On-grid and Off-grid Operation of Multi-Input Single-Output DC/DC Converter based Fuel Cell Generation System

Directory of Open Access Journals (Sweden)

Noroozian

2009-06-01

Full Text Available This paper presents the modeling and simulation of a proton exchange membrane fuel cell (PEMFC generation system for off-grid and on-grid operation and configuration. A fuel cell DG system consists of a fuel cell power plant, a DC/DC converter and a DC/AC inverter. The dynamic model for fuel cell array and its power electronic interfacing are presented also a multi-input single output (MISO DC/DC converter and its control scheme is proposed and analyzed. This DC/DC converter is capable of interfacing fuel cell arrays to the DC/AC inverter. Also the mathematical model of the inverter is obtained by using average technique. Then the novel control strategy of DC/AC inverter for different operating conditions is demonstrated. The simulation results show the effectiveness of the suggested control systems under both on-grid and off-grid operation modes.

SUBCONTRACT REPORT: DC-DC Converter for Fuel Cell and Hybrid Vehicles

Energy Technology Data Exchange (ETDEWEB)

Marlino, Laura D [ORNL; Zhu, Lizhi [Ballard Power Systems/Siemens VDO

2007-07-01

The goal of this project is to develop and fabricate a 5kW dc-dc converter with a baseline 14V output capability for fuel cell and hybrid vehicles. The major objectives for this dc-dc converter technology are to meet: Higher efficiency (92%); High coolant temperature,e capability (105 C); High reliability (15 Years/150,000miles); Smaller volume (5L); Lower weight (6kg); and Lower cost ($75/kW). The key technical challenge for these converters is the 105 C coolant temperatures. The power switches and magnetics must be designed to sustain these operating temperatures reliably, without a large cost/mass/volume penalty.

Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells.

Science.gov (United States)

Kulzer, Lorenz; Rubner, Yvonne; Deloch, Lisa; Allgäuer, Andrea; Frey, Benjamin; Fietkau, Rainer; Dörrie, Jan; Schaft, Niels; Gaipl, Udo S

2014-10-01

Despite the transient immunosuppressive properties of local radiotherapy (RT), this classical treatment modality of solid tumors is capable of inducing immunostimulatory forms of tumor-cell death. The resulting 'immunotoxicity' in the tumor, but not in healthy tissues, may finally lead to immune-mediated destruction of the tumor. However, little is known about the best irradiation scheme in this setting. This study examines the immunological effects of differently irradiated human colorectal tumor cells on human monocyte-derived dendritic cells (DC). Human SW480 tumor cells were irradiated with a norm-fractionation scheme (5 × 2 Gy), a hypo-fractionated protocol (3 × 5 Gy), and with a high single irradiation dose (radiosurgery; 1 × 15 Gy). Subsequently, human immature DC (iDC) were co-incubated with supernatants (SN) of these differently treated tumor cells. Afterwards, DC were analyzed regarding the expression of maturation markers, the release of cytokines, and the potential to stimulate CD4(+) T-cells. The co-incubation of iDC with SN of tumor cells exposed to norm- or hypo-fractionated RT resulted in a significantly increased secretion of the immune activating cytokines IL-12p70, IL-8, IL-6, and TNFα, compared to iDC co-incubated with SN of tumor cells that received a high single irradiation dose or were not irradiated. In addition, DC-maturation markers CD80, CD83, and CD25 were also exclusively elevated after co-incubation with the SN of fractionated irradiated tumor cells. Furthermore, the SN of tumor cells that were irradiated with norm- or hypo-fractionated RT triggered iDC to stimulate CD4(+) T-cells not only in an allogenic, but also in an antigen-specific manner like mature DC. Collectively, these results demonstrate that norm- and hypo-fractionated RT induces a fast human colorectal tumor-cell death with immunogenic potential that can trigger DC maturation and activation in vitro. Such findings may contribute to the improvement of

Analysis and Design of Bi-Directional DC-DC Converter in the Extended Run Time DC UPS System Based on Fuel Cell and Supercapacitor

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

2009-01-01

Abstract-In this paper, an extended run time DC UPS system structure with fuel cell and supercapacitor is investigated. A wide input range bi-directional dc-dc converter is described along with the phase-shift modulation scheme and phase-shift with duty cycle control, in different modes. The deli......Abstract-In this paper, an extended run time DC UPS system structure with fuel cell and supercapacitor is investigated. A wide input range bi-directional dc-dc converter is described along with the phase-shift modulation scheme and phase-shift with duty cycle control, in different modes...

Technical advance: Generation of human pDC equivalents from primary monocytes using Flt3-L and their functional validation under hypoxia.

Science.gov (United States)

Sekar, Divya; Brüne, Bernhard; Weigert, Andreas

2010-08-01

The division of labor between DC subsets is evolutionarily well-defined. mDC are efficient in antigen presentation, whereas pDC act as rheostats of the immune system. They activate NK cells, cause bystander activation of mDC, and interact with T cells to induce tolerance. This ambiguity positions pDC at the center of inflammatory diseases, such as cancer, arthritis, and autoimmune diseases. The ability to generate human mDC ex vivo made it possible to engineer them to suit therapy needs. Unfortunately, a similar, easily accessible system to generate human pDC is not available. We describe a method to generate human pDC equivalents ex vivo, termed mo-pDC from peripheral blood monocytes using Flt3-L. mo-pDC showed a characteristic pDC profile, such as high CD123 and BDCA4, but low CD86 and TLR4 surface expression and a low capacity to induce autologous lymphocyte proliferation and to phagocytose apoptotic debris in comparison with mDC. Interestingly, mo-pDC up-regulated the pDC lineage-determining transcription factor E2-2 as well as expression of BDCA2, which is under the transcriptional control of E2-2 but not its inhibitor ID2, during differentiation. mo-pDC produced high levels of IFN-alpha when pretreated overnight with TNF-alpha. Under hypoxia, E2-2 was down-regulated, and ID2 was induced in mo-pDC, whereas surface expression of MHCI, CD86, and BDCA2 was decreased. Furthermore, mo-pDC produced high levels of inflammatory cytokines when differentiated under hypoxia compared with normoxia. Hence, mo-pDC can be used to study differentiation and functions of human pDC under microenvironmental stimuli.

Human milk blocks DC-SIGN - pathogen interaction via MUC1

Directory of Open Access Journals (Sweden)

Nathalie eKoning

2015-03-01

Full Text Available Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens, as well as long term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on DC and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is DC-SIGN, which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastro-intestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out.

Isolated Full Bridge Boost DC-DC Converter Designed for Bidirectional Operation of Fuel Cells/Electrolyzer Cells in Grid-Tie Applications

DEFF Research Database (Denmark)

Pittini, Riccardo; Zhang, Zhe; Andersen, Michael A. E.

2013-01-01

Energy production from renewable energy sources is continuously varying, for this reason energy storage is becoming more and more important as the percentage of green energy increases. Newly developed fuel cells can operate in reverse mode as electrolyzer cells; therefore, they are becoming...... current. Dc-dc converter efficiency plays a fundamental role in the overall system efficiency since processed energy is always flowing through the converter; for this reason, loss analysis and optimization are a key component of the converter design. The paper presents an isolated full bridge boost dc...

A sea urchin lectin, SUL-1, from the Toxopneustid sea urchin induces DC maturation from human monocyte and drives Th1 polarization in vitro

International Nuclear Information System (INIS)

Takei, Masao; Nakagawa, Hideyuki

2006-01-01

The sea urchin Toxopneustes pileolus belonging to the family Toxopneustidae, they have well-developed globiferous pedicellariae with pharmacologically active substances. We have purified a novel sea urchin lectin-1 (SUL-1) from the large globiferous pedicellariae of T. pileolus. Dendritic cells (DC) are professional APC and play a pivotal role in controlling immune responses. This study investigated whether SUL-1 can drive DC maturation from human immature monocyte-derived DC in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days followed by another 1 day in the presence of SUL-1 or LPS. DC harvested on day 7 were examined using functional assays. The expression levels of CD1a, CD80, CD83, CD86 and HLA-DR as expressed by mean fluorescence intensity (MFI) on DC differentiated from immature DC after culture with 1.0 μg/ml of SUL-1 for 1 day were enhanced and decreased endocytic activity. SUL-1-treated DC also displayed enhanced T cell stimulatory capacity in an MLR, as measured by T cell proliferation. Cell surface expression of CD80, CD83 and CD86 on SUL-1-treated DC was inhibited by anti-DC-SIGN mAb, while anti-DC-SIGN mAb had no influence on allogeneic T cell proliferation by SUL-1-treated DC. DC differentiated with SUL-1 induced the differentiation of naive T cell towards a helper T cell type 1 (Th1) response at DC/T (1:5) cells ratio depending on IL-12 secretion. In CTL assay, the production of IFN-γ and 51 Cr release on SUL-1-treated DC were more augmented than of immature DC or LPS-treated DC. SUL-1-treated DC expressed CCR7 and had a high migration to MIP-3β. Intracellular Ca 2+ mobilization in SUL-1-treated DC was also induced by MIP-3β. These results suggest that SUL-1 bindings to DC-SIGN on surface of immature DC may lead to differentiate DC from immature DC. Moreover, it suggests that SUL-1 may be used on DC-based vaccines for cancer immunotherapy

Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation

Directory of Open Access Journals (Sweden)

Simone P. Sittig

2015-12-01

Full Text Available Dendritic cell (DC-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c+ and CD141+ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies.

Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors

Directory of Open Access Journals (Sweden)

Julie Helft

2017-07-01

Full Text Available Conventional dendritic cells (cDCs are thought to descend from a DC precursor downstream of the common myeloid progenitor (CMP. However, a mouse lymphoid-primed multipotent progenitor has been shown to generate cDCs following a DC-specific developmental pathway independent of monocyte and granulocyte poiesis. Similarly, here we show that, in humans, a large fraction of multipotent lymphoid early progenitors (MLPs gives rise to cDCs, in particular the subset known as cDC1, identified by co-expression of DNGR-1 (CLEC9A and CD141 (BDCA-3. Single-cell analysis indicates that over one-third of MLPs have the potential to efficiently generate cDCs. cDC1s generated from CMPs or MLPs do not exhibit differences in transcriptome or phenotype. These results demonstrate an early imprinting of the cDC lineage in human hematopoiesis and highlight the plasticity of developmental pathways giving rise to human DCs.

DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells.

Directory of Open Access Journals (Sweden)

Marion Avril

Full Text Available During blood stage infection, Plasmodium falciparum infected erythrocytes (IE bind to host blood vessels. This virulence determinant enables parasites to evade spleen-dependent killing mechanisms, but paradoxically in some cases may reduce parasite fitness by killing the host. Adhesion of infected erythrocytes is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1, a family of polymorphic adhesion proteins encoded by var genes. Whereas cerebral binding and severe malaria are associated with parasites expressing DC8 and DC13 var genes, relatively little is known about the non-brain endothelial selection on severe malaria adhesive types. In this study, we selected P. falciparum-IEs on diverse endothelial cell types and demonstrate that DC8 and DC13 var genes were consistently among the major var transcripts selected on non-brain endothelial cells (lung, heart, bone marrow. To investigate the molecular basis for this avid endothelial binding activity, recombinant proteins were expressed from the predominant upregulated DC8 transcript, IT4var19. In-depth binding comparisons revealed that multiple extracellular domains from this protein bound brain and non-brain endothelial cells, and individual domains largely did not discriminate between different endothelial cell types. Additionally, we found that recombinant DC8 and DC13 CIDR1 domains exhibited a widespread endothelial binding activity and could compete for DC8-IE binding to brain endothelial cells, suggesting they may bind the same host receptor. Our findings provide new insights into the interaction of severe malaria adhesive types and host blood vessels and support the hypothesis that parasites causing severe malaria express PfEMP1 variants with a superior ability to adhere to diverse endothelial cell types, and may therefore endow these parasites with a growth and transmission advantage.

A Rapid Culture Technique Produces Functional Dendritic-Like Cells from Human Acute Myeloid Leukemia Cell Lines

Directory of Open Access Journals (Sweden)

Jian Ning

2011-01-01

Full Text Available Most anti-cancer immunotherapeutic strategies involving dendritic cells (DC as vaccines rely upon the adoptive transfer of DC loaded with exogenous tumour-peptides. This study utilized human acute myeloid leukemia (AML cells as progenitors from which functional dendritic-like antigen presenting cells (DLC were generated, that constitutively express tumour antigens for recognition by CD8+ T cells. DLC were generated from AML cell lines KG-1 and MUTZ-3 using rapid culture techniques and appropriate cytokines. DLC were evaluated for their cell-surface phenotype, antigen uptake and ability to stimulate allogeneic responder cell proliferation, and production of IFN-γ; compared with DC derived from normal human PBMC donors. KG-1 and MUTZ-3 DLC increased expression of CD80, CD83, CD86, and HLA-DR, and MUTZ-3 DLC downregulated CD14 and expressed CD1a. Importantly, both KG-1 and MUTZ-3-derived DLC promoted proliferation of allogeneic responder cells more efficiently than unmodified cells; neither cells incorporated FITC-labeled dextran, but both stimulated IFN-γ production from responding allogeneic CD8+ T cells. Control DC produced from PBMC using the FastDC culture also expressed high levels of critical cell surface ligands and demonstrated good APC function. This paper indicates that functional DLC can be cultured from the AML cell lines KG-1 and MUTZ-3, and FastDC culture generates functional KG-1 DLC.

NK cell-derived IL-10 is critical for DC-NK cell dialogue at the maternal-fetal interface.

Science.gov (United States)

Blois, Sandra M; Freitag, Nancy; Tirado-González, Irene; Cheng, Shi-Bin; Heimesaat, Markus M; Bereswill, Stefan; Rose, Matthias; Conrad, Melanie L; Barrientos, Gabriela; Sharma, Surendra

2017-05-19

DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion. Remarkably, DC expansion in IL-10 -/- dams provoked pregnancy loss, which could be abrogated by the adoptive transfer of IL-10 +/+ NK cells and not by IL-10 -/- NK cells. Furthermore, the IL-10 expressing NK cells markedly enhanced angiogenic responses and placental development in DC expanded IL-10 -/- dams. Thus, the capacity of NK cells to secrete IL-10 plays a unique role facilitating the DC-NK cell dialogue during the establishment of a healthy gestation.

Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.

Science.gov (United States)

Aerts, Joachim G J V; de Goeje, Pauline L; Cornelissen, Robin; Kaijen-Lambers, Margaretha E H; Bezemer, Koen; van der Leest, Cor H; Mahaweni, Niken M; Kunert, André; Eskens, Ferry A L M; Waasdorp, Cynthia; Braakman, Eric; van der Holt, Bronno; Vulto, Arnold G; Hendriks, Rudi W; Hegmans, Joost P J J; Hoogsteden, Henk C

2018-02-15

Purpose: Mesothelioma has been regarded as a nonimmunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis. Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response toward malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source. The purpose of this study was to investigate whether allogeneic lysate-pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: First, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate or injected with PBS (negative control). Survival and tumor-directed T-cell responses of these mice were monitored. Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25, or 50 million DCs per vaccination. DC vaccination consisted of autologous monocyte-derived DCs pulsed with tumor lysate from five mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose-limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months [95% confidence interval (CI), 4.1-20.3] and median OS not reached (median follow-up = 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans. Clin Cancer Res; 24(4); 766-76. ©2017 AACR . ©2017 American Association for Cancer Research.

A review on DC/DC converter architectures for power fuel cell applications

International Nuclear Information System (INIS)

Kolli, Abdelfatah; Gaillard, Arnaud; De Bernardinis, Alexandre; Bethoux, Olivier; Hissel, Daniel; Khatir, Zoubir

2015-01-01

Highlights: • Different DC/DC power converter topologies for Fuel Cell systems are presented. • Advantages and drawbacks of the DC/DC power converter topologies are detailed. • Wide-BandGap semiconductors are attractive candidates for design of converters. • Wide-BandGap semiconductors improve efficiency and thermal limits of converters. • Different semiconductor technologies are assessed. - Abstract: Fuel cell-based power sources are attractive devices. Through multi-stack architecture, they offer flexibility, reliability, and efficiency. Keys to accessing the market are simplifying its architecture and each components. These include, among others, the power converter enabling the output voltage regulation. This article focuses on this specific component. The present paper gives a comprehensive overview of the power converter interfaces potentially favorable for the automotive, railways, aircrafts and small stationary domains. First, with respect to the strategic development of a modular design, it defines the specifications of a basic interface. Second, it inventories the best architecture opportunities with respect to these requirements. Based on this study, it fully designs a basic module and points out the outstanding contribution of the new developed silicon carbide switch technology. In conclusion, this review article exhibits the importance of choosing the right power converter architecture and the related technology. In this context it is highlighted that the output power interface can be efficient, compact and modular. In addition, its features enable a thermal compatibility with many ways of integrating this component in the global fuel cell based power source.

Human Blood CD1c+ Dendritic Cells Promote Th1 and Th17 Effector Function in Memory CD4+ T Cells.

Science.gov (United States)

Leal Rojas, Ingrid M; Mok, Wai-Hong; Pearson, Frances E; Minoda, Yoshihito; Kenna, Tony J; Barnard, Ross T; Radford, Kristen J

2017-01-01

Dendritic cells (DC) initiate the differentiation of CD4 + helper T cells into effector cells including Th1 and Th17 responses that play an important role in inflammation and autoimmune disease pathogenesis. In mice, Th1 and Th17 responses are regulated by different conventional (c) DC subsets, with cDC1 being the main producers of IL-12p70 and inducers of Th1 responses, while cDC2 produce IL-23 to promote Th17 responses. The role that human DC subsets play in memory CD4 + T cell activation is not known. This study investigated production of Th1 promoting cytokine IL-12p70, and Th17 promoting cytokines, IL-1β, IL-6, and IL-23, by human blood monocytes, CD1c + DC, CD141 + DC, and plasmacytoid DC and examined their ability to induce Th1 and Th17 responses in memory CD4 + T cells. Human CD1c + DC produced IL-12p70, IL-1β, IL-6, and IL-23 in response to R848 combined with LPS or poly I:C. CD141 + DC were also capable of producing IL-12p70 and IL-23 but were not as proficient as CD1c + DC. Activated CD1c + DC were endowed with the capacity to promote both Th1 and Th17 effector function in memory CD4 + T cells, characterized by high production of interferon-γ, IL-17A, IL-17F, IL-21, and IL-22. These findings support a role for CD1c + DC in autoimmune inflammation where Th1/Th17 responses play an important role in disease pathogenesis.

Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells

Directory of Open Access Journals (Sweden)

Inge L. Huibregtse

2012-01-01

Full Text Available Interleukin-10 (IL-10 plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.  lactisIL-10 on DC function in vitro. Monocyte-derived DC incubated with L.  lactisIL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L.  lactisIL-10-derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L.  lactisIL-10-derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130 pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases.

Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

Directory of Open Access Journals (Sweden)

Hui-Fang Chang

Full Text Available We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz. The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

Science.gov (United States)

Chang, Hui-Fang; Lee, Ying-Shan; Tang, Tang K; Cheng, Ji-Yen

2016-01-01

We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

A DC-DC Converter with Wide Input Voltage Range for Fuel Cell and Supercapacitor Application

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael Andreas E.

2009-01-01

This paper proposes a novel phase-shift plus duty cycle controlled hybrid bi-directional DC-DC converter based on fuel cells and supercapacitors. The described converter employs two high frequency transformers to couple the half-bridge and full-bridge circuits together in the primary side...

Binding of HIV-1 gp120 to DC-SIGN promotes ASK-1-dependent activation-induced apoptosis of human dendritic cells.

Directory of Open Access Journals (Sweden)

Yongxiong Chen

2013-01-01

Full Text Available During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC, including DC-SIGN⁺ cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN⁺ blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV⁺ serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN⁺ DC that were isolated directly from HIV-1⁺ individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential

A Two-stage DC-DC Converter for the Fuel Cell-Supercapacitor Hybrid System

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

2009-01-01

A wide input range multi-stage converter is proposed with the fuel cells and supercapacitors as a hybrid system. The front-end two-phase boost converter is used to optimize the output power and to reduce the current ripple of fuel cells. The supercapacitor power module is connected by push...... and designed. A 1kW prototype controlled by TMS320F2808 DSP is built in the lab. Simulation and experimental results confirm the feasibility of the proposed two stage dc-dc converter system.......-pull-forward half bridge (PPFHB) converter with coupled inductors in the second stage to handle the slow transient response of the fuel cells and realize the bidirectional power flow control. Moreover, this cascaded structure simplifies the power management. The control strategy for the whole system is analyzed...

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

Directory of Open Access Journals (Sweden)

Tobias Roider

2016-12-01

Full Text Available Antithymocyte globulin (ATG is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon® on human monocyte-derived dendritic cells (DC. ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.

Assessment of flhDC mRNA levels in Serratia liquefaciens swarm cells

DEFF Research Database (Denmark)

Tolker-Nielsen, Tim; Christensen, Allan Beck; Holmstrøm, K.

2000-01-01

We reported previously that artificial overexpression of the flhDC operon in liquid-grown Serratia liquefaciens resulted in the formation of filamentous, multinucleated, and hyperflagellated cells that were indistinguishable from surface-induced swarm cells (L. Eberl, G. Christiansen, S. Molin, a......, vegetative cells. This suggests that surface-induced S. liquefaciens swarm cell differentiation, although dependent on flhDC gene expression, does not occur through elevated flhDC mRNA levels....

Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts.

Science.gov (United States)

Zhao, Lei; Shao, Qianqian; Zhang, Yun; Zhang, Lin; He, Ying; Wang, Lijie; Kong, Beihua; Qu, Xun

2016-02-09

Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal-placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN(+)CD14(+)CD1a(-) phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS, and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4(+)CD25(+)Foxp3(+) Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal-fetal interface.

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

Directory of Open Access Journals (Sweden)

Jennifer Paijo

2016-04-01

Full Text Available 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.

Multi-cell DC-DC converters : modelling, analysis and control

International Nuclear Information System (INIS)

Feki, M.; El Aroudi, A.; Robert, B.G.M.

2011-01-01

This paper is devoted to modeling of a two-cell DC/DC buck converter, to the analysis of its behavior and to the design of control methods that yield to improve its performances. Various numerical simulations and dynamical aspects of this system are illustrated in the time domain and in the parameter space. Without control, the system may present many undesirable behaviors such as sub-harmonics and chaotic oscillations. The proposed controllers are able to widen the stability range of the system. Optimum values of parameters giving rise to fast response while maintaining stable periodic behavior are given in closed form. However, it is detected that in a certain region of the parameter space, the stabilized periodic orbit may coexist with a chaotic attractor. Boundary between basins of attraction are obtained by means of numerical simulations.

MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells

NARCIS (Netherlands)

Saeland, E.; Jong, de M.A.W.P.; Nabatov, A.; Kalay, H.; Kooijk, van Y.; Geijtenbeek, T.B.H.

2009-01-01

Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk,

Generation of dendritic cells from human bone marrow mononuclear cells: advantages for clinical application in comparison to peripheral blood monocyte derived cells.

Science.gov (United States)

Bai, L; Feuerer, M; Beckhove, P; Umansky, V; Schirrmacher, V

2002-02-01

Dendritic cells (DCs) currently used for vaccination in clinical studies to induce immunity against malignant cells are normally generated from peripheral blood-derived monocytes. Here we studied conditions for the generation of DCs from unseparated human bone marrow (BM) mononuclear cells and compared them functionally with DCs from blood. The two types of DCs, from bone marrow (BM-DC) and peripheral blood (BL-DC), were generated in parallel from the same normal healthy donors by culturing in serum-free X-VIVO 20 medium containing GM-CSF and IL-4, and then the phenotypes and functions were compared. BM-DC generation occurred in 14 days and involved proliferative expansion from CD34 stem cells and differentiation while BL-DC generation occurred in 7 days from CD14 monocytes and involved only differentiation. A 7- to 25-fold higher number of DCs could be obtained from BM than from blood. BM-DC had similar phenotypes as BL-DC. The capacity to stimulate MLR reactivity in allogeneic T lymphocytes was higher with BM-DC than that with BL-DC. Also, the capacity to stimulate autologous memory T cell responses to tetanus toxoid (TT) or tuberculin (PPD) was higher with BM-DC than with BL-DC. These results suggest that BM-DC as produced here may be a very economic and useful source of professional antigen-presenting cells for anti-tumor immunotherapeutic protocols.

Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation.

Science.gov (United States)

Li, Qian; Guo, Zhenhong; Xu, Xiongfei; Xia, Sheng; Cao, Xuetao

2008-10-01

The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E2 (PGE2) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-beta is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4+CD25+Foxp3+ Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung.

Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

LENUS (Irish Health Repository)

Ryan, Ruth CM

2011-10-24

Abstract Background Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival. Results Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3\\/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth. Conclusions Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.

Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.

Directory of Open Access Journals (Sweden)

Irene Tirado-González

Full Text Available Dendritic cell (DC and natural killer (NK cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression.

Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.

Science.gov (United States)

Tirado-González, Irene; González, Irene Tirado; Barrientos, Gabriela; Freitag, Nancy; Otto, Teresa; Thijssen, Victor L J L; Moschansky, Petra; von Kwiatkowski, Petra; Klapp, Burghard F; Winterhager, Elke; Bauersachs, Stefan; Blois, Sandra M

2012-01-01

Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression.

Analysis and Design of a Bidirectional Isolated DC-DC Converter for Fuel Cell and Super-Capacitor Hybrid System

DEFF Research Database (Denmark)

Zhang, Zhe; Ouyang, Ziwei; Thomsen, Ole Cornelius

2012-01-01

Electrical power system in future uninterruptible power supply (UPS) or electrical vehicle (EV) may employ hybrid energy sources, such as fuel cells and super-capacitors. It will be necessary to efficiently draw the energy from these two sources as well as recharge the energy storage elements...... by the DC bus. In this paper, a bidirectional isolated DC-DC converter controlled by phase-shift and duty cycle for the fuel cell hybrid energy system is analyzed and designed. The proposed topology minimizes the number of switches and their associated gate driver components by using two high frequency...

Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells.

Directory of Open Access Journals (Sweden)

Yu Cong

2016-05-01

Full Text Available Humans infected with yellow fever virus (YFV, a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM and dendritic cells (MoDC from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.

No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory regulator of human T cell activation.

Science.gov (United States)

Pfistershammer, Katharina; Klauser, Christoph; Pickl, Winfried F; Stöckl, Johannes; Leitner, Judith; Zlabinger, Gerhard; Majdic, Otto; Steinberger, Peter

2006-05-01

The B7 family member programmed-death-1-ligand 2 (PD-L2/B7-DC) is a ligand for programmed-death-receptor 1 (PD-1), a receptor involved in negative regulation of T cell activation. Several independent studies have reported that PD-L2, however, can also potently costimulate murine T cells via an additional yet unidentified receptor. In this study, we evaluated the contribution of PD-L2 to the activation of human T cells using a novel system of engineered T cell stimulators that expresses membrane-bound anti-CD3 antibodies. Analyzing early activation markers, cytokine production and proliferation, we found PD-L2 to consistently inhibit T cell activation. PD-L2 inhibition affected CD4+ and CD8+ T cells and was not abrogated by costimulation via CD28. Blocking PD-1 reverted the inhibitory effect of PD-L2, demonstrating involvement of this pathway. In human T cells, we found no evidence for any of the costimulatory effects described for PD-L2 in murine systems. In line with our functional data that do not point to stimulatory PD-L2-ligands, we show that binding of PD-L2-immunoglobulin to activated human T cells is abrogated by PD-1 antibodies. Our results demonstrate that PD-L2 negatively regulates human T cell activation and thus might be a candidate molecule for immunotherapeutic approaches aimed to attenuate pathological immune responses.

Proteome analysis demonstrates profound alterations in human dendritic cell nature by TX527, an analogue of vitamin D

DEFF Research Database (Denmark)

Ferreira, G. B.; van Etten, E.; Lage, K.

