infection of human arterial endothelial cells by Chlamydia pneumoniae.

    Science.gov (United States)

    Lin, T M; Campbell, L A; Rosenfeld, M E; Kuo, C C

    2001-05-01

    It has been shown that infection of human endothelial cells by Chlamydia pneumoniae is enhanced by co-culturing endothelial cells with human monocytes and is mediated by monocyte-derived soluble factors. This study was conducted to identify the infectivity-enhancing factor. Serum-free conditioned medium of human monocytic cells was fractionated by ultrafiltration. The enhancing activity was found in the fraction in the molecular mass range between 5000 and 10,000 kDa. Recombinant human insulin-like growth factor (IGF)-1 or -2, with a molecular mass of 7500 kDa, was added to the culture medium of human endothelial cells for growing C. pneumoniae. Only IGF-2 enhanced C. pneumoniae growth. Pretreatment of the conditioned medium with a monoclonal antibody against IGF-2 blocked the enhancing activity. This suggests that the infectivity-enhancing factor is IGF-2 and that paracrine interactions between monocytes and endothelial cells in vivo can induce secretory products and sustain infection with C. pneumoniae within atherosclerotic lesions.

  6. Induction of Th17 Lymphocytes and Treg Cells by Monocyte-Derived Dendritic Cells in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Lizbeth Estrada-Capetillo

    2013-01-01

    Full Text Available Dendritic cells (DCs have a key role in the regulation of immune response. We herein explored, in patients with inflammatory diseases, the role of monocyte derived DC’s (mo-DCs on the generation of Th17 and T regulatory (Treg lymphocytes. Peripheral blood was obtained from thirty-five patients with rheumatoid arthritis (RA, twelve with systemic lupus erythematosus (SLE, and twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF or tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10 conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs from SLE patients also released high levels of IL-6/IL-23, it did not show an increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients with RA and SLE generated under the engagement of PSGL-1, showed a defective capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE, when DC’s cells were generated under PDL-1 engagement. Our data indicate that DCs from patients with rheumatic inflammatory disease show an aberrant function that may have an important role in the pathogenesis of these conditions.

  7. Enhanced Inhibitory Effect of Ultra-Fine Granules of Red Ginseng on LPS-induced Cytokine Expression in the Monocyte-Derived Macrophage THP-1 Cells

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    Hong-Yeoul Kim

    2008-08-01

    Full Text Available Red ginseng is one of the most popular traditional medicines in Korea because its soluble hot-water extract is known to be very effective on enhancing immunity as well as inhibiting inflammation. Recently, we developed a new technique, called the HACgearshift system, which can pulverize red ginseng into the ultra-fine granules ranging from 0.2 to 7.0 μm in size. In this study, the soluble hot-water extract of those ultra-fine granules of red ginseng (URG was investigated and compared to that of the normal-sized granules of red ginseng (RG. The high pressure liquid chromatographic analyses of the soluble hot-water extracts of both URG and RG revealed that URG had about 2-fold higher amounts of the ginsenosides, the biologically active components in red ginseng, than RG did. Using quantitative RT-PCR, cytokine profiling against the Escherichia coli lipopolysaccharide (LPS in the monocyte-derived macrophage THP-1 cells demonstrated that the URG-treated cells showed a significant reduction in cytokine expression than the RG-treated ones. Transcription expression of the LPS-induced cytokines such as TNF-α, IL-1β, IL-6, IL-8, IL-10, and TGF-β was significantly inhibited by URG compared to RG. These results suggest that some biologically active and soluble components in red ginseng can be more effectively extracted from URG than RG by standard hot-water extraction.

  8. Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response.

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    Aldinucci, Alessandra; Bonechi, Elena; Manuelli, Cinzia; Nosi, Daniele; Masini, Emanuela; Passani, Maria Beatrice; Ballerini, Clara

    2016-07-08

    Histamine, a major mediator in allergic diseases, differentially regulates the polarizing ability of dendritic cells after Toll-like receptor (TLR) stimulation, by not completely explained mechanisms. In this study we investigated the effects of histamine on innate immune reaction during the response of human monocyte-derived DCs (mDCs) to different TLR stimuli: LPS, specific for TLR4, and Pam3Cys, specific for heterodimer molecule TLR1/TLR2. We investigated actin remodeling induced by histamine together with mDCs phenotype, cytokine production, and the stimulatory and polarizing ability of Th0. By confocal microscopy and RT-PCR expression of Rac1/CdC42 Rho GTPases, responsible for actin remodeling, we show that histamine selectively modifies actin cytoskeleton organization induced by TLR4, but not TLR2 and this correlates with increased IL4 production and decreased IFNγ by primed T cells. We also demonstrate that histamine-induced cytoskeleton organization is at least in part mediated by down-regulation of small Rho GTPase CdC42 and the protein target PAK1, but not by down-regulation of Rac1. The presence and relative expression of histamine receptors HR1-4 and TLRs were determined as well. Independently of actin remodeling, histamine down-regulates IL12p70 and CXCL10 production in mDCs after TLR2 and TLR4 stimulation. We also observed a trend of IL10 up-regulation that, despite previous reports, did not reach statistical significance.

  9. Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease.

    Science.gov (United States)

    Baillie, J Kenneth; Arner, Erik; Daub, Carsten; De Hoon, Michiel; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Carninci, Piero; Forrest, Alistair R R; Hayashizaki, Yoshihide; Faulkner, Geoffrey J; Wells, Christine A; Rehli, Michael; Pavli, Paul; Summers, Kim M; Hume, David A

    2017-03-01

    The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA) identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD) in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits) enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility from reanalysis

  10. The effect of cytosolic extract of Alternaria aternata fungus on Monocyte-derived dendritic cell maturation and T-lymphocyte polarization in the presence of myelin basic protein

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    Loghmanni A

    2013-03-01

    Full Text Available Background: Multiple Sclerosis (MS is an autoimmune disease with impairment in function of central nervous system. Macrophages and dendritic cells play important roles in alleviating or progression of the disease. These cells can cause inflammation and damage to the myelin of nerve cells by realizing of harmful substances when these cells get matured. We studied the effect of Alternaria alternata extract on maturation of monocyte- derived dendritic cell (modc and T-cell responses in the presence of Myelin Basic Protein (MBP as a laboratory model of multiple sclerosis (MS. The purpose of this study is suitable dendritic cells production for usage in MS immunotherapy.Methods: For this study plastic adherent monocytes were cultured with granulocyte/ macrophage- colony stimulating factor (GM-CSF and interleukin -4 for converting these cells to modc and pulsed with MBP and matured in the presence of monocyte-conditioned medium (MCM in control group and MCM + Alternaria alternata extract in treatment groups. Anti-CD14, anti-CD83, anti-human leukocyte antigen-DR (anti HLA-DR monoclonal antibody were carried out for phenotyping. Autologos T cell responses and cytokine production were evaluated.Results: The results showed that the expression of CD14 decreased and CD83, HLA-DR increased in treatment groups in comparison with control groups. The production amount of IL-10 overcame IL-12 and in T cell the production of cytokines, IL-17 and Interferon-γ (IFN-γ decreased and IL-4 was increased (P<0.05. These effects escalated with increasing of dosage from 50 to 100 (mg/ml (P<0.001.Conclusion: Alternaria alternata extract can cause maturation of MBP-pulsed modc and skewing of T- lymphocyte toward Th2 and thereby can evolve into a new strategy in immunotherapy of MS.

  11. Monocyte-derived dendritic cells from HLA-B27+ axial spondyloarthritis (SpA) patients display altered functional capacity and deregulated gene expression.

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    Talpin, Alice; Costantino, Félicie; Bonilla, Nelly; Leboime, Ariane; Letourneur, Franck; Jacques, Sébastien; Dumont, Florent; Amraoui, Sonia; Dutertre, Charles-Antoine; Garchon, Henri-Jean; Breban, Maxime; Chiocchia, Gilles

    2014-08-21

    This study aimed to compare the functional capacity and gene expression profile of monocyte-derived dendritic cells (MD-DCs) in HLA-B27+ axial spondyloarthritis (SpA) patients and healthy controls. MD-DCs were differentiated with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for seven days, starting from purified CD14+ monocytes and stimulated with lipopolysaccharide (LPS) for six and twenty four hours. Their capacity to stimulate allogeneic CD4+ T cells from unrelated healthy donor was tested. Transcriptomic study was performed with Affymetrix HuGene 1.0 ST microarrays. Gene expression levels were compared between patients and controls using a multivariate design under a linear model (LIMMA). Real-time quantitative PCR (qRT-PCR) was performed for validation of the most striking gene expression differences. The stimulatory capacity of allogeneic CD4+ T cells by MD-DCs from SpA patients was decreased. Transcriptomic analysis revealed 81 genes differentially expressed in MD-DCs between SpA patients and controls (P 1.5). Four selected genes were validated by q ADAMTS15, CITED2, F13A1 and SELL. Expression levels of ADAMTS15 and CITED2, encoding a metallopeptidase and a transcription factor, respectively, were inversely correlated with each other (R = 0.75, P = 0.0003). Furthermore, in silico analysis identified several genes of the Wnt signaling pathway having expression co-regulated with CITED2. This study revealed altered function and gene expression pattern in MD-DCs from HLA-B27+ axial SpA. Co-expression study showed an inverse correlation between ADAMTS15 and CITED2. Moreover, the Wnt signaling pathway appeared as deregulated in SpA MD-DCs, a finding which may be connected to Th17-driven inflammatory responses.

  12. Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain.

    Science.gov (United States)

    Ma, Jian; Wang, Shan-Shan; Lin, Yue-Zhi; Liu, Hai-Fang; Liu, Qiang; Wei, Hua-Mian; Wang, Xue-Feng; Wang, Yu-Hong; Du, Cheng; Kong, Xian-Gang; Zhou, Jian-Hua; Wang, Xiaojun

    2014-08-09

    The Chinese attenuated equine infectious anemia virus (EIAV) vaccine has successfully protected millions of equine animals from EIA disease in China. Given that the induction of immune protection results from the interactions between viruses and hosts, a better understanding of the characteristics of vaccine strain infection and host responses would be useful for elucidating the mechanism of the induction of immune protection by the Chinese attenuated EIAV strain. In this study, we demonstrate in equine monocyte-derived macrophages (eMDM) that EIAVFDDV13, a Chinese attenuated EIAV strain, induced a strong resistance to subsequent infection by a pathogenic strain, EIAVUK3. Further experiments indicate that the expression of the soluble EIAV receptor sELR1, Toll-like receptor 3 (TLR3) and interferon β (IFNβ) was up-regulated in eMDM infected with EIAVFDDV13 compared with eMDM infected with EIAVUK3. Stimulating eMDM with poly I:C resulted in similar resistance to EIAV infection as induced by EIAVFDDV13 and was correlated with enhanced TLR3, sELR1 and IFNβ expression. The knock down of TLR3 mRNA significantly impaired poly I:C-stimulated resistance to EIAV, greatly reducing the expression of sELR1 and IFNβ and lowered the level of infection resistance induced by EIAVFDDV13. These results indicate that the induction of restraining infection by EIAVFDDV13 in macrophages is partially mediated through the up-regulated expression of the soluble viral receptor and IFNβ, and that the TLR3 pathway activation plays an important role in the development of an EIAV-resistant intracellular environment.

  13. Global gene expression and systems biology analysis of bovine monocyte-derived macrophages in response to in vitro challenge with Mycobacterium bovis.

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    David A Magee

    Full Text Available BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1. Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. RESULTS: Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05. Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1 the inflammatory response; (2 cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3 apoptosis. CONCLUSIONS: The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in

  14. Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions.

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    Bonnie van Wilgenburg

    Full Text Available Human macrophages are specialised hosts for HIV-1, dengue virus, Leishmania and Mycobacterium tuberculosis. Yet macrophage research is hampered by lack of appropriate cell models for modelling infection by these human pathogens, because available myeloid cell lines are, by definition, not terminally differentiated like tissue macrophages. We describe here a method for deriving monocytes and macrophages from human Pluripotent Stem Cells which improves on previously published protocols in that it uses entirely defined, feeder- and serum-free culture conditions and produces very consistent, pure, high yields across both human Embryonic Stem Cell (hESC and multiple human induced Pluripotent Stem Cell (hiPSC lines over time periods of up to one year. Cumulatively, up to ∼3×10(7 monocytes can be harvested per 6-well plate. The monocytes produced are most closely similar to the major blood monocyte (CD14(+, CD16(low, CD163(+. Differentiation with M-CSF produces macrophages that are highly phagocytic, HIV-1-infectable, and upon activation produce a pro-inflammatory cytokine profile similar to blood monocyte-derived macrophages. Macrophages are notoriously hard to genetically manipulate, as they recognise foreign nucleic acids; the lentivector system described here overcomes this, as pluripotent stem cells can be relatively simply genetically manipulated for efficient transgene expression in the differentiated cells, surmounting issues of transgene silencing. Overall, the method we describe here is an efficient, effective, scalable system for the reproducible production and genetic modification of human macrophages, facilitating the interrogation of human macrophage biology.

  15. Differential intracellular fate of Burkholderia pseudomallei 844 and Burkholderia thailandensis UE5 in human monocyte-derived dendritic cells and macrophages

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    Engering Anneke

    2009-04-01

    Full Text Available Abstract Background Burkholderia pseudomallei (Bp is a category B biothreat organism that causes a potentially fatal disease in humans and animals, namely melioidosis. Burkholderia thailandensis (Bt is another naturally occurring species that is very closely related to Bp. However, despite this closely related genotype, Bt is considered avirulent as it does not cause the disease. In the present study, we compared the growth kinetics of B. pseudomallei strain 844 (Bp-844 in human monocyte-derived dendritic cells (MoDCs and macrophages (Mφs, as well as its ability to stimulate host cell responses with those of B. thailandensis strain UE5 (Bt-UE5. Results Primary human MoDCs and Mφs were infected with Bp-844 and its intracellular growth kinetics and ability to induce host cell responses were evaluated. The results were compared with those obtained using the Bt-UE5. In human MoDCs, both bacteria were similar in respect to their ability to survive and replicate intracellularly, induce upregulation of costimulatory molecules and cytokines and bias T helper cell differentiation toward a Th1 phenotype. By contrast, the two bacteria exhibited different growth kinetics in human Mφs, where the intracellular growth of Bt-UE5, but not Bp-844, was significantly suppressed. Moreover, the ability of Mφs to kill Bp-844 was markedly enhanced following stimulation with IFN-γ. Conclusion The data presented showed that while both strains were similar in their ability to survive and replicate in human MoDCs, only Bp-844 could readily replicate in human Mφs. Both bacteria induced similar host cellular responses, particularly with regard to their ability to bias T cell differentiation toward a Th1 phenotype.

  16. DC-SCRIPT regulates glucocorticoid receptor function and expression of its target GILZ in dendritic cells.

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    Hontelez, Saartje; Karthaus, Nina; Looman, Maaike W; Ansems, Marleen; Adema, Gosse J

    2013-04-01

    Dendritic cells (DCs) play a central role in the immune system; they can induce immunity or tolerance depending on diverse factors in the DC environment. Pathogens, but also tissue damage, hormones, and vitamins, affect DC activation and maturation. In particular, glucocorticoids (GCs) are known for their immunosuppressive effect on DCs, creating tolerogenic DCs. GCs activate the type I nuclear receptor (NR) glucocorticoid receptor (GR), followed by induced expression of the transcription factor glucocorticoid-inducible leucine zipper (GILZ). GILZ has been shown to be necessary and sufficient for GC-induced tolerogenic DC generation. Recently, we have identified the DC-specific transcript (DC-SCRIPT) as an NR coregulator, suppressing type I steroid NRs estrogen receptor and progesterone receptor. In this study, we analyzed the effect of DC-SCRIPT on GR activity. We demonstrate that DC-SCRIPT coexists with GR in protein complexes and functions as a corepressor of GR-mediated transcription. Coexpression of DC-SCRIPT and GR is shown in human monocyte-derived DCs, and DC-SCRIPT knockdown enhances GR-dependent upregulation of GILZ mRNA expression in DCs. This demonstrates that DC-SCRIPT serves an important role in regulating GR function in DCs, corepressing GR-dependent upregulation of the tolerance-inducing transcription factor GILZ. These data imply that by controlling GR function and GILZ expression DC-SCRIPT is potentially involved in the balance between tolerance and immunity.

  17. Human tolerogenic DC-10: perspectives for clinical applications

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    Amodio Giada

    2012-09-01

    Full Text Available Abstract Dendritic cells (DCs are critically involved in inducing either immunity or tolerance. During the last decades efforts have been devoted to the development of ad hoc methods to manipulate DCs in vitro to enhance or stabilize their tolerogenic properties. Addition of IL-10 during monocyte-derived DC differentiation allows the induction of DC-10, a subset of human tolerogenic DCs characterized by high IL-10/IL-12 ratio and co-expression of high levels of the tolerogenic molecules HLA-G and immunoglobulin-like transcript 4. DC-10 are potent inducers of adaptive type 1 regulatory T cells, well known to promote and maintain peripheral tolerance. In this review we provide an in-depth comparison of the phenotype and mechanisms of suppression mediated by DC-10 and other known regulatory antigen-presenting cells currently under clinical development. We discuss the clinical therapeutic application of DC-10 as inducers of type 1 regulatory T cells for tailoring regulatory T-cell-based cell therapy, and the use of DC-10 as adoptive cell therapy for promoting and restoring tolerance in T-cell-mediated diseases.

  18. Investigating the Role of Surface Materials and Three Dimensional Architecture on In Vitro Differentiation of Porcine Monocyte-Derived Dendritic Cells.

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    Sofie Bruun Hartmann

    Full Text Available In vitro generation of dendritic-like cells through differentiation of peripheral blood monocytes is typically done using two-dimensional polystyrene culture plates. In the process of optimising cell culture techniques, engineers have developed fluidic micro-devises usually manufactured in materials other than polystyrene and applying three-dimensional structures more similar to the in vivo environment. Polydimethylsiloxane (PDMS is an often used polymer for lab-on-a-chip devices but not much is known about the effect of changing the culture surface material from polystyrene to PDMS. In the present study the differentiation of porcine monocytes to monocyte-derived dendritic cells (moDCs was investigated using CD172apos pig blood monocytes stimulated with GM-CSF and IL-4. Monocytes were cultured on surfaces made of two- and three-dimensional polystyrene as well as two- and three-dimensional PDMS and carbonised three-dimensional PDMS. Cells cultured conventionally (on two-dimensional polystyrene differentiated into moDCs as expected. Interestingly, gene expression of a wide range of cytokines, chemokines, and pattern recognition receptors was influenced by culture surface material and architecture. Distinct clustering of cells, based on similar expression patterns of 46 genes of interest, was seen for cells isolated from two- and three-dimensional polystyrene as well as two- and three-dimensional PDMS. Changing the material from polystyrene to PDMS resulted in cells with expression patterns usually associated with macrophage expression (upregulation of CD163 and downregulation of CD1a, FLT3, LAMP3 and BATF3. However, this was purely based on gene expression level, and no functional assays were included in this study which would be necessary in order to classify the cells as being macrophages. When changing to three-dimensional culture the cells became increasingly activated in terms of IL6, IL8, IL10 and CCR5 gene expression. Further stimulation

  19. Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients.

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    Jung, Karen; Sabri, Siham; Hanson, John; Xu, Yaoxian; Wang, Ying Wayne; Lai, Raymond; Abdulkarim, Bassam S

    2015-01-01

    Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their "M1/M2" activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 m

  20. Investigating the Role of Surface Materials and Three Dimensional Architecture on In Vitro Differentiation of Porcine Monocyte-Derived Dendritic Cells

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    Hartmann, Sofie Bruun; Mohanty, Soumyaranjan; Skovgaard, Kerstin; Brogaard, Louise; Flagstad, Frederikke Bjergvang; Emnéus, Jenny; Wolff, Anders; Summerfield, Artur; Jungersen, Gregers

    2016-01-01

    In vitro generation of dendritic-like cells through differentiation of peripheral blood monocytes is typically done using two-dimensional polystyrene culture plates. In the process of optimising cell culture techniques, engineers have developed fluidic micro-devises usually manufactured in materials other than polystyrene and applying three-dimensional structures more similar to the in vivo environment. Polydimethylsiloxane (PDMS) is an often used polymer for lab-on-a-chip devices but not much is known about the effect of changing the culture surface material from polystyrene to PDMS. In the present study the differentiation of porcine monocytes to monocyte-derived dendritic cells (moDCs) was investigated using CD172apos pig blood monocytes stimulated with GM-CSF and IL-4. Monocytes were cultured on surfaces made of two- and three-dimensional polystyrene as well as two- and three-dimensional PDMS and carbonised three-dimensional PDMS. Cells cultured conventionally (on two-dimensional polystyrene) differentiated into moDCs as expected. Interestingly, gene expression of a wide range of cytokines, chemokines, and pattern recognition receptors was influenced by culture surface material and architecture. Distinct clustering of cells, based on similar expression patterns of 46 genes of interest, was seen for cells isolated from two- and three-dimensional polystyrene as well as two- and three-dimensional PDMS. Changing the material from polystyrene to PDMS resulted in cells with expression patterns usually associated with macrophage expression (upregulation of CD163 and downregulation of CD1a, FLT3, LAMP3 and BATF3). However, this was purely based on gene expression level, and no functional assays were included in this study which would be necessary in order to classify the cells as being macrophages. When changing to three-dimensional culture the cells became increasingly activated in terms of IL6, IL8, IL10 and CCR5 gene expression. Further stimulation with LPS resulted

  1. Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    J Kenneth Baillie

    2017-03-01

    Full Text Available The FANTOM5 consortium utilised cap analysis of gene expression (CAGE to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1 to bacterial lipopolysaccharide (LPS. We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility

  2. Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease

    Science.gov (United States)

    Arner, Erik; De Hoon, Michiel; Carninci, Piero; Hayashizaki, Yoshihide; Pavli, Paul; Summers, Kim M.; Hume, David A.

    2017-01-01

    The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA) identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD) in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits) enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility from reanalysis

  3. Phenotype and function of myeloid dendritic cells derived from African green monkey blood monocytes.

    Science.gov (United States)

    Mortara, Lorenzo; Ploquin, Mickaël J-Y; Faye, Abdourahmane; Scott-Algara, Daniel; Vaslin, Bruno; Butor, Cécile; Hosmalin, Anne; Barré-Sinoussi, Françoise; Diop, Ousmane M; Müller-Trutwin, Michaela C

    2006-01-20

    Myeloid dendritic cells probably play an important role in the immune response against HIV and SIV, and in the enhancement of CD4+ T cell infection. Here, we have investigated phenotypic and functional features of myeloid monocyte-derived DC (MDDC) from African green monkeys (AGMs). AGMs are natural hosts of SIV and exhibit no signs of abnormal T cell activation despite high SIV plasma viremia. We identified mAbs that cross-react specifically with homologous molecules expressed on AGM DC. We adapted a protocol to derive AGM MDDC by culture in the presence of GM-CSF and IL-4. The differentiated cells possessed a typical dendritic morphology and the majority were CD11c+ DC-SIGN+. AGM MDDC displayed a high expression of typical maturation markers, such as CD83, CD86 and DC-LAMP, and moderate immunostimulatory capacity, suggesting that the cells were in a semi-mature state. Stimulation resulted in further maturation, as shown by up-regulation of CD80 and decrease of endocytosis ability. However, neither increase of HLA-DR or CD40 expression nor enhanced immunostimulatory capacity was observed. The latter was associated with a low pro-inflammatory cytokine production during mixed lymphocyte reactions and a cytokine balance in favour of IL-10 in contrast to human MDDC. This is the first characterization of AGM MDDC. The tools described here are a crucial step for future studies in vivo or in vitro on the function of myeloid DC using the AGM animal model.

  4. Simian virus 40 inhibits differentiation and maturation of rhesus macaque DC-SIGN+-dendritic cells

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    Changyong G

    2010-09-01

    Full Text Available Abstract Dendritic cells (DC are the initiators and modulators of the immune responses. Some species of pathogenic microorganisms have developed immune evasion strategies by controlling antigen presentation function of DC. Simian virus 40 (SV40 is a DNA tumor virus of rhesus monkey origin. It can induce cell transformation and tumorigenesis in many vertebrate species, but often causes no visible effects and persists as a latent infection in rhesus monkeys under natural conditions. To investigate the interaction between SV40 and rhesus monkey DC, rhesus monkey peripheral blood monocyte-derived DC were induced using recombinant human Interleukin-4 (rhIL-4 and infective SV40, the phenotype and function of DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN+ DC were analyzed by flow cytometry (FCM and mixed lymphocyte reaction (MLR. Results showed that SV40 can down-regulate the expression of CD83 and CD86 on DC and impair DC-induced activation of T cell proliferation. These findings suggest that SV40 might also cause immune suppression by influencing differentiation and maturation of DC.

  5. Impairment of in vitro generation of monocyte-derived human dendritic cells by inactivated human immunodeficiency virus-1: Involvement of type I interferon produced from plasmacytoid dendritc cells.

    Science.gov (United States)

    Kodama, Akira; Tanaka, Reiko; Zhang, Li Feng; Adachi, Tetsuya; Saito, Mineki; Ansari, Aftab A; Tanaka, Yuetsu

    2010-06-01

    In an attempt to simplify the protocol of DC generation in vitro, studies conducted herein show that functional DCs could be generated from bulk peripheral blood mononuclear cells (PBMCs) in media containing GM-CSF and IL-4. Interestingly, when PBMCs, but not purified monocytes, were exposed to either CCR5- or CXCR4-tropic inactivated HIV-1 isolates (iHIV-1) at the initiation of the culture, DC yields were significantly reduced in a dose-dependent manner because of monocyte apoptosis. Similar impairment of DC generation was noted using type I IFNs and poly IC not only in cultures of PBMCs but also using highly enriched monocytes. This effect was reversed by antihuman type I IFN receptor, but not by anti-FasL, anti-TRAIL, anti-TNF, or a mixture of these antibodies. iHIV-1-exposed PBMCs, but not monocytes, produced high levels of IFN-alpha but not IFN-beta. PBMCs depleted of CD123(+) plasmacytoid DCs produced low levels of IFN-alpha and were resistant to iHIV-1-mediated DC impairment. Interestingly, exogenously added TNF reversed the impairment by iHIV-1 in the PBMC cultures. In conclusion, the present results indicate that iHIV-1 impairs the in vitro generation of functional DCs from PBMCs through the induction of IFN-alpha from plasmacytoid DCs in a CD4-dependent fashion in the absence of TNF.

  6. Engineering monocyte-derived dendritic cells to secrete interferon-alpha enhances their ability to promote adaptive and innate anti-tumor immune effector functions

    NARCIS (Netherlands)

    Willemen, Y.; Bergh, J.M. Van den; Lion, E.; Anguille, S.; Roelandts, V.A.; Acker, H.H. Van; Heynderickx, S.D.; Stein, B.M.; Peeters, M.; Figdor, C.G.; Tendeloo, V.F. Van; Vries, I.J.M. de; Adema, G.J.; Berneman, Z.N.; Smits, E.L.

    2015-01-01

    Dendritic cell (DC) vaccination has demonstrated potential in clinical trials as a new effective cancer treatment, but objective and durable clinical responses are confined to a minority of patients. Interferon (IFN)-alpha, a type-I IFN, can bolster anti-tumor immunity by restoring or increasing the

  7. Advanced DC/DC converters

    CERN Document Server

    Luo, Fang Lin

    2003-01-01

    INTRODUCTIONHistorical ReviewMultiple Quadrant ChoppersPump CircuitsDevelopment of DC/DC Conversion TechniqueCategorize Prototypes and DC/DC Converters Family TreeVOLTAGE-LIFT CONVERTERSIntroductionSeven Self-Lift ConvertersPositive Output Luo-ConvertersNegative Output Luo-ConvertersModified Positive Output Luo-Converters Double Output Luo-ConvertersPOSITIVE OUTPUT SUPER-LIFT LUO-CONVERTERS IntroductionMain SeriesAdditional SeriesEnhanced Series Re-Enhanced Series Multiple-Enhanced Series Summary of Positive Output

  8. DC + RSL

    DEFF Research Database (Denmark)

    Haxthausen, Anne

    1996-01-01

    This document gives some initial ideas of how the Duration Calculus (DC) can be integrated with the RAISE Specification Language (RSL).......This document gives some initial ideas of how the Duration Calculus (DC) can be integrated with the RAISE Specification Language (RSL)....

  9. Comparison of monocyte-derived dendritic cells from colorectal cancer patients, non-small-cell-lung-cancer patients and healthy donors

    DEFF Research Database (Denmark)

    Kvistborg, P; Bechmann, C M; Pedersen, A W;

    2009-01-01

    7, and the optimal expression pattern is considered as CD14(low), CD1a, CD83(high), CD86(high), MHC class II(high) and CCR7(high). In accordance with data from other studies including other types of cancer patients, especially breast cancer patients, we found that the maturation status of the DC...... blood monocytes loaded with allogeneic tumor cell lysate rich in cancer/testis antigens. This vaccine has at present been tested for activity in three phase II clinical trials including two cohorts of patients with advanced colorectal cancer (CRC) and one cohort of patients with advanced non...... were analyzed by flow cytometry and the obtained data were used as a basis to set guideline values for our quality control of GMP produced DC vaccines. Each vaccine batch was analyzed for the expression of the surface maturation and differentiation molecules CD14, CD1a, CD83, CD86, MHC class II and CCR...

  10. Peroxisome proliferator-activated receptor α agonist attenuates oxidized-low density lipoprotein induced immune maturation of human monocyte-derived dendritic cells

    Institute of Scientific and Technical Information of China (English)

    SHI Hong-yu; CAO Xue-tao; GE Jun-bo; FANG Wei-yi; YAO Kang; SUN Ai-jun; HUANG Rong-chong; JIA Qing-zhe; WANG Ke-qiang; ZOU Yun-zeng

    2008-01-01

    @@ Accumulating evidence suggests that the Th1 immune response induced by various antigens such as oxidized low density lipoprotein (ox-LDL) and heat shock proteins (HSPs) play a key role in the process of atherosclerosis.1 Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in the body with the unique ability to initiate a primary immune response to certain antigens by the activation of "naive" T cells.2 The maturation of DC with the upregulation of costimulatory molecules such as CD83,CD40,CD86,and major histocompatibility complex (MHC) class molecules such as human leukocyte antigen (HLA)-DR,is required for DC to activate T cells.

  11. Human monocyte-derived dendritic cells from leukoreduction system chambers after plateletpheresis are functional in an in vitro co-culture assay with intestinal epithelial cells.

    OpenAIRE

    Tiscornia, Inés; Sánchez-Martins, Viviana; Hernández, Ana; Bollati-Fogolín, Mariela

    2012-01-01

    International audience; The dendritic cells (DC) found in the intestine are involved both in the maintenance of tolerance towards commensal microbiota, and in the generation of protective immune responses against pathogens, thus contributing to gut immune homeostasis. There is an increasing interest in the use of lactic acid bacteria (LAB) as probiotics; among their beneficial effects we highlight the modulation of the immune system which is one of their fundamental properties. As these effec...

  12. Infection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeability

    Directory of Open Access Journals (Sweden)

    Lopez-Lastra Marcelo

    2011-05-01

    Full Text Available Abstract Background Andes virus (ANDV, a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS in South America, which is mainly characterized by a vascular leakage with high rate of fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but in despite that the severity of the disease directly correlates with the viral RNA load, considerable evidence suggests that immune mechanisms rather than direct viral cytopathology are responsible for plasma leakage in HCPS. Here, we assessed the possible effect of soluble factors, induced in viral-activated DCs, on endothelial permeability. Activated immune cells, including DC, secrete gelatinolytic matrix metalloproteases (gMMP-2 and -9 that modulate the vascular permeability for their trafficking. Methods A clinical ANDES isolate was used to infect DC derived from primary PBMC. Maturation and pro-inflammatory phenotypes of ANDES-infected DC were assessed by studying the expression of receptors, cytokines and active gMMP-9, as well as some of their functional status. The ANDES-infected DC supernatants were assessed for their capacity to enhance a monolayer endothelial permeability using primary human vascular endothelial cells (HUVEC. Results Here, we show that in vitro primary DCs infected by a clinical isolate of ANDV shed virus RNA and proteins, suggesting a competent viral replication in these cells. Moreover, this infection induces an enhanced expression of soluble pro-inflammatory factors, including TNF-α and the active gMMP-9, as well as a decreased expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. These viral activated cells are less sensitive to apoptosis. Moreover, supernatants from ANDV-infected DCs were able to indirectly enhance the permeability of a monolayer of primary HUVEC. Conclusions Primary human DCs

  13. Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity

    Science.gov (United States)

    Prestwood, Tyler R.; Spitzer, Matthew H.; Linde, Ian L.; Chabon, Jonathan; Reticker-Flynn, Nathan E.; Bhattacharya, Nupur; Zhang, Hong; Zhang, Xiangyue; Basto, Pamela A.; Burt, Bryan M.; Alonso, Michael N.; Engleman, Edgar G.

    2016-01-01

    BM-derived DC (BMDC) are powerful antigen-presenting cells. When loaded with immune complexes (IC), consisting of tumor antigens bound to antitumor antibody, BMDC induce powerful antitumor immunity in mice. However, attempts to employ this strategy clinically with either tumor-associated DC (TADC) or monocyte-derived DC (MoDC) have been disappointing. To investigate the basis for this phenomenon, we compared the response of BMDC, TADC, and MoDC to tumor IgG-IC. Our findings revealed, in both mice and humans, that upon exposure to IgG-IC, BMDC internalized the IC, increased costimulatory molecule expression, and stimulated autologous T cells. In contrast, TADC and, surprisingly, MoDC remained inert upon contact with IC due to dysfunctional signaling following engagement of Fcγ receptors. Such dysfunction is associated with elevated levels of the Src homology region 2 domain–containing phosphatase-1 (SHP-1) and phosphatases regulating Akt activation. Indeed, concomitant inhibition of both SHP-1 and phosphatases that regulate Akt activation conferred upon TADC and MoDC the capacity to take up and process IC and induce antitumor immunity in vivo. This work identifies the molecular checkpoints that govern activation of MoDC and TADC and their capacity to elicit T cell immunity. PMID:27812544

  14. Simplified dc to dc converter

    Science.gov (United States)

    Gruber, R. P. (Inventor)

    1984-01-01

    A dc to dc converter which can start with a shorted output and which regulates output voltage and current is described. Voltage controlled switches directed current through the primary of a transformer the secondary of which includes virtual reactance. The switching frequency of the switches is appropriately varied to increase the voltage drop across the virtual reactance in the secondary winding to which there is connected a low impedance load. A starting circuit suitable for voltage switching devices is provided.

  15. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation

    Science.gov (United States)

    Granelli-Piperno, Angela; Golebiowska, Angelika; Trumpfheller, Christine; Siegal, Frederick P.; Steinman, Ralph M.

    2004-05-01

    Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers. If different maturation stimuli are applied to DCs infected with HIV-1, the infected cells selectively fail to mature. When DCs from HIV-1-infected patients are infected and cultured with autologous T cells, IL-10 was produced in 6 of 10 patients. These DC-T cell cocultures could suppress another immune response, the MLR. The regulation was partially IL-10-dependent and correlated in extent with the level of IL-10 produced. Suppressor cells only developed from infected patients, rather than healthy controls, and the DCs had to be exposed to live virus rather than HIV-1 gag peptides or protein. These results indicate that HIV-1-infected DCs have two previously unrecognized means to evade immune responses: maturation can be blocked reducing the efficacy of antigen presentation from infected cells, and T cell-dependent suppression can be induced.

  16. Flow cytometric gating for spleen monocyte and DC subsets: differences in autoimmune NOD mice and with acute inflammation.

    Science.gov (United States)

    Dong, Matthew B; Rahman, M Jubayer; Tarbell, Kristin V

    2016-05-01

    The role of antigen presenting cells (APCs) in the pathogenesis of autoimmune and other inflammatory diseases is now better understood due to advances in multicolor flow cytometry, gene expression analysis of APC populations, and functional correlation of mouse to human APC populations. A simple but informative nomenclature of conventional and plasmacytoid dendritic cell subsets (cDC1, cDC2, pDC) and monocyte-derived populations incorporates these advances, but accurate subset identification is critical. Ambiguous gating schemes and alterations of cell surface markers in inflammatory condition can make comparing results between studies difficult. Both acute inflammation, such as TLR-ligand stimulation, and chronic inflammation as found in mouse models of autoimmunity can alter DC subset gating. Here, we address these issues using in vivo CpG stimulation as an example of acute inflammation and the non-obese diabetic (NOD) mouse as a model of chronic inflammation.We provide a flow cytometric antibody panel and gating scheme that differentiate 2 monocytic and 3DC subsets in the spleen both at steady state and after CpG stimulation. Using this method, we observed differences in the composition of NOD DCs that have been previously reported, and newly identified increases in the number of NOD monocyte-derived DCs. Finally, we established a protocol for DC phosphoflow to measure the phosphorylation state of intracellular proteins, and use it to confirm functional differences in the identified subsets. Therefore, we present optimized methods for distinguishing monocytic and DC populations with and without inflammation and/or autoimmunity associated with NOD mice.

  17. Effect of in vitro digested cod liver oil of different quality on oxidative, proteomic and inflammatory responses in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells

    DEFF Research Database (Denmark)

    Larsson, Karin; Istenič, Katja; Wulff, Tune

    2015-01-01

    digested fresh and oxidised cod liver oils in vitro, monitored the levels of lipid peroxidation products and evaluated oxidative, proteomic and inflammatory responses to the two types of digests in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells. RESULTS: Digests of cod liver......BACKGROUND: Upon oxidation of the polyunsaturated fatty acids in fish oil, either before ingestion or, as recently shown, during the gastro-intestinal passage, a cascade of potentially cytotoxic peroxidation products, such as malondialdehyde and 4-hydroxy-2-hexenal, can form. In this study, we...... oil with 22–53 µmol L−1 malondialdehyde and 0.26–3.7 µmol L−1 4-hydroxy-2-hexenal increased intracellular oxidation and cell energy metabolic activity compared to a digested blank in yeast cells and the influence of digests on mitochondrial protein expression was more pronounced for oxidised cod liver...

  18. DC generation from peripheral blood mononuclear cells in patients with chronic myeloid leukemia: Influence of interferons on DC yield and functional properties.

    Science.gov (United States)

    Flörcken, Anne; Kopp, Joachim; Kölsch, Uwe; Meisel, Christian; Dörken, Bernd; Pezzutto, Antonio; Westermann, Jörg

    2016-05-03

    In Chronic Myeloid Leukemia (CML), standard treatment consists of modern tyrosine-kinase inhibitors (TKI). Nevertheless, there is evidence that immune responses against leukemia-associated antigens (LAA) may play an important role in disease control. Dendritic cell (DC)- based immunotherapy is able to induce T cell responses against LAA and might therefore pose an interesting therapeutic option in CML, especially in the setting of minimal residual disease (MRD). GMP production of DC for clinical vaccination remains a time- and cost- intensive procedure and standardized DC generation is warranted. We asked whether maturation-induction with IFN-γ and IFN-α has an influence on functional properties of DC derived from peripheral blood mononuclear cells (PBMC) in CML patients. Monocyte-derived DC from healthy donors and from patients with CML were analyzed after maturation-induction with our TNF-α-containing standard cytokine cocktail with or without addition of IFN-α and/or IFN-γ. Our results confirm that the addition of IFN-γ leads to enhanced IL-12 secretion in healthy donors. In contrast, in CML patients, IFN-γ was not able to increase IL-12 secretion, possibly due to a higher degree of cell adherence and lower cell yield during the cell culture. Our data suggest, that- in contrast to healthy donors-, additional interferons are not beneficial for maturation induction during large-scale DC production in patients with CML.

  19. PWM DC/DC Converter

    OpenAIRE

    Chen, Juan

    2008-01-01

    This report is the result of a Master Thesis work done at Seaward Electronics Inc. in Beijing, China from June to December in 2007. The main goal for this thesis is to verify and improve the performance of Honey-PWM DC-DC converter, which has been fabricated by a standard 0.6um CMOS processes. The project was started with studying of Buck converter structure. After the understanding of the converter structure, the project goes in to the analyses phase for each sub-cells, including the theory,...

  20. Isolerad DC/DC-omvandlare

    OpenAIRE

    Andersson, Martin

    2011-01-01

    1 SammanfattningCrossControl är ett företag som bland annat tillverkar integrerade datorlösningar. Datorerna drivs normalt med 18-30 VDC och förbrukar som mest 50W. Datorerna säljs till flertalet olika kunder som monterar dem i allt från skogsmaskiner till tåg. I de olika fordonen varierar spänningen i de befintliga elnäten. Detta skapar behovet av att omvandla spänningen till en nivå som datorerna klarar av. En sådan apparat kallas DC/DC-omvandlare. Spänningsomvandling kan utföras genom linj...

  1. AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC-SIGN.

    Science.gov (United States)

    Serrano-Gómez, Diego; Martínez-Nuñez, Rocío T; Sierra-Filardi, Elena; Izquierdo, Nuria; Colmenares, María; Pla, Jesús; Rivas, Luis; Martinez-Picado, Javier; Jimenez-Barbero, Jesús; Alonso-Lebrero, José Luis; González, Salvador; Corbí, Angel L

    2007-07-01

    AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of Candida, Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and (1)D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.

  2. Differential regulatory activities of viral protein X for anti-viral efficacy of nucleos(t)ide reverse transcriptase inhibitors in monocyte-derived macrophages and activated CD4(+) T cells.

    Science.gov (United States)

    Hollenbaugh, Joseph A; Schader, Susan M; Schinazi, Raymond F; Kim, Baek

    2015-11-01

    Vpx encoded by HIV-2 and SIVsm enhances retroviral reverse transcription in macrophages in vitro by mediating the degradation of the host SAMHD1 protein that hydrolyzes dNTPs and by elevating cellular dNTP levels. Here we employed RT-SHIV constructs (SIV encoding HIV-1 RT) to investigate the contribution of Vpx to the potency of NRTIs, which compete against dNTPs, in monocyte-derived macrophages (MDMs) and activated CD4(+) T cells. Relative to HIV-1, both SIV and RT-SHIV exhibited reduced sensitivities to AZT, 3TC and TDF in MDMs but not in activated CD4(+) T cells. However, when SIV and RT-SHIV constructs not coding for Vpx were utilized, we observed greater sensitivities to all NRTIs tested using activated CD4(+) T cells relative to the Vpx-coding counterparts. This latter phenomenon was observed for AZT only when using MDMs. Our data suggest that Vpx in RT-SHIVs may underestimate the antiviral efficacy of NRTIs in a cell type dependent manner.

  3. Adaptable DC offset correction

    Science.gov (United States)

    Golusky, John M. (Inventor); Muldoon, Kelly P. (Inventor)

    2009-01-01

    Methods and systems for adaptable DC offset correction are provided. An exemplary adaptable DC offset correction system evaluates an incoming baseband signal to determine an appropriate DC offset removal scheme; removes a DC offset from the incoming baseband signal based on the appropriate DC offset scheme in response to the evaluated incoming baseband signal; and outputs a reduced DC baseband signal in response to the DC offset removed from the incoming baseband signal.

  4. "Forback" Dc-To-Dc Converters

    Science.gov (United States)

    Lukemire, Alan T.

    1992-01-01

    Dc-to-dc power-converter circuits called "forback" resemble circuits of standard configurations called "forward", "flyback", and "Cuk". Circuit employs minor modifications to existing topologies, combines advantages, while eliminating disadvantages, of older circuits.

  5. FastDC derived from human monocytes within 48 h effectively prime tumor antigen-specific cytotoxic T cells.

    Science.gov (United States)

    Dauer, Marc; Schad, Katharina; Herten, Jan; Junkmann, Jana; Bauer, Christian; Kiefl, Rosemarie; Endres, Stefan; Eigler, Andreas

    2005-07-01

    Previously, we have shown that dendritic cells (DCs) with full T-cell stimulatory capacity can be derived from human monocytes after 48 h of in vitro culture (FastDC). Compared to a standard 7-day protocol, this new strategy not only reduces the time span and the amount of recombinant cytokines required, but may also resemble DC development in vivo more closely. Using a melanoma antigen model, we show here that FastDC prime CTL responses against tumor antigens as effectively as standard monocyte-derived DCs (moDCs). FastDC and moDCs derived from monocytes of HLA-A2(+) donors were loaded with the melanoma-associated, HLA-A(*)0201-restricted peptide Melan-A and cocultured with autologous CD3(+) T cells. After two weekly restimulations with freshly prepared, peptide-loaded FastDC or moDCs, binding of CD8(+) T cells to fluorescently labeled MHC-I/Melan-A-peptide complexes and intracellular cytokine staining revealed that the two DC preparations had an equal capacity to prime Melan-A-specific, IFN-gamma producing CD8(+) T cells. CTLs derived from cocultures with FastDC lysed Melan-A-loaded T2 cells even more effectively than CTLs primed by moDCs. Comparative analysis also revealed that FastDC possess an equal capacity to migrate in response to the chemokine receptor CCR-7 ligand 6Ckine. Importantly, DCs can be generated with higher yield and purity using the FastDC-protocol. The reliability and efficacy of this new strategy for DC development from monocytes may facilitate clinical investigation of DC-based tumor immunotherapy.

  6. Multiport Resonant DC-DC Converter

    OpenAIRE

    Tran, Yan-Kim; Dujic, Drazen; Barrade, Philippe

    2015-01-01

    his paper presents a multiport galvanically isolated LLC resonant DC-DC converter suitable for DC applications. A three-port structure is analyzed, with full bidirectional power flow capabilities, simple control and behavior similar to that expected from a DC transformer. Each port is equipped with half-bridge modules accompanied with tuned resonant tank, partly realized with elements of a multi- winding high frequency transformer. With some restrictions that are explained in the paper, each ...

  7. VLSI Hybrid DC-DC Regulator

    OpenAIRE

    Cosp Vilella, Jordi; Martínez García, Herminio

    2015-01-01

    Hybrid DC-DC regulators are structures that combine both a linear voltage regulator and a switching DC-DC converter. The main objective of this hybrid topology is to converge, in a single circuit topology, the best of both alternatives: a small voltage output ripple, which is a common characteristic of linear regulator circuits, and good energy efficiency, as in switching alternatives. While the linear regulator fixes the required output voltage to a fixed value with negligible steady-state r...

  8. Local Bifurcations in DC-DC Converters

    OpenAIRE

    2012-01-01

    Three local bifurcations in DC-DC converters are reviewed. They are period-doubling bifurcation, saddle-node bifurcation, and Neimark bifurcation. A general sampled-data model is employed to study the types of loss of stability of the nominal (periodic) solution and their connection with local bifurcations. More accurate prediction of instability and bifurcation than using the averaging approach is obtained. Examples of bifurcations associated with instabilities in DC-DC converters are given.

  9. High-Efficiency dc/dc Converter

    Science.gov (United States)

    Sturman, J.

    1982-01-01

    High-efficiency dc/dc converter has been developed that provides commonly used voltages of plus or minus 12 Volts from an unregulated dc source of from 14 to 40 Volts. Unique features of converter are its high efficiency at low power level and ability to provide output either larger or smaller than input voltage.

  10. DC-SIGN Facilitates Fusion of Dendritic Cells with Human T-Cell Leukemia Virus Type 1-Infected Cells

    Science.gov (United States)

    Ceccaldi, Pierre-Emmanuel; Delebecque, Frédéric; Prevost, Marie-Christine; Moris, Arnaud; Abastado, Jean-Pierre; Gessain, Antoine; Schwartz, Olivier; Ozden, Simona

    2006-01-01

    Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1-infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin expressed in DCs, in HTLV-1-induced syncytium formation. DC-SIGN is known to bind with high affinity to various viral envelope glycoproteins, including human immunodeficiency virus (HIV) and hepatitis C virus, as well as to the cellular receptors ICAM-2 and ICAM-3. After cocultivating DCs and HTLV-1-infected cells, we found that anti-DC-SIGN monoclonal antibodies (MAbs) were able to decrease the number and size of HTLV-1-induced syncytia. Moreover, expression of the lectin in epithelial-cell lines dramatically enhanced the ability to fuse with HTLV-1-positive cells. Interestingly, in contrast to the envelope (Env) glycoproteins of HIV and other viruses, that of HTLV-1 does not bind directly to DC-SIGN. The facilitating role of the lectin in HTLV-1 syncytium formation is mediated by its interaction with ICAM-2 and ICAM-3, as demonstrated by use of MAbs directed against these adhesion molecules. Altogether, our results indicate that DC-SIGN facilitates HTLV-1 infection and fusion of DCs through an ICAM-dependent mechanism. PMID:16641270

  11. Acanthamoeba castellanii Genotype T4 Stimulates the Production of Interleukin-10 as Well as Proinflammatory Cytokines in THP-1 Cells, Human Peripheral Blood Mononuclear Cells, and Human Monocyte-Derived Macrophages.

    Science.gov (United States)

    Mattana, Antonella; Sanna, Manuela; Cano, Antonella; Delogu, Giuseppe; Erre, Giuseppe; Roberts, Craig W; Henriquez, Fiona L; Fiori, Pier Luigi; Cappuccinelli, Piero

    2016-10-01

    Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages during the early phase of infection. Here, THP-1 cells, primary human monocytes isolated from peripheral blood, and human monocyte-derived macrophages were either coincubated with trophozoites of a clinical isolate of Acanthamoeba (genotype T4) or stimulated with amoeba-derived cell-free conditioned medium. Production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-12), anti-inflammatory cytokine (IL-10), and chemokine (IL-8) was evaluated at specific hours poststimulation (ranging from 1.5 h to 23 h). We showed that both Acanthamoeba trophozoites and soluble amoebic products induce an early anti-inflammatory monocyte-macrophage phenotype, characterized by significant production of IL-10; furthermore, challenge with either trophozoites or their soluble metabolites stimulate both proinflammatory cytokines and chemokine production, suggesting that this protozoan infection results from the early induction of coexisting, opposed immune responses. Results reported in this paper confirm that the production of proinflammatory cytokines and chemokines by monocytes and macrophages can play a role in the development of the inflammatory response during Acanthamoeba infections. Furthermore, we demonstrate for the first time that Acanthamoeba stimulates IL-10 production in human innate immune cells, which might both promote the immune evasion of Acanthamoeba and limit the induced inflammatory response.

  12. PRRSV-infected monocyte-derived dendritic cells express high levels of SLA-DR and CD80/86 but do not stimulate PRRSV-naïve regulatory T cells to proliferate.

    Science.gov (United States)

    Rodríguez-Gómez, Irene M; Käser, Tobias; Gómez-Laguna, Jaime; Lamp, Benjamin; Sinn, Leonie; Rümenapf, Till; Carrasco, Librado; Saalmüller, Armin; Gerner, Wilhelm

    2015-05-20

    In vitro generated monocyte-derived dendritic cells (moDCs) have frequently been used to study the influence of porcine reproductive and respiratory syndrome virus (PRRSV) infection on antigen presenting cells. However, obtained results have often been conflicting in regard to expression of co-stimulatory molecules and interaction with T cells. In this study we performed a detailed phenotypic characterisation of PRRSV-infected moDCs and non-infected moDCs. For CD163 and CD169, which are involved in PRRSV-entry into host cells, our results show that prior to infection porcine moDCs express high levels of CD163 but only very low levels for CD169. Following infection with either PRRSV-1 or PRRSV-2 strains after 24 h, PRRSV-nucleoprotein (N-protein)(+) and N-protein(-) moDCs derived from the same microculture were analyzed for expression of swine leukocyte antigen-DR (SLA-DR) and CD80/86. N-protein(+) moDCs consistently expressed higher levels of SLA-DR and CD80/86 compared to N-protein(-) moDCs. We also investigated the influence of PRRSV-infected moDCs on proliferation and frequency of Foxp3(+) regulatory T cells present within CD4(+) T cells in in vitro co-cultures. Neither CD3-stimulated nor unstimulated CD4(+) T cells showed differences in regard to proliferation and frequency of Foxp3(+) T cells following co-cultivation with either PRRSV-1 or PRRSV-2 infected moDCs. Our results suggest that a more detailed characterisation of PRRSV-infected moDCs will lead to more consistent results across different laboratories and PRRSV strains as indicated by the major differences in SLA-DR and CD80/86 expression between PRRSV-infected and non-infected moDCs present in the same microculture.

  13. Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophages

    Directory of Open Access Journals (Sweden)

    Gopalan Sarla

    2007-11-01

    Full Text Available Abstract Background Several subtypes of HIV-1 circulate in infected people worldwide, including subtype B in the United States and subtype C in Africa and India. To understand the biological properties of HIV-1 subtype C, including cellular tropism, virus entry, replication efficiency and cytopathic effects, we reciprocally inserted our previously characterized envelope V3–V5 regions derived from 9 subtype C infected patients from India into a subtype B molecular clone, pNL4-3. Equal amounts of the chimeric viruses were used to infect T-lymphocyte cell lines (A3.01 and MT-2, coreceptor cell lines (U373-MAGI-CCR5/CXCR4, primary blood T-lymphocytes (PBL and monocyte-derived macrophages (MDM. Results We found that subtype C envelope V3–V5 region chimeras failed to replicate in T-lymphocyte cell lines but replicated in PBL and MDM. In addition, these chimeras were able to infect U373MAGI-CD4+-CCR5+ but not U373MAGI-CD4+-CXCR4+ cell line, suggesting CCR5 coreceptor utilization and R5 phenotypes. These subtype C chimeras were unable to induce syncytia in MT-2 cells, indicative of non-syncytium inducing (NSI phenotypes. More importantly, the subtype C envelope chimeras replicated at higher levels in PBL and MDM compared with subtype B chimeras and isolates. Furthermore, the higher levels subtype C chimeras replication in PBL and MDM correlated with increased virus entry in U373MAGI-CD4+-CCR5+. Conclusion Taken together, these results suggest that the envelope V3 to V5 regions of subtype C contributed to higher levels of HIV-1 replication compared with subtype B chimeras, which may contribute to higher viral loads and faster disease progression in subtype C infected individuals than other subtypes as well as rapid HIV-1 subtype C spread in India.

  14. Tumour-cytolytic human monocyte-derived macrophages: a simple and efficient method for the generation and long-term cultivation as non-adherent cells in a serum-free medium.

    Science.gov (United States)

    Streck, R J; Hurley, E L; Epstein, D A; Pauly, J L

    1992-01-01

    We report a simple and efficient culture procedure for the generation of tumour-cytolytic human monocyte-derived macrophages (MAC). In this method, normal human peripheral blood mononuclear cells, isolated using a conventional Ficoll-Hypaque density gradient procedure, are cultured as a heterogenous leukocyte population in Teflon or other hydrophobic cultureware, in a commercially available serum-free culture medium (M-SFM) that has been formulated specifically for the cultivation and ex vivo stimulation of human monocytes and MAC, and in the absence of exogenous mitogens, antigens, cytokines or other stimulants. This procedure features a negative-selection technique that takes advantage of the differential survival of blood leukocytes. Using the prescribed in vitro conditions, lymphocytes survived relatively poorly, whereas monocytes differentiated in the absence of exogenous stimulants into mature tumour-cytolytic MAC. The MAC were present as non-adherent, single cells that expressed good viability (greater than 95%) for a prolonged period (greater than 60 days). When compared to conventional procedures for generating MAC, the prescribed technique is thought to offer several important advantages in that it: (a) eliminates the tedious and cumbersome monocyte isolation procedures, thus providing a significant savings not only in time and money but also in eliminating repetitive cell manipulations that have often been associated with damage to monocyte morphology and/or function; (b) reduces the loss of monocyte subsets that are not recovered during specific isolation procedures; (c) facilitates harvesting a single cell, non-adherent suspension of immunocompetent MAC suitable for various examinations including analyses defining MAC morphology, cytochemistry, phenotype and function; and (d) eliminates variability and artifacts associated with different sera that are utilised frequently as medium supplements. The utility of the prescribed method is illustrated by the

  15. The abcEDCBA-Encoded ABC Transporter and the virB Operon-Encoded Type IV Secretion System of Brucella ovis Are Critical for Intracellular Trafficking and Survival in Ovine Monocyte-Derived Macrophages.

    Directory of Open Access Journals (Sweden)

    Auricelio A Macedo

    Full Text Available Brucella ovis infection is associated with epididymitis, orchitis and infertility in rams. Most of the information available on B. ovis and host cell interaction has been generated using murine macrophages or epithelial cell lines, but the interaction between B. ovis and primary ovine macrophages has not been studied. The aim of this study was to evaluate the role of the B. ovis abcEDCBA-encoded ABC transporter and the virB operon-encoded Type IV Secretion System (T4SS during intracellular survival of B. ovis in ovine peripheral blood monocyte-derived macrophages. ΔabcBA and ΔvirB2 mutant strains were unable to survive in the intracellular environment when compared to the WT B. ovis at 48 hours post infection (hpi. In addition, these mutant strains cannot exclude the lysosomal marker LAMP1 from its vacuolar membrane, and their vacuoles do not acquire the endoplasmic reticulum marker calreticulin, which takes place in the WT B. ovis containing vacuole. Higher levels of nitric oxide production were observed in macrophages infected with WT B. ovis at 48 hpi when compared to macrophages infected with the ΔabcBA or ΔvirB2 mutant strains. Conversely, higher levels of reactive oxygen species were detected in macrophages infected with the ΔabcBA or ΔvirB2 mutant strains at 48 hpi when compared to macrophages infected with the WT strain. Our results demonstrate that B. ovis is able to persist and multiply in ovine macrophages, while ΔabcBA and ΔvirB2 mutations prevent intracellular multiplication, favor phagolysosome fusion, and impair maturation of the B. ovis vacuole towards an endoplasmic reticulum-derived compartment.

  16. Acanthamoeba castellanii Genotype T4 Stimulates the Production of Interleukin-10 as Well as Proinflammatory Cytokines in THP-1 Cells, Human Peripheral Blood Mononuclear Cells, and Human Monocyte-Derived Macrophages

    Science.gov (United States)

    Sanna, Manuela; Cano, Antonella; Delogu, Giuseppe; Erre, Giuseppe; Roberts, Craig W.; Henriquez, Fiona L.; Fiori, Pier Luigi; Cappuccinelli, Piero

    2016-01-01

    Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages during the early phase of infection. Here, THP-1 cells, primary human monocytes isolated from peripheral blood, and human monocyte-derived macrophages were either coincubated with trophozoites of a clinical isolate of Acanthamoeba (genotype T4) or stimulated with amoeba-derived cell-free conditioned medium. Production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-12), anti-inflammatory cytokine (IL-10), and chemokine (IL-8) was evaluated at specific hours poststimulation (ranging from 1.5 h to 23 h). We showed that both Acanthamoeba trophozoites and soluble amoebic products induce an early anti-inflammatory monocyte-macrophage phenotype, characterized by significant production of IL-10; furthermore, challenge with either trophozoites or their soluble metabolites stimulate both proinflammatory cytokines and chemokine production, suggesting that this protozoan infection results from the early induction of coexisting, opposed immune responses. Results reported in this paper confirm that the production of proinflammatory cytokines and chemokines by monocytes and macrophages can play a role in the development of the inflammatory response during Acanthamoeba infections. Furthermore, we demonstrate for the first time that Acanthamoeba stimulates IL-10 production in human innate immune cells, which might both promote the immune evasion of Acanthamoeba and limit the induced inflammatory response. PMID:27481240

  17. Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response.

    Science.gov (United States)

    Silveira, G F; Strottmann, D M; de Borba, L; Mansur, D S; Zanchin, N I T; Bordignon, J; dos Santos, C N Duarte

    2016-01-01

    Dengue is the most prevalent arboviral disease worldwide. The outcome of the infection is determined by the interplay of viral and host factors. In the present study, we evaluated the cellular response of human monocyte-derived DCs (mdDCs) infected with recombinant dengue virus type 1 (DV1) strains carrying a single point mutation in the NS3hel protein (L435S or L480S). Both mutated viruses infect and replicate more efficiently and produce more viral progeny in infected mdDCs compared with the parental, non-mutated virus (vBACDV1). Additionally, global gene expression analysis using cDNA microarrays revealed that the mutated DVs induce the up-regulation of the interferon (IFN) signalling and pattern recognition receptor (PRR) canonical pathways in mdDCs. Pronounced production of type I IFN were detected specifically in mdDCs infected with DV1-NS3hel-mutated virus compared with mdDCs infected with the parental virus. In addition, we showed that the type I IFN produced by mdDCs is able to reduce DV1 infection rates, suggesting that cytokine function is effective but not sufficient to mediate viral clearance of DV1-NS3hel-mutated strains. Our results demonstrate that single point mutations in subdomain 2 have important implications for adenosine triphosphatase (ATPase) activity of DV1-NS3hel. Although a direct functional connection between the increased ATPase activity and viral replication still requires further studies, these mutations speed up viral RNA replication and are sufficient to enhance viral replicative capacity in human primary cell infection and circumvent type I IFN activity. This information may have particular relevance for attenuated vaccine protocols designed for DV.

  18. Bordetella pertussis commits human dendritic cells to promote a Th1/Th17 response through the activity of adenylate cyclase toxin and MAPK-pathways.

    Directory of Open Access Journals (Sweden)

    Giorgio Fedele

    Full Text Available The complex pathology of B. pertussis infection is due to multiple virulence factors having disparate effects on different cell types. We focused our investigation on the ability of B. pertussis to modulate host immunity, in particular on the role played by adenylate cyclase toxin (CyaA, an important virulence factor of B. pertussis. As a tool, we used human monocyte derived dendritic cells (MDDC, an ex vivo model useful for the evaluation of the regulatory potential of DC on T cell immune responses. The work compared MDDC functions after encounter with wild-type B. pertussis (BpWT or a mutant lacking CyaA (BpCyaA-, or the BpCyaA- strain supplemented with either the fully functional CyaA or a derivative, CyaA*, lacking adenylate cyclase activity. As a first step, MDDC maturation, cytokine production, and modulation of T helper cell polarization were evaluated. As a second step, engagement of Toll-like receptors (TLR 2 and TLR4 by B. pertussis and the signaling events connected to this were analyzed. These approaches allowed us to demonstrate that CyaA expressed by B. pertussis strongly interferes with DC functions, by reducing the expression of phenotypic markers and immunomodulatory cytokines, and blocking IL-12p70 production. B. pertussis-treated MDDC promoted a mixed Th1/Th17 polarization, and the activity of CyaA altered the Th1/Th17 balance, enhancing Th17 and limiting Th1 expansion. We also demonstrated that Th1 effectors are induced by B. pertussis-MDDC in the absence of IL-12p70 through an ERK1/2 dependent mechanism, and that p38 MAPK is essential for MDDC-driven Th17 expansion. The data suggest that CyaA mediates an escape strategy for the bacterium, since it reduces Th1 immunity and increases Th17 responses thought to be responsible, when the response is exacerbated, for enhanced lung inflammation and injury.

  19. Accessory cells with a veiled morphology and movement pattern generated from monocytes after avoidance of plastic adherence and of NADPH oxidase activation. A comparison with GM-CSF/IL-4-induced monocyte-derived dendritic cells.

    Science.gov (United States)

    Ruwhof, Cindy; Canning, Martha O; Grotenhuis, Kristel; de Wit, Harm J; Florencia, Zenovia Z; de Haan-Meulman, Meeny; Drexhage, Hemmo A

    2002-07-01

    Veiled cells (VC) present in afferent lymph transport antigen from the periphery to the draining lymph nodes. Although VC in lymph form a heterogeneous population, some of the cells clearly belong on morphological grounds to the Langerhans cell (LC)/ dendritic cell (DC) series. Here we show that culturing monocytes for 24 hrs while avoiding plastic adherence (polypropylene tubes) and avoiding the activation of NADPH oxidase (blocking agents) results in the generation of a population of veiled accessory cells. The generated VC were actively moving cells like lymph-borne VC in vivo. The monocyte (mo)-derived VC population existed of CD14(dim/-) and CD14(brighT) cells. Of these the CD14(dim/-) VC were as good in stimulating allogeneic T cell proliferation as immature DC (iDC) obtained after one week of adherent culture of monocytes in granulocyte-macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. This underscores the accessory cell function of the mo-derived CD14(dim/-) VC. Although the CD14(dim/-)VC had a modest expression of the DC-specific marker CD83 and were positive for S100, expression of the DC-specific markers CD1a, Langerin, DC-SIGN, and DC-LAMP were absent. This indicates that the here generated CD14(dim/-) VC can not be considered as classical LC/DC. It was also impossible to turn the CD14(dim/-) mo-derived VC population into typical DC by culture for one week in GM-CSF/IL-4 or LPS. In fact the cells died tinder such circumstances, gaining some macrophage characteristics before dying. The IL-12 production from mo-derived CD14(dim/-) VC was lower, whereas the production of IL-10 was higher as compared to iDC. Consequently the T cells that were stimulated by these mo-derived VC produced less IFN-gamma as compared with T cells stimulated by iDC. Our data indicate that it is possible to rapidly generate a population of CD14(dim/-) veiled accessory cells from monocytes. The marker pattern and cytokine production of these VC indicate that this

  20. CMOS Integrated Capacitive DC-DC Converters

    CERN Document Server

    Van Breussegem, Tom

    2013-01-01

    This book provides a detailed analysis of all aspects of capacitive DC-DC converter design: topology selection, control loop design and noise mitigation. Readers will benefit from the authors’ systematic overview that starts from the ground up, in-depth circuit analysis and a thorough review of recently proposed techniques and design methodologies.  Not only design techniques are discussed, but also implementation in CMOS is shown, by pinpointing the technological opportunities of CMOS and demonstrating the implementation based on four state-of-the-art prototypes.  Provides a detailed analysis of all aspects of capacitive DC-DC converter design;  Analyzes the potential of this type of DC-DC converter and introduces a number of techniques to unleash their full potential; Combines system theory with practical implementation techniques; Includes unique analysis of CMOS technology for this application; Provides in-depth analysis of four fabricated prototypes.

  1. Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall.

    Science.gov (United States)

    Blank, Fabian; Wehrli, Marc; Lehmann, Andrea; Baum, Oliver; Gehr, Peter; von Garnier, Christophe; Rothen-Rutishauser, Barbara M

    2011-01-01

    The human airway epithelium serves as structural and functional barrier against inhaled particulate antigen. Previously, we demonstrated in an in vitro epithelial barrier model that monocyte derived dendritic cells (MDDC) and monocyte derived macrophages (MDM) take up particulate antigen by building a trans-epithelial interacting network. Although the epithelial tight junction (TJ) belt was penetrated by processes of MDDC and MDM, the integrity of the epithelium was not affected. These results brought up two main questions: (1) Do MDM and MDDC exchange particles? (2) Are those cells expressing TJ proteins, which are believed to interact with the TJ belt of the epithelium to preserve the epithelial integrity? The expression of TJ and adherens junction (AJ) mRNA and proteins in MDM and MDDC monocultures was determined by RT-PCR, and immunofluorescence, respectively. Particle uptake and exchange was quantified by flow cytometry and laser scanning microscopy in co-cultures of MDM and MDDC exposed to polystyrene particles (1 μm in diameter). MDM and MDDC constantly expressed TJ and AJ mRNA and proteins. Flow cytometry analysis of MDM and MDDC co-cultures showed increased particle uptake in MDDC while MDM lost particles over time. Quantitative analysis revealed significantly higher particle uptake by MDDC in co-cultures of epithelial cells with MDM and MDDC present, compared to co-cultures containing only epithelial cells and MDDC. We conclude from these findings that MDM and MDDC express TJ and AJ proteins which could help to preserve the epithelial integrity during particle uptake and exchange across the lung epithelium.

  2. DC/DC Converter Stability Testing Study

    Science.gov (United States)

    Wang, Bright L.

    2008-01-01

    This report presents study results on hybrid DC/DC converter stability testing methods. An input impedance measurement method and a gain/phase margin measurement method were evaluated to be effective to determine front-end oscillation and feedback loop oscillation. In particular, certain channel power levels of converter input noises have been found to have high degree correlation with the gain/phase margins. It becomes a potential new method to evaluate stability levels of all type of DC/DC converters by utilizing the spectral analysis on converter input noises.

  3. 76 FR 31462 - Airworthiness Directives; The Boeing Company Model DC-10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10...

    Science.gov (United States)

    2011-06-01

    ... Model DC-10-10, DC- 10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590.... Applicability (c) This AD applies to all The Boeing Company Model DC-10-10, DC-10-10F, DC-10-15,......

  4. DC to DC converters: operation; Hacheurs: fonctionnement

    Energy Technology Data Exchange (ETDEWEB)

    Bernot, F. [Ecole d' Ingenieurs de Tours, 37 (France)

    2002-05-01

    This article deals with pulse width modulation (PWM) and pulse position modulation (PPM) DC to DC converters. A tri-phase PWM converter is made of 6 simple DC/DC converters grouped together into 3 reversible converters of the same type: 1 - single-quadrant voltage lowering converters (hydraulic analogy, study with ideal elements, full scheme with input and output filters); 2 - single-quadrant voltage raising converters (hydraulic analogy, operation); 3 - two quadrants reversible converters (structure construction, quadrants of operation, reversible converter connected to a DC motor); 4 - four-quadrants reversible converters; 5 - other converters structure (current converters and converters with intermediate storage, asymmetrical converters, converters with capacitive storage, insulated converters, resonating converters, status); 6 - conclusion. (J.S.)

  5. Voltage-gated sodium channel Nav1.7 maintains the membrane potential and regulates the activation and chemokine-induced migration of a monocyte-derived dendritic cell subset.

    Science.gov (United States)

    Kis-Toth, Katalin; Hajdu, Peter; Bacskai, Ildiko; Szilagyi, Orsolya; Papp, Ferenc; Szanto, Attila; Posta, Edit; Gogolak, Peter; Panyi, Gyorgy; Rajnavolgyi, Eva

    2011-08-01

    Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a(-) and CD1a(+) DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the frequency of cells expressing Na(+) current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+) cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (-8.7 ± 1.5 mV) in CD1a(+) IDC as compared with CD1a(-) cells lacking Nav1.7 (-47 ± 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca(2+) levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin sensitized the cells for activation signals. Fine-tuning of IDC functions by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and cytokine responses of these DC subsets.

  6. A resonant dc-dc power converter assembly

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a resonant DC-DC power converter assembly comprising a first resonant DC-DC power converter and a second resonant DC-DC power converter having identical circuit topologies. A first inductor of the first resonant DC-DC power converter and a second inductor...... of the second resonant DC-DC power converter are configured for magnetically coupling the first and second resonant DC-DC power converters to each other to forcing substantially 180 degrees phase shift, or forcing substantially 0 degree phase shift, between corresponding resonant voltage waveforms of the first...... and second resonant DC-DC power converters. The first and second inductors are corresponding components of the first and second resonant DC-DC power converters....

  7. Charge pump DC-DC converter comprising solid state batteries

    NARCIS (Netherlands)

    Reefman, D.; Roozeboom, F.; Notten, P.H.L.; Klootwijk, J.H.

    2013-01-01

    An electronic device is provided which comprises a DC-DC converter. The DC-DC converter comprises at least one solid-state rechargeable battery (B1, B2) for storing energy for the DC-DC conversion and an output capacitor (C2).

  8. DC source assemblies

    Science.gov (United States)

    Campbell, Jeremy B; Newson, Steve

    2013-02-26

    Embodiments of DC source assemblies of power inverter systems of the type suitable for deployment in a vehicle having an electrically grounded chassis are provided. An embodiment of a DC source assembly comprises a housing, a DC source disposed within the housing, a first terminal, and a second terminal. The DC source also comprises a first capacitor having a first electrode electrically coupled to the housing, and a second electrode electrically coupled to the first terminal. The DC source assembly further comprises a second capacitor having a first electrode electrically coupled to the housing, and a second electrode electrically coupled to the second terminal.

  9. Porphyromonas gingivalis Evasion of Autophagy and Intracellular Killing by Human Myeloid Dendritic Cells Involves DC-SIGN-TLR2 Crosstalk

    Science.gov (United States)

    El-Awady, Ahmed R.; Miles, Brodie; Scisci, Elizabeth; Kurago, Zoya B.; Palani, Chithra D.; Arce, Roger M.; Waller, Jennifer L.; Genco, Caroline A.; Slocum, Connie; Manning, Matthew; Schoenlein, Patricia V.; Cutler, Christopher W.

    2015-01-01

    Signaling via pattern recognition receptors (PRRs) expressed on professional antigen presenting cells, such as dendritic cells (DCs), is crucial to the fate of engulfed microbes. Among the many PRRs expressed by DCs are Toll-like receptors (TLRs) and C-type lectins such as DC-SIGN. DC-SIGN is targeted by several major human pathogens for immune-evasion, although its role in intracellular routing of pathogens to autophagosomes is poorly understood. Here we examined the role of DC-SIGN and TLRs in evasion of autophagy and survival of Porphyromonas gingivalis in human monocyte-derived DCs (MoDCs). We employed a panel of P. gingivalis isogenic fimbriae deficient strains with defined defects in Mfa-1 fimbriae, a DC-SIGN ligand, and FimA fimbriae, a TLR2 agonist. Our results show that DC-SIGN dependent uptake of Mfa1+P. gingivalis strains by MoDCs resulted in lower intracellular killing and higher intracellular content of P. gingivalis. Moreover, Mfa1+P. gingivalis was mostly contained within single membrane vesicles, where it survived intracellularly. Survival was decreased by activation of TLR2 and/or autophagy. Mfa1+P. gingivalis strain did not induce significant levels of Rab5, LC3-II, and LAMP1. In contrast, P. gingivalis uptake through a DC-SIGN independent manner was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores, a characteristic feature of autophagy. These results suggest that selective engagement of DC-SIGN by Mfa-1+P. gingivalis promotes evasion of antibacterial autophagy and lysosome fusion, resulting in intracellular persistence in myeloid DCs; however TLR2 activation can overcome autophagy evasion and pathogen persistence in DCs. PMID:25679217

  10. Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk.