2009-01-01

Structural analogues of vitamin D have been put forward as therapeutic agents able to exploit the immunomodulatory effects of vitamin D, without its undesired calcemic side effects. We have demonstrated that TX527 affects dendritic cell (DC) maturation in vitro, resulting in the generation...... of a tolerogenic cell. In the present study, we aimed to explore the global protein changes induced by the analogue in immature DC (iDC) and mature human DC and to correlate them with alterations in DC morphology and function. Human CD14(+) monocytes were differentiated toward iDC or mature DCs, in the presence...

Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation

Science.gov (United States)

Thomas, S; Przesdzing, I; Metzke, D; Schmitz, J; Radbruch, A; Baumgart, D C

2009-01-01

Saccharomyces boulardii (Sb) is a probiotic yeast preparation that has demonstrated efficacy in inflammatory and infectious disorders of the gastrointestinal tract in controlled clinical trials. Although patients clearly benefit from treatment with Sb, little is known on how Sb unfolds its anti-inflammatory properties in humans. Dendritic cells (DC) balance tolerance and immunity and are involved critically in the control of T cell activation. Thus, they are believed to have a pivotal role in the initiation and perpetuation of chronic inflammatory disorders, not only in the gut. We therefore decided to investigate if Sb modulates DC function. Culture of primary (native, non-monocyte-derived) human myeloid CD1c+CD11c+CD123– DC (mDC) in the presence of Sb culture supernatant (active component molecular weight < 3 kDa, as evaluated by membrane partition chromatography) reduced significantly expression of the co-stimulatory molecules CD40 and CD80 (P < 0·01) and the DC mobilization marker CC-chemokine receptor CCR7 (CD197) (P < 0·001) induced by the prototypical microbial antigen lipopolysaccharide (LPS). Moreover, secretion of key proinflammatory cytokines such as tumour necrosis factor-α and interleukin (IL)-6 were notably reduced, while the secretion of anti-inflammatory IL-10 increased. Finally, Sb supernatant inhibited the proliferation of naive T cells in a mixed lymphocyte reaction with mDC. In summary, our data suggest that Sb may exhibit part of its anti-inflammatory potential through modulation of DC phenotype, function and migration by inhibition of their immune response to bacterial microbial surrogate antigens such as LPS. PMID:19161443

Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells.

Science.gov (United States)

Cougoule, Céline; Lastrucci, Claire; Guiet, Romain; Mascarau, Rémi; Meunier, Etienne; Lugo-Villarino, Geanncarlo; Neyrolles, Olivier; Poincloux, Renaud; Maridonneau-Parini, Isabelle

2018-01-01

Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo , or in collagen matrices in vitro . However, the mechanisms of 3D migration used by human immature DC (iDC) are still poorly characterized. Here, we reveal that human monocyte-derived DC are able to use two migration modes in 3D. In porous matrices of fibrillar collagen I, iDC adopted the amoeboid migration mode. In dense matrices of gelled collagen I or Matrigel, iDC used the protease-dependent, ROCK-independent mesenchymal migration mode. Upon TLR4 activation by LPS, mDC-LPS lose the capacity to form podosomes and degrade the matrix along with impaired mesenchymal migration. TLR2 activation by Pam 3 CSK 4 resulted in DC maturation, podosome maintenance, and efficient mesenchymal migration. Under all these conditions, when DC used the mesenchymal mode in dense matrices, they formed 3D podosomes at the tip of cell protrusions. Using PGE 2 , known to disrupt podosomes in DC, we observed that the cells remained in an immature status and the mesenchymal migration mode was abolished. We also observed that, while CCL5 (attractant of iDC) enhanced both amoeboid and mesenchymal migration of iDC, CCL19 and CCL21 (attractants of mDC) only enhanced mDC-LPS amoeboid migration without triggering mesenchymal migration. Finally, we examined the migration of iDC in tumor cell spheroids, a tissue-like 3D environment. We observed that iDC infiltrated spheroids of tumor cells using both migration modes. Altogether, these results demonstrate that human DC adopt the mesenchymal mode to

NOD/scid IL-2Rgnull mice: a preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo

Directory of Open Access Journals (Sweden)

Spranger Stefani

2012-02-01

Full Text Available Abstract Background To date very few systems have been described for preclinical investigations of human cellular therapeutics in vivo. However, the ability to carry out comparisons of new cellular vaccines in vivo would be of substantial interest for design of clinical studies. Here we describe a humanized mouse model to assess the efficacy of various human dendritic cell (DC preparations. Two reconstitution regimes of NOD/scid IL2Rgnull (NSG mice with adult human peripheral blood mononuclear cells (PBMC were evaluated for engraftment using 4-week and 9-week schedules. This led to selection of a simple and rapid protocol for engraftment and vaccine evaluation that encompassed 4 weeks. Methods NSG recipients of human PBMC were engrafted over 14 days and then vaccinated twice with autologous DC via intravenous injection. Three DC vaccine formulations were compared that varied generation time in vitro (3 days versus 7 days and signals for maturation (with or without Toll-like receptor (TLR3 and TLR7/8 agonists using MART-1 as a surrogate antigen, by electroporating mature DC with in vitro transcribed RNA encoding full length protein. After two weekly vaccinations, the splenocyte populations containing human lymphocytes were recovered 7 days later and assessed for MART-1-specific immune responses using MHC-multimer-binding assays and functional assessment of specific killing of melanoma tumor cell lines. Results Human monocyte-derived DC generated in vitro in 3 days induced better MART-1-specific immune responses in the autologous donor T cells present in the humanized NSG mice. Moreover, consistent with our in vitro observations, vaccination using mature DC activated with TLR3 and TLR7/8 agonists resulted in enhanced immune responses in vivo. These findings led to a ranking of the DC vaccine effects in vivo that reflected the hierarchy previously found for these mature DC variations in vitro. Conclusions This humanized mouse model system enables

CISH is induced during DC development and regulates DC-mediated CTL activation.

Science.gov (United States)

Miah, Mohammad Alam; Yoon, Cheol-Hee; Kim, Joonoh; Jang, Jinah; Seong, Young-Rim; Bae, Yong-Soo

2012-01-01

The cytokine inducible SH2-domain protein (CISH) is a well-known STAT5 target gene, but its role in the immune system remains uncertain. In this study, we found that CISH is predominantly induced during dendritic cell (DC) development from mouse bone marrow (BM) cells and plays a crucial role in type 1 DC development and DC-mediated CTL activation. CISH knockdown reduced the expression of MHC class I, co-stimulatory molecules and pro-inflammatory cytokines in BMDCs. Meanwhile, the DC yield was markedly enhanced by CISH knockdown via cell-cycle activation and reduction of cell apoptosis. Down-regulation of cell proliferation at the later stage of DC development was found to be associated with CISH-mediated negative feedback regulation of STAT5 activation. In T-cell immunity, OT-1 T-cell proliferation was significantly reduced by CISH knockdown in DCs, whereas OT-2 T-cell proliferation was not affected by CISH knockdown. CTLs generated by DC vaccination were also markedly reduced by CISH knockdown, followed by significant impairment of DC-based tumor immunotherapy. Taken together, our data suggest that CISH expression at the later stage of DC development triggers the shutdown of DC progenitor cell proliferation and facilitates DC differentiation into a potent stimulator of CTLs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immature and maturation-resistant human dendritic cells generated from bone marrow require two stimulations to induce T cell anergy in vitro.

Directory of Open Access Journals (Sweden)

Thomas G Berger

Full Text Available Immature dendritic cells (DC represent potential clinical tools for tolerogenic cellular immunotherapy in both transplantation and autoimmunity. A major drawback in vivo is their potential to mature during infections or inflammation, which would convert their tolerogenicity into immunogenicity. The generation of immature DC from human bone marrow (BM by low doses of GM-CSF (lowGM in the absence of IL-4 under GMP conditions create DC resistant to maturation, detected by surface marker expression and primary stimulation by allogeneic T cells. This resistence could not be observed for BM-derived DC generated with high doses of GM-CSF plus IL-4 (highGM/4, although both DC types induced primary allogeneic T cell anergy in vitro. The estabishment of the anergic state requires two subsequent stimulations by immature DC. Anergy induction was more profound with lowGM-DC due to their maturation resistance. Together, we show the generation of immature, maturation-resistant lowGM-DC for potential clinical use in transplant rejection and propose a two-step-model of T cell anergy induction by immature DC.

LPV model for PV cell and fractional control of DC/DC converter for photovoltaic systems

OpenAIRE

Martínez González, Rubén; Bolea Monte, Yolanda; Grau Saldes, Antoni; Martínez García, Herminio

2011-01-01

This paper deals with the fractional modelling of a DC-DC converter, suitable in solar-powered electrical generation systems, and the design of a fractional controller for the aforementioned switching converter. A new model for PV cells is proposed in order to obtain a linear equation for V-I characteristic via scheduling dependence of temperature and irradiance. Due to the fractional nature of the ultracapacitors this kind of controller gives a suitable and good performance. Peer Reviewed

LPV model for PV cells and fractional control of DC/DC converter for photovoltaic systems

OpenAIRE

Martínez González, Rubén; Bolea Monte, Yolanda; Grau Saldes, Antoni; Martínez García, Herminio

2011-01-01

This paper deals with the fractional modelling of a DC-DC converter, suitable in solar-powered electrical generation systems, and the design of a fractional controller for the aforementioned switching converter. A new model for PV cells is proposed in order to obtain a linear equation for VI characteristic via scheduling dependence of temperature and irradiance. Due to the fractional nature of the ultracapacitors this kind of controller gives a suitable and good performance. Peer Rev...

Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells.