    Directory of Open Access Journals (Sweden)

    Ahmed R El-Awady

    2015-02-01

    Full Text Available Signaling via pattern recognition receptors (PRRs expressed on professional antigen presenting cells, such as dendritic cells (DCs, is crucial to the fate of engulfed microbes. Among the many PRRs expressed by DCs are Toll-like receptors (TLRs and C-type lectins such as DC-SIGN. DC-SIGN is targeted by several major human pathogens for immune-evasion, although its role in intracellular routing of pathogens to autophagosomes is poorly understood. Here we examined the role of DC-SIGN and TLRs in evasion of autophagy and survival of Porphyromonas gingivalis in human monocyte-derived DCs (MoDCs. We employed a panel of P. gingivalis isogenic fimbriae deficient strains with defined defects in Mfa-1 fimbriae, a DC-SIGN ligand, and FimA fimbriae, a TLR2 agonist. Our results show that DC-SIGN dependent uptake of Mfa1+P. gingivalis strains by MoDCs resulted in lower intracellular killing and higher intracellular content of P. gingivalis. Moreover, Mfa1+P. gingivalis was mostly contained within single membrane vesicles, where it survived intracellularly. Survival was decreased by activation of TLR2 and/or autophagy. Mfa1+P. gingivalis strain did not induce significant levels of Rab5, LC3-II, and LAMP1. In contrast, P. gingivalis uptake through a DC-SIGN independent manner was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores, a characteristic feature of autophagy. These results suggest that selective engagement of DC-SIGN by Mfa-1+P. gingivalis promotes evasion of antibacterial autophagy and lysosome fusion, resulting in intracellular persistence in myeloid DCs; however TLR2 activation can overcome autophagy evasion and pathogen persistence in DCs.

  11. Radiation effects on DC-DC Converters

    Science.gov (United States)

    Zhang, Dexin; Attia, John O.; Kankam, Mark D. (Technical Monitor)

    2000-01-01

    DC-DC switching converters are circuits that can be used to convert a DC voltage of one value to another by switching action. They are increasing being used in space systems. Most of the popular DC-DC switching converters utilize power MOSFETs. However power MOSFETs, when subjected to radiation, are susceptible to degradation of device characteristics or catastrophic failure. This work focuses on the effects of total ionizing dose on converter performance. Four fundamental switching converters (buck converter, buck-boost converter, cuk converter, and flyback converter) were built using Harris IRF250 power MOSFETs. These converters were designed for converting an input of 60 volts to an output of about 12 volts with a switching frequency of 100 kHz. The four converters were irradiated with a Co-60 gamma source at dose rate of 217 rad/min. The performances of the four converters were examined during the exposure to the radiation. The experimental results show that the output voltage of the converters increases as total dose increases. However, the increases of the output voltage were different for the four different converters, with the buck converter and cuk converter the highest and the flyback converter the lowest. We observed significant increases in output voltage for cuk converter at a total dose of 24 krad (si).

  12. 75 FR 61989 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-8-31, DC-8-32, DC-8-33, DC-8-41...

    Science.gov (United States)

    2010-10-07

    ... Corporation Model DC- 8-31, DC-8-32, DC-8-33, DC-8-41, DC-8-42, and DC-8-43 Airplanes; Model DC-8-50 Series Airplanes; Model DC-8F-54 and DC-8F-55 Airplanes; Model DC-8-60 Series Airplanes; Model DC-8-60F Series Airplanes; Model DC-8- 70 Series Airplanes; and Model DC-8-70F Series Airplanes AGENCY:......

  13. 75 FR 36298 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-8-31, DC-8-32, DC-8-33, DC-8-41...

    Science.gov (United States)

    2010-06-25

    ... Corporation Model DC- 8-31, DC-8-32, DC-8-33, DC-8-41, DC-8-42, and DC-8-43 Airplanes; Model DC-8-50 Series Airplanes; Model DC-8F-54 and DC-8F-55 Airplanes; Model DC-8-60 Series Airplanes; Model DC-8-61 Series Airplanes; Model DC-8-70 Series Airplanes; and Model DC-8-70F Series Airplanes AGENCY:......

  14. A DC Transformer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — During the period of this project three different possible DC transformer concepts were proposed, theoretically modeled, and then experimentally tested with the...

  15. Bovine Peripheral Blood Monocyte Derived Dendritic Cell Culture and Identification in Vitro%奶牛外周血树突状细胞体外诱导培养与鉴定

    Institute of Scientific and Technical Information of China (English)

    詹康; 赵倩明; 隋雁南; 封飞飞; 占今舜; 赵国琦

    2016-01-01

    通过粒-巨噬细胞集落刺激因子( GM⁃CSF)和白细胞介素-4( IL⁃4)体外诱导外周血单核细胞为树突状细胞,为利用树突状细胞免疫疗法治疗奶牛乳房炎奠定基础和提供细胞模型。利用淋巴细胞分离液分离获得奶牛外周血单核细胞,在6孔板内培养2h后,弃掉含有大量的T细胞和B细胞上清液,贴壁的基本上是单核细胞,磷酸盐缓冲液清洗5次,加入含有GM⁃CSF和IL⁃4的2 mL培养基进行3 d诱导。之后,从培养基顶部小心吸弃1.4 mL的培养基,然后再补加含有GM⁃CSF和IL⁃4的1.8 mL培养基继续诱导3 d。每天通过显微镜观察细胞形态。第7天经流式检测细胞表面抗原 CD11c、CD14、主要组织相容性复合体Ⅱ( MHCⅡ)、CD40、CD80、CD86的表达。结果表明:1)第2天,一些细胞表面可以生长出刺突并伴随着伪足的生长。第3天,细胞表面的刺突和伪足越来越多。第4、5天,一些带有刺突和伪足的细胞开始聚集和融合。第6天,单核细胞基本被诱导为树突状细胞,细胞表面含有大量清晰可见的刺突和伪足。2)经流式检测,CD14、CD11c、MHCⅡ阳性表达细胞分别占诱导细胞的6.8%、65.0%、75.9%,CD80和CD86阳性表达细胞分别占诱导细胞的2.0%和1.2%。综上所述,采用奶牛外周血单核细胞经体外诱导能够获得一定纯度的奶牛树突状细胞。%This study aimed to induce bovine peripheral blood monocyte derived dendritic cell by granulocyte⁃macrophage colony stimulating factor ( GM⁃CSF) and interleukin⁃4 ( IL⁃4) cytokines, which could lay founda⁃tion and provide cell model for dairy cow mastitis treatment using cell immunotherapy. The bovine peripheral blood monocyte was acquired by lymphocyte separation medium and seeded in 6⁃proe plate to culture for 2 h. Then, suspended cells containing an amount of B and T cells were discarded, and

  16. Radiation Effects on DC-DC Converters

    Science.gov (United States)

    Zhang, De-Xin; AbdulMazid, M. D.; Attia, John O.; Kankam, Mark D. (Technical Monitor)

    2001-01-01

    In this work, several DC-DC converters were designed and built. The converters are Buck Buck-Boost, Cuk, Flyback, and full-bridge zero-voltage switched. The total ionizing dose radiation and single event effects on the converters were investigated. The experimental results for the TID effects tests show that the voltages of the Buck Buck-Boost, Cuk, and Flyback converters increase as total dose increased when using power MOSFET IRF250 as a switching transistor. The change in output voltage with total dose is highest for the Buck converter and the lowest for Flyback converter. The trend of increase in output voltages with total dose in the present work agrees with those of the literature. The trends of the experimental results also agree with those obtained from PSPICE simulation. For the full-bridge zero-voltage switch converter, it was observed that the dc-dc converter with IRF250 power MOSFET did not show a significant change of output voltage with total dose. In addition, for the dc-dc converter with FSF254R4 radiation-hardened power MOSFET, the output voltage did not change significantly with total dose. The experimental results were confirmed by PSPICE simulation that showed that FB-ZVS converter with IRF250 power MOSFET's was not affected with the increase in total ionizing dose. Single Event Effects (SEE) radiation tests were performed on FB-ZVS converters. It was observed that the FB-ZVS converter with the IRF250 power MOSFET, when the device was irradiated with Krypton ion with ion-energy of 150 MeV and LET of 41.3 MeV-square cm/mg, the output voltage increased with the increase in fluence. However, for Krypton with ion-energy of 600 MeV and LET of 33.65 MeV-square cm/mg, and two out of four transistors of the converter were permanently damaged. The dc-dc converter with FSF254R4 radiation hardened power MOSFET's did not show significant change at the output voltage with fluence while being irradiated by Krypton with ion energy of 1.20 GeV and LET of 25

  17. 75 FR 38943 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-30, DC...

    Science.gov (United States)

    2010-07-07

    ... Corporation Model DC- 10-10, DC-10-10F, DC-10-30, DC-10-30F (KDC-10), DC-10-40, and DC-10-40F Airplanes AGENCY... propose to adopt a new airworthiness directive (AD) for certain Model DC-10-10, DC-10-10F, DC-10-30, DC-10-30F (KDC-10), DC-10- 40, and DC-10-40F airplanes. This proposed AD would require......

  18. Radiation-Tolerant DC-DC Converters

    Science.gov (United States)

    Skutt, Glenn; Sable, Dan; Leslie, Leonard; Graham, Shawn

    2012-01-01

    A document discusses power converters suitable for space use that meet the DSCC MIL-PRF-38534 Appendix G radiation hardness level P classification. A method for qualifying commercially produced electronic parts for DC-DC converters per the Defense Supply Center Columbus (DSCC) radiation hardened assurance requirements was developed. Development and compliance testing of standard hybrid converters suitable for space use were completed for missions with total dose radiation requirements of up to 30 kRad. This innovation provides the same overall performance as standard hybrid converters, but includes assurance of radiation- tolerant design through components and design compliance testing. This availability of design-certified radiation-tolerant converters can significantly reduce total cost and delivery time for power converters for space applications that fit the appropriate DSCC classification (30 kRad).

  19. Bidirectional dc-to-dc Power Converter

    Science.gov (United States)

    Griesbach, C. R.

    1986-01-01

    Solid-state, series-resonant converter uses high-voltage thyristors. Converter used either to convert high-voltage, low-current dc power to lowvoltage, high current power or reverse. Taking advantage of newly-available high-voltage thyristors to provide better reliability and efficiency than traditional converters that use vacuum tubes as power switches. New converter essentially maintenance free and provides greatly increased mean time between failures. Attractive in industrial applications whether or not bidirectional capability is required.

  20. Forback DC-to-DC converter

    Science.gov (United States)

    Lukemire, Alan T.

    1995-05-01

    A pulse-width modulated DC-to-DC power converter including a first inductor, i.e. a transformer or an equivalent fixed inductor equal to the inductance of the secondary winding of the transformer, coupled across a source of DC input voltage via a transistor switch which is rendered alternately conductive (ON) and nonconductive (OFF) in accordance with a signal from a feedback control circuit is described. A first capacitor capacitively couples one side of the first inductor to a second inductor which is connected to a second capacitor which is coupled to the other side of the first inductor. A circuit load shunts the second capacitor. A semiconductor diode is additionally coupled from a common circuit connection between the first capacitor and the second inductor to the other side of the first inductor. A current sense transformer generating a current feedback signal for the switch control circuit is directly coupled in series with the other side of the first inductor so that the first capacitor, the second inductor and the current sense transformer are connected in series through the first inductor. The inductance values of the first and second inductors, moreover, are made identical. Such a converter topology results in a simultaneous voltsecond balance in the first inductance and ampere-second balance in the current sense transformer.

  1. Forback DC-to-DC converter

    Science.gov (United States)

    Lukemire, Alan T. (Inventor)

    1993-01-01

    A pulse-width modulated DC-to-DC power converter including a first inductor, i.e. a transformer or an equivalent fixed inductor equal to the inductance of the secondary winding of the transformer, coupled across a source of DC input voltage via a transistor switch which is rendered alternately conductive (ON) and nonconductive (OFF) in accordance with a signal from a feedback control circuit is described. A first capacitor capacitively couples one side of the first inductor to a second inductor which is connected to a second capacitor which is coupled to the other side of the first inductor. A circuit load shunts the second capacitor. A semiconductor diode is additionally coupled from a common circuit connection between the first capacitor and the second inductor to the other side of the first inductor. A current sense transformer generating a current feedback signal for the switch control circuit is directly coupled in series with the other side of the first inductor so that the first capacitor, the second inductor and the current sense transformer are connected in series through the first inductor. The inductance values of the first and second inductors, moreover, are made identical. Such a converter topology results in a simultaneous voltsecond balance in the first inductance and ampere-second balance in the current sense transformer.

  2. Intelligent dc-dc Converter Technology Developed and Tested

    Science.gov (United States)

    Button, Robert M.

    2001-01-01

    The NASA Glenn Research Center and the Cleveland State University have developed a digitally controlled dc-dc converter to research the benefits of flexible, digital control on power electronics and systems. Initial research and testing has shown that conventional dc-dc converters can benefit from improved performance by using digital-signal processors and nonlinear control algorithms.

  3. Implication of scavenger receptors in the interactions between diesel exhaust particles and immature or mature dendritic cells

    Directory of Open Access Journals (Sweden)

    Lassalle Philippe

    2009-03-01

    Full Text Available Abstract Background The exposure to pollutants such as diesel exhaust particles (DEP is associated with an increased incidence of respiratory diseases. However, the mechanisms by which DEP have an effect on human health are not completely understood. In addition to their action on macrophages and airway epithelial cells, DEP also modulate the functions of dendritic cells (DC. These professional antigen-presenting cells are able to discriminate unmodified self from non-self thanks to pattern recognition receptors such as the Toll like Receptors (TLR and Scavenger Receptors (SR. SR were originally identified by their ability to bind and internalize modified lipoproteins and microorganisms but also particles and TLR agonists. In this study, we assessed the implication of SR in the effects of DEP associated or not with TLR agonists on monocyte-derived DC (MDDC. For this, we studied the regulation of CD36, CXCL16, LOX-1, SR-A1 and SR-B1 expression on MDDC treated with DEP associated or not with TLR2, 3 and 4 ligands. Then, the capacity of SR ligands (dextran sulfate and maleylated-ovalbumin to block the effects of DEP on the function of lipopolysaccharide (LPS-activated DC has been evaluated. Results Our data demonstrate that TLR2 agonists mainly augmented CXCL16, LOX-1 and SR-B1 expression whereas DEP alone had only a weak effect. Interestingly, DEP modulated the action of TLR2 and TLR4 ligands on the expression of LOX-1 and SR-B1. Pretreatment with the SR ligand maleylated-ovalbumin but not dextran sulfate inhibited the endocytosis of DEP by MDDC. Moreover, this SR ligand blocked the effect by DEP at low dose (1 μg/ml on MDDC phenotype (a decrease of CD86 and HLA-DR expression and on the secretion of CXCL10, IL-12 and TNF-α. In contrast, the decrease of IL-12 and CXCL10 secretion and the generation of oxygen metabolite induced by DEP at 10 μg/ml was not affected by SR ligands Conclusion Our results show for the first time that the modulation of

  4. 75 FR 20790 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

    Science.gov (United States)

    2010-04-21

    ... Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F... (AD) for certain Model DC-10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC- 10A and KDC-10), DC-10-40, DC-10-40F, MD-10-10F, MD-10-30F, MD-11, and MD-11F airplanes. This proposed......

  5. 75 FR 68246 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

    Science.gov (United States)

    2010-11-05

    ... Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F... to supersede an existing airworthiness directive (AD) that applies to all Model DC-10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F, MD-10-......

  6. Three-port DC-DC converter with new integrated transformer for DC Distribution Systems

    DEFF Research Database (Denmark)

    Ouyang, Ziwei; Andersen, Michael A. E.

    2014-01-01

    A new integrated transformer for three-port dc-dc converter is proposed to overcome the power coupling effect existed in some known multiple inputs dc-dc converters. Orthogonal primary windings arrangement and in series connection of diagonal secondary Windings enables a fully power decoupling...

  7. Culture of Porcine Peripheral Blood Monocyte-derived Dendritic Cells in vitro%猪外周血单核细胞来源的树突状细胞体外诱导培养

    Institute of Scientific and Technical Information of China (English)

    乔艳艳; 薛洋; 闫延华; 杜芳芳; 张俊; 张红英; 王学兵

    2016-01-01

    [目的]建立猪外周血单核细胞来源的树突状细胞(MoDC)体外培养模型.[方法]从猪外周新鲜血液中分离外周血单核细胞(PBMC),通过贴壁法获得树突状细胞前体细胞,采用重组猪的集落共刺激因子(rpGM-SCF)和重组猪的白细胞介素4(rpIL-4)双因子诱导及脂多糖(LPS)刺激成熟法,收集不同时间段的细胞,利用扫描电子显微镜观察其形态,流式细胞分析仪检测表面分子表达率及其对FITC-dextran的吞噬能力,混合淋巴细胞反应检测细胞对同种异体T细胞的刺激能力.[结果]经体外诱导的DC具有典型的树突状形态;LPS刺激的DC表型分子CDla、CD80、CD86、SLAⅡ、CD172a与LPS未刺激的DC有明显增高,其吞噬能力有所下降,刺激同种异体T淋巴细胞的能力有所增强.[结论]该试验成功建立了猪MoDC的体外诱导培养方法,为进一步研究猪MoDC在机体免疫调节和抗病毒感染中的作用奠定了基础.

  8. Overview of Multi-DC-Bus Solutions for DC Microgrids

    DEFF Research Database (Denmark)

    Ricchiuto, D.; Mastromauro, R.A.; Liserre, Marco;

    2013-01-01

    DC Microgrids have recently received a lot of attention in the last years due to high penetration of renewable energy sources as well as distributed energy storage systems. In the future DC microgrids could be preferable respect to AC microgrids in terms of redundancy since multi-DC-Bus solutions...... could provide a continuative power supply to the loads. An overview of Multi-DC-Bus solutions is presented in this paper. The performances are compared on the basis of possible DC microgrid configurations, redundancy, different DC voltage levels....

  9. 75 FR 60602 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

    Science.gov (United States)

    2010-10-01

    ... Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F.... ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Model DC-10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40,......

  10. 75 FR 23571 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

    Science.gov (United States)

    2010-05-04

    ... Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F.... ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Model DC-10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40,......

  11. DC-DC powering for the CMS pixel upgrade

    Science.gov (United States)

    Feld, Lutz; Fleck, Martin; Friedrichs, Marcel; Hensch, Richard; Karpinski, Waclaw; Klein, Katja; Rittich, David; Sammet, Jan; Wlochal, Michael

    2013-12-01

    The CMS experiment plans to replace its silicon pixel detector with a new one with improved rate capability and an additional detection layer at the end of 2016. In order to cope with the increased number of detector modules the new pixel detector will be powered via DC-DC converters close to the sensitive detector volume. This paper reviews the DC-DC powering scheme and reports on the ongoing R&D program to develop converters for the pixel upgrade. Design choices are discussed and results from the electrical and thermal characterisation of converter prototypes are shown. An emphasis is put on system tests with up to 24 converters. The performance of pixel modules powered by DC-DC converters is compared to conventional powering. The integration of the DC-DC powering scheme into the pixel detector is described and system design issues are reviewed.

  12. DC-DC Powering for the CMS Pixel Upgrade

    CERN Document Server

    Feld, Lutz Werner; Marcel Friedrichs; Richard Hensch; Karpinski, Waclaw; Klein, Katja; Rittich, David Michael; Sammet, Jan Domenik; Wlochal, Michael

    2013-01-01

    The CMS experiment plans to replace its silicon pixel detector with a new one with improved rate capability and an additional detection layer at the end of 2016. In order to cope with the increased number of detector modules the new pixel detector will be powered via DC-DC converters close to the sensitive detector volume. This paper reviews the DC-DC powering scheme and reports on the ongoing R and D program to develop converters for the pixel upgrade. Design choices are discussed and results from the electrical and thermal characterisation of converter prototypes are shown. An emphasis is put on system tests with up to24 converters. The performance of pixel modules powered by DC-DC converters is compared to conventional powering. The integration of the DC-DC powering scheme into the pixel detector is described and system design issues are reviewed.

  13. Influence of Skin Epithelial cells and Human Umbilical VEIN CELLS Conditioned Media on Maturation of Type 1 Dendritic Cells(DC1

    Directory of Open Access Journals (Sweden)

    M Ganjybakhsh

    2011-06-01

    Full Text Available Introduction: Dendritic cells have a high potential in presentation of antigens and can be generated and manipulated in invitro culture conditions. Dendritic cells(DC are therefore used in cancer immunotherapy, in prevention of graft rejection, treatment of allergy, autoimmune diseases and certain infectious diseases. Methods: Dendritic cell was generated in two stages. IN the first stage, monocyte cells were converted to immature DC affected GM-CSF and IL-4 .In the second stage, dendritic cells were maturated in the presence of supernatant skin epithelial cells(A375 and human umbilical vein endothelial cells(HUVEC and maturation factors. The ability of phagocytosis, expression phenotype, stimulation of T lymphocytes and cytokines was studied. Results: Mature Dendritic cells decreased their power of phagocytosis and increased expression of their surface markers. The ability of T cells stimulation and cytokine production(IL-12 increased . Conclusion: Mixture condition medium of epithelial cells and human skin umbilical vein endothelium cells induces maturation of monocyte-derived DCs. This condition medium improves their phenotype and their functions. The mentioned condition medium generates DC1 and Th1 in vitro.

  14. Early Oscillation Detection for DC/DC Converter Fault Diagnosis

    Science.gov (United States)

    Wang, Bright L.

    2011-01-01

    The electrical power system of a spacecraft plays a very critical role for space mission success. Such a modern power system may contain numerous hybrid DC/DC converters both inside the power system electronics (PSE) units and onboard most of the flight electronics modules. One of the faulty conditions for DC/DC converter that poses serious threats to mission safety is the random occurrence of oscillation related to inherent instability characteristics of the DC/DC converters and design deficiency of the power systems. To ensure the highest reliability of the power system, oscillations in any form shall be promptly detected during part level testing, system integration tests, flight health monitoring, and on-board fault diagnosis. The popular gain/phase margin analysis method is capable of predicting stability levels of DC/DC converters, but it is limited only to verification of designs and to part-level testing on some of the models. This method has to inject noise signals into the control loop circuitry as required, thus, interrupts the DC/DC converter's normal operation and increases risks of degrading and damaging the flight unit. A novel technique to detect oscillations at early stage for flight hybrid DC/DC converters was developed.

  15. 75 FR 6160 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

    Science.gov (United States)

    2010-02-08

    ... Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F, MD-10-10F, MD-10-30F, MD-11, and MD-11F Airplanes AGENCY: Federal Aviation... airworthiness directive (AD) for certain Model DC-10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC- 10A...

  16. Control of improved full-bridge three-level DC/DC converter for wind turbines in a DC grid

    DEFF Research Database (Denmark)

    Deng, Fujin; Chen, Zhe

    2013-01-01

    transformer in the IFBTL dc/dc converter. A modulation strategy, including two operation modes, is proposed for the IFBTL dc/dc converter. Then, a voltage balancing control strategy is proposed for the IFBTL dc/dc converter. Furthermore, the control of the wind turbine based on the IFBTL dc/dc converter......This paper presents an improved full-bridge three-level (IFBTL) dc/dc converter for a wind turbine in a dc grid by inserting a passive filter into the dc/dc converter to improve the performance of the converter. The passive filter can effectively reduce the voltage stress of the medium frequency...... in a dc-grid system is presented. Finally, a small-scale IFBTL dc/dc converter prototype was built and tested in the laboratory, and the results verify the theoretical analysis....

  17. 75 FR 47242 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-14, DC-9-15, and DC-9-15F...

    Science.gov (United States)

    2010-08-05

    ... Corporation Model DC- 9-14, DC-9-15, and DC-9-15F Airplanes; and Model DC-9-20, DC-9-30, DC- 9-40, and DC-9-50... airworthiness directive (AD) that applies to certain Model DC-9-14 and DC-9-15 airplanes; and Model DC-9-20, DC-9-30, DC-9-40, and DC-9-50 series airplanes. The existing AD currently......

  18. Isolated Bidirectional DC-DC Converter for Hybrid Electric Vehicle Application

    Science.gov (United States)

    2006-06-13

    34Approved for public release: distribution is unlimited" Isolated Bidirectional DC-DC Converter for Hybrid Electric Vehicle Applications Sonya...requirements for DC-DC converters for electric and hybrid vehicles . This paper introduces a bidirectional, isolated DC-DC converter for medium power...the design and build of a medium power DC-DC converter . Key words: Power Converter , DC-DC, Hybrid Electric Vehicle , Battery, Galvanically Isolation

  19. 75 FR 63040 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-30, DC...

    Science.gov (United States)

    2010-10-14

    ... Corporation Model DC- 10-10, DC-10-10F, DC-10-30, DC-10-30F (KDC-10), DC-10-40, and DC-10-40F Airplanes AGENCY..., Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION CONTACT... (b) None. Applicability (c) This AD applies to McDonnell Douglas Corporation Model DC- 10-10,...

  20. A new optimum topology switching dc-to-dc converter

    Science.gov (United States)

    Cuk, S.; Middlebrook, R. D.

    1977-01-01

    A novel switching dc-to-dc converter is presented, which has the same general conversion property (increase or decrease of the input dc voltage) as does the conventional buck-boost converter, and which offers through its new optimum topology higher efficiency, lower output voltage ripple, reduced EMI, smaller size and weight, and excellent dynamic response. One of its most significant advantages is that both input and output current are not pulsating but are continuous (essentially dc with small superimposed switching current ripple), thus resulting in a close approximation to the ideal physically nonrealizable dc-to-dc transformer. The converter retains the simplest possible structure with the minimum number of components which, when interconnected in its optimum topology, yield the maximum performance.

  1. Conception de convertisseurs DC/DC à base de MEMS

    OpenAIRE

    Ghandour, Sahar

    2011-01-01

    Current trends towards miniaturization of electronic circuits had led to the advent of System onChip containing different types of circuits indented to perform different functions. These sub-systemsrequire different supply voltages that are delivered from the SoC supply voltage using several DC/DCconverters. Currently, most of the electronic circuits of portable applications use conventional SMPS(switch mode power supply) DC/DC converters containing an inductor element to stock temporally the...

  2. A Novel FPSM Controller for DC-DC Switching Converters

    Institute of Scientific and Technical Information of China (English)

    Yong Feng; Shun-Ping Wang; Ping Luo; Quan-Ming Niu; Zhao-Ji Li

    2007-01-01

    This paper presents a novel fuzzy pulse skip modulation (FPSM) controller for switching direct current to direct current (DC-DC) converters based on fuzzy ratiocination modeling approach. Owing to the optimal consideration during the design and the nonlinear characteristics of the controller, improved dynamic responses of the FPSM controller can be achieved over conventional controllers. Compared with conventional proportion integral derivative (PID) control, FPSM control has 60% lower overshoot and 10% lower setting time under the same input voltage and output load change. The presented approach is general and can be applied to other types of DC-DC converters.

  3. High performance dc-dc conversion with voltage multipliers

    Science.gov (United States)

    Harrigill, W. T.; Myers, I. T.

    1974-01-01

    The voltage multipliers using capacitors and diodes first developed by Cockcroft and Walton in 1932 were reexamined in terms of state of the art fast switching transistors and diodes, and high energy density capacitors. Because of component improvements, the voltage multiplier, used without a transformer, now appears superior in weight to systems now in use for dc-dc conversion. An experimental 100-watt 1000-volt dc-dc converter operating at 100 kHz was built, with a component weight of about 1 kg/kW. Calculated and measured values of output voltage and efficiency agreed within experimental error.

  4. Human dendritic cell maturation and cytokine secretion upon stimulation with Bordetella pertussis filamentous haemagglutinin.

    Science.gov (United States)

    Dirix, Violette; Mielcarek, Nathalie; Debrie, Anne-Sophie; Willery, Eve; Alonso, Sylvie; Versheure, Virginie; Mascart, Françoise; Locht, Camille

    2014-07-01

    In addition to antibodies, Th1-type T cell responses are also important for long-lasting protection against pertussis. However, upon immunization with the current acellular vaccines, many children fail to induce Th1-type responses, potentially due to immunomodulatory effects of some vaccine antigens, such as filamentous haemagglutinin (FHA). We therefore analysed the ability of FHA to modulate immune functions of human monocyte-derived dendritic cells (MDDC). FHA was purified from pertussis toxin (PTX)-deficient or from PTX- and adenylate cyclase-deficient Bordetella pertussis strains, and residual endotoxin was neutralized with polymyxin B. FHA from both strains induced phenotypic maturation of human MDDC and cytokine secretion (IL-10, IL-12p40, IL-12p70, IL-23 and IL-6). To identify the FHA domains responsible for MDDC immunomodulation, MDDC were stimulated with FHA containing a Gly→Ala substitution at its RGD site (FHA-RAD) or with an 80-kDa N-terminal moiety of FHA (Fha44), containing its heparin-binding site. Whereas FHA-RAD induced maturation and cytokine production comparable to those of FHA, Fha44 did not induce IL-10 production, but maturated MDDC at least partially. Nevertheless, Fha44 induced the secretion of IL-12p40, IL-12p70, IL-23 and IL-6 by MDDC, albeit at lower levels than FHA. Thus, FHA can modulate MDDC responses in multiple ways, and IL-10 induction can be dissociated from the induction of other cytokines.

  5. Improved DC Gun Insulator

    Energy Technology Data Exchange (ETDEWEB)

    M.L. Neubauer, K.B. Beard, R. Sah, C. Hernandez-Garcia, G. Neil

    2009-05-01

    Many user facilities such as synchrotron light sources and free electron lasers require accelerating structures that support electric fields of 10-100 MV/m, especially at the start of the accelerator chain where ceramic insulators are used for very high gradient DC guns. These insulators are difficult to manufacture, require long commissioning times, and have poor reliability, in part because energetic electrons bury themselves in the ceramic, creating a buildup of charge and causing eventual puncture. A novel ceramic manufacturing process is proposed. It will incorporate bulk resistivity in the region where it is needed to bleed off accumulated charge caused by highly energetic electrons. This process will be optimized to provide an appropriate gradient in bulk resistivity from the vacuum side to the air side of the HV standoff ceramic cylinder. A computer model will be used to determine the optimum cylinder dimensions and required resistivity gradient for an example RF gun application. A ceramic material example with resistivity gradient appropriate for use as a DC gun insulator will be fabricated by glazing using doping compounds and tested.

  6. Hysteretic Current Controlled Zvs Dc/Dc Converter For Automobile

    DEFF Research Database (Denmark)

    Cernat, M.; Scortarul, P.; Tanase, A.

    2007-01-01

    A novel bi-directional dc-dc converter with ZVS and interleaving for dual voltage systems in automobiles is presented. A variable frequency extended band hysteretic current control method is proposed. In comparison with classical fixed frequency current control PWM, the reverse polarity peak curr...

  7. Very High Frequency Half Bridge DC/DC Converter

    DEFF Research Database (Denmark)

    Madsen, Mickey Pierre; Knott, Arnold; Andersen, Michael A. E.

    2014-01-01

    This paper presents the first, off chip, class DE (resonant half bridge) converter working in the Very High Frequency (VHF) range. The benefits of using half bridge circuits both in the inverter and rectifier part of a VHF resonant dc/dc converter are analyzed and design equations for all...

  8. A Plasma-Based DC-DC Electrical Transformer

    Science.gov (United States)

    Nebel, Richard; Finn, John

    2013-10-01

    Previous work has indicated that it may be possible to make DC-DC electrical transformers using plasmas. The mechanism is an MHD electromagnetic relaxation process induced by helical electrodes. This process is now being tested on the Bismark device at Tibbar Technologies.

  9. A Current-Fed Isolated Bidirectional DC-DC Converter

    DEFF Research Database (Denmark)

    Sun, Xiaofeng; Wu, Xiaoying; Shen, Yanfeng;

    2017-01-01

    This paper proposes a current-fed isolated bidirectional DC-DC converter (CF-IBDC) which has the advantages of wide input voltage range, low input current ripple, low conduction losses, and soft switching over the full operating range. Compared with conventional CF-IBDCs, the voltage spikes of th...

  10. SCM Handbooks for dc-to-dc Converters

    Science.gov (United States)

    Lee, F.; Mohmoud, M.; Yu, Y.

    1984-01-01

    Two documents aid in design of control modules for dc-to-dc converters. Features of SCM include: Adaptive stability, power component stress limiting, implementation of various control laws, unified design approach. Analysis and quidelines contained in handbooks enable engineer to design SCM circuit and confidently predict resulting overall performance.

  11. Efficient Design in a DC to DC Converter Unit

    Science.gov (United States)

    Bruemmer, Joel E.; Williams, Fitch R.; Schmitz, Gregory V.

    2002-01-01

    Space Flight hardware requires high power conversion efficiencies due to limited power availability and weight penalties of cooling systems. The International Space Station (ISS) Electric Power System (EPS) DC-DC Converter Unit (DDCU) power converter is no exception. This paper explores the design methods and tradeoffs that were utilized to accomplish high efficiency in the DDCU. An isolating DC to DC converter was selected for the ISS power system because of requirements for separate primary and secondary grounds and for a well-regulated secondary output voltage derived from a widely varying input voltage. A flyback-current-fed push-pull topology or improved Weinberg circuit was chosen for this converter because of its potential for high efficiency and reliability. To enhance efficiency, a non-dissipative snubber circuit for the very-low-Rds-on Field Effect Transistors (FETs) was utilized, redistributing the energy that could be wasted during the switching cycle of the power FETs. A unique, low-impedance connection system was utilized to improve contact resistance over a bolted connection. For improved consistency in performance and to lower internal wiring inductance and losses a planar bus system is employed. All of these choices contributed to the design of a 6.25 KW regulated dc to dc converter that is 95 percent efficient. The methodology used in the design of this DC to DC Converter Unit may be directly applicable to other systems that require a conservative approach to efficient power conversion and distribution.

  12. Dc-To-Dc Converter Uses Reverse Conduction Of MOSFET's

    Science.gov (United States)

    Gruber, Robert P.; Gott, Robert W.

    1991-01-01

    In modified high-power, phase-controlled, full-bridge, pulse-width-modulated dc-to-dc converters, switching devices power metal oxide/semiconductor field-effect transistors (MOSFET's). Decreases dissipation of power during switching by eliminating approximately 0.7-V forward voltage drop in anti-parallel diodes. Energy-conversion efficiency increased.

  13. An organic integrated capacitive DC-DC up-converter

    NARCIS (Netherlands)

    Marien, H.; Steyaert, M.; Steudel, S.; Vicca, P.; Smout, S.; Gelinck, G.H.; Heremans, P.L.

    2010-01-01

    In this paper a fully integrated organic DC-DC upconverter is presented in a pentacene p-type only technology. This 3-stage Dickson converter reaches a voltage conversion factor of 3 for a purely capacitive load and 2.5 for a 10 μA load current. The maximal output voltage goes up to 75 V and the Dic

  14. Sheppard-Taylor Isolated High Boost DC-DC Converter

    DEFF Research Database (Denmark)

    Chub, Andrii; Siwakoti, Yam Prasad; Vinnikov, Dmitri

    2017-01-01

    This paper presents a new galvanically isolated step-up dc-dc converter intended for low-power but high step-up applications. The proposed converter is capable of regulating output voltage within a wide range of the input voltage or load variations. In contrast to competitors, the converter can b...

  15. Methamphetamine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells

    OpenAIRE

    2008-01-01

    The US is currently experiencing an epidemic of methamphetamine (Meth) use as a recreational drug. Recent studies also show a high prevalence of HIV-1 infection among Meth users. We report that Meth enhances HIV-1 infectivity of dendritic cells as measured by multinuclear activation of a galactosidase indicator (MAGI) cell assay, p24 assay, and LTR-RU5 amplification. Meth induces increased HIV-1 infection in association with an increase in the HIV-1 coreceptors, CXCR4 and CCR5, and infection ...

  16. Early Oscillation Detection Technique for Hybrid DC/DC Converters

    Science.gov (United States)

    Wang, Bright L.