Directory of Open Access Journals (Sweden)

Junping Ren

Full Text Available Human metapneumovirus (hMPV is a leading cause of lower respiratory infection in young children, the elderly and immunocompromised patients. Repeated hMPV infections occur throughout life. However, immune evasion mechanisms of hMPV infection are largely unknown. Recently, our group has demonstrated that hMPV M2-2 protein, an important virulence factor, contributes to immune evasion in airway epithelial cells by targeting the mitochondrial antiviral-signaling protein (MAVS. Whether M2-2 regulates the innate immunity in human dendritic cells (DC, an important family of immune cells controlling antigen presenting, is currently unknown. We found that human DC infected with a virus lacking M2-2 protein expression (rhMPV-ΔM2-2 produced higher levels of cytokines, chemokines and IFNs, compared to cells infected with wild-type virus (rhMPV-WT, suggesting that M2-2 protein inhibits innate immunity in human DC. In parallel, we found that myeloid differentiation primary response gene 88 (MyD88, an essential adaptor for Toll-like receptors (TLRs, plays a critical role in inducing immune response of human DC, as downregulation of MyD88 by siRNA blocked the induction of immune regulatory molecules by hMPV. Since M2-2 is a cytoplasmic protein, we investigated whether M2-2 interferes with MyD88-mediated antiviral signaling. We found that indeed M2-2 protein associated with MyD88 and inhibited MyD88-dependent gene transcription. In this study, we also identified the domains of M2-2 responsible for its immune inhibitory function in human DC. In summary, our results demonstrate that M2-2 contributes to hMPV immune evasion by inhibiting MyD88-dependent cellular responses in human DC.

Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells

Science.gov (United States)

Porter, Michael; Karp, Matthew; Killedar, Smruti; Bauer, Stephen M.; Guo, Jia; Williams, D'Ann; Breysse, Patrick; Georas, Steve N.; Williams, Marc A.

2007-01-01

Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-γ (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-γ production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material. PMID:17630318

Progestin and thrombin regulate tissue factor expression in human term decidual cells.

Science.gov (United States)

Lockwood, C J; Murk, W; Kayisli, U A; Buchwalder, L F; Huang, S-T; Funai, E F; Krikun, G; Schatz, F

2009-06-01

Perivascular cell membrane-bound tissue factor (TF) initiates hemostasis via thrombin generation. The identity and potential regulation of TF-expressing cells at the human maternal-fetal interface that confers hemostatic protection during normal and preterm delivery is unclear. The objective of the study were to identify TF-expressing cells at the maternal-fetal interface in term and preterm decidual sections by immunohistochemistry and evaluate progestin, thrombin, TNF-alpha, and IL-1beta effects on TF expression by cultured human term decidual cells (DCs). Serial placental sections were immunostained for TF. Leukocyte-free term DC monolayers were incubated with 10(-8) M estradiol (E2) or E2 plus 10(-7) M medroxyprogestrone acetate (MPA) +/- thrombin or TNF-alpha or IL-1beta. ELISA and Western blotting assessed TF in cell lysates. Quantitative real-time RT-PCR measured TF mRNA levels. Immunolocalized TF in DC membranes in preterm and term placental sections displayed higher Histologic Scores than villous mesenchymal cells (P term placental sections, DC-expressed TF exceeds that of other cell types at the maternal-fetal interface and is localized at the cell membranes in which it can bind to factor VII and meet the hemostatic demands of labor and delivery via thrombin formation. Unlike the general concept that TF is constitutive in cells that highly express it, MPA and thrombin significantly enhanced TF expression in term DC monolayers.

DC-STAMP, a novel multimembrane-spanning molecule preferentially expressed by dendritic cells.

NARCIS (Netherlands)

Hartgers, F.C.; Vissers, J.L.M.; Looman, M.W.G.; Zoelen, C. van; Huffine, C.; Figdor, C.G.; Adema, G.J.

2000-01-01

Dendritic cells (DC) are unique in their ability to present antigen to naive T cells, and therefore play a central role in the initiation of immune responses. Characterization of DC-specific genes may help to unravel the mechanism underlying their potent antigen presenting capacity. Here we describe

Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk--a pivotal role of HMGB1.

Directory of Open Access Journals (Sweden)

Marie-Thérèse Melki

2010-04-01

Full Text Available Early stages of Human Immunodeficiency Virus-1 (HIV-1 infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK cells and dendritic cells (DCs. Immature DCs (iDCs capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process" at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL-Death Receptor 4 (DR4 pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV. The escape of DC(HIV from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP and the cellular inhibitor of apoptosis 2 (c-IAP2, induced by NK-DC(HIV cognate interaction. High-mobility group box 1 (HMGB1, an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV. Finally, we demonstrate that restoration of DC(HIV susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific

Soft-Switched Dual-Input DC-DC Converter Combining a Boost-Half-Bridge Cell and a Voltage-Fed Full-Bridge Cell

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

2013-01-01

This paper presents a new zero-voltage-switching (ZVS) isolated dc-dc converter which combines a boost halfbridge (BHB) cell and a full-bridge (FB) cell, so that two different type of power sources, i.e. both current-fed and voltage-fed, can be coupled effectively by the proposed converter...... for various applications, such as fuel cell and super-capacitor hybrid energy system. By fully using two high frequency transformers and a shared leg of switches, number of the power devices and associated gate driver circuits can be reduced. With phase-shift control, the converter can achieve ZVS turn......-on of active switches and zero-current switching (ZCS) turn-off of diodes. In this paper, derivation, analysis and design of the proposed converter are presented. Finally, a 25~50 V input, 300~400 V output prototype with a 600 W nominal power rating is built up and tested to demonstrate the effectiveness...

CD56 marks human dendritic cell subsets with cytotoxic potential

NARCIS (Netherlands)

Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

2013-01-01

Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56(+) DCs are endowed with an unconventional cytotoxic capacity.

Superconducting energy stabilizer with charging and discharging DC-DC converters

International Nuclear Information System (INIS)

Kim, S.H.; Kostecki, E.L.; DeWinkel, C.C.

1992-01-01

This patent describes a superconducting energy stabilizer having multiple load connections and employing DC-DC conversion for storing energy in a superconducting inductive energy storage device having a first end and a second end, and for releasing the stored energy from the superconducting inductive energy storage device to a load or loads or to a utility or an industrial electrical distribution system, the superconducting energy stabilizer having multiple load connections and employing DC-DC conversion. It comprises: energy storage cell means for supplying energy to the load, discharging DC-DC converter means for releasing energy from the superconducting inductive energy storage device to the energy storage cell means, the discharging DC-DC converter means having input terminals, output terminals, and a discharging control line means for carrying signals controlling the operation of the discharging DC-DC converter means, one of the input terminals of the discharging DC-DC converter means coupled to the first end of the superconducting energy storage device

DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology

NARCIS (Netherlands)

Geijtenbeek, Teunis B. H.; Engering, Anneke; van Kooyk, Yvette

2002-01-01

Dendritic cells (DC) are present in essentially every tissue where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T cells. It is becoming clear that not all C-type lectins on DC serve as antigen receptors recognizing

Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum.

Science.gov (United States)

Mann, Elizabeth R; Bernardo, David; English, Nicholas R; Landy, Jon; Al-Hassi, Hafid O; Peake, Simon T C; Man, Ripple; Elliott, Timothy R; Spranger, Henning; Lee, Gui Han; Parian, Alyssa; Brant, Steven R; Lazarev, Mark; Hart, Ailsa L; Li, Xuhang; Knight, Stella C

2016-02-01

Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC. Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction. A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1β) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4(+)FoxP3(+)IL-10(+) (regulatory) T cells. There were enhanced proportions of CD103(+)Sirpα(-) DC in the colon, with increased proportions of CD103(+)Sirpα(+) DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103(+)Sirpα(+) DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103(+) DC, in particular CD103(+)Sirpα(+) DC. However, expression of ILT3 was associated with CD103(-) DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells. The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Effect of dcEFs on migration behavior of A549 cells and Integrin beta1 expression

Directory of Open Access Journals (Sweden)

Yunjie WANG

2008-04-01

Full Text Available Background and objective The effect of direct-current electric fields (dcEFs on cells attracted extensive attention. Moreover the metastasis and its potential are considered to be related to dcEFs. The aim is to study the effect of dcEFs on migration behavior of A549 cells, Integrin ?1 and its signal pathways. Methods According to exposure to 5 V/cm dcEFs or not and the time of exposure, the A549 cells were divided into 4 groups. Images were taken per 5 min within 2 h to recode the migration of the cells. The data of results were analyzed statistically. Results Most of A549cells exposed to the dcEFs aligned and elongated perpendicularly to the electric field lines and migrated to the cathode continually during 2 h. On the contrary, cells unexposed to dcEFs showed slightly random movements. Immunofluorescence showed that Integrin ?1 on plasma membrane polarized to the cathode of the dcEFs. Western blot showed that Integrin beta1 downstream signal pathways p-FAK and p-ERK were overexpressed in the dcEFs. Conclusion A549 cells have a galvanotatic feature of cathodal directed migration while exposed to the dcEFs. The polarization of Integrin beta1 and the promotion of its downstream signal pathways may play an important roles in the galvanotaxis of A549 cells.

Gene expression profiles of human dendritic cells interacting with Aspergillus fumigatus in a bilayer model of the alveolar epithelium/endothelium interface.

Directory of Open Access Journals (Sweden)

Charles Oliver Morton

Full Text Available The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549 and endothelium (human pulmonary artery epithelial cells, HPAEC on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC, monocyte-derived DC (moDC and myeloid DC (mDC, were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Zheng, Jin [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Qiang [Department of Hematology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jiandong [Department of Hepatobiliary Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Ren, Qinyou [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Cao, Wei [Department of Interventional Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jingyue; Yu, Zhaocai [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yu, Fang [Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Xi' an, Shaanxi (China); Wu, Yanlan [Department of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Shi, Hengjun [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Wenchao [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China)

2012-04-27

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

International Nuclear Information System (INIS)

Zheng, Jin; Liu, Qiang; Yang, Jiandong; Ren, Qinyou; Cao, Wei; Yang, Jingyue; Yu, Zhaocai; Yu, Fang; Wu, Yanlan; Shi, Hengjun; Liu, Wenchao

2012-01-01

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells

Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function.

Science.gov (United States)

Steeghs, Liana; van Vliet, Sandra J; Uronen-Hansson, Heli; van Mourik, Andries; Engering, Anneke; Sanchez-Hernandez, Martha; Klein, Nigel; Callard, Robin; van Putten, Jos P M; van der Ley, Peter; van Kooyk, Yvette; van de Winkel, Jan G J

2006-02-01

Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.

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

In order to use hydrogen fuel cell in domestic applications either as main power supply or backup power source, the low DC output voltage of the fuel cell has to be matched to the voltage level and frequency of the utility grid AC voltage. The interfacing power converter systems usually consist...... system is designed for interfacing a 2kW proton exchange membrane (PEM) fuel cell....

Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells.

Science.gov (United States)

Blois, Sandra M; Klapp, Burghard F; Barrientos, Gabriela

2011-03-01

Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical for the establishment and maintenance of gestation. The regulatory functions of decidual leukocytes during early pregnancy, particularly dendritic cells (DC) and NK cells, may be important not only for the generation of maternal immunological tolerance but also in the regulation of stromal cell differentiation and the vascular responses associated with the implantation process. However, the specific contributions of DC and NK cells during implantation are still difficult to dissect mainly due to reciprocal regulatory interactions established between them within the decidualizing microenvironment. The present review article discusses current evidence on the regulatory pathways driving decidualization in mice, suggesting that NK cells promote uterine vascular modifications that assist decidual growth but DC directly control stromal cell proliferation, angiogenesis and the homing and maturation of NK cell precursors in the pregnant uterus. Thus, successful implantation appears to result from an interplay between cellular components of the decidualizing endometrium involving immunoregulatory and pro-angiogenic functions of DC and NK cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Interleaved Boost-Half-Bridge Dual–Input DC-DC Converter with a PWM plus Phase-Shift Control for Fuel Cell Applications

DEFF Research Database (Denmark)

Zhang, Zhe; Andersen, Michael A. E.

2013-01-01

This paper presents an isolated dual-input DC-DC converter with a PWM plus phase-shift control for fuel cell hybrid energy systems. The power switches are controlled by phase shifted PWM signals with a variable duty cycle, and thus the two input voltages as well as the output voltage can...

Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model

DEFF Research Database (Denmark)

Foged, Camilla; Brodin, Birger; Frøkjær, Sven

2005-01-01

Current vaccine development includes optimization of antigen delivery to antigen presenting cells, such as dendritic cells (DC). Particulate systems have attracted increasing attention in the development of vaccine delivery systems. In the present study, we investigated DC uptake of model...... fluorescent polystyrene particles with a broad size range and variable surface properties. Localization of particles was investigated using confocal laser scanning microscopy and uptake was quantified by flow cytometry. Immature DC were generated from mononuclear cells isolated from human blood...

MECHANICAL VIBRATION INHIBITS OSTEOCLAST FORMATION BY REDUCING DC-STAMP RECEPTOR EXPRESSION IN OSTEOCLAST PRECURSOR CELLS

Science.gov (United States)

Kulkarni, R.N.; Voglewede, P.A.; Liu, D.

2014-01-01

It is well known that physical inactivity leads to loss of muscle mass, but it also causes bone loss. Mechanistically, osteoclastogenesis and bone resorption have recently been shown to be regulated by vibration. However, the underlying mechanism behind the inhibition of osteoclast formation is yet unknown. Therefore, we investigated whether mechanical vibration of osteoclast precursor cells affects osteoclast formation by the involvement of fusion-related molecules such as dendritic cell-specific transmembrane protein (DC-STAMP), and P2X7 receptor (P2X7R). RAW264.7 (a murine osteoclastic-like cell line) cells were treated with 20 ng/ml receptor activator of NF-κB ligand (RANKL). For 3 consecutive days, the cells were subjected to 1 hour of mechanical vibration with 20 µm displacement at a frequency of 4 Hz and compared to the control cells that were treated under the same condition but without the vibration. After 5 days of culture, osteoclast formation was determined. Gene expression of DC-STAMP and P2X7R by RAW264.7 cells were determined after 1 hour mechanical vibration, while protein production of the DC-STAMP was determined after 6 hours of post incubation after vibration. As a result, mechanical vibration of RAW264.7 cells inhibited the formation of osteoclasts. Vibration down-regulated DC-STAMP gene expression by 1.6-fold in the presence of RANKL and by 1.4-fold in the absence of RANKL. Additionally, DC-STAMP protein production was also down-regulated by 1.4-fold in the presence of RANKL and by 1.2-fold in the absence of RANKL in RAW264.7 cells in response to mechanical vibration. However, vibration did not affect P2X7R gene expression. Mouse anti-DC-STAMP antibody inhibited osteoclast formation in the absence of vibration. Our results suggest that mechanical vibration of osteoclast precursor cells reduce DC-STAMP expression in osteoclast precursor cells leading to the inhibition of osteoclast formation. PMID:23994170

Mechanical vibration inhibits osteoclast formation by reducing DC-STAMP receptor expression in osteoclast precursor cells.

Science.gov (United States)

Kulkarni, Rishikesh N; Voglewede, Philip A; Liu, Dawei

2013-12-01

It is well known that physical inactivity leads to loss of muscle mass, but it also causes bone loss. Mechanistically, osteoclastogenesis and bone resorption have recently been shown to be regulated by vibration. However, the underlying mechanism behind the inhibition of osteoclast formation is yet unknown. Therefore, we investigated whether mechanical vibration of osteoclast precursor cells affects osteoclast formation by the involvement of fusion-related molecules such as dendritic cell-specific transmembrane protein (DC-STAMP) and P2X7 receptor (P2X7R). RAW264.7 (a murine osteoclastic-like cell line) cells were treated with 20ng/ml receptor activator of NF-κB ligand (RANKL). For 3 consecutive days, the cells were subjected to 1h of mechanical vibration with 20μm displacement at a frequency of 4Hz and compared to the control cells that were treated under the same condition but without the vibration. After 5days of culture, osteoclast formation was determined. Gene expression of DC-STAMP and P2X7R by RAW264.7 cells was determined after 1h of mechanical vibration, while protein production of the DC-STAMP was determined after 6h of postincubation after vibration. As a result, mechanical vibration of RAW264.7 cells inhibited the formation of osteoclasts. Vibration down-regulated DC-STAMP gene expression by 1.6-fold in the presence of RANKL and by 1.4-fold in the absence of RANKL. Additionally, DC-STAMP protein production was also down-regulated by 1.4-fold in the presence of RANKL and by 1.2-fold in the absence of RANKL in RAW264.7 cells in response to mechanical vibration. However, vibration did not affect P2X7R gene expression. Mouse anti-DC-STAMP antibody inhibited osteoclast formation in the absence of vibration. Our results suggest that mechanical vibration of osteoclast precursor cells reduces DC-STAMP expression in osteoclast precursor cells leading to the inhibition of osteoclast formation. © 2013 Elsevier Inc. All rights reserved.

Peptide-loaded dendritic cells prime and activate MHC-class I-restricted T cells more efficiently than protein-loaded cross-presenting DC

DEFF Research Database (Denmark)

Met, Ozcan; Buus, Søren; Claesson, Mogens H

2003-01-01

-pulsed DC. Moreover, SIINFEKL-loaded DC were up to 50 times more efficient than DC-pulsed with OVA-protein for generation of an H-2K(b)-restricted response. Immunization of mice with SIINFEKL-loaded DC resulted in a much stronger H-2K(b)-restricted response than immunization with OVA-pulsed DC. These data......Undifferentiated and differentiated dendritic cells (uDC and dDC, respectively), derived from the bone marrow, were studied in vitro and in vivo. Ovalbumin (OVA) and two OVA-derived peptides binding to H-2K(b) and I-A(b), respectively, were used. Two IL-2 secreting T cell hybridomas specific...... for the OVA-derived epitopes were used in the in vitro read-out. The ability to cross-present the H-2K(b) binding OVA(257-264)-peptide (SIINFEKL) was restricted to dDC, which express CD11c(+), CD86(+), and MHC-II(+). In vitro, the antigenicity of SIINFEKL-loaded DC declined at a slower rate than that of OVA...