    2011-01-01

    Oscillation or instability is a situation that must be avoided for reliable hybrid DC/DC converters. A real-time electronics measurement technique was developed to detect catastrophic oscillations at early stages for hybrid DC/DC converters. It is capable of identifying low-level oscillation and determining the degree of the oscillation at a unique frequency for every individual model of the converters without disturbing their normal operations. This technique is specially developed for space-used hybrid DC/DC converters, but it is also suitable for most of commercial and military switching-mode power supplies. This is a weak-electronic-signal detection technique to detect hybrid DC/DC converter oscillation presented as a specific noise signal at power input pins. It is based on principles of feedback control loop oscillation and RF signal modulations, and is realized by using signal power spectral analysis. On the power spectrum, a channel power amplitude at characteristic frequency (CPcf) and a channel power amplitude at switching frequency (CPsw) are chosen as oscillation level indicators. If the converter is stable, the CPcf is a very small pulse and the CPsw is a larger, clear, single pulse. At early stage of oscillation, the CPcf increases to a certain level and the CPsw shows a small pair of sideband pulses around it. If the converter oscillates, the CPcf reaches to a higher level and the CPsw shows more high-level sideband pulses. A comprehensive stability index (CSI) is adopted as a quantitative measure to accurately assign a degree of stability to a specific DC/DC converter. The CSI is a ratio of normal and abnormal power spectral density, and can be calculated using specified and measured CPcf and CPsw data. The novel and unique feature of this technique is the use of power channel amplitudes at characteristic frequency and switching frequency to evaluate stability and identify oscillations at an early stage without interfering with a DC/DC converter s

  17. A DC Transformer

    Science.gov (United States)

    Youngquist, Robert C.; Ihlefeld, Curtis M.; Starr, Stanley O.

    2013-01-01

    A component level dc transformer is described in which no alternating currents or voltages are present. It operates by combining features of a homopolar motor and a homopolar generator, both de devices, such that the output voltage of a de power supply can be stepped up (or down) with a corresponding step down (or up) in current. The basic theory for this device is developed, performance predictions are made, and the results from a small prototype are presented. Based on demonstrated technology in the literature, this de transformer should be scalable to low megawatt levels, but it is more suited to high current than high voltage applications. Significant development would be required before it could achieve the kilovolt levels needed for de power transmission.

  18. DC Microgrids—Part II

    DEFF Research Database (Denmark)

    Dragicevic, Tomislav; Lu, Xiaonan; Quintero, Juan Carlos Vasquez

    2016-01-01

    distribution applications such as traction, telecom, vehicular and distributed power systems can be classified under DC MG framework and ongoing development and expansion of the field is largely influenced by concepts used over there. This paper aims firstly to shed light on the practical design aspects of DC...

  19. Modular Power System Configured with Standard Product Hybrid DC-DC Converters Project

    Data.gov (United States)

    National Aeronautics and Space Administration — VPT proposes an innovative concept whereby complex, multiple-output, DC-DC converter systems can be configured through use of only 2 standard product hybrid DC-DC...

  20. Triple voltage dc-to-dc converter and method

    Science.gov (United States)

    Su, Gui-Jia

    2008-08-05

    A circuit and method of providing three dc voltage buses and transforming power between a low voltage dc converter and a high voltage dc converter, by coupling a primary dc power circuit and a secondary dc power circuit through an isolation transformer; providing the gating signals to power semiconductor switches in the primary and secondary circuits to control power flow between the primary and secondary circuits and by controlling a phase shift between the primary voltage and the secondary voltage. The primary dc power circuit and the secondary dc power circuit each further comprising at least two tank capacitances arranged in series as a tank leg, at least two resonant switching devices arranged in series with each other and arranged in parallel with the tank leg, and at least one voltage source arranged in parallel with the tank leg and the resonant switching devices, said resonant switching devices including power semiconductor switches that are operated by gating signals. Additional embodiments having a center-tapped battery on the low voltage side and a plurality of modules on both the low voltage side and the high voltage side are also disclosed for the purpose of reducing ripple current and for reducing the size of the components.

  1. GaN Microwave DC-DC Converters

    Science.gov (United States)

    Ramos Franco, Ignacio

    Increasing the operating frequency of switching converters can have a direct impact in the miniaturization and integration of power converters. The size of energy-storage passive components and the difficulty to integrate them with the rest of the circuitry is a major challenge in the development of a fully integrated power supply on a chip. The work presented in this thesis attempts to address some of the difficulties encountered in the design of high-frequency converters by applying concepts and techniques usually used in the design of high-efficiency power amplifiers and high-efficiency rectifiers at microwave frequencies. The main focus is in the analysis, design, and characterization of dc-dc converters operating at microwave frequencies in the low gigahertz range. The concept of PA-rectifier duality, where a high-efficiency power amplifier operates as a high-efficiency rectifier is investigated through non-linear simulations and experimentally validated. Additionally, the concept of a self-synchronous rectifier, where a transistor rectifier operates synchronously without the need of a RF source or driver is demonstrated. A theoretical analysis of a class-E self-synchronous rectifier is presented and validated through non-linear simulations and experiments. Two GaN class-E2 dc-dc converters operating at a switching frequency of 1 and 1.2 GHz are demonstrated. The converters achieve 80 % and 75 % dc-dc efficiency respectively and are among the highest-frequency and highest-efficiency reported in the literature. The application of the concepts established in the analysis of a self-synchronous rectifier to a power amplifier culminated in the development of an oscillating, self-synchronous class-E 2 dc-dc converter. Finally, a proof-of-concept fully integrated GaN MMIC class-E 2 dc-dc converter switching at 4.6 GHz is demonstrated for the first time to the best of our knowledge. The 3.8 mm x 2.6 mm chip contains distributed inductors and does not require any

  2. Bi-Directional DC-DC Converter for PHEV Applications

    Energy Technology Data Exchange (ETDEWEB)

    Abas Goodarzi

    2011-01-31

    Plug-In Hybrid Electric Vehicles (PHEV) require high power density energy storage system (ESS) for hybrid operation and high energy density ESS for Electric Vehicle (EV) mode range. However, ESS technologies to maximize power density and energy density simultaneously are not commercially feasible. The use of bi-directional DC-DC converter allows use of multiple energy storage, and the flexible DC-link voltages can enhance the system efficiency and reduce component sizing. This will improve fuel consumption, increase the EV mode range, reduce the total weight, reduce battery initial and life cycle cost, and provide flexibility in system design.

  3. Transformerless DC-DC Converter Using Cockcroft-Walton Voltage Multiplier to Obtain High DC Voltage

    Directory of Open Access Journals (Sweden)

    Meghana G Naik,

    2014-11-01

    Full Text Available In the present scenario the use of transformer for high voltages in converter circuit reduces the overall operating efficiency due to leakage inductance and use of transformer also increases the operational cost. . Therefore the proposed system is implemented with transformer less DC-DC converter so as to obtain high DC voltage with the use of nine stage Cockcroft-Walton (CW voltage multiplier. The proposed converter operates in CCM (continuous conduction mode, so that the converter switch stress, the switching losses are reduced. The DC voltage at the input of the proposed model is low and is boosted up by boost inductor (Ls in DC-DC converter stage and performs inverter operation. The number of stages in CW-voltage multiplier circuit is applied with low input pulsating DC (AC Voltage voltage where it is getting converted to high DC output voltage. The proposed converter switches operates at two independent frequencies, modulating (fsm andalternating (fsc frequency. The fsm operates at higher frequency of the output while the fsc operates at lower frequency of the desired output voltage ripple and the output ripples can be adjusted by the switch Sc1 and Sc2. The regulation of the output voltage is achieved by controlling the Duty ratio.The simulation is carried over by the MATLABSIMULINK.

  4. An Efficient DC- DC Converter with Bidirectional Power Flow

    Directory of Open Access Journals (Sweden)

    N.RAJARAJESWARI

    2008-07-01

    Full Text Available This paper introduces a Bi-directional DC-DC converter with adaptive fuzzy logic controller. Bidirectional power flow is obtained by same power components and provides a simple, efficient, and galvanically isolated converter. In the presence of DC mains the converter operates as buck converter and charges the battery. When the DC mains fails, the converter operates as boost converter and the down stream converter is fed by the battery. The power switches are controlled by Pulse Width Modulation technique and the pulses are generated by the application of fuzzy logic with an adoption algorithm. The proposed converter is simulated using MATLAB and laboratory prototype was developed to validate the simulation results.

  5. Fuzzy Control of DC-DC Converters with Input Constraint

    Directory of Open Access Journals (Sweden)

    D. Saifia

    2012-01-01

    Full Text Available This paper proposes a method for designing fuzzy control of DC-DC converters under actuator saturation. Because linear control design methods do not take into account the nonlinearity of the system, a T-S fuzzy model and a controller design approach is used. The designed control not only handles the external disturbance but also the saturation of duty cycle. The input constraint is first transformed into a symmetric saturation which is represented by a polytopic model. Stabilization conditions for the state feedback system of DC-DC converters under actuator saturation are established using the Lyapunov approach. The proposed method has been compared and verified with a simulation example.

  6. General-purpose fuzzy controller for dc-dc converters

    Energy Technology Data Exchange (ETDEWEB)

    Mattavelli, P.; Rossetto, L.; Spiazzi, G.; Tenti, P. [Univ. of Padova (Italy)

    1997-01-01

    In this paper, a general-purpose fuzzy controller for dc-dc converters is investigated. Based on a qualitative description of the system to be controlled, fuzzy controllers are capable of good performances, even for those systems where linear control techniques fail, e.g., when a mathematical description is not available or is in the presence of wide parameter variations. The presented approach is general and can be applied to any dc-dc converter topologies. Controller implementation is relatively simple and can guarantee a small-signal response as fast and stable as other standard regulators and an improved large-signal response. Simulation results of Buck-Boost and Sepic converters show control potentialities.

  7. Step-Up DC-DC Power Converter

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a step-up DC-DC power converter which comprises a primary side circuit and a secondary side circuit coupled through a galvanic isolation barrier. The primary side circuit comprises a positive and a negative input terminal for receipt of an input voltage and an input...... being charged from the input voltage and discharged to the output capacitor through the galvanic isolation barrier in accordance with a switch control signal to produce the converter output voltage. The step-up DC-DC power converter comprises an electrical short-circuit connection across the galvanic...... capacitor coupled between the positive and negative input terminals and the secondary side circuit comprises an output capacitor chargeable to a converter output voltage between a first positive electrode and a second negative electrode. A switched energy storage network is configured for alternatingly...

  8. A Novel High Gain DC-DC Step up Converter

    Directory of Open Access Journals (Sweden)

    M. Al Mamun

    2016-07-01

    Full Text Available High gain dc-dc converters are widely used to maximize the energy harvest for renewable energy systems, for example, photovoltaic systems and fuel cell. Conventional boost converters usually operates at extreme duty cycle to obtain high voltage gain. Operation at extreme duty cycle leads to reverse recovery problem at the switches, high conduction loss, electromagnetic interference etc. This paper proposes a very high gain dc-dc step up converter operating at very low duty cycle (i.e. duty cycle <0.5. The additional advantage of the proposed converter is that a single control signal is used for the switches which reduces the operation complexity. The steady-state theoretical analysis described in this paper is finally verified by simulation results

  9. Decentralized Interleaving of Paralleled Dc-Dc Buck Converters: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Brian B [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Rodriguez, Miguel [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-01

    We present a decentralized control strategy that yields switch interleaving among parallel connected dc-dc buck converters without communication. The proposed method is based on the digital implementation of the dynamics of a nonlinear oscillator circuit as the controller. Each controller is fully decentralized, i.e., it only requires the locally measured output current to synthesize the pulse width modulation (PWM) carrier waveform. By virtue of the intrinsic electrical coupling between converters, the nonlinear oscillator-based controllers converge to an interleaved state with uniform phase-spacing across PWM carriers. To the knowledge of the authors, this work represents the first fully decentralized strategy for switch interleaving of paralleled dc-dc buck converters.

  10. Active pre-filters for dc/dc Boost regulators

    Directory of Open Access Journals (Sweden)

    Carlos Andrés Ramos-Paja

    2014-07-01

    Full Text Available This paper proposes an active pre-filter to mitigate the current harmonics generated by classical dc/dc Boost regulators, which generate current ripples proportional to the duty cycle. Therefore, high output voltage conditions, i.e., high voltage conversion ratios, produce high current harmonics that must be filtered to avoid damage or source losses. Traditionally, these current components are filtered using electrolytic capacitors, which introduce reliability problems because of their high failure rate. The solution introduced in this paper instead uses a dc/dc converter based on the parallel connection of the Boost canonical cells to filter the current ripples generated by the Boost regulator, improving the system reliability. This solution provides the additional benefits of improving the overall efficiency and the voltage conversion ratio. Finally, the solution is validated with simulations and experimental results.

  11. A Feed-Forward Control Realizing Fast Response for Three-Branch Interleaved DC-DC Converter in DC Microgrid

    DEFF Research Database (Denmark)

    Wang, Haojie; Han, Minxiao; Yan, Wenli

    2016-01-01

    It is a common practice for storage batteries to be connected to DC microgrid buses through DC-DC converters for voltage support on islanded operation mode. A feed-forward control based dual-loop constant voltage PI control for three-branch interleaved DC-DC converters (TIDC) is proposed for stor......It is a common practice for storage batteries to be connected to DC microgrid buses through DC-DC converters for voltage support on islanded operation mode. A feed-forward control based dual-loop constant voltage PI control for three-branch interleaved DC-DC converters (TIDC) is proposed...... for storage batteries in DC microgrids. The working principle of TIDC is analyzed, and the factors influencing the response rate based on the dual-loop constant voltage control for TIDC are discussed, and then the method of feed-forward control for TIDC is studied to improve the response rate for load...

  12. DC-SIGN/DC-SIGNR基因多态性与病原微生物感染%Polymorphisms of DC-SIGN/DC-SIGNR and pathogen infection

    Institute of Scientific and Technical Information of China (English)

    许利军; 潘晨; 李勤光

    2010-01-01

    DC-SIGN和DC-SIGNR是两种表达于DC表面的蛋白,被认为是许多病原微生物的黏附受体,参与很多病原微生物的感染.DC-SIGN和DC-SIGNR(DC-SIGN/DC-SIGNR)的多态性或许影响病原微生物的感染过程和结果.此文对DC-SIGN/DC-SIGNR的结构功能以及与HIV、HCV感染、肺结核、登革热的关系进行了综述.%DC-SIGN and DC-SIGNR are two surface proteins on dendritic cells with complex stmction, and are regarded as attachment receptors of many pathogens, DC-SIGN/DC-SIGNR participate in pathogen infection.Polymorphisms of DC-SIGN/DC-SIGNR probably influence the procedure and outcome of pathogen infection. In this article, the structure and function of DC-SIGN/DC-SIGNR are discussed as well as the relation between the DC-SIGN/DC-SIGNR and pathogens such as HIV, HCV infection, pulmonary tuberculosis, dengue fever.

  13. DC injection into low voltage AC networks

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This report summarises the results of a study investigating the impact of levels of injected DC current injections on a low voltage AC distribution network systems in order to recommend acceptable limits of DC from microgeneration. Relevant literature is reviewed, and the impact of DC levels in distribution transformers, transformer modelling, and instrumental transformers are discussed. The impact of DC in residual current devices (RCD) and in domestic electricity watt hour meters is examined along with DC enhanced corrosion, corrosion failure, and the measurement of DC current injection. Sources of DC injection outlined include DC from computer power supplies, network faults, geomagnetic phenomena, lighting circuits/dimmers, and embedded generators.

  14. DC-Compensated Current Transformer.

    Science.gov (United States)

    Ripka, Pavel; Draxler, Karel; Styblíková, Renata

    2016-01-20

    Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component.

  15. Modified Multiport Dc-Dc Converter Topology For Smart Grid

    Directory of Open Access Journals (Sweden)

    Dhamodharan Shanmugam

    2013-10-01

    Full Text Available The development of a Solid State Transformer (SST that incorporates a DC-DC multiport converter to integrate both photovoltaic (PV power generation and battery energy storage is presented in this dissertation. The DC-DC stage is based on a quad active-bridge (QAB converter which not only provides isolation for the load, but also for the PV and storage. The AC-DC stage is implemented with a pulse-widthmodulated (PWM single phase rectifier. A unified gyrator-based average model is developed for a general multi-active-bridge (MAB converter controlled through phase-shift modulation (PSM. Expressions to determine the power rating of the MAB ports are also derived. The developed gyrator-based average model is applied to the QAB converter for faster simulations of the proposed SST during the control design process as well for deriving the state-space representation of the plant. Both linear quadratic regulator (LQR and singleinput-single-output (SISO types of controllers are designed for the DC-DC stage. A novel technique that complements the SISO controller by taking into account the cross coupling characteristics of the QAB converter is also presented herein. Cascaded SISO controllers are designed for the AC-DC stage. The QAB demanded power is calculated at the QAB controls and then fed into the rectifier controls in order to minimize the effect of the interaction between the two SST stages. The dynamic performance of the designed control loops based on the proposed control strategies are verified through extensive simulation of the SST average and switching models.

  16. Emissions Tests Of Two Dc-To-Dc Converters

    Science.gov (United States)

    Mclyman, W. T.

    1992-01-01

    Report describes tests to characterize unwanted electric and magnetic fields, at frequencies up to few megahertz, radiated by two dc-to-dc converters, one 20-kHz square-wave converter; the other, a 33-kHz sine-wave converter. Part of effort to develop "quiet" power converter for use aboard spacecraft. Converter required to interfere minimally with delicate instruments measuring electric and magnetic fields.

  17. Hybrid battery with bi-directional DC/DC converter

    Directory of Open Access Journals (Sweden)

    DUDRIK Jaroslav

    2010-05-01

    Full Text Available Bi-directional buck-boost DC/DC converterfor hybrid battery is described in this paper. The firstpart of the paper is aimed at concept of hybrid battery;main advance compared to conventional accumulatoris explained there. Control circuit with UC3637 andpower circuit of the converter are described in thesecond part of the paper. Experimental results frommeasuring of converter are mentioned in the last part.

  18. Digital Control Technologies for Modular DC-DC Converters

    Science.gov (United States)

    Button, Robert M.; Kascak, Peter E.; Lebron-Velilla, Ramon

    2002-01-01

    Recent trends in aerospace Power Management and Distribution (PMAD) systems focus on using commercial off-the-shelf (COTS) components as standard building blocks. This move to more modular designs has been driven by a desire to reduce costs and development times, but is also due to the impressive power density and efficiency numbers achieved by today's commercial DC-DC converters. However, the PMAD designer quickly learns of the hidden "costs" of using COTS converters. The most significant cost is the required addition of external input filters to meet strict electromagnetic interference (MIAMI) requirements for space systems. In fact, the high power density numbers achieved by the commercial manufacturers are greatly due to the lack of necessary input filters included in the COTS module. The NASA Glenn Research Center is currently pursuing a digital control technology that addresses this problem with modular DC-DC converters. This paper presents the digital control technologies that have been developed to greatly reduce the input filter requirements for paralleled, modular DC-DC converters. Initial test result show that the input filter's inductor size was reduced by 75 percent, and the capacitor size was reduced by 94 percent while maintaining the same power quality specifications.

  19. Linking DC together with TRSL

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth; Yong, X.

    2000-01-01

    Duration Calculus (DC) is an interval-based real-time logic, which can be used in capturing and eliciting users' real-time requirements. The Timed RAISE Specification Language (TRSL) is an extension of the RAISE Specification Language with real-time features. This paper links DC and TRSL together...... approach for linking state-based real-time logics together with event-based, timed process algebra languages....

  20. DC superconducting fault current limiter

    Science.gov (United States)

    Tixador, P.; Villard, C.; Cointe, Y.

    2006-03-01

    There is a lack of satisfying solutions for fault currents using conventional technologies, especially in DC networks, where a superconducting fault current limiter could play a very important part. DC networks bring a lot of advantages when compared to traditional AC ones, in particular within the context of the liberalization of the electric market. Under normal operation in a DC network, the losses in the superconducting element are nearly zero and only a small, i.e. a low cost, refrigeration system is then required. The absence of zero crossing of a DC fault current favourably accelerates the normal zone propagation. The very high current slope at the time of the short circuit in a DC grid is another favourable parameter. The material used for the experiments is YBCO deposited on Al2O3 as well as YBCO coated conductors. The DC limitation experiments are compared to AC ones at different frequencies (50-2000 Hz). Careful attention is paid to the quench homogenization, which is one of the key issues for an SC FCL. The University of Geneva has proposed constrictions. We have investigated an operating temperature higher than 77 K. As for YBCO bulk, an operation closer to the critical temperature brings a highly improved homogeneity in the electric field development. The material can then absorb large energies without degradation. We present tests at various temperatures. These promising results are to be confirmed over long lengths.

  1. Simulation and Implementation of Quasi Resonant DC-DC Converter

    Directory of Open Access Journals (Sweden)

    N. Devarajan

    2012-01-01

    Full Text Available Problem statement: A half-bridge LLC resonant converter with a voltage doubler rectifier has a simple structure and its Zero-Voltage-Switching (ZVS capability is excellent from zero to full load condition. But conduction loss is more due to high circulating energy thus reducing the system efficiency. Moreover a variable frequency control method makes the control circuits more complicated than those using the Pulse Width Modulation (PWM control method. Thus, DC drive has lower efficiency when it operates on light loads. Approach: To improve the efficiency of the DC drive under light loads, a PWM-controlled quasi-resonant converter is proposed .It has simple control circuits and less conduction loss compared to a half-bridge LLC resonant converter under light load conditions. The proposed converter has a half-bridge LLC resonant converter along with an auxiliary circuit. The load regulation of the proposed converter can be achieved by an auxiliary circuit. Thus the proposed converter is expected to be suitable sustaining power module for the efficiency enhancement of DC drives. As the magnetizing inductance of the proposed converter is larger the circulating energy is considerably reduced under light load conditions. In this study the operational principle, design and modeling of QRC DC-DC converters for DC drives are presented. The PWM controlled quasi resonant converter is implemented using PIC microcontroller 16F184A. Results: The capacitor filter in the output is replaced by pi filter to produce DC with minimum ripple. The experimental results and simulation results are compared. This converter has the advantages like reduced number of switches, reduced transformer and filter size, reduced ripple, reduced switching losses, reduced switching stresses and increased power density. Conclusion: The experimental results closely agree with the simulation results.

  2. Mono-switch AC-DC/DC-DC converter for single-phase UPS%单相UPS的单开关AC-DC/DC-DC变换电路

    Institute of Scientific and Technical Information of China (English)

    李宋; 叶满园; 袁义生

    2011-01-01

    A mono-switch AC-DC/DC-DC converter used in single-phase UPS system is introduced,which consists of one power switch and six diodes. As both AC-DC rectifier and DC-DC booster,its operating modes and working principle are detailed. The single-cycle nonlinear control is adopted,which applies two low-speed PI regulators to control the voltage of two capacitors on DC link and a high-speed PI regulator to control the input current. Simulative results prove that,being simple and reliable,it outputs stable DC bus voltage with high input power factor and low THD.%介绍了一种应用在单相UPS系统中的新型单开关AC-DC/DC-DC变换电路,该电路由1个功率开关器件和6个二极管组成,能够实现AC/DC整流和DC/DC升压2种功能.在详细分析了该电路运行模式及工作原理的基础上,采用了单周期非线性控制理论对其进行控制,利于2个低速PI调节器对直流母线上的2个电容器电压进行控制,1个高速PI调节器对输入电流进行控制.仿真结果表明,该电路简单可靠,输入功率因数高,电流谐波失真小,可以获得稳定的正负直流母线电压.

  3. DC Hierarchical Control System for Microgrid Applications

    OpenAIRE

    Lu, Xiaonan; Sun, Kai; Guerrero, Josep M.; Huang, Lipei

    2013-01-01

    In order to enhance the DC side performance of AC-DC hybrid microgrid,a DC hierarchical control system is proposed in this paper.To meet the requirement of DC load sharing between the parallel power interfaces,droop method is adopted.Meanwhile,DC voltage secondary control is employed to restore the deviation in the DC bus voltage.The hierarchical control system is composed of two levels.DC voltage and AC current controllers are achieved in the primary control level.

  4. Pulsewidth modulated DC-to-DC power conversion circuits, dynamics, and control designs

    CERN Document Server

    Choi, Byungcho

    2013-01-01

    This is the definitive reference for anyone involved in pulsewidth modulated DC-to-DC power conversion Pulsewidth Modulated DC-to-DC Power Conversion: Circuits, Dynamics, and Control Designs provides engineers, researchers, and students in the power electronics field with comprehensive and complete guidance to understanding pulsewidth modulated (PWM) DC-to-DC power converters. Presented in three parts, the book addresses the circuitry and operation of PWM DC-to-DC converters and their dynamic characteristics, along with in-depth discussions of control design of PWM DC-to

  5. DC-DC converter for discharging energy storage magnets

    Science.gov (United States)

    Eyssa, Yehia M.; Huang, Xianrui

    1994-07-01

    A new DC-DC converter to control the output power delivered from a magnetic energy storage magnet or an equivalent current source is discussed. The circuit consists of: (1) highly coupled transformer (air or iron core) with coupling coefficient better than 0.95; (2) low frequency mechanical or superconducting switches (0.1 - 10 Hz) or high frequency (10 - 1000 Hz) GTO switches depending on the application; and (3) small voltage source (capacitor or battery) to control the output voltage. Two examples illustrating the application of this circuit are discussed. They are a step up dc current converter for use in uninterruptible power supplies and a step down one for use in discharging large current storage coil into a small current load. The efficiency expected to exceed 90%.

  6. Pulse-width modulated DC-DC power converters

    CERN Document Server

    Kazimierczuk, Marian K

    2008-01-01

    This book studies switch-mode power supplies (SMPS) in great detail. This type of converter changes an unregulated DC voltage into a high-frequency pulse-width modulated (PWM) voltage controlled by varying the duty cycle, then changes the PWM AC voltage to a regulated DC voltage at a high efficiency by rectification and filtering. Used to supply electronic circuits, this converter saves energy and space in the overall system. With concept-orientated explanations, this book offers state-of-the-art SMPS technology and promotes an understanding of the principle operations of PWM converters,

  7. Radiated electromagnetic emissions of DC-DC converters

    Energy Technology Data Exchange (ETDEWEB)

    Feld, L; Jussen, R; Karpinski, W; Klein, K; Sammet, J; Wlochal, M, E-mail: sammet@cern.ch [Physikalisches Institut IB, RWTH Aachen University, Aachen (Germany)

    2010-12-15

    For the CMS tracker at SLHC a new powering scheme is considered to be mandatory to allow the detector to provide at least the same performance as today at the LHC. The baseline solution of CMS foresees the use of DC-DC converters to provide larger currents with smaller losses. An important component of most converters are inductors which, however, tend to radiate the switching noise generated by the converter. The emissions of different inductors have been measured and simulated, the coil design has been optimized and noise susceptibility measurements, with present CMS hardware, have been performed. This article summarizes the results.

  8. Radiated electromagnetic emissions of DC-DC converters

    CERN Document Server

    Sammet, Jan Domenik

    2010-01-01

    A new powering scheme is considered to be mandatory for the CMS tracker at SLHC. The baseline solution of CMS foresees the use of DC-DC converters, allowing to provide larger currents while reducing losses. An important component of most converters are inductors, which, however, tend to radiate the switching noise generated by the converter. The radiated emissions of several converters have been measured and simulated. In addition noise susceptibility measurements with radiated noise and present CMS hardware have been performed. A summary of the results will be presented.

  9. Low dose failures of hardened DC-DC power converters

    Science.gov (United States)

    Lehman, J.; Yui, C.; Rax, B. G.; Miyahira, T. F.; Weideman, M.; Schrick, P.; Swift, G. M.; Johnston, A. H.

    2002-01-01

    Box-level total dose testing of the FOG (Fiber Optic Gyro) by IXSEA at ESA's GammabeamFacility were abruptly terminated at 8krad (Si) due to catastrophic failure (complete shutdown). This was unexpected because all components within the gyro were supposedly radiation tolerant. Further testing showed that the components responsible for the failure were two DC-DC converters, manufactured by Interpoint, that stopped regulating shortly before shutdown. This paper summarizes diagnostic test results for the converters to determine the underlying cause of the unexpected failure at low levels of radiation.

  10. Power flow analysis for DC voltage droop controlled DC microgrids

    DEFF Research Database (Denmark)

    Li, Chendan; Chaudhary, Sanjay; Dragicevic, Tomislav

    2014-01-01

    This paper proposes a new algorithm for power flow analysis in droop controlled DC microgrids. By considering the droop control in the power flow analysis for the DC microgrid, when compared with traditional methods, more accurate analysis results can be obtained. The algorithm verification...... is carried out by comparing the calculation results with detailed time domain simulation results. With the droop parameters as variables in the power flow analysis, their effects on power sharing and secondary voltage regulation can now be analytically studied, and specialized optimization in the upper level...... control can also be made accordingly. Case studies on power sharing and secondary voltage regulation are carried out using proposed power flow analysis....

  11. Isoflavones, genistein and daidzein, regulate mucosal immune response by suppressing dendritic cell function.

    Directory of Open Access Journals (Sweden)

    John Wei

    Full Text Available Lipopolysaccharide (LPS, a component of gram-negative bacterial cell walls, has been shown to have a strong adjuvant effect towards inhaled antigens contributing to airway inflammation. Isoflavones are anti-inflammatory molecules present in abundant quantities in soybeans. We investigated the effect of isoflavones on human dendritic cell (DC activation via LPS stimulation and subsequent DC-mediated effector cell function both in vitro and in a mouse model of upper airway inflammation. Human monocyte-derived DCs (MDDC were matured with LPS (or TNF-α +/- isoflavones (genistein or daidzein. The surface expression levels of DC activation markers were analyzed by flow cytometry. Mature DCs +/- isoflavones were washed and cultured with freshly-isolated allogenic naïve CD4⁺ T cells for 5 days or with autologous natural killer (NK cells for 2 hours. The percentages of proliferating IFN-γ⁺ CD4⁺ T cells and cytokine levels in culture supernatants were assessed. NK cell degranulation and DC cytotoxicity were measured by flow cytometry. Isoflavones significantly suppressed the activation-induced expression of DC maturation markers (CD83, CD80, CD86 and MHC class I but not MHC class II molecules in vitro. Isoflavone treatment inhibited the ability of LPS-DCs to induce IFN-γ in CD4⁺ T cells. NK cell degranulation and the percentage of dead DCs were significantly increased in isoflavone-treated DC-NK co-culture experiments. Dietary isoflavones suppressed the mucosal immune response to intra-nasal sensitization of mice to ovalbumin. Similar results were obtained when isoflavones were co-administered during sensitization. These results demonstrate that soybean isoflavones suppress immune sensitization by suppressing DC-maturation and its subsequent DC-mediated effector cell functions.

  12. Switching coordination of distributed dc-dc converters for highly efficient photovoltaic power plants

    Science.gov (United States)

    Agamy, Mohammed; Elasser, Ahmed; Sabate, Juan Antonio; Galbraith, Anthony William; Harfman Todorovic, Maja

    2014-09-09

    A distributed photovoltaic (PV) power plant includes a plurality of distributed dc-dc converters. The dc-dc converters are configured to switch in coordination with one another such that at least one dc-dc converter transfers power to a common dc-bus based upon the total system power available from one or more corresponding strings of PV modules. Due to the coordinated switching of the dc-dc converters, each dc-dc converter transferring power to the common dc-bus continues to operate within its optimal efficiency range as well as to optimize the maximum power point tracking in order to increase the energy yield of the PV power plant.

  13. Optimization of control sequences for DC-DC-converters; Optimierung der Stellgroessenfolge eines DC-DC-Wandler

    Energy Technology Data Exchange (ETDEWEB)

    Kroeger, Claus [Hochschule Aalen (Germany). Wirtschaftsingenieurwesen

    2009-07-01

    DC-DC-Converters are used in power electronics to adapt different voltage levels of electrical sources and sinks with respect of high efficiency. To minimize electrical losses these power electronic converters always work with switching power semiconductors. This switching principle of the converter is causing a control constraint which limits the achievable performance for the voltage control drastically. This paper presents an optimization for the control sequence in a high dynamic converter control which is based on the dead-beat control design. Thus the non-avoidable control constraint will not be violated. (orig.)

  14. An Integrated Multifunctional Bidirectional AC/DC and DC/DC Converter for Electric Vehicles Applications

    Directory of Open Access Journals (Sweden)

    Liwen Pan

    2016-06-01

    Full Text Available This paper presents an on-board vehicular battery charger that integrates bidirectional AC/DC converter and DC/DC converter to achieve high power density for application in electric vehicles (EVs. The integrated charger is able to transfer electrical energy between the battery pack and the electric traction system and to function as an AC/DC battery charger. The integrated charger topology is presented and the design of passive components is discussed. The control schemes are developed for motor drive system and battery-charging system with a power pulsation reduction circuit. Simulation results in MATLAB/Simulink and experiments on a 30-kW motor drive and 3.3-kW AC/DC charging prototype validate the performance of the proposed technology. In addition, power losses, efficiency comparison and thermal stress for the integrated charger are illustrated. The results of the analyses show the validity of the advanced integrated charger for electric vehicles.

  15. Quasi Y-Source Boost DC-DC Converter

    DEFF Research Database (Denmark)

    Siwakoti, Yam P.; Blaabjerg, Frede; Loh, Poh Chiang

    2015-01-01

    A new topology called “quasi-Y-source impedance network” is presented in this paper. It inherits all the advantages of the original Y-source network. In addition, the new topology draws continuous current from the source which is required for many renewable sources. It also has dc-current-blockin...

  16. Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment.

    Science.gov (United States)

    Pichavant, Muriel; Charbonnier, Anne-Sophie; Taront, Solenne; Brichet, Anne; Wallaert, Benoît; Pestel, Joel; Tonnel, André-Bernard; Gosset, Philippe

    2005-04-01

    Airway dendritic cells (DCs) are crucial for allergen-induced sensitization and inflammation in allergic asthma. After allergen challenge, an increased number of DCs is observed in airway epithelium from patients with allergy. Because Der p 1, a cysteine protease allergen from Dermatophagoides pteronyssinus , induces chemokine production by bronchial epithelial cells (BECs), the purpose of this investigation was to evaluate the capacity of BEC exposed to Der p 1 to recruit DCs. Chemotactic activity of BEAS-2B, a bronchial epithelial cell line, and BECs from nonatopic controls and patients with allergic asthma was evaluated on the migration of precursors, immature and mature monocyte-derived DCs (MDDCs), and CD34 + -derived Langerhans cells (LCs). C-C chemokine ligand (CCL)-2, CCL5, and C-X-C chemokine ligand 10 production by BEAS-2B and BEC was increased after Der p 1 exposure, whereas the proenzyme proDer p 1 devoid of enzymatic activity had no effect. Der p 1 stimulation of BEAS-2B and BEC from both groups increased significantly the recruitment of MDDC precursors, depending on CCL2, CCL5, and C-X-C chemokine ligand 10 production. In a reconstituted polarized epithelium, apical application of Der p 1 enhanced MDDC precursor migration into the epithelial layer. Moreover, Der p 1 stimulation of BEC from patients with asthma but not from controls increased the migration of LC precursors, mainly dependent on CCL20 secretion. No migration of immature and mature DCs was observed. These data confirmed that BECs participate in the homeostasis of the DC network present within the bronchial epithelium through the secretion of chemokines. In allergic asthma, upregulation of CCL20 production induced LC recruitment, the role of which remains to be determined.

  17. Antibodies to P-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death.

    Science.gov (United States)

    Ren, Xiao-Xin; Li, Chuan; Xiong, Si-Dong; Huang, Zhong; Wang, Jian-Hua; Wang, Hai-Bo

    2015-01-01

    P-selectin glycoprotein ligand-1 (PSGL-1) has been proved to serve as the functional receptor for enterovirus 71 (EV71). We found the abundant expression of PSGL-1 on monocyte-derived dendritic cells (MDDCs). However, we have previously demonstrated that MDDCs did not support efficient replication of EV71. Dendritic cells (DCs) have been described to be subverted by various viruses including EV71 for viral dissemination, we thus explore the potential contribution of PSGL-1 on DC-mediated EV71 transmission. We found that the cell-surface-expressing PSGL-1 on MDDCs mediated EV71 binding, and intriguingly, these loaded-viruses on MDDCs could be transferred to encountered target cells; Prior-treatment with PSGL-1 antibodies or interference with PSGL-1 expression diminished MDDC-mediated EV71 transfer and rescued virus-induced cell death. Our data uncover a novel role of PSGL-1 in DC-mediated EV71 spread, and provide an insight into blocking primary EV71 infection.

  18. Experiments with a DC Motor

    Science.gov (United States)

    Kraftmakher, Yaakov

    2010-01-01

    Experiments with an electric motor provide good opportunity to demonstrate some basic laws of electricity and magnetism. The aim of the experiments with a low-power dc motor is to show how the motor approaches its steady rotation and how its torque, mechanical power and efficiency depend on the rotation velocity. The tight relationship between the…

  19. 75 FR 62331 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-14, DC-9-15, and DC-9-15F...