Sulforaphane inhibits osteoclast differentiation by suppressing the cell-cell fusion molecules DC-STAMP and OC-STAMP

International Nuclear Information System (INIS)

Takagi, Tomohiro; Inoue, Hirofumi; Takahashi, Nobuyuki; Katsumata-Tsuboi, Rie; Uehara, Mariko

2017-01-01

Sulforaphane (SFN), a kind of isothiocyanate, is derived from broccoli sprouts. It has anti-tumor, anti-inflammatory, and anti-oxidation activity. The molecular function of SFN in the inhibition of osteoclast differentiation is not well-documented. In this study, we assessed the effect of SFN on osteoclast differentiation in vitro. SFN inhibited osteoclast differentiation in both bone marrow cells and RAW264.7 cells. Key molecules involved in the inhibitory effects of SFN on osteoclast differentiation were determined using a microarray analysis, which showed that SFN inhibits osteoclast-associated genes, such as osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells cytoplasmic-1, tartrate-resistant acid phosphatase, and cathepsin K. Moreover, the mRNA expression levels of the cell-cell fusion molecules dendritic cell specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP) were strongly suppressed in cells treated with SFN. Furthermore, SFN increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), a regulator of macrophage and osteoclast cell fusion. Thus, our data suggested that SFN significantly inhibits the cell-cell fusion molecules DC-STAMP and OC-STAMP by inducing the phosphorylation of STAT1 (Tyr701), which might be regulated by interactions with OSCAR. - Highlights: • Sulforaphane inhibited osteoclast differentiation and osteoclast cell-fusion. • Sulforaphane suppressed not only NFATc1, but also cell-cell fusion molecules, DC-STAMP and OC-STAMP. • Sulforaphane decreased multinucleated osteoclasts, whereas increased mono-nucleated osteoclasts. • Sulforaphane inhibits the cell-cell fusion by inducing the phosphorylation of STAT1 (Tyr701).

Multi Bus DC-DC Converter in Electric Hybrid Vehicles

Science.gov (United States)

Krithika, V.; Subramaniam, C.; Sridharan, R.; Geetha, A.

2018-04-01

This paper is cotncerned with the design, simulation and fabrication of the prototype of a Multi bus DC- DC converter operating from 42V DC and delivering 14V DC and 260V DC. As a result, three DC buses are interconnected through a single power electronic circuitry. Such a requirement is energized in the development of a hybrid electric automobile which uses the technology of fuel cell. This is implemented by using a Bidirectional DC-DC converter configuration which is ideally suitable for multiple outputs with mutual electrical isolation. For the sake of reduced size and cost of step-up transformer, selection of a high frequency switching cycle at 10 KHz was done.

DC Home Appliances for DC Distribution System

Directory of Open Access Journals (Sweden)

MUHAMMAD KAMRAN

2017-10-01

Full Text Available This paper strengthens the idea of DC distribution system for DC microgrid consisting of a building of 50 apartments. Since the war of currents AC system has been dominant because of the paucity of research in the protection of the DC system. Now with the advance research in power electronics material and components, generation of electricity is inherently DC as by solar PV, fuel cell and thermoelectric generator that eliminates the rectification process. Transformers are replaced by the power electronics buck-boost converters. DC circuit breakers have solved the protection problems for both DC transmission and distribution system. In this paper 308V DC microgrid is proposed and home appliances (DC internal are modified to operate on 48V DC from DC distribution line. Instead of using universal and induction motors in rotary appliances, BLDC (Brushless DC motors are proposed that are highly efficient with minimum electro-mechanical and no commutation losses. Proposed DC system reduces the power conversion stages, hence diminishes the associated power losses and standby losses that boost the overall system efficiency. So in view of all this a conventional AC system can be replaced by a DC system that has many advantages by cost as well as by performance

Digital Simulation of Closed Loop Zvs-Zcs Bidirectional Dc-Dc Converter for Fuel Cell and Battery Application

Directory of Open Access Journals (Sweden)

V. V. Subrahmanya Kumar Bhajana

2010-08-01

Full Text Available A closed loop ZVS-ZCS bidirectional dc-dc converter is modeled and appropriate digital simulations are provided. With the ZVS-ZCS concept, the MATLAB simulation results of application to a fuel cell and battery application have been obtained whenever the input voltage exceeds the given 24V, at that time the load voltage will change from 180V to 230V. But due to this usage the load is disturbed and there is instability in the model. Using closed loop the output voltage is stabilized.

Single Cell Dissection of Human Pancreatic Islet Dysfunction in Diabetes

Science.gov (United States)

2017-06-01

of memory T cells , innate cells and the differentiation potential of naive T cells during ME/CFS; and 3) To determine the T cell and innate cell ...apoptosis and the innate immune response in human pancreatic β- cells . Diabetes 64: 3808–3817. Marselli L, Thorne J, Dahiya S, Sgroi DC, Sharma A, Bonner-Weir...interactive nature of CellView aids in cell doublet identification. In the PBMC data, ‘Subcluster-analysis’ reveals a mixture of lymphoid and myeloid

Tolerogenic dendritic cells for regulatory T cell induction in man

Directory of Open Access Journals (Sweden)

Verena eRaker

2015-11-01

Full Text Available Dendritic cells are (DC highly specialized professional antigen-presenting cells (APC that regulate immune responses, maintaining the balance between tolerance and immunity. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, inhibition of memory T cell responses, T cell anergy and induction of regulatory T cells. These properties have led to the analysis of human tolerogenic DC as a therapeutic strategy for induction or re-establishment of tolerance. In the recent years, numerous protocols for the generation of human tolerogenic DC have been developed and their tolerogenic mechanisms, including induction of regulatory T cells, are relatively well understood. Phase I trials have been conducted in autoimmune disease, with results that emphasize the feasibility and safety of treatments with tolerogenic DC. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of transplantation medicine and allergic and autoimmune diseases is strong. This review will give an overview on efforts and protocols to generate human tolerogenic DC with focus on IL-10-modulated DC as inducers of regulatory T cells and discuss their clinical applications and challenges faced in further developing this form of immunotherapy.

Activation of human CD141+ and CD1c+ dendritic cells in vivo with combined TLR3 and TLR7/8 ligation.

Science.gov (United States)

Pearson, Frances E; Chang, Karshing; Minoda, Yoshihito; Rojas, Ingrid M Leal; Haigh, Oscar L; Daraj, Ghazal; Tullett, Kirsteen M; Radford, Kristen J

2018-04-01

Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141 + and CD1c + myeloid and CD123 + plasmacytoid dendritic cells (DC) develop from human cord blood CD34 + cells in immunodeficient mice. CD141 + DC are the human equivalents of murine CD8 + /CD103 + DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte responses, making them attractive targets to exploit for the development of new cancer immunotherapies. We used CD34 + -engrafted NSG-A2 mice to investigate activation of DC subsets by synthetic dsRNA or ssRNA analogs polyinosinic-polycytidylic acid/poly I:C and Resiquimod/R848, agonists for TLR3 and TLR8, respectively, both of which are expressed by CD141 + DC. Injection of hu mice with these agonists resulted in upregulation of costimulatory molecules CD80, CD83 and CD86 by CD141 + and CD1c + DC alike, and their combination further enhanced expression of these molecules by both subsets. When combined, poly I:C and R848 enhanced serum levels of key cytokines associated with cross-presentation and the induction of cytotoxic T lymphocyte responses including IFN-α, IFN-β, IL-12 and CXCL10. These data advocate a combination of poly I:C and R848 TLR agonists as means of activating human DC for immunotherapy. © 2018 Australasian Society for Immunology Inc.

Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.

Directory of Open Access Journals (Sweden)

Jacques C Mbongue

Full Text Available Dendritic cells (DC interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS. Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1. Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention

Asymmetrical Interleaved DC/DC Switching Converters for Photovoltaic and Fuel Cell Applications—Part 1: Circuit Generation, Analysis and Design 

Directory of Open Access Journals (Sweden)

Sergio Serna

2012-11-01

Full Text Available A novel asymmetrical interleaved dc/dc switching converters family intended for photovoltaic and fuel cell applications is presented in this paper. The main requirements on such applications are small ripples in the generator and load, as well as high voltage conversion ratio. Therefore, interleaved structures and voltage multiplier cells have been asymmetrically combined to generate new converters, which inherently operate indiscontinuous conduction mode. The novel family is derived from boost, buck-boost and flyback-based structures. This converter family is analyzed to obtain the design equations and synthesize a design process based on the typical requirements of photovoltaic and fuel cell applications. Finally, the experimental results validate the characteristics and usefulness of the asymmetrical interleaved converter family. 

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.

Science.gov (United States)

Liu, Yan-Ping; Zhu, Hui-Fang; Liu, Ding-Li; Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

2016-11-22

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

Hybrid electric system based on fuel cell and battery and integrating a single dc/dc converter for a tramway

International Nuclear Information System (INIS)

Fernandez, Luis M.; Garcia, Pablo; Garcia, Carlos Andres; Jurado, Francisco

2011-01-01

Research highlights: → Hybrid electric power system for a real surface tramway. → Hybrid system based on PEM fuel cell with dc/dc converter and Ni-MH battery. → New control strategy for the energy management of the tramway. → Hybrid system demonstrated to meet appropriate driving cycle of the tramway. -- Abstract: This paper presents a hybrid electric power system for a real surface tramway. The hybrid system consists of two electrical energy sources integrating a single dc/dc converter to provide the power demanded by the tramway loads (four electric traction motors and auxiliary services): (1) a Polymer Electrolyte Membrane (PEM) fuel cell (FC) as the primary and (2) a rechargeable Ni-MH battery as electrical energy storage to supplement the FC over the driving cycle. According to the requirements of the real driving cycle of the tramway, it was considered a 200 kW PEM FC system with two FCs connected in parallel and a 34 Ah Ni-MH battery. The PEM FC and Ni-MH battery models were designed from commercially available components. The power conditioning system provides the appropriate power for the tramway. It is composed of: (1) a unique dc/dc boot converter which adapts the FC output voltage to the 750 V traction standard dc bus; (2) three phase inverters to drive properly each electric motors; and (3) a braking chopper to dissipate excess of regenerative braking energy. Suitable state machine control architecture is presented for the hybrid system, its objective being to provide demanded power by the driving cycle, optimizing the energy generated. Following this objective, a new state machine control strategy based on eight states decides the operating point of each component of the system and a cascade control structure allows achieving the operating points determined by the strategy. Simulation results of the real driving cycle of the tramway check the adequacy of the hybrid electric power system.