    Science.gov (United States)

    2010-10-08

    ... Directives; McDonnell Douglas Corporation Model DC- 9-14, DC-9-15, and DC-9-15F Airplanes; and DC-9-20, DC-9-30, DC-9-40, and DC-9-50 Series Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. Hand Delivery: Deliver to...

  20. 76 FR 39251 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-07-06

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION CONTACT: Roger Durbin, Aerospace.... Applicability (c) This AD applies to all The Boeing Company Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83...

  1. 76 FR 53346 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-08-26

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Jersey Avenue, SE., Washington, DC 20590. Hand Delivery: Deliver to Mail address above between 9 a.m. and...) This AD applies to The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83),...

  2. 76 FR 1993 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-01-12

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION.... Applicability (c) This AD applies to The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83...

  3. 76 FR 41651 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-07-15

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION...) This AD applies to The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83),...

  4. 75 FR 68686 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-14, DC-9-15, and DC-9-15F...

    Science.gov (United States)

    2010-11-09

    ...; AD 2010-23-10] RIN 2120-AA64 Airworthiness Directives; McDonnell Douglas Corporation Model DC- 9-14, DC-9-15, and DC-9-15F Airplanes; and Model DC-9-20, DC-9-30, DC- 9-40, and DC-9-50 Series Airplanes... Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER...

  5. DC motor operation controlled from a DC/DC power converter in pulse mode with low duty cycle

    OpenAIRE

    Stefanov, Goce; Kukuseva, Maja; Citkuseva Dimitrovska, Biljana

    2016-01-01

    In this paper pulse mode of operation of DC motor controlled by DC/DC power converter is analyzed. DC motor operation with time intervals in which the motor operates without output load is of interest. In this mode it is possible the motor to restore energy. Also, in the paper are represented calculations for the amount of the restored energy in the pulse mode operation of the motor for different duty cycles.

  6. DC to DC power converters and methods of controlling the same

    Science.gov (United States)

    Steigerwald, Robert Louis; Elasser, Ahmed; Sabate, Juan Antonio; Todorovic, Maja Harfman; Agamy, Mohammed

    2012-12-11

    A power generation system configured to provide direct current (DC) power to a DC link is described. The system includes a first power generation unit configured to output DC power. The system also includes a first DC to DC converter comprising an input section and an output section. The output section of the first DC to DC converter is coupled in series with the first power generation unit. The first DC to DC converter is configured to process a first portion of the DC power output by the first power generation unit and to provide an unprocessed second portion of the DC power output of the first power generation unit to the output section.

  7. Speed Control of DC Motor using AC/AC/DC Converter Based on Intelligent Techniques

    Directory of Open Access Journals (Sweden)

    Rakan Kh Antar

    2013-05-01

    Full Text Available    This paper describes the application of ac/ac/dc and ac/dc converters to control the speed of a separately excited DC motor. Artificial neural network and PI controller are trained to select the desired values of firing angles for triggering thyristors of the ac/ac/dc and ac/dc bridge converters in order to control the speed of the dc motor at a desired value with constant and different load torques in order to obtain the best speed response. Simulation results show that the rising time for ac/dc and ac/ac/dc converters at 250rpm are reduced about 79% and 89% respectively, while delay time it reduced about 69% and 64% respectively. Therefore, speed response of the dc motor is more efficient for closed loop system compared with open loop also the response of ac/ac/dc converter is better than ac/dc converter.

  8. Dilation and Curettage (D&C)

    Science.gov (United States)

    ... For Patients About ACOG Dilation and Curettage (D&C) Home For Patients Search FAQs Dilation and Curettage ( ... February 2016 PDF Format Dilation and Curettage (D&C) Special Procedures What is dilation and curettage (D& ...

  9. Dilation and Curettage (D&C)

    Science.gov (United States)

    ... For Patients About ACOG Dilation and Curettage (D&C) Home For Patients Search FAQs Dilation and Curettage ( ... February 2016 PDF Format Dilation and Curettage (D&C) Special Procedures What is dilation and curettage (D& ...

  10. Optimization of DC-DC Converters via Geometric Programming

    Directory of Open Access Journals (Sweden)

    U. Ribes-Mallada

    2011-01-01

    Full Text Available The paper presents a new methodology for optimizing the design of DC-DC converters. The magnitudes that we take into account are efficiency, ripples, bandwidth, and RHP zero placement. We apply a geometric programming approach, because the variables are positives and the constraints can be expressed in a posynomial form. This approach has all the advantages of convex optimization. We apply the proposed methodology to a boost converter. The paper also describes the optimum designs of a buck converter and a synchronous buck converter, and the method can be easily extended to other converters. The last example allows us to compare the efficiency and bandwidth between these optimal-designed topologies.

  11. RESONANT STEP-DOWN DC-DC POWER CONVERTERS

    DEFF Research Database (Denmark)

    2015-01-01

    charged from the input voltage and discharged to the output capacitor through the galvanic isolation barrier by a semiconductor switch arrangement in accordance with a switch control signal to produce the converter output voltage. The resonant step-down DC-DC power converter comprises an electrical short...... of the primary side circuit thereby establishing in both the first and second cases a series coupling of the output capacitor and the input capacitor. A load connection is established, in the first case, between the first positive electrode of the output capacitor and the positive input terminal or......-circuit connection across the galvanic isolation barrier connecting, in a first case, the second negative electrode of the output capacitor to the positive input terminal of the primary side circuit or, in a second case, connecting the second positive electrode of the output capacitor to the negative input terminal...

  12. DC/DC converter with improved rectification for higher efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Maisel, Peter; Saliternig, Martin [Continental AG, Nuernberg (Germany)

    2010-07-01

    High-power dc-dc converters are an important element of the electrical system of electric vehicles and hybrid electric vehicles. These complex modular components provide the link between the high-voltage level used for the powertrain and the low-voltage bus for the lighting system, engine management and auxiliary needs in the vehicle. The essential requirements for all converters are high efficiency, compact size, lightweight and reliability. A very popular method to increase the efficiency is the synchronous rectification. Parasitic inductances in the commutation circuit and reverse recovery effects can produce a ringing with voltage overshoots at the diodes and the transistors. These spikes can cause higher average power dissipation in the seminconductors and higher EMI (electromagnetic interference).

  13. Study of nonlinear phenomena in switching DC/DC converters

    Science.gov (United States)

    Iu, Herbert Ho-Ching

    This thesis studies some nonlinear phenomena such as bifurcation and chaos in DC/DC switching converters. Five phases of investigations are described. The first phase reviews the existing tools for analyzing nonlinear systems that are helpful to the investigation of nonlinear phenomena in power electronic circuits. Some of these existing tools are employed to study the nonlinear behaviour of power electronic circuits in the subsequent phases. The second phase focuses on the analysis of bifurcation behaviour of parallel-connected DC/DC converters under a master-slave current sharing scheme. An iterative discrete-time map and its Jacobian are established to predict the onset of period-doubling or Neimark-Sacker bifurcation. Both parallel-connected buck converters and boost converters are studied. The third phase studies an autonomous free-running Cuk converter under a hysteretic current-mode control. Hopf bifurcation is observed, for the first time, in this kind of autonomous power electronic circuits. The method of state-space averaging is employed to predict the occurrence of such bifurcation. Extensive simulations and experiments confirm the predicted results. A typical bifurcation sequence from stable fixed points to chaos, via limit cycles and quasiperiodic orbits, is demonstrated. The fourth phase investigates the possibility of synchronization of two chaotic autonomous free-running Cuk converters. With a particular capacitor voltage as driving signal, synchronization is found possible. Averaged state equations and conditional Lyapunov exponents are used to predict the possibility of synchronization while computer simulations and PSPICE simulations provide the verification. The last phase gives suggestions for future research.

  14. A simple DC-DC convertor of high accuracy

    CERN Document Server

    Hausler, M

    1974-01-01

    Origin and dimension of measurement faults are given for the application of a current source driven convertor having parallel ring transformers. Particularly described in this paper is the behaviour of this dc convertor at measurements taken near the zero point and at change of current polarity. The importance of an additional ring transformer in order to improve the ripple of the device is explained; hints to choose the optimal number of turns of the ring transformer are given. (2 refs).

  15. Mesoscopic electronics beyond DC transport

    Science.gov (United States)

    di Carlo, Leonardo

    Since the inception of mesoscopic electronics in the 1980's, direct current (dc) measurements have underpinned experiments in quantum transport. Novel techniques complementing dc transport are becoming paramount to new developments in mesoscopic electronics, particularly as the road is paved toward quantum information processing. This thesis describes seven experiments on GaAs/AlGaAs and graphene nanostructures unified by experimental techniques going beyond traditional dc transport. Firstly, dc current induced by microwave radiation applied to an open chaotic quantum dot is investigated. Asymmetry of mesoscopic fluctuations of induced current in perpendicular magnetic field is established as a tool for separating the quantum photovoltaic effect from classical rectification. A differential charge sensing technique is next developed using integrated quantum point contacts to resolve the spatial distribution of charge inside a double quantum clot. An accurate method for determining interdot tunnel coupling and electron temperature using charge sensing is demonstrated. A two-channel system for detecting current noise in mesoscopic conductors is developed, enabling four experiments where shot noise probes transmission properties not available in dc transport and Johnson noise serves as an electron thermometer. Suppressed shot noise is observed in quantum point contacts at zero parallel magnetic field, associated with the 0.7 structure in conductance. This suppression evolves with increasing field into the shot-noise signature of spin-lifted mode degeneracy. Quantitative agreement is found with a phenomenological model for density-dependent mode splitting. Shot noise measurements of multi-lead quantum-dot structures in the Coulomb blockade regime distill the mechanisms by which Coulomb interaction and quantum indistinguishability correlate electron flow. Gate-controlled sign reversal of noise cross correlation in two capacitively-coupled dots is observed, and shown to

  16. Implementation of hierarchical control in DC microgrids

    DEFF Research Database (Denmark)

    Jin, Chi; Wang, Peng; Xiao, Jianfang

    2014-01-01

    DC microgrids are becoming popular in low-voltage distribution systems due to the better compatibility with photovoltaic panels, electric vehicles, and dc loads. This paper presents a practical dc microgrid developed in the Water and Energy Research Laboratory (WERL) in the Nanyang University...

  17. Hierarchical Power Sharing Control in DC Microgrids

    DEFF Research Database (Denmark)

    Peyghami Akhuleh, Saeed; Mokhtari, Hossein; Blaabjerg, Frede

    2016-01-01

    Because of the advances in power electronics, DC-based power systems, have been used in industrial applications such as data centers [18], space applications [10], aircraft [12], offshore wind farms, electric vehicles [56], DC home systems [5, 20], and high-voltage DC transmission systems...

  18. DC-DC conversion powering for the CMS tracker at SLHC

    Energy Technology Data Exchange (ETDEWEB)

    Feld, L., E-mail: Lutz.Feld@cern.c [RWTH Aachen University, Sommerfeldstrasse 14, D-52074 Aachen (Germany); Jussen, R.; Karpinski, W.; Klein, K.; Merz, J.; Sammet, J. [RWTH Aachen University, Sommerfeldstrasse 14, D-52074 Aachen (Germany)

    2011-02-01

    A tracker powering scheme based on DC-DC converters close to the detector modules can supply more power through thinner cables. This will allow to satisfy the increased power demands of tracking systems at the SLHC. This article describes the development of DC-DC converters for upgrades of the CMS pixel and tracking systems and addresses system integration issues.

  19. DC-DC Conversion Powering for the CMS Tracker at SLHC

    CERN Document Server

    Feld, Lutz

    2010-01-01

    A tracker powering scheme based on DC-DC converters close to the detector modules can supply more power through thinner cables. This will allow to satisfy the increased power demands of tracking systems at the SLHC. This article describes the development of DC-DC converters for upgrades of the CMS pixel and tracking systems and addresses system integration issues.

  20. Full wave dc-to-dc converter using energy storage transformers

    Science.gov (United States)

    Moore, E. T.; Wilson, T. G.

    1969-01-01

    Full wave dc-to-dc converter, for an ion thrustor, uses energy storage transformers to provide a method of dc-to-dc conversion and regulation. The converter has a high degree of physical simplicity, is lightweight and has high efficiency.

  1. A DC-DC Conversion Powering Scheme for the CMS Phase-1 Pixel Upgrade

    CERN Document Server

    Feld, Lutz Werner; Marcel Friedrichs; Richard Hensch; Karpinski, Waclaw; Klein, Katja; Sammet, Jan Domenik; Wlochal, Michael

    2012-01-01

    The powering scheme of the CMS pixel detector will be described, and the performance of prototype DC-DC buck converters will be presented, including power efficiency, system tests with DC-DC converters and pixel modules, thermal management, reliability at low temperature, and studies of potential frequency locking betwe...

  2. The DC-DC Conversion Power System of the CMS Phase-1 Pixel Upgrade

    CERN Document Server

    Klein, Katja

    2014-01-01

    The power system of the Phase-1 pixel detector will be described and the performance of the new components, including DC-DC converters, DC-DC converter motherboards and various power distribution boards, will be detailed. The outcome of system tests in terms of electrical behaviour, thermal management and pixel module performance will be discussed.

  3. A Survey on Voltage Boosting Techniques for Step-Up DC-DC Converters

    DEFF Research Database (Denmark)

    Forouzesh, Mojtaba; Siwakoti, Yam Prasad; Gorji, Saman Asghari;

    2016-01-01

    Step-up dc-dc converters are used to boost the voltage level of the input to a higher output level. Despite of its features such as simplicity of implementation, the fundamental boost dc-dc converter has shortcomings such as low boost ability and low power density. With these limitations, researc...

  4. AC-DC PFC Converter Using Combination of Flyback Converter and Full-bridge DC-DC Converter

    Directory of Open Access Journals (Sweden)

    Moh. Zaenal Efendi

    2014-06-01

    Full Text Available This paper presents a combination of power factor correction converter using Flyback converter and Full-bridge dc-dc converter in series connection. Flyback converter is operated in discontinuous conduction mode so that it can serve as a power factor correction converter and meanwhile Full-bridge dc-dc converter is used for dc regulator. This converter system is designed to produce a 86 Volt of output voltage and 2 A of output current. Both simulation and experiment results show that the power factor of this converter achieves up to 0.99 and meets harmonic standard of IEC61000-3-2. Keywords: Flyback Converter, Full-bridge DC-DC Converter, Power Factor Correction.

  5. Five-Level Active-Neutral-Point-Clamped DC/DC Converter for Medium-Voltage DC Grids

    DEFF Research Database (Denmark)

    Liu, Dong; Deng, Fujin; Chen, Zhe

    2017-01-01

    effectively eliminate high voltage leaps caused by the dead time effect. In addition, a capacitor voltage control strategy is proposed for the 5L-ANPC dc/dc converter to ensure the balanced flying capacitor voltage and desired five-level voltage waveforms. Finally, simulation and experimental studies......This paper proposes a five-level active-neutralpoint- clamped (5L-ANPC) dc/dc converter for applications in medium voltage dc (MVDC) grids. A modulation strategy is proposed for the 5L-ANPC dc/dc converter to generate multilevel voltage waveforms, which can effectively reduce voltage change rate dv...... are conducted, and the results have verified the proposed converter and control strategies....

  6. A Feed-Forward Control Realizing Fast Response for Three-Branch Interleaved DC-DC Converter in DC Microgrid

    Directory of Open Access Journals (Sweden)

    Haojie Wang

    2016-07-01

    Full Text Available It is a common practice for storage batteries to be connected to DC microgrid buses through DC-DC converters for voltage support on islanded operation mode. A feed-forward control based dual-loop constant voltage PI control for three-branch interleaved DC-DC converters (TIDC is proposed for storage batteries in DC microgrids. The working principle of TIDC is analyzed, and the factors influencing the response rate based on the dual-loop constant voltage control for TIDC are discussed, and then the method of feed-forward control for TIDC is studied to improve the response rate for load changing. A prototype of the TIDC is developed and an experimental platform is built. The experiment results show that DC bus voltage sags or swells caused by load changing can be reduced and the time for voltage recovery can be decreased significantly with the proposed feed-forward control.

  7. Transformerless dc-Isolated Converter

    Science.gov (United States)

    Rippel, Wally E.

    1987-01-01

    Efficient voltage converter employs capacitive instead of transformer coupling to provide dc isolation. Offers buck/boost operation, minimal filtering, and low parts count, with possible application in photovoltaic power inverters, power supplies and battery charges. In photovoltaic inverter circuit with transformerless converter, Q2, Q3, Q4, and Q5 form line-commutated inverter. Switching losses and stresses nil because switching performed when current is zero.

  8. Power Network impedance effects on noise emission of DC-DC converters

    Science.gov (United States)

    Esteban, M. C.; Arteche, F.; Iglesias, M.; Gimeno, A.; Arcega, F. J.; Johnson, M.; Cooper, W. E.

    2012-01-01

    The characterization of electromagnetic noise emissions of DC-DC converters is a critical issue that has been analyzed during the desing phase of CMS tracker upgrade. Previous simulation studies showed important variations in the level of conducted emissions when DC-DC converters are loaded/driven by different impedances and power network topologies. Several tests have been performed on real DC-DC converters to validate the Pspice model and simulation results. This paper presents these test results. Conducted noise emissions at the input and at the output terminals of DC-DC converters has been measured for different types of power and FEE impedances. Special attention has been paid to influence on the common-mode emissions by the carbon fiber material used to build the mechanical structure of the central detector. These study results show important recommendations and criteria to be applied in order to decrease the system noise level when integrating the DC-DC.

  9. FLYWHEEL AND A DC MACHINE

    Directory of Open Access Journals (Sweden)

    IVAN ALCALÁ

    2014-01-01

    Full Text Available Este artículo describe el análisis, modelado y simulación de un vehículo eléctrico (EV enfocado al desarrollo de un banco de pruebas para reproducir la dinámica del EV. El banco está formado por un drive de motor de inducción (IM acoplado directamente a una máquina de DC y a un volante de inercia a través de una transmisión. El volante de inercia y la máquina de DC reproducen la dinámica y las fuerzas que actúan en el vehículo. Se propone una metodología para diseñar un banco de pruebas de EV para estudiar el comportamiento de vehículos eléctricos cercano a las condiciones de operación reales. El análisis de las fuerzas en el EV en conjunto con la máquina DC define las condiciones de operación del EV. El modelado y la simulación son desarrollados en MATLAB/Simulink, el banco de pruebas implementado es controlado por un DSP. Finalmente, los resultados de simulación y experimentales obtenidos validan el funcionamiento del banco de prueba.

  10. Research on the Effects of the Fluconazole resistance and Fluconazole susceptible Candida Albicans Strains in RVVC on the Shapes and the Surface Molecules of the Human Peripheral Blood Monocyte-Derived DCs%RVVC白念珠菌氟康唑敏感株和耐药株对外周血DCs分化成熟的影响

    Institute of Scientific and Technical Information of China (English)

    宣晓梅; 刘静; 沈丽; 刘瑞琴; 李艳佳; 刘丽娟; 李英涛; 于亮

    2012-01-01

    目的 探讨复发性外阴阴道念珠菌病(RVVC)患者阴道白念珠菌对氟康唑敏感情况及其对人外周血单核细胞源树突状细胞(DCs)形态及表面分子的影响.方法 科玛嘉念珠菌显色培养基及芽管试验分离、鉴定白念珠菌;MIC法判断敏感菌及耐药菌;体外培养正常人外周血单核细胞源DCs,实验组以不同剂量氟康唑敏感菌悬液、耐药菌悬液刺激,对照组以同等剂量标准菌悬液刺激后,倒置显微镜观察细胞形态变化,流式细胞仪检测细胞表面分子的表达.结果 RVVC患者阴道分泌物共分离出白念珠菌108株,其中对氟康唑敏感67株(62.04%),耐药41株(37.96%);各实验组与对照组DCs细胞形态无明显差别.DCs表面分子CD80,CD86表达量均与白念珠菌悬液剂量呈正相关;加入标准菌株悬液的对照组DCs表面分子CD80,CD86表达明显高于同等剂量加入敏感菌悬液和耐药菌悬液的实验组,且加入敏感菌悬液的实验1组DCs表面分子CD80,CD86表达明显高于同等剂量加入耐药菌悬液的实验2组.结论 在一定剂量范围内,白念珠菌可促进DCs表面分子CD80,CD86表达,使DCs进一步成熟,氟康唑敏感菌株优于耐药菌株,但两者均不及标准菌株.%Objective To investigate the effects of the fluconazole resistance and fluconazole susceptible Candida albicans strains in recurrent vulvovaginal candidiasis( RVVC) on the Shapes and the Surface Molecules of the Human Peripheral Blood Monocyte-Derived dendritic cells ( DCs ). Methods Candida albicans in RVVC were separated and were judged by the CHROMagar Monilia colouration nutritive medium and the genn-tube-formming tests, and then were judged the fluconazole-resistance or fluconazole-usceptible strains by MIC tests. The dendritic cells were obtained by culture in vitro. Then after they were stimulated by the different doses of Candida albicans including the fluconazole-esistance and fluconazole-usceptible strains

  11. 76 FR 13543 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-03-14

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. Hand Delivery: Deliver to Mail... stabilizer is similar in design and loading to that of the Model DC-9-81 (MD-81), DC- 9-82 (MD-82),...

  12. DC

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    金属材质机身拥有三层镀膜工艺,1210万像素CCD,采用4倍变焦28mm广角镜头。配合16:9屏幕以及720p高清短片拍摄为卖点.整体感觉有别于佳能一贯的风格。

  13. DC

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    近期.单反市场最受期待的产品非尼康D40x莫属了,D40x的上市弥补了尼康在低价位千万像素级别无产品的空白,形成了其完整的产品线,D200、D80,D40x和D40.随着D70s的停产,D40x充当这一价位的角色,直接挑战佳能400D及索尼a100.目前千万像素已经普及到了低档单反之中,不难看出尼康D40x是2007年单反市场中的一颗重磅炸弹,相信随着D40x的上市单反的价格战又会再次拉开。

  14. DC

    Institute of Scientific and Technical Information of China (English)

    姚文秋

    2005-01-01

    阳春三月,细雨绵绵,冷却了火爆的年前DC市场,但是也活跃离一部分即将崭露头角的新芽。纵观市场,几大品牌中要数尼康的销售情况最好,这主要是尼康的机器价位合理,外形时尚,功能全面,品质优良。比如尼康5200,这款机器500万像素,才两多块,而且外观十分小巧,性价比很高。

  15. DC

    Institute of Scientific and Technical Information of China (English)

    姚文秋

    2005-01-01

    八月,驴友们的黄金时节。九寨沟清凉的水、张家界翠绿的树、黄山神秘的云雾……都是大家向往的好去处。拿起自己心爱的DC把这些美景定格保留作为美好的纪念是必不可少啦。而厂商们当然不会放过暑期这最后的机会,力求分得暑期市场的最后一块蛋糕。总而言之,与硝烟弥漫的七月市场相比,本月DC市场仍然延续着上月的强劲势头。

  16. DC

    Institute of Scientific and Technical Information of China (English)

    姚文秋

    2005-01-01

    纵观年底DC市场,风云变幻,惊喜不断。各大DC厂商纷纷对自己的产品价格进行调整。降价似乎成了最主流的声音。市场霸主佳能继PowerShot S50在市场上大获成功之后,在今年夏天紧接着发布了其第一款5百万像素的相机PowerShot S60,近这款数码相机做了一次大的价格调整。另外,随着家庭用户要求的不断增加,更高水平的家用数码相机也浮出水面。

  17. DC

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    一般来说数码相机镜头等效焦距在200mm以上的机型,就可以称之为长焦相机。长焦数码相机因其超长的焦距、丰富的功能受到了消费者的喜爱,它们也一直是消费级数码相机市场的热点所在。但是由于过大的体积,让携带长焦相机成为一件很费力的事情。现在,随着机身设计的进一步轻便和防抖技术的进一步成熟,长焦相机正在逐渐变得更加小巧、实用。原来拥有超长焦距的机型现在也可以像卡片机一样随身携带,近期上市的索尼DSC—H3就是其中不错的一款。

  18. DC

    Institute of Scientific and Technical Information of China (English)

    姚文秋

    2005-01-01

    DC市场在经过10月份的促销鏖战之后,行情慢慢稳定下来,各个厂家也不断推出自己在2005下半年的主流DC。家用机和长焦数码已经进入了一个新格局。以前我们耳熟能详的佳能A95、尼康5900等一批经典机型已经慢慢退下一线,取而代之的最新产品昂首进入激烈的数码相机战场。而时尚轻薄是在这些新品中刮起来的一阵旋风。

  19. DC

    Institute of Scientific and Technical Information of China (English)

    姚文秋

    2005-01-01

    进入七月,学校都已放假,不少学生教师也将外出旅游当作假期第一选择。要外出旅游当然少不了带上心爱的DC啦。有需求就会有供给,这是市场规律的铁定原则,因此各大厂商自然不会错过机会一一推新的推新、降价的降价。整个市场一片热火朝天的场面。

  20. DC

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    本月市场动态:第十届中国国际照相机械影像器材与技术博览会(2007 CHINA P&E)于7月1日在北京落幕,作为目前中国规模最大的摄影器材展会,其影响力不言而喻。国际知名的几大品牌,如佳能.尼康,索尼均带来了主流的产品,腾龙、适马也推出了各自最新的镜头。从展出的产品来看.有一个非常明显的信号就是,

  1. SDF-1, DC1/DC2, and Tumor Angiogenesis

    Science.gov (United States)

    2006-04-01

    However, the presence of functional immunogenic (mature) myeloid DCs is rare in human ovarian tumours35, breast tumours40,41, prostate cancer42 and...cyclooxygenase-2 ( COX2 )50–52. COX2 promotes prostaglandin E2 (PGE2) production in the tumour environment. PGE2 in turn suppresses DC differentiation and...Abundance of VEGF, IL-6, M-CSF, TGFβ, IL-10, COX2 , PGE2, gangliosides and other suppressive molecules versus negligible GM-CSF, IL-4, B7-H1 A recently

  2. A Feedback Passivation Design for DC Microgrid and Its DC/DC Converters

    Directory of Open Access Journals (Sweden)

    Feifan Ji

    2016-12-01

    Full Text Available There are difficulties in analyzing the stability of microgrids since they are located on various network structures. However, considering that the network often consists of passive elements, the passivity theory is applied in this paper to solve the above-mentioned problem. It has been formerly shown that when the network is weakly strictly positive real (WSPR, the DC microgrid is stable if all interfaces between the microgrid and converters are made to be passive, which is called interface passivity. Then, the feedback passivation method is proposed for the controller design of various DC–DC converters to achieve the interface passivity. The interface passivity is different from the passivity of closed-loop systems on which the passivity based control (PBC concentrates. The feedback passivation design is detailed for typical buck converters and boost converters in terms of conditions that the controller parameters should satisfy. The theoretical results are verified by a hardware-in-loop real-time labotray (RTLab simulation of a DC microgrid with four generators.

  3. DC Voltage Droop Control Implementation in the AC/DC Power Flow Algorithm: Combinational Approach

    DEFF Research Database (Denmark)

    Akhter, F.; Macpherson, D.E.; Harrison, G.P.

    2015-01-01

    In this paper, a combinational AC/DC power flow approach is proposed for the solution of the combined AC/DC network. The unified power flow approach is extended to include DC voltage droop control. In the VSC based MTDC grids, DC droop control is regarded as more advantageous in terms...... of operational flexibility, as more than one VSC station controls the DC link voltage of the MTDC system. This model enables the study of the effects of DC droop control on the power flows of the combined AC/DC system for steady state studies after VSC station outages or transient conditions without needing...... to use its complete dynamic model. Further, the proposed approach can be extended to include multiple AC and DC grids for combined AC/DC power flow analysis. The algorithm is implemented by modifying the MATPOWER based MATACDC program and the results shows that the algorithm works efficiently....

  4. Energy Factor and Mathematical Modeling for Power DC/DC Converters

    Institute of Scientific and Technical Information of China (English)

    Fang Lin LUO; Hong YE

    2004-01-01

    Mathematical modelling for power DC/DC converters is a historical problem accompanying DC/DC conversion technology since 1940's. The traditional mathematical modelling is not available for complex structure converters since the differential equation order increases very high. We have to search other way to establish mathematical modelling for power DC/DC converters. We have theoretically defined a new concept - Energy Factor (EF) in this paper and researched the relations between EF and the mathematical modelling for power DC/DC converters. EF is a new concept in power DC/DC conversion technology, which thoroughly differs from the traditional concepts such as power factor (PF), power transfer efficiency (η), total harmonic distortion (THD) and ripple factor (RF). EF and the subsequential EFv (and EFvD ) can illustrate the system stability, reference response and interference recovery. This investigation is very helpful for system design and DC/DC converters characteristics foreseeing. Two DC/DC converters: Buck converter and Super-Lift Luo-Converter as the samples are analysed in this paper to demonstrate the applications of EF, EFv (and EFvD), PE,SE, VE (and VED ), time constant τ and damping time constant τd .

  5. Silicon carbide DC-DC multilevel Cuk converter

    Science.gov (United States)

    Almalaq, Yasser; Alateeq, Ayoob; Matin, Mohammad

    2016-09-01

    In this paper, DC-DC multilevel cuk converter using silicon carbide (SiC) Components is presented. Cuk converter gives output voltage with negative polarity. This topology is useful for applications require high gain with limitation on duty cycle. The gain of the design can be enhanced by increasing the number of multiplier level (N). This relation between the gain and the number of levels is the major advantage of this multilevel cuk converter. In the proposed cuk converter, a single SiC MOSFET, 2N-1 SiC schottky diodes, 2N capacitors, 2 inductors, and single input voltage are used to supply a load with negative polarity. 300V input voltage, 50KHz switching frequency, and 75% duty cycle are the main parameters used in the design. The output parameters are 3KW power and -5.7 KV voltage. Because this design can be used in applications which temperature plays a critical role, the relation between increasing temperature and output voltage and power are tested. The design is simulated using LTspice software and the results are discussed.

  6. DC Magnetics Measurement System Design

    Science.gov (United States)

    Mastny, Timothy

    2012-01-01

    This report will detail the updates to the magnetics measurement system design and testing procedures that are required for performing static (DC) magnetics testing of future flight hardware. An older magnetics testing system had to be integrated with new procedures and hardware to meet the demands of future testing programs and accommodate an upcoming magnetics tests. The next test will be for the Geostationary Operational Environmental Satellite R-Series (GOES-R), which will verify that the SAFT Battery component meets its specifications for magnetic cleanliness. The satellite is scheduled to launch in 2015 with magnetics testing to be completed on the battery in November 2012.

  7. Linking DC together with TRSL

    DEFF Research Database (Denmark)

    Haxthausen, Anne; Yong, Xia

    1999-01-01

    of constraints on the durations of states of the system, i.e. at a high level of abstraction.However, as a state-based logic, it lacks the ability to specifysequential programs and communicating concurrent processes at a concrete level. The Timed RAISE Specification Language (TRSL) [XG99] has this ability...... (parts of) the history of the observables of the system,and then define a satisfaction relation in terms of behaviours. DC has previously been linked together with subsets of other event-based process algebra languages, but using another approach:the event-based languages were given a denotational...

  8. Power factor controller used as DC-DC converter for photovoltaic sources

    Energy Technology Data Exchange (ETDEWEB)

    Mukerjee, A.K.; Dasgupta, Nivedita [Centre for Energy Studies, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016 (India)

    2008-06-15

    An active power factor controller (PFC) integrated circuit, normally used in AC circuits, has been used for DC-to-DC boost conversion with a stable output voltage for a variable DC input voltage as obtained from photovoltaic (PV) sources. The circuit described here uses a power factor controller MC 34262 to give approximately 400 V{sub DC} output for an input variation from 90 to 280 V{sub DC}. The maximum efficiency achieved was 98% at 450 W. Comparisons between AC and DC operations have been made. (author)

  9. Chaos analysis and chaotic EMI suppression of DC-DC converters

    CERN Document Server

    Zhang, Bo

    2014-01-01

    Introduces chaos theory, its analytical methods and the means to apply chaos to the switching power supply design DC-DC converters are typical switching systems which have plenty of nonlinear behaviors, such as bifurcation and chaos. The nonlinear behaviors of DC-DC converters have been studied heavily over the past 20 years, yet researchers are still unsure of the practical application of bifurcations and chaos in switching converters. The electromagnetic interference (EMI), which resulted from the high rates of changes of voltage and current, has become a major design criterion in DC-DC co

  10. Elimination of output voltage oscillations in DC-DC converter using PWM with PI controller

    Directory of Open Access Journals (Sweden)

    Sreenivasappa Veeranna Bhupasandra

    2010-01-01

    Full Text Available In this paper the SIMULINK model of a PWM controlled DC-DC converter is modeled using switching function concept to control the speed of the DC motor. The presence of the voltage oscillation cycles due to higher switching frequency in the DC-DC converter is identified. The effect of these oscillations on the output voltage of the converter, Armature current, Developed torque and Speed of the DC motor is analyzed. In order to minimize the oscillation cycles the PI controller is proposed in the PWM controller.

  11. Hierarchical Velocity Control Based on Differential Flatness for a DC/DC Buck Converter-DC Motor System

    Directory of Open Access Journals (Sweden)

    R. Silva-Ortigoza

    2014-01-01

    Full Text Available This paper presents a hierarchical controller that carries out the angular velocity trajectory tracking task for a DC motor driven by a DC/DC Buck converter. The high level control is related to the DC motor and the low level control is dedicated to the DC/DC Buck converter; both controls are designed via differential flatness. The high level control provides a desired voltage profile for the DC motor to achieve the tracking of a desired angular velocity trajectory. Then, a low level control is designed to ensure that the output voltage of the DC/DC Buck converter tracks the voltage profile imposed by the high level control. In order to experimentally verify the hierarchical controller performance, a DS1104 electronic board from dSPACE and Matlab-Simulink are used. The switched implementation of the hierarchical average controller is accomplished by means of pulse width modulation. Experimental results of the hierarchical controller for the velocity trajectory tracking task show good performance and robustness against the uncertainties associated with different system parameters.

  12. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC derived-exosomes: results of thefirst phase I clinical trial

    Directory of Open Access Journals (Sweden)

    Piperno Sophie

    2005-03-01

    Full Text Available Abstract Background DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. Patients and methods Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules or peptides (10 versus 100 μg/ml were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. Results The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. Conclusion The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.

  13. DC operating points of transistor circuits

    Science.gov (United States)

    Trajkovic, Ljiljana

    Finding a circuit's dc operating points is an essential step in its design and involves solving systems of nonlinear algebraic equations. Of particular research and practical interests are dc analysis and simulation of electronic circuits consisting of bipolar junction and field-effect transistors (BJTs and FETs), which are building blocks of modern electronic circuits. In this paper, we survey main theoretical results related to dc operating points of transistor circuits and discuss numerical methods for their calculation.

  14. Control of Parallel DC/DC Converters in DC Microgrid%直流微网中平行DC/DC变换器的控制

    Institute of Scientific and Technical Information of China (English)

    叶友泉; 杨冠鲁

    2016-01-01

    提出以多墙体光伏为研究对象的光伏直流微网系统。将在逆变器并联控制中广泛使用的下垂控制策略应用到平行DC/DC变换器的控制中,与电压、电流环构成三闭环控制,从而抑制平行DC/DC变换器之间的环流。通过Simulink 仿真分析,该方法能够实现直流母线电压的稳定及有效抑制各平行DC/DC变换器之间的环流。最后,在实验室搭建实验平台,验证该控制策略的可行性。%This article proposes a photovoltaic ( PV) DC microgrid system which employs multi-wall PV. In the DC microgrid, the droop control strategy widely used in parallel control of inverter is adopted for the control of parallel DC/DC converters, forming a triple-loop control together with voltage and current loops, which restrains the loop current between parallel DC/DC converters. Simulink simulation shows that, stable DC bus voltage and effective control over the loop current among parallel DC / DC converters can be achieved by this way. In the end, an experimental platform is built in the lab to verify the feasibility of this control strategy.

  15. How Much DC Power is Necessary

    Science.gov (United States)

    2010-04-01

    must transform essentially all of the available AC power to DC, including all of the power for the ship propulsion drive. This approach by the...in Fig. 1 convert the AC source power to DC and energize the associated DC busses. At the power levels anticipated, i.e., for ship propulsion load...for a ship propulsion application. We begin by assuming that the variable frequency power electronics associated with the rotor will only deliver

  16. Energy Evaluation for DC/DC Converters in DC-Based Wind Farms

    Energy Technology Data Exchange (ETDEWEB)

    Max, Lena

    2007-02-15

    In this thesis the suitability of three topologies for DC/DC converters in a DC wind farm grid is investigated from an energy efficiency and energy production cost point of view. The three selected topologies are the fullbridge converter, the single active bridge converter and the series parallel resonant converter. The losses are calculated for all three topologies as a function of the wind speed considering the losses in the semiconductor components and in the transformer. To obtain the average losses, the losses for each converter are integrated over the wind distribution for different average wind speeds. It is found that the resonant converter has the lowest losses of the three types for the DC wind farm application with power losses of about 2.0 - 2.5 % of the input power and the fullbridge converter has slightly higher losses with 2.3 - 3.5 % losses depending on the position in the wind turbine grid. The single active bridge converter has considerably higher losses than the other two topologies with 3.5 - 5.0 % losses. It is shown that the variable operating conditions create problems for all three converters, and as mentioned the single active bridge converter is most affected by the wide range of operation conditions. When comparing the resonant converter and the fullbridge converter, the fullbridge converter has a smaller transformer as well as lower peak current and peak voltage, but also a higher number of diode modules in the output bridge. Comparing the contribution to the energy production cost for the converters, the topology with the lowest contribution varies between the positions in the wind turbine grid. For some positions, the cost of the higher losses for the fullbridge converter are compensated by lower investment cost for the fullbridge converter compared to the resonant converter. Considering the resonant capacitor, the higher peak voltage and the variable frequency control for the resonant converter, the fullbridge converter is here found

  17. Zero-voltage switching technique in dc/dc converters

    Science.gov (United States)

    Liu, Kwang-Hwa; Lee, Fred C. Y.

    1990-07-01

    A novel resonant switch operating under the principle of zero-voltage switching is presented. In contrast to the zero-current switching, this technique eliminates the switching loss and dv/dt noise due to the discharging of MOSFET junction capacitances and the reverse recovery of diodes, and enables the converters to operate at high frequencies. A dc analysis of the converter is carried out. The duality relationship between the zero-current switching technique and the zero-voltage switching technique is derived. The two techniques are compared using an example showing the duality between a current-mode quasi-resonant Buck converter and a voltage-mode quasi-resonant boost converter. A 5-MHz 50 V to 5 V flyback converter employing the zero-voltage switching technique has been implemented. The circuit contains the smallest number of components possible, and yet maintains high efficiency at high switching frequency.

  18. SIMPLIFIED APPROACHES FOR CONTROLLING DC-DC POWER CONVERTERS

    Directory of Open Access Journals (Sweden)

    M. M. ABDEL AZIZ

    2012-02-01

    Full Text Available This paper represents the design procedures of different compensation schemes for voltage mode controlled (VMC dc–dc switching converters. Proportional integral derivative (PID controllers, Fuzzy logic controllers (FLC, parallel combination of PID and FLC, and FLC tuned by PI controller have been investigated. MATLAB software is used to depict the buck converter performance with each compensator type when it is electrically simulated, and analytically modeled using its equivalent transfer function (TF. The comparative study Resultsemphasize that FLC tuned by PI controller is superior to the other control strategies because of fast transient response, minimum steady state error and good disturbance rejection under various variations of the operating conditions. Hence, it achieves the most tightly output voltage regulation.

  19. Teaching about operation of brushless DC motors

    OpenAIRE

    Čufar, Aleksandra

    2013-01-01

    Brush DC motor is being replaced by brushless DC motors on every area of application. My diploma thesis is a presentation of brushless DC motor, how it works and its application. Within first part we describe various electric motors and their application. There are several types of electric motors division. Last to be added is a brushless motor. Within second part of thesis we look into a brushless DC motor, how it works, its application and control. In the third part of thesis we construct a...

  20. The good routing of a non-insulated DC/DC converter; Bien router un convertisseur DC/DC non-isole

    Energy Technology Data Exchange (ETDEWEB)

    Lenoir, E.

    2001-03-01

    DC to DC converters are important sources of magnetic and electric fields with frequencies that can exceed 100 MHz. Thus, their positioning on a circuit board is of prime importance to minimize the magnetic and capacitive couplings with other parts and components of the circuit. This article summarizes the important rules to follow for a good routing of non-insulated switching DC/DC converters: taking the ohmic voltage drops into consideration, managing the MOSFET commutation, limiting the current loop disturbances, correct routing of power tracks. (J.S.)

  1. Drilling history core hole DC-8

    Energy Technology Data Exchange (ETDEWEB)

    1978-10-01

    Core hole DC-8 was completed in August, 1978 by Boyles Brothers Drilling Company, Spokane, Washington, under subcontract to Fenix and Scission, Inc. The hole was cored for the US Department of Energy and the Rockwell Hanford Operations' Basalt Waste Isolation Program. Fenix and Scisson, Inc. furnished the engineering, daily supervision of the core drilling activities, and geologic core logging for hole DC-8. Core hole DC-8 is located on the Hanford Site near the Wye Barricade and 50 feet northwest of rotary hole DC-7. The Hanford Site vation coordinates for DC-8 are North 14,955.94 feet and West 14,861.92 coordinates for DC-8 are North 14,955.94 feet and West 14,861.92 mean sea level. The purpose of core hole DC-8 was to core drill vertically through the basalt and interbed units for stratigraphic depth determination and core collection, and to provide a borehole for hydrologic testing and cross-hole seismic shear and pressure wave velocity studies with rotary hole DC-7. The total depth of core hole DC-8 was 4100.5 feet. Core recovery exceeded 97 percent of the total footage cored.

  2. DC-SIGN:Binding receptor for HCV?

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua Feng; Quan-Chu Wang; Qing-He Nie; Zhan-Sheng Jia; Yong-Xin Zhou

    2004-01-01

    DC-SIGN, a dendritic Cell-specific adhesion receptor and a type Ⅱ transmembrane mannose-binding C-type lectin, is very important in the function of DC, both in mediating naive T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by viral and bacterial pathogens including Human Immunodeficiency Virus (HIV), HCV, Ebola Virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis,by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropropriate entry receptors. Recent work showed that DC-SIGN are highaffinity binding receptors for HCV. Besides playing a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental for the interaction of DC with T cells during antigen presentation. The clinical strategies that target DCSIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.

  3. Modular Power System Configured with Standard Product Hybrid DC-DC Converters Project

    Data.gov (United States)

    National Aeronautics and Space Administration — VPT proposes an innovative concept whereby complex NASA space power electronic systems can be configured using a small number of qualified hybrid DC-DC converter and...

  4. Improved Control Strategy for T-type Isolated DC/DC Converters

    DEFF Research Database (Denmark)

    Liu, Dong; Deng, Fujin; Wang, Yanbo

    2017-01-01

    T-type isolated DC/DC converters have recently attracted attention due to their numerous advantages, including few components, low cost, and symmetrical operation of transformers. This study proposes an improved control strategy for increasing the efficiency of T-type isolated DC/DC converters....... Under the proposed strategy, the primary circulating current flows through the auxiliary switches (metal–oxide–semiconductor field-effect transistors) instead of their body diodes in free-wheeling periods. Such feature can reduce conduction losses, thereby improving the efficiency of T-type isolated DC....../DC converters. The operation principles and performances of T-type isolated DC/DC converters under the proposed control strategy are analyzed in detail and verified through the simulation and experimental results....

  5. Development of a DC-DC conversion powering scheme for the CMS Phase-1 pixel upgrade

    Science.gov (United States)

    Feld, L.; Fimmers, C.; Karpinski, W.; Klein, K.; Lipinski, M.; Preuten, M.; Rauch, M.; Rittich, D.; Sammet, J.; Wlochal, M.

    2014-01-01

    A novel powering scheme based on the DC-DC conversion technique will be exploited to power the CMS Phase-1 pixel detector. DC-DC buck converters for the CMS pixel project have been developed, based on the AMIS5 ASIC designed by CERN. The powering system of the Phase-1 pixel detector is described and the performance of the converter prototypes is detailed, including power efficiency, stability of the output voltage, shielding, and thermal management. Results from a test of the magnetic field tolerance of the DC-DC converters are reported. System tests with pixel modules using many components of the future pixel barrel system are summarized. Finally first impressions from a pre-series of 200 DC-DC converters are presented.

  6. Wide Temperature Range DC-DC Boost Converters for Command/Control/Drive Electronics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We shall develop wide temperature range DC-DC boost converters that can be fabricated using commercial CMOS foundries. The boost converters will increase the low...

  7. Digitally intensive DC-DC converter for extreme space environments Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Space Micro –Arizona State University (ASU) team will develop an all-digitally controlled, wide temperature range point-of-load switch-mode DC-DC regulator...

  8. DIAGNOSTIC/PROGNOSTIC EXPERIMENTS FOR CAPACITOR DEGRADATION AND HEALTH MONITORING IN DC-DC CONVERTERS

    Data.gov (United States)

    National Aeronautics and Space Administration — Studying and analyzing the ageing mechanisms of electronic components avionics in systems such as the GPS and INAV are of critical importance. In DC-DC power...

  9. Decentralized Nonlinear Controller Based SiC Parallel DC-DC Converter Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal is aimed at demonstrating the feasibility of a Decentralized Control based SiC Parallel DC-DC Converter Unit (DDCU) with targeted application for...

  10. Development of a DC-DC conversion powering scheme for the CMS Phase-1 pixel upgrade

    CERN Document Server

    Feld, Lutz Werner; Karpinski, Waclaw; Klein, Katja; Lipinski, Martin; Preuten, Marius; Max Rauch; Rittich, David Michael; Sammet, Jan Domenik; Wlochal, Michael

    2014-01-01

    A novel powering scheme based on the DC-DC conversion technique will be exploited to power the CMS Phase-1 pixel detector. DC-DC buck converters for the CMS pixel project have been developed, based on the AMIS5 ASIC designed by CERN. The powering system of the Phase-1 pixel detector is described and the performance of the converter prototypes is detailed, including power efficiency, stability of the output voltage, shielding, and thermal management. Results from a test of the magnetic field tolerance of the DC-DC converters are reported. System tests with pixel modules using many components of the future pixel barrel system are summarized. Finally first impressions from a pre-series of 200 DC-DC converters are presented.

  11. Hybrid-Circuit Module For Dc-To-Dc Power Converter

    Science.gov (United States)

    Vorperian, Vatche; Detwiler, Robert; Karmon, Dan

    1996-01-01

    Power hybrid module is general-purpose power-switching module providing flexibility in design and application. Complete dc-to-dc power converter constructed by adding input/output filters and feedback circuitry to module to suit specific application.

  12. High Efficiency Interleaved Active Clamped Dc-Dc Converter with Fuel Cell for High Voltage Applications

    Directory of Open Access Journals (Sweden)

    Sona P

    2014-02-01

    Full Text Available A high efficiency interleaved ZVS active clamped current fed dc-dc converter is proposed in this paper specially used for fuel cell applications. As the fuel cell output is very low we are in need of a step up dc-dc converter. Here a current fed dc-dc converter is used. Two current fed dc-dc converters are interleaved by connecting their inputs in parallel and outputs in series. With this proposed methodology input current ripples in the fuel cell stacks can be reduced and a regulated output voltage ripples can be obtained. The active clamping circuit used in this model absorbs the turn off voltage spikes hence low voltage devices with low on state resistance can be used.Voltage doubler circuits will give double the output voltage than normal with smaller transformer turns ratio and flexibility. The proposed method is simulated in MATLAB for verifying the accuracy of the proposed design.

  13. Effect of Antioxidants on DC Tree and Grounded DC Tree in XLPE

    Science.gov (United States)

    Kawanami, Hiroshi; Komatsu, Isao; Sekii, Yasuo; Saito, Mitsugu; Sugi, Kazuyuki

    To study the effects of antioxidants on the initiation of the DC tree and the grounded DC tree, experiments were conducted using XLPE specimens containing phenolic and sulfur type antioxidants. Experimental results showed that sulfur type antioxidants in XLPE have the effect of increasing inception voltages of both the DC tree and the grounded DC tree. Based on results of those experiments, the mechanism of increase in the inception voltage of the DC tree and the grounded DC tree by antioxidants was examined along with the mechanism of polarity effects on those trees. Results showed a promotional effect of charge injection from a needle electrode by antioxidants, which are responsible for the increased inception voltages of the DC tree. Charge trapping by antioxidants explains the increase of inception voltages of the grounded DC tree.

  14. Digitally intensive DC-DC converter for extreme space environments Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Space Micro-Arizona State University (ASU) team will develop an all-digitally controlled, wide temperature range point-of-load switch-mode DC-DC regulator core...

  15. 76 FR 52225 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-08-22

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION... ADs (b) None. Applicability (c) This AD applies to The Boeing Company Model DC-9-81 (MD-81),...

  16. Studies of Interleaved DC-DC Boost Converters with Coupled Inductors

    Science.gov (United States)

    2011-04-01

    power density requirements, interleaved buck and boost converters have been studied in recent years for their potential to improve power converter ...duty ratio of switch S1. Figure 1: Conventional DC-DC Boost Converter Topology (1) Vout/Vin...interleaved DC-DC boost converters with coupled inductors. Included are discussions on a 10kW prototype, a 2kW high temperature prototype, and two 2kW

  17. A Family of Four Quadrant DC/DC Converters with Reduced Number of Components

    DEFF Research Database (Denmark)

    Mostaan, Ali; Soltani, Mohsen

    2015-01-01

    A family of four quadrant DC/DC converters is presented in this paper. Compare with existing four quadrant DC/DC converters that have been introduced in literature, the proposed converters have lower number of components. There are two bidirectional switches, two coupled inductors and one capacit...... effect is minimized in these converters. The effectiveness of the proposed converters is validated with simulation using MATLAB/SIMULINK....

  18. A Fixed-Frequency Bidirectional Resonant DC-DC Converter Suitable for Wide Voltage Gain Range

    DEFF Research Database (Denmark)

    Shen, Yanfeng; Wang, Huai; Al-Durra, Ahmed;

    2017-01-01

    This paper proposes a new bidirectional resonant dc-dc converter suitable for wide voltage gain range applications (e.g., energy storage systems). The proposed converter overcomes the narrow voltage gain range of conventional resonant DC-DC converters, and meanwhile achieves high efficiency...... and characteristics of the proposed converter are analyzed. Finally, a 1-kW converter prototype is built and the experimental results verify the theoretical analyses....

  19. 多路输出DC-DC电路设计%Design of multiple-output DC-DC circuit

    Institute of Scientific and Technical Information of China (English)

    郑晓庆; 杨日杰; 杨立永; 赵轩坤

    2012-01-01

    In order to convert a single input voltage to multiple outputs,a multiple-output DC-DC conversion circuit based LTC1624 and AMS1117 was designed in this paper. The circuit can convert the input voltage of 12V offered by a lead-acid battery to 5 V,3. 3 V and 1. 8 V as the output,and as tested,the output voltage of the DC-DC circuit designed in this paper is stable and reliable. Supplying power to different modules of a temperature measurement system, the circuit performance meets system requirements.%为了将单一输入电压变换为多路稳压输出,设计了基于LTC1624和AMS1117的DC-DC变换电路,该电路能够将铅酸蓄电池12V输入电压经过DC-DC变换后得到5V、3.3V和1.8V三路输出电压,经测试,设计的DC-DC电路输出电压稳定可靠.该电路应用于某温度测试系统的不同模块供电,电路性能满足系统要求.

  20. 雷公藤红素对 CD1+4单核细胞来源的树突细胞分化及成熟的影响%Effect of celastrol on differentiation and maturation of CD1+4 monocyte-derived dendritic cells

    Institute of Scientific and Technical Information of China (English)

    王瑄; 刘郁莹; 彭美玉; 薛振毅

    2014-01-01

    Objective To Make the differentiation and activation models of dendritic cells ( DCs ) and to investigate the effect of celastrol on the differentiation and maturation of human DCs in vitro .Methods Fresh human buffy coat was obtained , and peripheral blood mononuclear cells were isolated .Purified CDl4+monocytes were analyzed by FACSCalibur to confirm the purity of CD1+4 cells.The purified CD1+4 cells were cultured in complete 1640 medium supplemented with GM-CSF and IL-4 for 5 days and 7 days.For DC maturation, cells were stimulated with 5?g/mL lipopolysaccharide (LPS) at day 5.The control group was not added celastrol , but the celastrol group was added 10 and 20 nM celastrol, respectively. Then immature DCs ( iDC ) and mature DCs ( mDC ) were collected to detect the mean fluorescent intensity ( MFI ) of CD80 , CD83 , CD86 , HLA-DR and the absorb capacity of FITC-dextran by flow cytometry .Results Compared with the control group, the MFI of CD80 , CD83 , CD86 and HLA-DR of iDC and mDC in the celastrol group was lower , and the treat-ment of 20 nM was lower than the treatment of 10 nM, all P<0.05.The MFI of FITC-dextran in the negative control group (10.1 ±2.1) was the lowest, and was the highest in control group (243.7 ±31.3);in addition, the MFI of FITC-dextran in the 20 nM celastrol group (72.4 ±10.2) was lower than that of the 10 nM celastrol group (186.3 ±22.6), all P<0.05.Conclusions Celastrol inhibits CD1+4 monocytes differentiating into DCs , further inhibits phenotypic maturation of LPS-induced DCs , and suppresses the antigen-presenting function of iDC .%目的:制作免疫树突细胞( DC)分化和激活模型,观察雷公藤红素对人DC体外分化和成熟的影响。方法采集浓缩人白细胞,淋巴细胞分离液分离单个核细胞,利用免疫磁珠法分离CD1+4细胞,流式细胞分选仪确认分选纯度。将分选的CD1+4细胞在含IL-4和GM-CSF的完全1640培养基中分别培养5 d(分化)和7 d(5 d

  1. Extra-High-Voltage DC-DC Boost Converters Topology with Simple Control Strategy

    Directory of Open Access Journals (Sweden)

    K. Rajambal

    2009-01-01

    Full Text Available This paper presents the topology of operating DC-DC buck converter in boost mode for extra-high-voltage applications. Traditional DC-DC boost converters are used in high-voltage applications, but they are not economical due to the limited output voltage, efficiency and they require two sensors with complex control algorithm. Moreover, due to the effect of parasitic elements the output voltage and power transfer efficiency of DC-DC converters are limited. These limitations are overcome by using the voltage lift technique, opens a good way to improve the performance characteristics of DC-DC converter. The technique is applied to DC-DC converter and a simplified control algorithm in this paper. The performance of the controller is studied for both line and load disturbances. These converters perform positive DC-DC voltage increasing conversion with high power density, high efficiency, low cost in simple structure, small ripples, and wide range of control. Simulation results along theoretical analysis are provided to verify its performance.

  2. Characterization of diode valve in medium voltage dc/dc converter for wind turbines

    DEFF Research Database (Denmark)

    Dincan, Catalin Gabriel; Kjær, Philip Carne

    2016-01-01

    This paper proposes a methodology for characterization of medium voltage (MV), medium frequency (MF) rectifier diode valve. The intended application is for 10MW dc/dc converters used in DC offshore wind turbines. Sensitivity to semiconductor component parameter variation, snubber component...

  3. Analysis of DC/DC Converter Efficiency for Energy Storage System Based on Bidirectional Fuel Cells

    DEFF Research Database (Denmark)

    Pittini, Riccardo; Zhang, Zhe; Andersen, Michael A. E.

    2013-01-01

    Renewable energy sources are fluctuating depending on the availability of the energy source. For this reason, energy storage is becoming more important and bidirectional fuel cells represent an attractive technology. Fuel cells require highcurrent low-voltage dc-dc or dc-ac converters as power...

  4. Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3- and alpha-(1-6-D-mannose specific plant lectins : Implication for microbicide development

    Directory of Open Access Journals (Sweden)

    Balzarini Jan

    2007-06-01

    Full Text Available Abstract Background Plant lectins such as Galanthus nivalis agglutinin (GNA and Hippeastrum hybrid agglutinin (HHA are natural proteins able to link mannose residues, and therefore inhibit HIV-target cell interactions. Plant lectins are candidate for microbicide development. Objective To evaluate the activity against HIV of the mannose-specific plant lectins HHA and GNA at the cellular membrane level of epithelial cells and monocyte-derived dendritic cells (MDDC, two potential target cells of HIV at the genital mucosal level. Methods The inhibitory effects of HHA and GNA were evaluated on HIV adsorption to genital epithelial HEC-1A cell line, on HIV transcytosis throughout a monolayer of polarized epithelial HEC-1A cells, on HIV adsorption to MDDC and on transfer of HIV from MDDC to autologous T lymphocytes. Results HHA faintly inhibited attachment to HEC-1A cells of the R5-tropic HIV-1Ba-L strain, in a dose-dependent manner, whereas GNA moderately inhibited HIV adsorption in the same context, but only at high drug doses. Only HHA, but not GNA, inhibited HIV-1JR-CSF transcytosis in a dose-dependent manner. By confocal microscopy, HHA, but not GNA, was adsorbed at the epithelial cell surface, suggesting that HHA interacts specifically with receptors mediating HIV-1 transcytosis. Both plant lectins partially inhibited HIV attachment to MDDC. HHA inhibited more efficiently the transfer of HIV from MDDC to T cell, than GNA. Both HHA and GNA lacked toxicity below 200 μg/ml irrespective the cellular system used and do not disturb the monolayer integrity of epithelial cells. Conclusion These observations demonstrate higher inhibitory activities of the lectin plant HHA by comparison to GNA, on HIV adsorption to HEC-1A cell line, HIV transcytosis through HEC-1A cell line monolayer, HIV adsorption to MDDC and HIV transfer from MDDC to T cells, highlighting the potential interest of HHA as effective microbicide against HIV.

  5. Startup Capability of Boost DC/DC Converter%Boost DC/DC的低压启动能力

    Institute of Scientific and Technical Information of China (English)

    向乾尹; 冯全源

    2011-01-01

    An analytical model was proposed to calculate the minimum startup voltage of a boost DC/ DC converter under a constant current load. The factors, such as the current load, the parasitic parameters, the saturation current and on-resistance of the power switch, the switching frequency, and the minimum startup voltage, etc. , which affect the startup capability of the boost DC/DC converter were analyzed with a steady-state analysis method. The model was applied to the design of a boost DC/ DC converter with a 0. 6 jxm CMOS process, and the maximum error of the minimum startup voltage calculated by the proposed model was 4. 5% compared with that by the HSPICE simulator.%为了准确预测Boost DC/DC低压启动能力,采用稳态分析方法,分析了电流负载、寄生参数、功率开关饱和电流及导通阻抗、开关频率、启动电路最低工作电压等因素对Boost DC/DC低压启动能力的影响,提出了预测Boost DC/DC恒流负载下最小启动电压的解析模型.将该模型应用于采用0.6 μm CMOS工艺的Boost DC/DC设计中,模型计算结果相对HSPICE仿真结果的最大误差为4.5%.本模型可推广至恒定电阻负载的情况.

  6. DC/DC converters for integration of double-layer condensers in onboard power supply; DC/DC-Wandler zur Einbindung von Doppelschichtkondensatoren in das Fahrzeugenergiebordnetz

    Energy Technology Data Exchange (ETDEWEB)

    Polenov, Dieter

    2010-01-15

    The paper discusses DC/DC converters for integration of double layer condensers into the onboard power system. First, requirements on DC/DC converters are listed and compared on the basis of three exemplary applications. A DC/DC converter concept is developed for decoupling transient high-power loads like electric steering systems. Three different topologies are compared using a specially developed method in order to find the best solution for the given application. In order to establish adequate criteria for selecting the switching frequency and inductivities of storage throttles, the influence of the trottle power change on the switching characteristics of the MOSFETs and on certain ranges of EMP interference emissions is investigated. As methods of optimising the operation of the synchronous rectifiers, parallel connection of Schottky diodes and synchronous rectifiers as well as the variation of the shut-off dead times of synchronous rectifiers were investigated. Further, a concept for converter control was developed in consideration of the intended application and topology. Finally, selected aspects for implementation of the DC/DC converter concept are presented as well as the results of experimental investigations.

  7. DC KIDS COUNT e-Databook Indicators

    Science.gov (United States)

    DC Action for Children, 2012

    2012-01-01

    This report presents indicators that are included in DC Action for Children's 2012 KIDS COUNT e-databook, their definitions and sources and the rationale for their selection. The indicators for DC KIDS COUNT represent a mix of traditional KIDS COUNT indicators of child well-being, such as the number of children living in poverty, and indicators of…

  8. DC-based immunotherapy for hematological malignancies.

    Science.gov (United States)

    Kitawaki, Toshio

    2014-02-01

    Great advances have been made in the treatment of hematological malignancies, but achieving a definitive cure remains an elusive goal for the majority of patients. Antigen-specific tumor immunotherapy has the potential to improve clinical outcome in patients with such diseases by eradicating chemotherapy-resistant tumor cell clones without damaging normal tissues. Dendritic cells (DCs) serve as an essential link between the innate and the adaptive immune systems, acting as key controllers of antigen-specific T cell responses. Molecular identification of tumor-specific antigens recognized by T lymphocytes and technical advances in ex vivo generation of human DCs has enabled us to develop DC-based tumor immunotherapies (also called "DC vaccines"). To date, a large number of clinical trials of DC vaccines have been conducted for a variety of tumors, including hematological malignancies. Overall, these trials have demonstrated that DC vaccines have excellent safety profiles, moderate immunological activity, and mild clinical efficacy. To establish a role for DC vaccines in the treatment of hematological malignancies, we need both to define patient populations that can obtain clinical benefit from DC vaccines and to develop combination therapies that augment clinical efficacy of DC vaccines. In this review, I will describe current status of DC-based immunotherapy for hematological malignancies, and discuss future perspectives in this field.

  9. ALA 2010: Where to Eat in DC

    Science.gov (United States)

    Library Journal, 2010

    2010-01-01

    As host to visitors and transplants from around the world, Washington, DC, benefits from the constant infusion of different cultures. Although most neighborhoods lack a unified culinary flavor, make no mistake: DC is a city of distinctive areas, each with its own style, ensuring that hungry American Library Association (ALA) 2010 conference…

  10. Modelling of flow phenomena during DC casting

    NARCIS (Netherlands)

    Zuidema, J.

    2005-01-01

    Modelling of Flow Phenomena during DC Casting Jan Zuidema The production of aluminium ingots, by semi-continuous casting, is a complex process. DC Casting stands for direct chill casting. During this process liquid aluminium transforms to solid aluminium while cooling down. This is not an instanta

  11. Modelling of flow phenomena during DC casting

    NARCIS (Netherlands)

    Zuidema, J.

    2005-01-01

    Modelling of Flow Phenomena during DC Casting Jan Zuidema The production of aluminium ingots, by semi-continuous casting, is a complex process. DC Casting stands for direct chill casting. During this process liquid aluminium transforms to solid aluminium while cooling down. This is not an

  12. Close-Range Gunfire around DC Schools

    Science.gov (United States)

    Bieler, Sam; La Vigne, Nancy

    2014-01-01

    This report examines the incidence of gunfire as measured by gunshot detection technology using data from the 2011-2012 school year. It finds that a disproportionate volume of gunfire happened near a small share of DC schools. About half of DC schools covered by gunshot detection sensors are in close proximity to gunfire, and four schools were…

  13. Electronic DC transformer with high power density

    NARCIS (Netherlands)

    Pavlovský, M.

    2006-01-01

    This thesis is concerned with the possibilities of increasing the power density of high-power dc-dc converters with galvanic isolation. Three cornerstones for reaching high power densities are identified as: size reduction of passive components, reduction of losses particularly in active components

  14. DC-based magnetic field controller

    Energy Technology Data Exchange (ETDEWEB)

    Kotter, Dale K. (Shelley, ID); Rankin, Richard A. (Ammon, ID); Morgan, John P,. (Idaho Falls, ID)

    1994-01-01

    A magnetic field controller for laboratory devices and in particular to dc operated magnetic field controllers for mass spectrometers, comprising a dc power supply in combination with improvements to a hall probe subsystem, display subsystem, preamplifier, field control subsystem, and an output stage.

  15. DC-based magnetic field controller

    Energy Technology Data Exchange (ETDEWEB)

    Kotter, D.K.; Rankin, R.A.; Morgan, J.P.

    1994-05-31

    A magnetic field controller is described for laboratory devices and in particular to dc operated magnetic field controllers for mass spectrometers, comprising a dc power supply in combination with improvements to a Hall probe subsystem, display subsystem, preamplifier, field control subsystem, and an output stage. 1 fig.

  16. A Component-Reduced Zero-Voltage Switching Three-Level DC-DC Converter

    DEFF Research Database (Denmark)

    Qin, Zian; Pang, Ying; Wang, Huai;

    2016-01-01

    The basic Zero-Voltage Switching (ZVS) three-level DC-DC converter has one clamping capacitor to realize the ZVS of the switches, and two clamping diodes to clamp the voltage of the clamping capacitor. In order to reduce the reverse recovery loss of the diode as well as its cost, this paper...... proposes to remove one of the clamping diodes in basic ZVS three-level DC-DC converter. With less components, the proposed converter can still have a stable clamping capacitor voltage, which is clamped at half of the dc link voltage. Moreover, the ZVS performance will be influenced by removing the clamping...

  17. Drilling history core hole DC-4

    Energy Technology Data Exchange (ETDEWEB)

    1978-12-01

    Core hole DC-4 was completed at a depth of 3998 feet in December, 1978 by Boyles Brothers Drilling Company, Spokane, Washington, under subcontract to Fenix and Scission, Inc. The hole was cored for the US Department of Energy and the Rockwell Hanford Operations' Basalt Waste Isolation Program. Fenix and Sicsson, Inc. furnished the engineering, daily supervision of the cable tool and core drilling activities, and geological core logging for DC-4. Core hole DC-4 is located on the Hanford Site about 3 miles east of the Yakima Barricade and approximately 103 feet southwest of rotary hole DC-5, which was completed to 3990 feet in February, 1978. Hanford Site coordinates reported for hole DC-4 are north 49,385.62 feet and west 85,207.63 feet, and Washington State coordinates are north 454,468.73 feet and east 2,209,990.87 feet. No elevation survey is available for hole DC-4, but it is approximately 745 feet above mean sea level based upon the survey of hole DC-5, which has a reported elevation of 745.16 feet on the top of the 3-inch flange. The purpose of core hole DC-4 was to core drill vertically through the basalt and interbed units for stratigraphic depth determination and core collection, and to provide a borehole for hydrologic testing, cross-hole seismic shear, and pressure wave velocity studies with rotary hole DC-5. Hole DC-4 was drilled through the overburden into basalt bedrock by cable tool methods (0-623 feet) and continuously cored through the final interval (623 to 3998 feet).Core recovery was 95.8 percent of the total footage cored.

  18. Controlling DC-DC converters by chaos-based pulse width modulation to reduce EMI

    Energy Technology Data Exchange (ETDEWEB)

    Li Hong [Department of Mathematics and Computer Science, FernUniversitaet in Hagen, 58084 Hagen (Germany)], E-mail: hong.li@FernUni-Hagen.de; Zhang Bo [School of Electric Power, South China University of Technology, Guangzhou (China); Li Zhong; Halang, Wolfgang A. [Department of Mathematics and Computer Science, FernUniversitaet in Hagen, 58084 Hagen (Germany); Chen Guanrong [Department of Electronic Engineering, City University of Hong Kong, Hong Kong (China)

    2009-11-15

    In this paper, periodic and chaotic behaviors of DC-DC converters under certain parametric conditions are simulated, experimentally verified, and analyzed. Motivated by the work of J.H.B. Deane and D.C. Hamill in 1996, where chaotic phenomena are useful in suppressing electromagnetic interference (EMI) by adjusting the parameters of the DC-DC converter and making it operate in chaos, a chaos-based pulse width modulation (CPWM) is proposed to distribute the harmonics of the DC-DC converters continuously and evenly over a wide frequency range, thereby reducing the EMI. The output waves and spectral properties of the EMI are simulated and analyzed as the carrier frequency or amplitude changes with regard to different chaotic maps. Simulation and experimental results are given to illustrate the effectiveness of the proposed CPWM, which provides a good example of applying chaos theory in engineering practice.

  19. Voltage Tracking of a DC-DC Flyback Converter Using Neural Network Control

    Directory of Open Access Journals (Sweden)

    Wahyu Mulyo Utomo

    2012-01-01

    Full Text Available This paper proposes a neural network control scheme of a DC-DC Flyback converter that will step up a 12V DC and applied it on brushless DC motor with 12 and 24V dc. In this technique, a back propagation learning algorithm is derived. The controller is designed to track the output voltage of the DC-DC converter and to improve performance of the Flyback converter during transient operations. Furthermore, to investigate the effectiveness of the proposed controller, some operations such as starting-up and reference voltage variations are verified. The numerical simulation results show that the proposed controller has a better performance compare to the conventional PI-Controller method.

  20. High Current Planar Magnetics for High Efficiency Bidirectional DC-DC Converters for Fuel Cell Applications

    DEFF Research Database (Denmark)

    Pittini, Riccardo; Zhang, Zhe; Andersen, Michael A. E.

    2014-01-01

    Efficiency is one of the main concerns during the design phase of switch mode power supply. Planar magnetics based on PCB windings have the potential to reduce the magnetic manufacturing cost however, one of their main drawbacks comes from their low filling factor and high stray capacitance....... This paper presents an analysis of different planar windings configurations focusing on dc and ac resistances in order to achieve highly efficiency in dc-dc converters. The analysis considers different copper thicknesses form 70 μm up to 1500 μm (extreme copper PCB) taking into account manufacturing...... complexity and challenges. The analysis is focused on a high current inductor for a dc-dc converter for fuel cell applications and it is based on FEM simulations. Analysis and results are verified on a 6 kW dc-dc isolated full bridge boost converter prototype based on fully planar magnetics achieving a peak...

  1. A high voltage ratio and low ripple interleaved DC-DC converter for fuel cell applications.

    Science.gov (United States)

    Chang, Long-Yi; Chao, Kuei-Hsiang; Chang, Tsang-Chih

    2012-01-01

    This paper proposes a high voltage ratio and low ripple interleaved boost DC-DC converter, which can be used to reduce the output voltage ripple. This converter transfers the low DC voltage of fuel cell to high DC voltage in DC link. The structure of the converter is parallel with two voltage-doubler boost converters by interleaving their output voltages to reduce the voltage ripple ratio. Besides, it can lower the current stress for the switches and inductors in the system. First, the PSIM software was used to establish a proton exchange membrane fuel cell and a converter circuit model. The simulated and measured results of the fuel cell output characteristic curve are made to verify the correctness of the established simulation model. In addition, some experimental results are made to validate the effectiveness in improving output voltage ripple of the proposed high voltage ratio interleaved boost DC-DC converters.

  2. Theory of multi-phase PWM DC/DC converter%多相PWM控制DC/DC变换器

    Institute of Scientific and Technical Information of China (English)

    陈小明

    2001-01-01

    @@ 概述 近年来,随着一些高性能CPU的出现,如Pentium 4、Athlon等,需要输出电压更小,更大电流的DC/DC变换器,对热性能、EMI及负载瞬变应答(Load Transient)的要求也不断提高.传统的单相DC/DC变换器日益显示出局限性.多相DC/DC变换器以其独特的性能,为高性能CPU电源的解决方案开辟的一条新路.

  3. Swarming Speed Control for DC Permanent Magnet Motor Drive via Pulse Width Modulation Technique and DC/DC Converter

    Directory of Open Access Journals (Sweden)

    A.S. Oshaba

    2013-05-01

    Full Text Available This study presents an approach for the speed control of a permanent magnet DC motor drive via Pulse Width Modulation (PWM technique and a DC/DC converter. The Particle Swarm Optimization (PSO technique is used to minimize a time domain objective function and obtain the optimal controller parameters. The performance of the proposed technique has been evaluated using various types of disturbances including load torque variations. Simulation results illustrate clearly the robustness of the controller and validity of the design technique for controlling the speed of permanent magnet motors.

  4. DC/DC开关变换器混沌现象研究综述%Summary of the Research on Chaos Phenomena of DC/DC Converter

    Institute of Scientific and Technical Information of China (English)

    蔚洋; 冯平

    2012-01-01

    DC/DC功率开关变换器是开关电源的核心部分,通过对其混沌现象的研究可以更加深刻地认识DC/DC变换器的本质,也会在将来基于混沌现象提出新的设计方法和控制策略,实现现有DC/DC变换器无法达到的性能.本文介绍了DC/DC变换器混沌现象的研究现状,对DC/DC变换器混沌现象的基本建模方法进行了综合对比分析,展望了DC/DC变换器混沌研究的发展和未来应用前景.%DC/DC power switch converter is the core part of switch power supply. Through the study of chaos phenomena, the essence of DC/DC converter can be more deeply understand, the new design methods and control strategies based on chaos phenomena will be put forward in the future, to achieve the existing DC/DC converter that cannot reach. This paper introduces the research status of the DC/DC converter chaos phenomena, makes comprehensive comparative analysis of the basic modeling method of DC/DC converter chaos phenomena, and looks to its development and future application prospect.

  5. Pulsed-DC DBD Plasma Actuators

    Science.gov (United States)

    Duong, Alan; McGowan, Ryan; Disser, Katherine; Corke, Thomas; Matlis, Eric

    2016-11-01

    A new powering system for dielectric barrier discharge (DBD) plasma actuators that utilizes a pulsed-DC waveform is presented. The plasma actuator arrangement is identical to most typical AC-DBD designs with staggered electrodes that are separated by a dielectric insulator. However instead of an AC voltage input to drive the actuator, the pulsed-DC utilizes a DC voltage source. The DC source is supplied to both electrodes, and remains constant in time for the exposed electrode. The DC source for the covered electrode is periodically grounded for very short instants and then allowed to rise to the source DC level. This process results in a plasma actuator body force that is significantly larger than that with an AC-DBD at the same voltages. The important characteristics used in optimizing the pulsed-DC plasma actuators are presented. Time-resolved velocity measurements near the actuator are further used to understand the underlying physics of its operation compared to the AC-DBD. Supported by NASA Glenn RC.

  6. Control and dynamic analysis of a parallel-connected single active bridge DC-DC converter for DC-grid wind farm application

    DEFF Research Database (Denmark)

    Park, Kiwoo; Chen, Zhe

    2015-01-01

    This study presents a control strategy and its dynamic analysis of a high-power dc-dc converter, which is constructed with the parallel-connected single active bridge (SAB) dc-dc converters for dc-grid wind farm applications. The structural and operational characteristics of the SAB dc-dc converter...... have several advantages for high-power applications, and the modular concept of the parallel-connected converter is highly beneficial especially for offshore wind farm applications in terms of maintenance cost and fault tolerance. To justify the feasibility of the parallel-connected SAB dc-dc converter...... for dc-grid wind farm applications, an input voltage control method based on the PI control will be introduced and the dynamics of the overall system will be analysed. The analysis results are to be verified by means of simulations and experiments....

  7. Expression of DC-SIGN and DC-SIGNRs in placentas of HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Komala Pillay

    2014-09-01

    Full Text Available Background. Human dendritic cell-specific intracellular adhesion molecule-3 (ICAM3-grabbing non-integrin (DC-SIGN is a mannose-binding lectin that initiates interaction between dendritic cells and resting T-lymphocytes. DC-SIGN is highly expressed in placental tissue on dendritic cells and Hofbauer cells, and it is suggested that HIV may become adsorbed to DC-SIGN on Hofbauer cells as part of the mechanism of mother-to-child HIV transmission. A possible mechanism of transfer of the virus from the Hofbauer cells to the fetus is the subsequent adsorption to DC-SIGN-related molecules (DC-SIGNRs, present on immediately adjacent capillary vascular endothelium. However, data on DC-SIGN and DC-SIGNR expression in the placenta are few.Methods. Forty term placentas from HIV-positive mothers and 21 term placentas from HIV-negative mothers underwent immunohistochemistry staining for DC-SIGN and DC-SIGNR expression. Five random sets of 10 villi were assessed, and the average number of positive cells were counted in each case. In addition, where possible, maternal and cord blood viral loads and maternal CD4+ counts were performed in the HIV-positive group only.Results. The median maternal CD4+ count was 377 cells/µl and 27% of participants had undetectable viral loads; the median detectable viral load was 3.72 log. Most (97% of the cord bloods tested in infants from HIV-positive mothers had lower than detectable viral loads. HIV-positive cases had significantly greater expression of both DC-SIGNRs (median values in HIV-positive cases, 14.5 positive cells/10 villi (pc/10villi, compared with 11 pc/10villi in HIV-negative cases, p=0.020 and DC-SIGN (median value in HIV-positive cases, 26.5 pc/10villi, compared with 23 pc/10villi in HIV-negative cases, p=0.037. DC-SIGNR expression was also noted in Hofbauer cells and decidual macrophages in addition to endothelium (reported currently. There was no difference in expression of DC-SIGN and DC-SIGNRs in patients

  8. Robust DC/DC converter control for polymer electrolyte membrane fuel cell application

    Science.gov (United States)

    Wang, Ya-Xiong; Yu, Duck-Hyun; Chen, Shi-An; Kim, Young-Bae

    2014-09-01

    This study investigates a robust controller in regulating the pulse width modulation (PWM) of a DC/DC converter for a polymer electrolyte membrane fuel cell (PEMFC) application. A significant variation in the output voltage of a PEMFC depends on the power requirement and prevents a PEMFC from directly connecting to a subsequent power bus. DC/DC converters are utilized to step-up or step-down voltage to match the subsequent power bus voltage. In this study, a full dynamic model, which includes a PEMFC and boost and buck DC/DC converters, is developed under MATLAB/Simulink environment for control. A robust PWM duty ratio control for the converters is designed using time delay control (TDC). This control enables state variables to accurately follow the dynamics of a reference model using time-delayed information of plant input and output information within a few sampling periods. To prove the superiority of the TDC performance, traditional proportional-integral control (PIC) and model predictive control (MPC) are designed and implemented, and the simulation results are compared. The efficacies of TDC for the PEMFC-fed PWM DC/DC converters are validated through experimental test results using a 100 W PEMFC as well as boost and buck DC/DC converters.

  9. High power density dc/dc converter: Selection of converter topology

    Science.gov (United States)

    Divan, Deepakraj M.

    1990-01-01

    The work involved in the identification and selection of a suitable converter topology is described. Three new dc/dc converter topologies are proposed: Phase-Shifted Single Active Bridge DC/DC Converter; Single Phase Dual Active Bridges DC/DC Converter; and Three Phase Dual Active Bridges DC/DC Converter (Topology C). The salient features of these topologies are: (1) All are minimal in structure, i.e., each consists of an input and output bridge, input and output filter and a transformer, all components essential for a high power dc/dc conversion process; (2) All devices of both the bridges can operate under near zero-voltage conditions, making possible a reduction of device switching losses and hence, an increase in switching frequency; (3) All circuits operate at a constant frequency, thus simplifying the task of the magnetic and filter elements; (4) Since, the leakage inductance of the transformer is used as the main current transfer element, problems associated with the diode reverse recovery are eliminated. Also, this mode of operation allows easy paralleling of multiple modules for extending the power capacity of the system; (5) All circuits are least sensitive to parasitic impedances, infact the parasitics are efficently utilized; and (6) The soft switching transitions, result in low electromagnetic interference. A detailed analysis of each topology was carried out. Based on the analysis, the various device and component ratings for each topology operating at an optimum point, and under the given specifications, are tabulated and discussed.

  10. Novel bidirectional DC-DC converters based on the three-state switching cell

    Science.gov (United States)

    da Silva Júnior, José Carlos; Robles Balestero, Juan Paulo; Lessa Tofoli, Fernando

    2016-05-01

    It is well known that there is an increasing demand for bidirectional DC-DC converters for applications that range from renewable energy sources to electric vehicles. Within this context, this work proposes novel DC-DC converter topologies that use the three-state switching cell (3SSC), whose well-known advantages over conventional existing structures are ability to operate at high current levels, while current sharing is maintained by a high frequency transformer; reduction of cost and dimensions of magnetics; improved distribution of losses, with consequent increase of global efficiency and reduction of cost associated to the need of semiconductors with lower current ratings. Three distinct topologies can be derived from the 3SSC: one DC-DC converter with reversible current characteristic able to operate in the first and second quadrants; one DC-DC converter with reversible voltage characteristic able to operate in the first and third quadrants and one DC-DC converter with reversible current and voltage characteristics able to operate in four quadrants. Only the topology with bidirectional current characteristic is analysed in detail in terms of the operating stages in both nonoverlapping and overlapping modes, while the design procedure of the power stage elements is obtained. In order to validate the theoretical assumptions, an experimental prototype is also implemented, so that relevant issues can be properly discussed.

  11. Studi Komparasi Fungsi Keanggotaan Fuzzy sebagai Kontroler Bidirectional DC-DC Converter pada Sistem Penyimpan Energi

    Directory of Open Access Journals (Sweden)

    Eka Prasetyono

    2015-09-01

    Full Text Available Bidirectional DC-DC converter is needed in the energy storage system. The converter topology used in this paper was a non-isolated bidirectional DC-DC buck-boost converter. This converter worked in two ways, which the charging mode stored energy into battery when load current was less than nominal main DC current (set point and discharging mode transferred energy from battery to the load when its current exceeded set point value. Both of these modes worked automatically according to the load current. The charging and discharging currents were controlled by fuzzy logic controller which was implemented on microcontroller ARM Cortex-M4F STM32F407VG. This paper compares two types of fuzzy membership function (triangular and sigmoid in controlling bidirectional DC-DC converter. The results showed that fuzzy logic controller with triangle membership function and sigmoid as control bidirectional DC-DC converter had no significant different response, both had an average error for charging and discharging process under 4% with ripple current on the main DC bus around 0.5%. The computing time of program for fuzzy logic controller with triangular membership functions had 19.01% faster than sigmoid, and fuzzy logic computation time on a microcontroller with hardware floating point was 60% faster than software floating point.

  12. Study on the Control Algorithm of Two-Stage DC-DC Converter for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Changhao Piao

    2014-01-01

    Full Text Available The fast response, high efficiency, and good reliability are very important characteristics to electric vehicles (EVs dc/dc converters. Two-stage dc-dc converter is a kind of dc-dc topologies that can offer those characteristics to EVs. Presently, nonlinear control is an active area of research in the field of the control algorithm of dc-dc converters. However, very few papers research on two-stage converter for EVs. In this paper, a fixed switching frequency sliding mode (FSFSM controller and double-integral sliding mode (DISM controller for two-stage dc-dc converter are proposed. And a conventional linear control (lag is chosen as the comparison. The performances of the proposed FSFSM controller are compared with those obtained by the lag controller. In consequence, the satisfactory simulation and experiment results show that the FSFSM controller is capable of offering good large-signal operations with fast dynamical responses to the converter. At last, some other simulation results are presented to prove that the DISM controller is a promising method for the converter to eliminate the steady-state error.

  13. Superconducting DC homopolar motors for ship propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Heiberger, M.; Reed, M.R.; Creedon, W.P.; O' Hea, B.J. [General Atomic (United States)

    2000-07-01

    Superconducting DC homopolar motors have undergone recent advances in technology, warranting serious consideration of their use for ship propulsion. Homopolar motor propulsion is now practical because of two key technology developments: cryogen-free superconducting refrigeration and high performance motor fiber brushes. These compact motors are ideal for podded applications, where reduced drag and fuel consumption are predicted. In addition, the simple DC motor controller is more efficient and reliable compared with AC motor controllers. Military ships also benefit from increased stealth implicit in homopolar DC excitation, which also allows the option for direct hull or pod mounting. (authors)

  14. DC-Compensated Current Transformer †

    Science.gov (United States)

    Ripka, Pavel; Draxler, Karel; Styblíková, Renata

    2016-01-01

    Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component. PMID:26805830

  15. A series array of dc SQUIDs

    Energy Technology Data Exchange (ETDEWEB)

    Welty, R.P. (Colorado Univ., Boulder, CO (United States). Dept. of Electrical Engineering); Martinis, J.M. (Geraghty and Miller, Inc., Reston, VA (United States))

    1991-03-01

    This paper reports on a series array of 100 dc SQUIDs using trilayer Nb-AlO{sub x}-Nb junctions. The SQUIDs are modulated with a common flux bias line and produce an output voltage swing of several millivolts across the array. The large output voltage will allow direct connection to room temperature electronics without the transformer coupling and resulting frequency limitations commonly associated with dc SQUID amplifiers. The authors measured a bandwidth of dc to at least 175 MHz for a 100-SQUID array. The series array will be used as the output stage for a multistage integrated SQUID amplifier.

  16. Constant switching frequency control-based linear-assisted DC/DC regulator for photovoltaic solar-powered facilities

    OpenAIRE

    Martínez García, Herminio; Grau Saldes, Antoni

    2015-01-01

    Hybrid DC-DC regulators or linear–assisted DC-DC regulators are structures that combine both a linear voltage regulator and a switching DC-DC converter. The main objective of this hybrid topology is to converge, in a single circuit topology, the best of both alternatives: One the one hand, obtaining small voltage output ripple, which is typical of linear regulator structures, and, on the other, achieving good energy efficiency, as in switching alternatives. While the linear regulator fixes th...

  17. LLC resonant half-bridge circuit design with DC-DC%LLC谐振半桥DC-DC电路设计

    Institute of Scientific and Technical Information of China (English)

    杨磊; 吴晓光; 羊彦

    2013-01-01

    LED drive power level after the DC-DC constant current circuit using LLC resonant half-bridge topology structure, and through the output current and voltage feedback loop to achieve constant current limiting function.LLC resonant half-bridge DC-DC constant current circuit power part comprises a resonant circuit and the output of the rectifier circuit, the control part chip power supply circuit, the control chip peripheral circuit, an output feedback loop, the test shows that the system has stable output can be good, long time working with high efficiency.%LED驱动电源的后级DC-DC恒流电路采用LLC谐振半桥的拓扑结构,并通过输出的电流电压双环反馈来实现恒流限压功能.LLC谐振半桥DC-DC恒流电路的功率部分包括了谐振电路和输出整流电路,控制部分有芯片供电电路、控制芯片外围电路、输出反馈回路等,经试验证明该系统输出稳定好,能够长时间高效工作.

  18. Determination of input/output characteristics of full-bridge AC/DC/DC converter for arc welding

    OpenAIRE

    Stefanov, Goce; Karadzinov, Ljupco; Sarac, Vasilija; Cingoski, Vlatko; Gelev, Saso

    2016-01-01

    This paper describes the design and practical implementation of AC/DC/DC converter in mode of arc welding. An analysis of the operation of AC/DC/DC converter and its input/output characteristics are determined with computer simulations. The practical part is consisted of AC/DC/DC converter prototype for arc welding with output power of 3 kW and switching frequency of 64 kHz. The operation of AC/DC/DC converter is validated with experimental measurements.

  19. (PFC) converters feeding brushless DC motor drive

    African Journals Online (AJOL)

    DR OKE

    harmonic distortion (THD) of supply current at AC mains for a wide range of ... An uncontrolled diode bridge rectifier (DBR) with high value of DC link ...... ac transmission systems), HVDC (High voltage direct current) transmission systems. Prof.

  20. Nonlinear Phenomena and Resonant Parametric Perturbation Control in QR-ZCS Buck DC-DC Converters

    Science.gov (United States)

    Hsieh, Fei-Hu; Liu, Feng-Shao; Hsieh, Hui-Chang

    The purpose of this study is to investigate the chaotic phenomena and to control in current-mode controlled quasi-resonant zero-current-switching (QR-ZCS) DC-DC buck converters, and to present control of chaos by resonant parametric perturbation control methods. First of all, MATLAB/SIMULINK is used to derive a mathematical model for QR-ZCS DC-DC buck converters, and to simulate the converters to observe the waveform of output voltages, inductance currents and phase-plane portraits from the period-doubling bifurcation to chaos by changing the load resistances. Secondly, using resonant parametric perturbation control in QR-ZCS buck DC-DC converters, the simulation results of the chaotic converter form chaos state turn into stable state period 1, and improve ripple amplitudes of converters under the chaos, to verify the validity of the proposes method.

  1. DC-DC Conversion Powering Schemes for the CMS Tracker at Super-LHC

    CERN Document Server

    Klein, Katja; Jussen, Rüdiger; Karpinski, Waclaw; Merz, Jennifer; Sammet, Jan

    2010-01-01

    The CMS experiment at the Large Hadron Collider (LHC) at CERN, Geneva, houses the largest silicon strip tracker ever built. For the foreseen luminosity upgrade of the LHC, the Super-LHC, however, a completely new silicon tracker will have to be constructed. One out of several major improvements currently under consideration is the implementation of a track trigger, with tracking information being provided to the first level trigger. Such an intelligent tracker design, utilising fast digital readout electronics, will most certainly lead to an increased power consumption, compared to today's tracker. In combination with the desire to reduce the amount of passive material inside the tracking volume and the impracticality to exchange or even add additional supply cables, a novel powering scheme will be inevitable. In this article a powering scheme based on DC-DC conversion is proposed, and requirements for the DC-DC converters are discussed. Studies of important DC-DC converter quantities such as th...

  2. The DC-DC conversion power system of the CMS Phase-1 pixel upgrade

    Science.gov (United States)

    Feld, L.; Karpinski, W.; Klein, K.; Lipinski, M.; Preuten, M.; Rauch, M.; Schmitz, St.; Wlochal, M.

    2015-01-01

    The pixel detector of the CMS experiment will be exchanged during the year-end technical stop in 2016/2017, as part of the experiment's Phase-1 upgrade. The new device will feature approximately twice the number of readout channels, and consequently the power consumption will be doubled. By moving to a DC-DC conversion powering scheme, it is possible to power the new pixel detector with the existing power supplies and cable plant. The power system of the Phase-1 pixel detector is described and the performance of the new components, including DC-DC converters, DC-DC converter motherboards and various power distribution boards, is detailed. The outcome of system tests in terms of electrical behaviour, thermal management and pixel module performance is discussed.

  3. Modelling and Simulation of Digital Compensation Technique for dc-dc Converter by Pole Placement

    Science.gov (United States)

    Shenbagalakshmi, R.; Sree Renga Raja, T.

    2015-09-01

    A thorough and effective analysis of the dc-dc converters is carried out in order to achieve the system stability and to improve the dynamic performance. A small signal modelling based on state space averaging technique for dc-dc converters is carried out. A digital state feedback gain matrix is derived by pole placement technique in order to achieve the stability of a completely controllable system. A prediction observer for the dc-dc converters is designed and a dynamic compensation (observer plus control law) is provided using separation principle. The output is very much improved with zero output voltage ripples, zero peak overshoot, and much lesser settling time in the range of ms and with higher overall efficiency (>90 %).

  4. DC-DC converters with reduced mass for trackers at the HL-LHC

    Science.gov (United States)

    Affolder, A.; Allongue, B.; Blanchot, G.; Faccio, F.; Fuentes, C.; Greenall, A.; Michelis, S.

    2011-11-01

    The development at CERN of low noise DC-DC converters for the powering of front-end systems enables the implementation of efficient powering schemes for the physics experiments at the HL-LHC. Recent tests made on the ATLAS short strip tracker modules confirm the full electromagnetic compatibility of the DC-DC converter prototypes with front-end detectors. The integration of the converters in the trackers front-ends needs to address also the material budget constraints. The impact of the DC-DC converters onto the material budget of the ATLAS tracker modules is discussed and mass reduction techniques are explored, leading to a compromise between electromagnetic compatibility and mass. Low mass shield implementations and Aluminum core inductors are proposed. Also, the impact on emitted noise due to a size reduction of critical components is discussed. Finally, material reduction techniques are discussed at the board layout and manufacturing levels.

  5. Efficient and ripple-mitigating dc-dc converter for residential fuel cell system

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yong [Danfoss Solar Inverters, Hardware, Jyllandsgade 28, 6400 Soenderborg (Denmark); Choi, Seeyoung [Digital Appliance Division, Samsung Electronics Co. Ltd., Maetan-3Dong, Suwon, Gyeonggi (Korea); Lee, Eunchul [Willings Co. Ltd., SK Ventium, 522 Dangjung-Dong, Gunpo-Si, Gyeonggi-Do (Korea)

    2009-01-15

    Proton exchange membrane fuel cell (PEMFC) systems for residential application require efficient and ripple-mitigating power conditioning system (PCS). The key point to reach it, is the design and control of the dc-dc converter. Based on the theoretical and experimental analysis of the traditional converter, this paper proposes a novel parallel-series full bridge (P-SFB) dc-dc converter, and improves its phase shifting scheme. This paper also proposes a novel controller for low frequency ripple current suppressing applied on the converter. The experimental results verify that, the dc-dc converter achieves a peak efficiency of 95.5%. Therefore PCS's maximum efficiency reaches 92.9%. And the input current ripple is reduced significantly with the new controller. (author)

  6. Critical conditions of saddle-node bifurcations in switching DC-DC converters

    Science.gov (United States)

    Fang, Chung-Chieh

    2013-08-01

    Although existence of multiple periodic orbits in some DC-DC converters have been known for decades, linking the multiple periodic orbits with the saddle-node bifurcation (SNB) is rarely reported. The SNB occurs in popular DC-DC converters, but it is generally reported as a strange instability. Recently, design-oriented instability critical conditions are of great interest. In this article, average, sampled-data and harmonic balance analyses are applied and they lead to equivalent results. Many new critical conditions are derived. They facilitate future research on the instability associated with multiple periodic orbits, sudden voltage jumps or disappearances of periodic orbits observed in DC-DC converters. The effects of various converter parameters on the instability can be readily seen from the derived critical conditions. New Nyquist-like plots are also proposed to predict or prevent the occurrence of the instability.

  7. Simulation and Implementation of Interleaved Boost DC-DC Converter for Fuel Cell Application

    Directory of Open Access Journals (Sweden)

    Ahmad Saudi Samosir

    2011-10-01

    Full Text Available This paper deals with a boost dc-dc converter for fuel cell application. In fuel cell electric vehicles application, a high power boost dc-dc converter is adopted to adjust the output voltage, current and power of fuel cell engine to meet the vehicle requirements. One of challenge in designing a boost converter for high power application is how to handle the high current at the input side. In this paper an interleaved boost dc-dc converter is proposed for current sharing on high power application. Moreover, this converter also reduces the fuel ripple current. Performance of the interleaved boost converter is tested through simulation and experimental results. Keywords: component; Interleaved Boost Converter; Fuel Cell Electric Vehicle; high power application.  

  8. Application handbook for a Standardized Control Module (SCM) for DC-DC converters, volume 1

    Science.gov (United States)

    Lee, F. C.; Mahmoud, M. F.; Yu, Y.

    1980-01-01

    The standardized control module (SCM) was developed for application in the buck, boost and buck/boost DC-DC converters. The SCM used multiple feedback loops to provide improved input line and output load regulation, stable feedback control system, good dynamic transient response and adaptive compensation of the control loop for changes in open loop gain and output filter time constraints. The necessary modeling and analysis tools to aid the design engineer in the application of the SCM to DC-DC Converters were developed. The SCM functional block diagram and the different analysis techniques were examined. The average time domain analysis technique was chosen as the basic analytical tool. The power stage transfer functions were developed for the buck, boost and buck/boost converters. The analog signal and digital signal processor transfer functions were developed for the three DC-DC Converter types using the constant on time, constant off time and constant frequency control laws.

  9. Optimized photovoltaic generator-water electrolyser coupling through a controlled DC-DC converter

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Valverde, R.; Miguel, C.; Urbina, A. [Universidad Politecnica de Cartagena, Departamento de Electronica, Tecnologia de Computadoras y Proyectos, Plaza del Hospital, 1, Cartagena, 30203 Murcia (Spain); Martinez-Bejar, R. [Universidad de Murcia, Departamento de Ingenieria de la Informacion y las Comunicaciones, Facultad de Informatica, Campus de Espinardo, 30071 Murcia (Spain)

    2008-10-15

    The coupling of a photovoltaic generator and an electrolyser is one of the most promising options for obtaining hydrogen from a renewable energy source. Both are well known technologies, however, since the high variability of the solar radiation, an efficient coupling still presents some challenges. Direct or through a DC-DC converter couplings are the options in isolated applications. In this work, three models, respectively, for a photovoltaic (PV) generator, a controlled DC-DC converter and a complete proton exchange membrane (PEM) electrolyser have been designed by using Matlab/Simulink. A PV-electrolyser specific algorithm to search for the optimum and safe working point for both elements is presented. Simulation results demonstrate that the use of a controlled DC-DC converter with the proposed algorithm shows better adaptability to the variable radiation conditions than the other coupling options. Therefore, it leads to a better compliance between the electrolyser and the sizing of the PV generator. (author)

  10. Test Results of Selected Commercial DC/DC Converters under Cryogenic Temperatures - A Digest

    Science.gov (United States)

    Patterson, Richard; Hammoud, Ahmad

    2010-01-01

    DC/DC converters are widely used in space power systems in the areas of power management and distribution, signal conditioning, and motor control. Design of DC/DC converters to survive cryogenic temperatures will improve the power system performance, simplify design, and reduce development and launch costs. In this work, the performance of nine COTS modular, low-tomedium power DC/DC converters was investigated under cryogenic temperatures. The converters were evaluated in terms of their output regulation, efficiency, and input and output currents. At a given temperature, these properties were obtained at various input voltages and at different load levels. A summary on the performance of the tested converters was given. More comprehensive testing and in-depth analysis of performance under long-term exposure to extreme temperatures are deemed necessary to establish the suitability of these and other devices for use in the harsh environment of space exploration missions.

  11. Advanced DC/DC Converters Towards Higher Volumetric Efficiencies For Space Applications

    Science.gov (United States)

    Shaw, Harry; Shue, Jack; Liu, David; Wang, Bright; Plante, Jeanette

    2005-01-01

    A new emphasis on planetary exploration by NASA drives the need for small, high power DC/DC converters which are functionally modular. NASA GSFC and other government space organizations are supporting technology development in the DC/DC converter area to both meet new needs and to promote more sources of supply. New technologies which enable miniaturization such as embedded passive technologies and thermal management using high thermal conductivity materials are features of the new designs. Construction of some simple DC/DC converter core circuits using embedded components was found to be successful for increasing volumetric efficiency to 37 W/inch. The embedded passives were also able to perform satisfactorily in this application in cryogenic temperatures.

  12. Ultra-high Efficiency DC-DC Converter using GaN Devices

    DEFF Research Database (Denmark)

    Ramachandran, Rakesh

    2016-01-01

    The demands for high efficiency dc-dc power converters are increasing day by day in various applications such as telecommunication, data-centers, electric vehicles and various renewable energy systems. Silicon (Si) has been used as the semiconductor material in majority of the power devices...... properties of GaN devices can be utilized in power converters to make them more compact and highly efficient. This thesis entitled “Ultra-high Efficiency DC-DC Converter using GaN devices” focuses on achieving ultra-high conversion efficiency in an isolated dc-dc converter by the optimal utilization of Ga......N devices. Simple replacement of Si or SiC devices with GaN devices in the converter will not give an expected increase in efficiency or any improvement in the performance of the converter. The use of GaN devices has defined another dimension in the design of power converters, which mainly deals...

  13. Efficiency Enhancement of DC to DC Multilevel Boost Converter and Its Applications

    Directory of Open Access Journals (Sweden)

    R. Ravikumar

    2015-03-01

    Full Text Available The aim of this study is to propose a experimental verification for single-phase to three phase drive system composed of two parallel single-phase rectifiers, a three-phase inverter and an induction motor. Apart from traditional application in dc motor drives, new applications of BDC include energy storage in renewable energy systems, fuel cell energy systems, Hybrid Electric Vehicles (HEV and Uninterruptible Power Supplies (UPS. A dc-dc converter is always required to allow energy exchange between storage device and the rest of system. In HEV applications, BDCs are required to link different dc voltage buses and transfer energy between them. A non-isolated bi-directional dc-dc converters is used in our project to achieve better efficiency.

  14. The DC-DC converter reduces its size and increases its efficiency; Le convertisseur DC-DC reduit sa taille et augmente son rendement

    Energy Technology Data Exchange (ETDEWEB)

    Feste, J.P.

    2000-03-01

    The DC to DC converters built by the US SynQor company use a dual stage conversion technique. One stage is devoted to regulation and the other to insulation. This technique allows to combine a high efficiency (up to 90%) with small dimensions. Instead of the classical Schottky diodes, a synchronous MOSFET is used for the rectification of the low voltage current. A simple air flow is required for the cooling of these converters. Short paper. (J.S.)

  15. Solid-State dc Circuit Breaker

    Science.gov (United States)

    Harvey, P.

    1983-01-01

    Circuit breaker with no moving parts protects direct-current (dc) loads. Current which circuit breaker opens (trip current) is adjustable and so is time delay before breaker trips. Forward voltage drop rises from 0.6 to 1.2 V as current rises to trip point. Breaker has two terminals, like fuse, therefore replaces fuse in dc circuit. Powered by circuit it protects and reset by either turning off power source or disconnecting load.

  16. Brushless DC Motors, Velocity and Position Control of the Brushless DC Motor.

    Science.gov (United States)

    1986-06-01

    DC motor was designed using the Hall effect sensors. In addition, the position control of the brushless DC motor was developed using an optical encoder to sense angular position changes and a microprocessor to provide the desired position control. A Pittman 5111 wdg 1 brushless DC motor was used for this study. The design of the digital tachometer and pulse width modulator for velocity control and the design of the Z-80 based microprocessor controller and software design are described in

  17. The application of standardized control and interface circuits to three dc to dc power converters.

    Science.gov (United States)

    Yu, Y.; Biess, J. J.; Schoenfeld, A. D.; Lalli, V. R.

    1973-01-01

    Standardized control and interface circuits were applied to the three most commonly used dc to dc converters: the buck-boost converter, the series-switching buck regulator, and the pulse-modulated parallel inverter. The two-loop ASDTIC regulation control concept was implemented by using a common analog control signal processor and a novel digital control signal processor. This resulted in control circuit standardization and superior static and dynamic performance of the three dc-to-dc converters. Power components stress control, through active peak current limiting and recovery of switching losses, was applied to enhance reliability and converter efficiency.

  18. Model predictive control of bidirectional isolated DC-DC converter for energy conversion system

    Science.gov (United States)

    Akter, Parvez; Uddin, Muslem; Mekhilef, Saad; Tan, Nadia Mei Lin; Akagi, Hirofumi

    2015-08-01

    Model predictive control (MPC) is a powerful and emerging control algorithm in the field of power converters and energy conversion systems. This paper proposes a model predictive algorithm to control the power flow between the high-voltage and low-voltage DC buses of a bidirectional isolated full-bridge DC-DC converter. The predictive control algorithm utilises the discrete nature of the power converters and predicts the future nature of the system, which are compared with the references to calculate the cost function. The switching state that minimises the cost function is selected for firing the converter in the next sampling time period. The proposed MPC bidirectional DC-DC converter is simulated with MATLAB/Simulink and further verified with a 2.5 kW experimental configuration. Both the simulation and experimental results confirm that the proposed MPC algorithm of the DC-DC converter reduces reactive power by avoiding the phase shift between primary and secondary sides of the high-frequency transformer and allow power transfer with unity power factor. Finally, an efficiency comparison is performed between the MPC and dual-phase-shift-based pulse-width modulation controlled DC-DC converter which ensures the effectiveness of the MPC controller.

  19. Design of the DC-DC power stage of the capacitor charger for MAXIDISCAP power converters

    CERN Document Server

    Cravero, Jean-Marc

    2013-01-01

    This technical report presents the design of the DC-DC power stage of the capacitor charger for MAXIDISCAP power converters. The power stage is based on a half bridge series resonant converter in Discontinuous Conduction Mode (DCM). This simple and robust topology allows obtaining a current source behavior with a low switching losses power stage. The associated control stage is implemented using a commercial controller which has differenti nternal circuits that allows a high integration of the converter control system. The report presents the design and tuning criteria for the DC-DC converter, including the power stage and the control system.

  20. A Reduced-Part, Triple-Voltage DC-DC Converter for Electric Vehicle Power Management

    Energy Technology Data Exchange (ETDEWEB)

    Su, Gui-Jia [ORNL; Tang, Lixin [ORNL

    2007-01-01

    Electrical power systems in future hybrid and fuel cell vehicles may consist of three voltage nets; 14 V, 42 V and high voltage (>200 V) buses. A soft-switched, bi-directional dc-dc converter using only four switches was proposed for interconnecting the three nets. This paper presents a reduced- part dc-dc converter, which decreases the converter cost while retaining all the favorable features of the original topology. Simulation and experimental data are included to verify a simple power flow control scheme.

  1. High-Voltage DC-DC Converter Topology for PV Energy Utilization - Investigation and Implementation

    DEFF Research Database (Denmark)

    Sanjeevikumar, Padmanaban; Blaabjerg, Frede; Wheeler, Patrick

    2017-01-01

    This paper exploited the utilization of photovoltaic (PV) energy system with high-voltage (HV) output DC-DC converter. Classical boost converters are used for both renewable energy integration and HV applications, but limited by reducing output/efficiency in performance. Moreover, as parasitic...... elements suppress the power transfer ratio, converter needs to maximize the PV energy utilization. This investigation study focused to include additional parasitic elements (voltage-lift technique) to a standard DC-DC buck converter and to overcome all the above drawbacks to maximize the PV power...

  2. Laboratory manual for pulse-width modulated DC-DC power converters

    CERN Document Server

    Kazimierczuk, Marian K

    2015-01-01

    Designed to complement a range of power electronics study resources, this unique lab manual helps students to gain a deep understanding of the operation, modeling, analysis, design, and performance of pulse-width modulated (PWM) DC-DC power converters.  Exercises focus on three essential areas of power electronics: open-loop power stages; small-signal modeling, design of feedback loops and PWM DC-DC converter control schemes; and semiconductor devices such as silicon, silicon carbide and gallium nitride. Meeting the standards required by industrial employers, the lab manual combines program

  3. Efficiency and Regulation of Commercial Low Power DC/DC Converter Modules at Low Temperatures

    Science.gov (United States)

    Elbuluk, Malik E.; Gerber, Scott; Hammoud, Ahmad; Patterson, Richard L.

    2000-01-01

    DC/DC converters that are capable of operating at cryogenic temperatures are anticipated to play an important role in the power systems of future NASA deep space missions. Design of these converters to survive cryogenic temperatures will improve the power system performance, and reduce development and launch costs. At the NASA Glenn Research Center Low Temperature Electronics Laboratory, several commercial off-the-shelf dc/dc converter modules were evaluated for their low temperature performance. Various parameters were investigated as a function of temperature, in the range of 20 C to -190 C. Data pertaining to the efficiency and voltage regulation of the tested converters is presented and discussed.

  4. High power density dc/dc converter: Component selection and design

    Science.gov (United States)

    Divan, Deepakraj M.

    1989-01-01

    Further work pertaining to design considerations for the new high power, high frequency dc/dc converters is discussed. The goal of the project is the development of high power, high power density dc/dc converters at power levels in the multi-kilowatt to megawatt range for aerospace applications. The prototype converter is rated for 50 kW at a switching frequency of 50 kHz, with an input voltage of 200 Vdc and an output of 2000 Vdc. The overall power density must be in the vicinity of 0.2 to 0.3 kg/kW.

  5. Analysis of high voltage step-up nonisolated DC-DC boost converters

    Science.gov (United States)

    Alisson Alencar Freitas, Antônio; Lessa Tofoli, Fernando; Junior, Edilson Mineiro Sá; Daher, Sergio; Antunes, Fernando Luiz Marcelo

    2016-05-01

    A high voltage step-up nonisolated DC-DC converter based on coupled inductors suitable to photovoltaic (PV) systems applications is proposed in this paper. Considering that numerous approaches exist to extend the voltage conversion ratio of DC-DC converters that do not use transformers, a detailed comparison is also presented among the proposed converter and other popular topologies such as the conventional boost converter and the quadratic boost converter. The qualitative analysis of the coupled-inductor-based topology is developed so that a design procedure can be obtained, from which an experimental prototype is implemented to validate the theoretical assumptions.

  6. Interleaved DC-DC Converter with Discrete Duty Cycle and Open Loop Control

    Science.gov (United States)

    Kroics, K.; Sokolovs, A.

    2016-08-01

    The authors present the control principle of the multiphase interleaved DC-DC converter that can be used to vastly reduce output current ripple of the converter. The control algorithm can be easily implemented by using microcontroller without current loop in each phase. The converter works in discontinuous conduction mode (DCM) but close to boundary conduction mode (BCM). The DC-DC converter with such a control algorithm is useful in applications that do not require precise current adjustment. The prototype of the converter has been built. The experimental results of the current ripple are presented in the paper.

  7. Interleaved DC-DC Converter with Discrete Duty Cycle and Open Loop Control

    Directory of Open Access Journals (Sweden)

    Kroics K.

    2016-08-01

    Full Text Available The authors present the control principle of the multiphase interleaved DC-DC converter that can be used to vastly reduce output current ripple of the converter. The control algorithm can be easily implemented by using microcontroller without current loop in each phase. The converter works in discontinuous conduction mode (DCM but close to boundary conduction mode (BCM. The DC-DC converter with such a control algorithm is useful in applications that do not require precise current adjustment. The prototype of the converter has been built. The experimental results of the current ripple are presented in the paper.

  8. Design of current source DC/DC converter and inverter for 2kW fuel cell application

    DEFF Research Database (Denmark)

    Andreiciks, A.; Steiks, I.; Krievs, O.

    2013-01-01

    of a DC/DC converter and an inverter. In this paper a detailed simulation study of such interfacing converter system comprising a double inductor push-pull step-up DC/DC converter and a cascaded H-bridge inverter has been carried out and further confirmed with experimental results. The power converter...

  9. Research on Two-channel Interleaved Two-stage Paralleled Buck DC-DC Converter for Plasma Cutting Power Supply

    DEFF Research Database (Denmark)

    Yang, Xi-jun; Qu, Hao; Yao, Chen

    2014-01-01

    As for high power plasma power supply, due to high efficiency and flexibility, multi-channel interleaved multi-stage paralleled Buck DC-DC Converter becomes the first choice. In the paper, two-channel interleaved two- stage paralleled Buck DC-DC Converter powered by three-phase AC power supply...

  10. Novel Step-Up DC/DC Converter with No Right Half Plane Zero and Reduced Switched Voltage Stress Characteristics

    DEFF Research Database (Denmark)

    Mostaan, Ali; Alizadeh, Ebrahim; Soltani, Mohsen

    2014-01-01

    Novel step-up DC/DC converter is introduced in this paper. This converter is realized with adding the switched capacitor voltage multiplier cell to the three switch step-down DC/DC converter that has been proposed in the literature. The proposed converter is analyzed in the steady state and the v...

  11. Comparative efficiency evaluation of buck and hybrid buck DC-DC converters for automotive applications

    DEFF Research Database (Denmark)

    Pelan, Ovidiu; Cornea, Octavian; Muntean, Nicolae

    2014-01-01

    This paper presents and discusses design considerations and efficiency investigation of a conventional step-down and a hybrid switched-capacitor DC-DC converter. Three MOSFETs with low on-resistance have been tested for each converter in order to find the most adequate switch for this application...

  12. Single Event Burnout in DC-DC Converters for the LHC Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Claudio H. Rivetta et al.

    2001-09-24

    High voltage transistors in DC-DC converters are prone to catastrophic Single Event Burnout in the LHC radiation environment. This paper presents a systematic methodology to analyze single event effects sensitivity in converters and proposes solutions based on de-rating input voltage and output current or voltage.

  13. Very High Frequency Resonant DC/DC Converters for LED Lighting

    DEFF Research Database (Denmark)

    Madsen, Mickey Pierre; Knott, Arnold; Andersen, Michael A. E.

    2013-01-01

    This paper presents a very high frequency DC/DC converter for LED lighting. Several resonant topologies are compared and their usability discussed. At the end the resonant SEPIC converter is chosen based on the achievable power density and total bill of material. Simulations of a 51 MHz converter...

  14. Area-Efficiency Trade-Offs in Integrated Switched-Capacitor DC-DC Converters

    DEFF Research Database (Denmark)

    Spliid, Frederik Monrad; Larsen, Dennis Øland; Knott, Arnold

    2016-01-01

    This paper analyzes the relationship between efficiency and chip area in a fully integrated switched capacitor voltage divider dc-dc converter implemented in 180nm-technology and a 1/2 topology. A numerical algorithm for choosing the optimal sizes of individual components, in terms of power loss...

  15. A novel DC-DC convertor using LTCC technology for magnetic integration application

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Z Q [Research Institutes, University of Electronic Science and Technology of China, Chengdu (China); Shi, Y; Guo, H P; Yang, B C, E-mail: nanterxu@uestc.edu.cn [State key Laboratory of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, Chengdu (China)

    2011-01-01

    A compact DC-DC convertor is proposed and fabricated in multilayer ferrite substrate using LTCC technology. The spiral conductors are buried into the ferrite substrate with a multilayer 3-D structure to reduce the volume of convertor. The passive integration of magnetic components and surface circuitry are achieved in a whole substrate and the size of module can be reduced markedly. The whole height of module is only 3mm, 1/3 of the height of conventional modules. Testing results indicate that the performance of the module is excellent in Point-of-Load (POL) field. The step-down DC-DC converter converts input voltage of 5V to output voltage of 3.3V. It is confirmed that the maximum conversion efficiency of 93.2% is sufficient for actual DC-DC converter application. Such a compact DC-DC convertor provides a compact, low cost and high reliability approach for power supply and magnetic integration application.

  16. Five-Level Active-Neutral-Point-Clamped DC/DC Converter

    DEFF Research Database (Denmark)

    Liu, Dong; Deng, Fujin; Chen, Zhe

    Multi-level converters are getting more and more attentions because of their obvious merits such as lower voltage stress and harmonic, smaller size of output filters, and so on. In this paper, a five-level active-neutral-point-clamped (5L-ANPC) dc/dc converter is proposed for power transfer...

  17. DC-DC conversion powering schemes for the CMS tracker at Super-LHC

    Energy Technology Data Exchange (ETDEWEB)

    Klein, K; Feld, L; Jussen, R; Karpinski, W; Merz, J; Sammet, J, E-mail: katja.klein@cern.c [I. Physikalisches Institut B, RWTH Aachen University, Aachen (Germany)

    2010-07-15

    The CMS experiment at the Large Hadron Collider (LHC) at CERN, Geneva, houses the largest silicon strip tracker ever built. For the foreseen luminosity upgrade of the LHC, the Super-LHC, however, a completely new silicon tracker will have to be constructed. One out of several major improvements currently under consideration is the implementation of a track trigger, with tracking information being provided to the first level trigger. Such an intelligent tracker design, utilising fast digital readout electronics, will most certainly lead to an increased power consumption, compared to today's tracker. In combination with the desire to reduce the amount of passive material inside the tracking volume and the impracticality to exchange or even add additional supply cables, a novel powering scheme will be inevitable. In this article a powering scheme based on DC-DC conversion is proposed, and requirements for the DC-DC converters are discussed. Studies of important DC-DC converter quantities such as the power efficiency, conducted and radiated noise levels, and material budget are presented, and a possible implementation of DC-DC buck converters into one proposed track trigger layout is sketched.

  18. Computer-aided analysis and simulation of switched dc-dc converters

    Science.gov (United States)

    Lee, F. C.; Yu, Y.

    1978-01-01

    State space techniques are employed to derive an equivalent nonlinear recurrent time-domain model that describes the switched dc-dc converter behavior exactly. This model is employed effectively to analyze both large signal behavior by propagating the recurrence equation and matching boundary conditions through digital computation and small signal behavior by linearizing it about the equilibrium state.

  19. Low noise DC to DC converters for the sLHC experiments

    Energy Technology Data Exchange (ETDEWEB)

    Allongue, B; Blanchot, G; Faccio, F; Fuentes, C; Michelis, S; Orlandi, S, E-mail: georges.blanchot@cern.c [CERN, Route de Meyrin, CH-1211 Geneva 23 (Switzerland)

    2010-11-15

    The development of front-end systems for the ATLAS tracker at the sLHC is now in progress and the availability of radiation tolerant buck converter ASICs enables the implementation of DC to DC converter based powering schemes. The front-end systems powered in this manner will be exposed to the radiated and conducted noise emitted by the converters. The electromagnetic compatibility between DC to DC converters and ATLAS short strip tracker hybrid prototypes has been studied with specific susceptibility tests. Different DC to DC converter prototypes have been designed following a noise optimization methodology to match the noise requirements of these front-end systems. The DC to DC converter developed in this manner presents a negligible emission of noise that was confirmed by system tests on an ATLAS tracker front-end module prototype. As a result of this, power converters can now be integrated in close vicinity of front-end chips without compromising their overall noise performance.

  20. A DC-DC conversion powering scheme for the CMS Phase-1 pixel upgrade

    Science.gov (United States)

    Feld, L.; Fleck, M.; Friedrichs, M.; Hensch, R.; Karpinski, W.; Klein, K.; Sammet, J.; Wlochal, M.

    2013-02-01

    The CMS pixel detector was designed for a nominal instantaneous LHC luminosity of 1ṡ1034 cm-2s-1. During Phase-1 of the LHC upgrade, the instantaneous luminosity will be increased to about twice this value. To preserve the excellent performance of the pixel detector despite the increase in particle rates and track densities, the CMS Collaboration foresees the exchange of its pixel detector in the shutdown 2016/2017. The new pixel detector will be improved in many respects, and will comprise twice the number of readout channels. A powering scheme based on DC-DC conversion will be adopted, which will enable the provision of the required power with the present cable plant. The powering scheme of the CMS pixel detector will be described, and the performance of prototype DC-DC buck converters will be presented, including power efficiency, system tests with DC-DC converters and pixel modules, thermal management, reliability at low temperature, and studies of potential frequency locking between DC-DC converters.

  1. Operation and control of a DC-grid offshore wind farm under DC transmission system faults

    DEFF Research Database (Denmark)

    Deng, Fujin; Chen, Zhe

    2013-01-01

    So far, all existing offshore wind farms have an ac collection system, and the collected power in the offshore wind farm is sent to an onshore ac grid through high-voltage ac (HVAC) or DC (HVDC) transmission lines. However, future of fshore wind farms may use dc also for power collection. Consequ...

  2. A Bidirectional Multi-Port DC-DC Converter Integrating Voltage Equalizer

    DEFF Research Database (Denmark)

    Chen, Jianfei; Hou, Shiying; Deng, Fujin

    2015-01-01

    with a uniform voltage level while eliminating the voltage imbalance. In addition, high step-down and step-up ratios with low component voltage stress can be achieved in the proposed converter. A bidirectional four-port dc-dc converter is presented to do theoretical analysis for the voltage equalization of three...

  3. DC-DC converter with a wide load range and a wide input-voltage range

    NARCIS (Netherlands)

    Ting, Y.

    2015-01-01

    This thesis investigated the possibility of increasing the efficiency of a DC-DC converter over a wide load range and a wide input-voltage range based on the Single Active Bridge (SAB) topology with two approaches. The first approach involved making changes to the topology whereas the second made us

  4. Modelling, Simulation and Construction of a DC/DC Boost Power Converter: A School Experimental System

    Science.gov (United States)

    Silva-Ortigoza, R.; Silva-Ortigoza, G.; Hernandez-Guzman, V. M.; Saldana-Gonzalez, G.; Marcelino-Aranda, M.; Marciano-Melchor, M.

    2012-01-01

    We introduce a dc/dc boost power converter as a didactic prototype intended to support courses on electric circuit analysis experimentally. The corresponding mathematical model is obtained, the converter is designed and an experimental setup is described, constructed and tested. Simplicity of construction as well as low cost of components renders…

  5. A Novel Quasi-SEPIC High-Voltage Boost DC-DC Converter

    DEFF Research Database (Denmark)

    Siwakoti, Yam Prasad; N. Soltani, Mohsen; Mostaan, Ali

    2017-01-01

    This paper proposes a modified coupled-inductor SEPIC dc-dc converter for low power and high voltage gain applications such as for piezoelectric drive systems. The converter uses the same components as of SEPIC converter with an additional diode. Compared to conventional topologies with similar v...

  6. Trans-inverse (Tx−1) high step-up DC-DC converter

    DEFF Research Database (Denmark)

    Siwakoti, Yam Prasad; Blaabjerg, Frede; Loh, Poh Chiang

    2015-01-01

    In this paper, a new magnetically coupled single-switch non-isolated dc-dc converter with a high voltage gain is proposed. The new topology utilizes a transformer to boost the output voltage. However, unlike other converter topologies with transformer or coupled magnetics, the voltage gain in the...

  7. Ultra-Step-Up DC-DC Converter with Integrated Autotransformer and Coupled Inductor

    DEFF Research Database (Denmark)

    Siwakoti, Yam Prasad; Blaabjerg, Frede; Loh, Poh Chiang

    2016-01-01

    This paper introduces a new single-switch nonisolated dc-dc converter with very high voltage transfer ratio and reduced semiconductor voltage stress. The converter utilizes an integrated autotransformer and a coupled inductor on the same core to achieve a high step-up voltage gain without extreme...

  8. Y-source impedance-network-based isolated boost DC/DC converter

    DEFF Research Database (Denmark)

    Siwakoti, Yam P.; Town, Graham; Loh, Poh Chiang

    2014-01-01

    A dc-dc converter with very high voltage gain is proposed in this paper for any medium-power application requiring a high voltage boost with galvanic isolation. The proposed converter topology can be realized using only two switches. With this topology a very high voltage boost can be achieved ev...

  9. Magnetically coupled high-gain Y-source isolated DC/DC converter

    DEFF Research Database (Denmark)

    Siwakoti, Yam P.; Loh, Poh Chiang; Blaabjerg, Frede

    2014-01-01

    A new form of magnetically coupled DC/DC converter is proposed for medium power applications (250 W to 2 kW), requiring a high-voltage gain, short inductive charging time and galvanic isolation. The proposed converter can be realised using a unique Y-source impedance network and a two-switch push...

  10. A high voltage gain quasi Z-source isolated DC/DC converter

    DEFF Research Database (Denmark)

    Siwakoti, Yam P.; Blaabjerg, Frede; Loh, Poh Chiang

    2014-01-01

    A compact quasi-Z-source DC/DC converter is presented with high voltage gain, isolated output, and improved efficiency. The improvements in size and performance were achieved by using a square wave inverter with only two output switches driving an isolating transformer in push-pull mode, followed...

  11. Planar integrated magnetics design in wide input range DC-DC converter for fuel cell application

    DEFF Research Database (Denmark)

    Ouyang, Ziwei; Zhang, Zhe; Thomsen, Ole Cornelius

    2010-01-01

    , hereby increasing the power density of converters. A new planar integrated magnetics (PIM) technique for a phase-shift plus duty cycle controlled hybrid bi-directional DC/DC converter is presented and investigated in this paper. The main magnetic components including one boost inductor and two...

  12. A Dual-Buck–Boost AC/DC Converter for DC Nanogrid With Three Terminal Outputs

    DEFF Research Database (Denmark)

    Wu, Weimin; Wang, Houqing; Liu, Yuan

    2017-01-01

    such as the low-voltage ac power system. There are three typical grounding configurations for a dc nanogrid: the united grounding, the unidirectional grounding, and the virtual isolated grounding. Each grounding configuration has its own specifications to ac/dc converters. In this paper, a dual-buck-boost ac...

  13. Quasiperiodicity and Torus Breakdown in a Power Electronic DC/DC Converter

    DEFF Research Database (Denmark)

    Zhusubaliyev, Zhanybai; Soukhoterin, Evgeniy; Mosekilde, Erik

    2007-01-01

    This paper discusses the mechanisms of torus formation and torus destruction in a dc/dc converter with relay control and hysteresis. We establish a chart of the dynamical modes in the input voltage versus load resistance parameter plane. This chart displays several different torus bifurcations...

  14. Multistability and hidden attractors in a multilevel DC/DC converter

    DEFF Research Database (Denmark)

    Zhusubaliyev, Zhanybai T.; Mosekilde, Erik

    2015-01-01

    for the hidden set in most cases has been so complicated that special analytic and/or numerical techniques have been required to locate the set. By simulating the model of a multilevel DC/DC converter that operates in the regime of high feedback gain, the paper illustrates how pulse-width modulated control can...

  15. Analysis and design of PPFHB bidirectional DC-DC converter with coupled inductors

    DEFF Research Database (Denmark)

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael Andreas E.

    2009-01-01

    In this paper, a novel push-pull-forward half-bridge (PPFHB) bi-directional DC-DC converter with coupled inductors is proposed. All switches can operate under zero-voltage-switching (ZVS). The operation principle with phase-shift modulation scheme, characteristics of coupled inductors, the steady...

  16. A VHF Class E DC-DC Converter with Self-Oscillating Gate Driver

    DEFF Research Database (Denmark)

    Andersen, Toke Meyer; Christensen, Søren K.; Knott, Arnold

    2011-01-01

    This paper describes the analysis and design of a DC-DC converter topology which is operational at frequencies in the Very High Frequency (VHF) band ranging from 30 MHz − 300 MHz. The presented topology, which consists of a class E inverter, class E rectifier, and self-oscillating gate driver, is...

  17. A New Sliding Mode Controller for DC/DC Converters in Photovoltaic Systems

    Directory of Open Access Journals (Sweden)

    M. Sarvi

    2013-01-01

    Full Text Available DC/DC converters are widely used in many industrial and electrical systems. As DC/DC converters are nonlinear and time-variant systems, the application of linear control techniques for the control of these converters is not suitable. In this paper, a new sliding mode controller is proposed as the indirect control method and compared to a simple direct control method in order to control a buck converter in photovoltaic applications. The solar arrays are dependent power sources with nonlinear voltage-current characteristics under different environmental conditions (insolation and temperature. From this point of view, the DC/DC converter is particularly suitable for the application of the sliding mode control in photovoltaic application, because of its controllable states. Simulations are performed in Matlab/Simulink software. The simulation results are presented for a step change in reference voltage and input voltage as well as step load variations. The simulations results of proposed method are compared with the conventional PID controller. The results show the good performance of the proposed sliding mode controller. The proposed method can be used for the other DC/DC converter.

  18. Interleaved Self-Oscillating Class E Derived Resonant DC/DC Converters

    DEFF Research Database (Denmark)

    Kovacevic, Milovan; Knott, Arnold; Andersen, Michael A. E.

    2012-01-01

    A new method for achieving self-oscillating, self-interleaved operation of class E derived resonant DC/DC converters is presented. The proposed method is suitable for operation at frequencies in the Very High Frequency (VHF) band. Interleaved and self-oscillating modes of operation are achieved...

  19. Integrated S-band transmitter with on-chip DC-DC converter and control loop

    NARCIS (Netherlands)

    Brouzes, H.; Geurts, S.; Besselink, M.; Telli, A.; Hek, A.P. de; Bent, G. van der; Vliet, F.E. van

    2012-01-01

    A highly integrated high-power transmitter has been designed in a high breakdown GaAs MMIC technology. The transmitter includes, on top of an S-Band 10 W class-F HPA, a DC/DC converter and its associated gate driver, the full voltage regulation control loop, which provides a significant step for pha

  20. Y-Source Boost DC/DC Converter for Distributed Generation

    DEFF Research Database (Denmark)

    Siwakoti, Yam P.; Loh, Poh Chiang; Blaabjerg, Frede

    2015-01-01

    This paper introduces a versatile Y-source boost dc/dc converter intended for distributed power generation, where high gain is often demanded. The proposed converter uses a Y-source impedance network realized with a tightly coupled three-winding inductor for high voltage boosting that is presently...

  1. Regulation of a lightweight high efficiency capacitator diode voltage multiplier dc-dc converter

    Science.gov (United States)

    Harrigill, W. T., Jr.; Myers, I. T.

    1976-01-01

    A method for the regulation of a capacitor diode voltage multiplier dc-dc converter has been developed which has only minor penalties in weight and efficiency. An auxiliary inductor is used, which only handles a fraction of the total power, to control the output voltage through a pulse width modulation method in a buck boost circuit.

  2. Regulation of a lightweight high efficiency capacitor diode voltage multiplier dc-dc converter

    Science.gov (United States)

    Harrigill, W. T., Jr.; Myers, I. T.

    1976-01-01

    A method for the regulation of a capacitor diode voltage multiplier dc-dc converter has been developed which has only minor penalties in weight and efficiency. An auxiliary inductor is used, which only handles a fraction of the total power, to control the output voltage through a pulse width modulation method in a buck boost circuit.

  3. A buck DC-DC controller based on WSAR-ADC%基于 WSAR-ADC的降压型 DC-DC 控制器设计

    Institute of Scientific and Technical Information of China (English)

    田登尧; 冯全源

    2014-01-01

    设计了一种基于加窗逐次逼近寄存器( WSAR)模拟数字转换器( ADC)的降压型DC-DC控制器,这种WSAR-ADC适用于数字电源系统,通过对输入电压进行加窗处理,能有效地降低芯片的复杂度;并利用蚁群算法,对该DC-DC控制器的比例积分微分(PID)参数进行了整定,使得整个系统能够稳定工作。电路使用BCD(Bipolar/CMOS/DMOS)0.5μm工艺,输入电压3.3 V,输出电压1 V,设计最大负载电流2 A,纹波小于9 mV,开关频率500 kHz。经过验证,该降压型DC-DC控制器能满足数字电源的采样需求。%A buck DC-DC controller based on window successive approximation register ( WSAR) and analog-to-digital converter ( ADC) was designed.It is applicable to digital power system.The circuit complexity can be re-duced by adding the window function to process input voltage;and the PID (proportion integration differentiation) parameters setting of the DC-DC controller is completed using the ant colony algorithm, which makes the whole sys-tem work stably.The circuit is implemented under Bipolar/CMOS/DMOS ( BCD) 0.5μm process, the input volt-age is 3.3 V, and the output voltage is 1 V.The designed maximum load current is 2 A, the ripple of output voltage is less than 9 mV.After verification, the switch frequency is 500 kHz.This buck DC-DC controller can meet the demand of digital power sampling.

  4. The Role of the p38-MNK-eIF4E Signaling Axis in TNF Production Downstream of the NOD1 Receptor.

    Science.gov (United States)

    Pashenkov, Mikhail V; Balyasova, Lyudmila S; Dagil, Yulia A; Pinegin, Boris V

    2017-02-15

    Activation of nucleotide-binding oligomerization domain (NOD) 1 and NOD2 by muropeptides triggers a complex transcriptional program in innate immune cells. However, little is known about posttranscriptional regulation of NOD1- and NOD2-dependent responses. When stimulated with a prototypic NOD1 agonist, N-acetylglucosaminyl-N-acetylmuramyl-l-alanyl-d-isoglutamyl-meso-diaminopimelic acid (GM-triDAP), human monocyte-derived macrophages (MDM) produced an order of magnitude more TNF, IL-6, and pro-IL-1β than did monocyte-derived dendritic cells (MDDC), despite similar NOD1 expression, similar cytokine mRNA kinetics, and comparable responses to LPS. TNF production by GM-triDAP-activated MDM was independent of autocrine IL-1. However, GM-triDAP-activated MDM translated TNF mRNA more efficiently than did MDDC. As an underlying mechanism, NOD1 triggering in MDM caused a more potent and long-lasting activation of the signaling axis involving p38 MAPK, MAPK-interacting kinase (MNK), and eukaryotic translation initiation factor 4E, which is a critical regulator of translation. Furthermore, MNK controlled TNF mRNA abundance in MDDC and MDM upon NOD1 triggering. NOD1-dependent responses were more sensitive to MNK inhibition than were TLR4-dependent responses. These results demonstrate the importance of the p38-MNK-eukaryotic translation initiation factor 4E axis in TNF production downstream of NOD1.

  5. A suitable model plant for control of the set fuel cell-DC/DC converter

    Energy Technology Data Exchange (ETDEWEB)

    Andujar, J.M.; Segura, F.; Vasallo, M.J. [Departamento de Ingenieria Electronica, Sistemas Informaticos y Automatica, E.P.S. La Rabida, Universidad de Huelva, Ctra. Huelva - Palos de la Frontera, S/N, 21819 La Rabida - Palos de la Frontera Huelva (Spain)

    2008-04-15

    In this work a state and transfer function model of the set made up of a proton exchange membrane (PEM) fuel cell and a DC/DC converter is developed. The set is modelled as a plant controlled by the converter duty cycle. In addition to allow setting the plant operating point at any point of its characteristic curve (two interesting points are maximum efficiency and maximum power points), this approach also allows the connection of the fuel cell to other energy generation and storage devices, given that, as they all usually share a single DC bus, a thorough control of the interconnected devices is required. First, the state and transfer function models of the fuel cell and the converter are obtained. Then, both models are related in order to achieve the fuel cell+DC/DC converter set (plant) model. The results of the theoretical developments are validated by simulation on a real fuel cell model. (author)

  6. Optimization of Shielded PCB Air-Core Toroids for High-Efficiency DC-DC Converters

    CERN Document Server

    Orlandi, S; Buso, S; Michelis, S; Fuentes, C A; Kayal, M; Faccio, F; Spiazzi, G

    2011-01-01

    The paper describes the design of optimized printed circuit board (PCB) air-core toroids for high-frequency dc-dc converters with strict requirements in terms of volume and noise. The effect of several design parameters on the overall inductor volume, on dc and ac winding resistance, and on the radiated noise will be investigated. PCB toroids are compared to standard air-core solenoids and other state-of-the-art air-core toroids both theoretically and experimentally: at first, using ANSOFT Maxwell and ANSOFT Q3D simulation tools, and subsequently, with laboratory measurements (irradiated noise, efficiency, and frequency response) on several prototypes. These very flexible and rather easy to manufacture inductors appear very attractive for compact high-frequency dc-dc converters where high efficiency, low volume, and low noise are of primary concern.

  7. Topologies Research of High Voltage and High Power DC/DC Converters Used in DC Grids%用于直流电网的高压大容量DC/DC变换器拓扑研究

    Institute of Scientific and Technical Information of China (English)

    魏晓光; 王新颖; 高冲; 张升

    2014-01-01

    随着世界范围内大力发展直流电网,作为直流电网中关键器件之一的高压大容量 DC/DC 变换器的研究尤为重要。针对目前关于DC/DC变换器研究主要集中于中低压小功率场合的现状,该文首先从多个角度对直流电网用的高压大容量DC/DC变换器进行了需求分析;其次,对现有文献中提出的适用于直流电网的 DC/DC 变换器拓扑进行了研究,并将输入端串联输出端串联(input-series output-series, ISOS)结构和低压 DC/DC 变换器相结合,提出了用于直流电网中输入端和输出端均为高电压场合的 ISOS 型 DC/DC变换器。比较分析了不同拓扑变换器的电压变比、开关器件的电气应力和故障处理能力等,为选择合适的高压大容量DC/DC变换器拓扑提供了依据。%ABSTRACT:As DC/DC converter is one of the most critical components in DC grids, the study of high voltage and high power DC/DC converter is increasingly important with the rapid development of DC grid all over the world. However, the study of DC/DC converter is mostly focused on low or middle voltage and low power applications. In this paper, the requirements of DC/DC Converters used in large DC grids are addressed firstly. And then possible DC/DC converter topologies are reviewed and input-series and output series DC/DC converter is proposed. Finally, in order to provide a basis for selecting suitable high voltage and high power converters in DC grids, the voltage stresses, voltage conversion ratios and fault management ability of different converters topologies are analyzed.

  8. Monocyte differentiation in localized juvenile periodontitis is skewed toward the dendritic cell phenotype.

    Science.gov (United States)

    Barbour, Suzanne E; Ishihara, Yuichi; Fakher, Mohammed; Al-Darmaki, Salma; Caven, Timothy H; Shelburne, C P; Best, Al M; Schenkein, Harvey A; Tew, John G

    2002-06-01

    Several lines of evidence indicate that the monocytes of subjects with localized juvenile periodontitis (LJP) are functionally distinct from cells of age- and race-matched nonperiodontitis (NP) subjects. Among the abnormalities are the propensity to secrete large amounts of prostaglandin E(2) and the induction of immunoglobulin G2 (IgG2) antibodies. The experiments described here were performed to further characterize the LJP monocytes and to determine if these cells mature differently than NP monocytes. When adherent monocytes from LJP subjects were cultured in the presence of human serum, both macrophages and cells with the morphology of immature monocyte-derived dendritic cells (MDDC) were observed. Within 4 days the prevalence of the immature MDDC was approximately twofold higher in LJP cultures than in NP cultures. In addition to their dendritic morphology, these cells were CD11c(+) and CD14(-) or CD14(low) and stimulated potent autologous mixed leukocyte reactions, consistent with differentiation to the MDDC phenotype. Like LJP monocytes, cultures of MDDC generated with interleukin-4 and granulocyte-macrophage colony-stimulating factor selectively induced IgG2 in cultures of pokeweed mitogen-stimulated NP leukocytes. Together, these data suggest that the monocytes of LJP subjects have a propensity to differentiate into MDDC and that this differentiation may be related to the high levels of IgG2 that are observed in the sera of LJP subjects. As high levels of circulating IgG2 are correlated with less severe disease, the propensity of LJP monocytes to differentiate into MDDC may have important implications for both the host response against oral pathogens and the progression of LJP.

  9. Research borehole drilling activity for boreholes DH-18, DH-19, DC-12, DC-13, DC-14, DC-15, and deepening of existing borehole DC-7

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    This report is an environmental evaluation of the impacts of proposed borehole drilling activities at the Hanford Site, northwest of Richland, Washington. The proposed action is to drill six research boreholes ranging in depth from 137 to 1372 meters (m) (250 to 4500 +- feet (ft)). In addition, an existing borehole (DC-7) will be extended from 1249 to 1524 m (4099 to 5000 +- ft). The purpose of the US Department of Energy's (DOE) borehole drilling activities is to collect data on in situ rock formations that are considered potentialy suitable for nuclear waste repositories. The technical program efforts necessary to identify and qualify specific underground waste facility sites in candidate rock formations include geologic and hydrologic studies (seismicity and tectonics, rock structure and stratigraphy, lithology, etc.). Borehole drilling is an integral part of the geological studies and is essential to a thorough understanding of potentially suitable geologic formations. The purpose of the proposed drilling activities is to obtain data for evaluating Columbia River basalts that are being evaluated by the National Waste Terminal Storage (NWTS) Program to determine their suitability potential for nuclear waste repositories. Unavoidable impact to the environment is limited primarily to the clearing of land needed for access and drilling operations. Considerations exercised during site preparation, drilling, and subsequent site restoration will limit modification of the natural environment to the minimum required for accomplishment of test objectives.

  10. DC Conductivity of Magnetised Holographic Matter

    CERN Document Server

    Donos, Aristomenis; Griffin, Tom; Melgar, Luis

    2015-01-01

    We consider general black hole solutions of Einstein-Maxwell-scalar theory that are holographically dual to conformal field theories at finite charge density with non-vanishing magnetic fields and local magnetisation currents, which generically break translation invariance explicitly. We show that the thermoelectric DC conductivity of the field theory can be obtained by solving a system of generalised Stokes equations on the black hole horizon. For various examples, including Q-lattices and one-dimensional lattices, we solve the Stokes equations explicitly and obtain expressions for the DC conductivity in terms of the solution at the black hole horizon.

  11. Start-stop and recuperation: DC/DC current inverters with integrated double-layer condensers; Start-Stopp und Rekuperation: DC/DC-Wandler mit integrierten Doppelschichtkondensatoren

    Energy Technology Data Exchange (ETDEWEB)

    Igel, Juergen; Ollhaeuser, Helmut; Jeuck, Marc; Apfelbacher, Thomas [Alcoa/AFL Europe GmbH, Frickenhausen (Germany)

    2008-09-15

    Start-stop systems may be made more efficient, and energy recovery in regenerative brakes may be made more economical. The contribution describes a new DC/DC current inverter with integrated double-layer condensers developed by the electric/electronics department of Alcoa. The so-called Energy Conversion Module (ECM) will result in considerable fuel savings and also help to stabilize board grids which are nearing their limits because of the increasing number of electrified service aggregates. Motor car producers are currently testing the module. (orig.)

  12. Hierarchical Control for Multiple DC Microgrids Clusters

    DEFF Research Database (Denmark)

    Shafiee, Qobad; Dragicevic, Tomislav; Vasquez, Juan Carlos;

    2014-01-01

    This paper presents a distributed hierarchical control framework to ensure reliable operation of dc Microgrid (MG) clusters. In this hierarchy, primary control is used to regulate the common bus voltage inside each MG locally. An adaptive droop method is proposed for this level which determines....... Another distributed policy is employed then to regulate the power flow among the MGs according to their local SOCs. The proposed distributed controllers on each MG communicate with only the neighbor MGs through a communication infrastructure. Finally, the small signal model is expanded for dc MG clusters...

  13. Thermoelectric DC conductivities from black hole horizons

    CERN Document Server

    Donos, Aristomenis

    2014-01-01

    An analytic expression for the DC electrical conductivity in terms of black hole horizon data was recently obtained for a class of holographic black holes exhibiting momentum dissipation. We generalise this result to obtain analogous expressions for the DC thermoelectric and thermal conductivities. We illustrate our results using some holographic Q-lattice black holes as well as for some black holes with linear massless axions, in both $D=4$ and $D=5$ bulk spacetime dimensions, which include both spatially isotropic and anisotropic examples. We show that some recently constructed ground states of holographic Q-lattices, which can be either electrically insulating or metallic, are all thermal insulators.

  14. DC Characterization of the Coaxial Superconducting Cable

    Science.gov (United States)

    Šouc, J.; Gömöry, F.; Vojenčiak, M.; Frolek, L.; Isfort, D.; Ehrenberg, J.; Bock, J.

    2008-01-01

    Coaxial cable model with superconducting core and superconducting shield conductor was constructed and tested in DC regime. While the core was already examined in our previous works, in this contribution the detailed study of the superconducting shield conductor in DC conditions is presented. It consists of 16 ReBCO coated tapes with critical current 35 A each connected in parallel. Using shunts with known values placed in series the currents in individual tapes were possible to measure. Distribution of the total cable current into the individual tapes was monitored and its influence on critical current of the cable is discussed.

  15. Three phase full wave dc motor decoder

    Science.gov (United States)

    Studer, P. A. (Inventor)

    1977-01-01

    A three phase decoder for dc motors is disclosed which employs an extremely simple six transistor circuit to derive six properly phased output signals for fullwave operation of dc motors. Six decoding transistors are coupled at their base-emitter junctions across a resistor network arranged in a delta configuration. Each point of the delta configuration is coupled to one of three position sensors which sense the rotational position of the motor. A second embodiment of the invention is disclosed in which photo-optical isolators are used in place of the decoding transistors.

  16. DC Motor Drive with PFC Rectifier

    Directory of Open Access Journals (Sweden)

    Lascu Mihaela

    2008-05-01

    Full Text Available The goal of this work is to study theperformances of a hybrid controller used to controlDC Motor drive with a single-phase power factorcorrection rectifier. This study is made usingcomputer simulation (Simulink. The first part isdevoted to the control system of the DC Motors. Inthe second part, the design of the hybrid controllerwill be presented. The third part is the design ofthe fast response single-phase boost power factorcorrection rectifier. The last parts are devoted tosimulation and experimental results.

  17. Voltage control of DC islanded microgrids

    DEFF Research Database (Denmark)

    Tucci, Michele; Riverso, Stefano; Quintero, Juan Carlos Vasquez

    2015-01-01

    We propose a new decentralized control scheme for DC Islanded microGrids (ImGs) composed by several Distributed Generation Units (DGUs) with a general interconnection topology. Each local controller regulates to a reference value the voltage of the Point of Common Coupling (PCC) of the correspond......We propose a new decentralized control scheme for DC Islanded microGrids (ImGs) composed by several Distributed Generation Units (DGUs) with a general interconnection topology. Each local controller regulates to a reference value the voltage of the Point of Common Coupling (PCC...

  18. "DC:0-3" to "DC:0-3R" to "DC:0-5": A New Edition

    Science.gov (United States)

    Zeanah, Charles H., Jr.; Carter, Alice; Cohen, Julie; Egger, Helen; Keren, Miri; Gleason, Mary Margaret; Lieberman, Alicia F.; Mulrooney, Kathleen; Oser, Cindy

    2015-01-01

    Originally published in 1994 by ZERO TO THREE as the "Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood" ("DC:0-3") and revised in 2005 by ZERO TO THREE as the "Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised…

  19. Stability analysis of a high-step-Up DC grid-connected two-stage boost DC-DC converter

    Directory of Open Access Journals (Sweden)

    El Aroudi A.

    2014-01-01

    Full Text Available High conversion ratio switching converters are used whenever there is a need to step-up dc source voltage level to a much higher output dc voltage level such as in photovoltaic systems, telecommunications and in some medical applications. A simple solution for achieving this high conversion ratio is by cascading different stages of dc-dc boost converters. The individual converters in such a cascaded system are usually designed separately applying classical design criteria. However these criteria may not be applicable for the complete cascaded system . This paper first presents a glimpse on the bifurcation behavior that a cascade connection of two boost converters can exhibit. It is shown that the desired periodic orbit can undergo period doubling leading to subharmonic oscillations and chaotic regimes. Then, in order to simplify the analysis the second stage is considered as constant current sink and design-oriented analysis is carried out to obtain stability boundaries in the parameter space by taking into account slope interactions between the state variables in the two-different stages.

  20. Homopolar dc motor and trapped flux brushless dc motor using high temperature superconductor materials

    Science.gov (United States)

    Crapo, Alan D.; Lloyd, Jerry D.

    1991-03-01

    Two motors have been designed and built for use with high-temperature superconductor (HTSC) materials. They are a homopolar dc motor that uses HTSC field windings and a brushless dc motor that uses bulk HTSC materials to trap flux in steel rotor poles. The HTSC field windings of the homopolar dc motor are designed to operate at 1000 A/sq cm in a 0.010-T field. In order to maximize torque in the homopolar dc motor, an iron magnetic circuit with small air gaps gives maximum flux for minimum Ampere turns in the field. A copper field winding version of the homopolar dc motor has been tested while waiting for 575 A turn HTSC coils. The trapped flux brushless dc motor has been built and is ready to test melt textured bulk HTSC rings that are currently being prepared. The stator of the trapped flux motor will impress a magnetic field in the steel rotor poles with warm HTSC bulk rings. The rings are then cooled to 77 K to trap the flux in the rotor. The motor can then operate as a brushless dc motor.