Hybrid electric system based on fuel cell and battery and integrating a single dc/dc converter for a tramway

Energy Technology Data Exchange (ETDEWEB)

Fernandez, Luis M., E-mail: luis.fernandez@uca.e [Department of Electrical Engineering, EPS Algeciras, University of Cadiz, Avda. Ramon Puyol, s/n. 11202 Algeciras (Cadiz) (Spain); Garcia, Pablo, E-mail: pablo.garcia@uca.e [Department of Electrical Engineering, EPS Algeciras, University of Cadiz, Avda. Ramon Puyol, s/n. 11202 Algeciras (Cadiz) (Spain); Garcia, Carlos Andres, E-mail: carlosandres.garcia@uca.e [Department of Electrical Engineering, EPS Algeciras, University of Cadiz, Avda. Ramon Puyol, s/n. 11202 Algeciras (Cadiz) (Spain); Jurado, Francisco, E-mail: fjurado@ujaen.e [Department of Electrical Engineering, EPS Linares, University of Jaen, C/Alfonso X, No. 28. 23700 Linares (Jaen) (Spain)

2011-05-15

Research highlights: {yields} Hybrid electric power system for a real surface tramway. {yields} Hybrid system based on PEM fuel cell with dc/dc converter and Ni-MH battery. {yields} New control strategy for the energy management of the tramway. {yields} Hybrid system demonstrated to meet appropriate driving cycle of the tramway. -- Abstract: This paper presents a hybrid electric power system for a real surface tramway. The hybrid system consists of two electrical energy sources integrating a single dc/dc converter to provide the power demanded by the tramway loads (four electric traction motors and auxiliary services): (1) a Polymer Electrolyte Membrane (PEM) fuel cell (FC) as the primary and (2) a rechargeable Ni-MH battery as electrical energy storage to supplement the FC over the driving cycle. According to the requirements of the real driving cycle of the tramway, it was considered a 200 kW PEM FC system with two FCs connected in parallel and a 34 Ah Ni-MH battery. The PEM FC and Ni-MH battery models were designed from commercially available components. The power conditioning system provides the appropriate power for the tramway. It is composed of: (1) a unique dc/dc boot converter which adapts the FC output voltage to the 750 V traction standard dc bus; (2) three phase inverters to drive properly each electric motors; and (3) a braking chopper to dissipate excess of regenerative braking energy. Suitable state machine control architecture is presented for the hybrid system, its objective being to provide demanded power by the driving cycle, optimizing the energy generated. Following this objective, a new state machine control strategy based on eight states decides the operating point of each component of the system and a cascade control structure allows achieving the operating points determined by the strategy. Simulation results of the real driving cycle of the tramway check the adequacy of the hybrid electric power system.

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

OpenAIRE

Selleri, Silvia; Bifsha, Panojot; Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Ren?e; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle

2016-01-01

Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-...

Asymmetrical Interleaved DC/DC Switching Converters for Photovoltaic and Fuel Cell Applications—Part 2: Control-Oriented Models

Directory of Open Access Journals (Sweden)

Sergio Ignacio Serna-Garces

2013-10-01

Full Text Available A previous article has presented the members of the asymmetrical interleaved dc/dc switching converters family as very appropriate candidates to interface between photovoltaic or fuel cell generators and their loads because of their reduced ripple and increased current processing capabilities. After a review of the main modeling methods suitable for high-order converters operating, as the asymmetrical interleaved converters (AIC ones, in discontinuous current conduction mode a full-order averaged model has been adapted and improved to describe the dynamic behavior of AIC. The excellent agreement between the mathematical model predictions, the switched simulations and the experimental results has allowed for satisfactory design of a linear-quadratic regulator (LQR in a fuel-cell application example, which demonstrates the usefulness of the improved control-oriented modeling approach when the switching converters operate in discontinuous conduction mode.

The Topologies Research of a Soft Switching Bidirectional DC/DC Converter

DEFF Research Database (Denmark)

Zhang, Qi; Zhang, Yongping; Sun, Xiangdong

2017-01-01

A soft-switching solution implemented to the traditional bidirectional DC/DC converter is developed. The soft-switching cell, which composed of three auxiliary switches, one resonant capacitor and one resonant inductor, is equipped in the traditional bidirectional DC/DC converter to realize circuit...... circle. And the proposed topology of bidirectional soft-switching dc-dc converter(TASBC) performs ideal soft switching at boost operations. The characteristics of the proposed converter has been verified by MATLAB simulations and experimental results....

NADPH oxidase-2 derived ROS dictates murine DC cytokine-mediated cell fate decisions during CD4 T helper-cell commitment.

Directory of Open Access Journals (Sweden)

Meghan A Jendrysik

Full Text Available NADPH oxidase-2 (Nox2/gp91(phox and p47(phox deficient mice are prone to hyper-inflammatory responses suggesting a paradoxical role for Nox2-derived reactive oxygen species (ROS as anti-inflammatory mediators. The molecular basis for this mode of control remains unclear. Here we demonstrate that IFNγ/LPS matured p47(phox-/--ROS deficient mouse dendritic cells (DC secrete more IL-12p70 than similarly treated wild type DC, and in an in vitro co-culture model IFNγ/LPS matured p47(phox-/- DC bias more ovalbumin-specific CD4(+ T lymphocytes toward a Th1 phenotype than wild type (WT DC through a ROS-dependent mechanism linking IL-12p70 expression to regulation of p38-MAPK activation. The Nox2-dependent ROS production in DC negatively regulates proinflammatory IL-12 expression in DC by constraining p38-MAPK activity. Increasing endogenous H(2O(2 attenuates p38-MAPK activity in IFNγ/LPS stimulated WT and p47(phox-/- DC, which suggests that endogenous Nox 2-derived ROS functions as a secondary messenger in the activated p38-MAPK signaling pathway during IL-12 expression. These findings indicate that ROS, generated endogenously by innate and adaptive immune cells, can function as important secondary messengers that can regulate cytokine production and immune cell cross-talk to control during the inflammatory response.

DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans

International Nuclear Information System (INIS)

Wang, S.-F.; Huang, Jason C.; Lee, Y.-M.; Liu, S.-J.; Chan, Yu-Jiun; Chau, Y.-P.; Chong, P.; Chen, Y.-M.A.

2008-01-01

DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing α-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capable of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans

Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

Directory of Open Access Journals (Sweden)

Brett Eugene Phillips

2017-10-01

Full Text Available Tolerogenic dendritic cell (tDC-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS, and Crohn’s disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells are, for the most part, increased in frequency in the circulation. Other than this observation, there are significant differences in the major phenotypes of the tDC. These differences may affect the outcome in efficacy of recently launched and impending phase II trials. Recent efforts to establish a catalog listing where tDC converge and diverge in phenotype and functional outcome are an important first step toward understanding core mechanisms of action and critical “musts” for tDC to be therapeutically successful. In our view, the most critical parameter to efficacy is in vivo stability of the tolerogenic activity over phenotype. As such, methods that generate tDC that can induce and stably maintain immune hyporesponsiveness to allo- or disease-specific autoantigens in the presence of powerful pro-inflammatory signals are those that will fare better in primary endpoints in phase II clinical trials (e.g., disease improvement, preservation of autoimmunity-targeted tissue, allograft survival. We propose that pre-treatment phenotypes of tDC in the absence of functional stability are of secondary value especially as such phenotypes can dramatically change following administration, especially under dynamic changes in the inflammatory state of the patient. Furthermore, understanding the outcomes of different methods of cell delivery and sites

R5 human immunodeficiency virus type 1 with efficient DC-SIGN use is not selected for early after birth in vertically infected children.

Science.gov (United States)

Borggren, Marie; Navér, Lars; Casper, Charlotte; Ehrnst, Anneka; Jansson, Marianne

2013-04-01

The binding of human immunodeficiency virus (HIV) to C-type lectin receptors may result in either enhanced trans-infection of T-cells or virus degradation. We have investigated the efficacy of HIV-1 utilization of DC-SIGN, a C-type lectin receptor, in the setting of intrauterine or intrapartum mother-to-child transmission (MTCT). Viruses isolated from HIV-1-infected mothers at delivery and from their vertically infected children both shortly after birth and later during the progression of the disease were analysed for their use of DC-SIGN, binding and ability to trans-infect. DC-SIGN use of a child's earlier virus isolate tended to be reduced as compared with that of the corresponding maternal isolate. Furthermore, the children's later isolate displayed enhanced DC-SIGN utilization compared with that of the corresponding earlier virus. These results were also supported in head-to-head competition assays and suggest that HIV-1 variants displaying efficient DC-SIGN use are not selected for during intrauterine or intrapartum MTCT. However, viruses with increased DC-SIGN use may evolve later in paediatric HIV-1 infections.

DC-CIK cells derived from ovarian cancer patient menstrual blood activate the TNFR1-ASK1-AIP1 pathway to kill autologous ovarian cancer stem cells.

Science.gov (United States)

Qin, Wenxing; Xiong, Ying; Chen, Juan; Huang, Yongyi; Liu, Te

2018-03-22

Ovarian cancer stem cells (OCSCs) are highly carcinogenic and have very strong resistance to traditional chemotherapeutic drugs; therefore, they are an important factor in ovarian cancer metastasis and recurrence. It has been reported that dendritic cell (DC)-cytokine-induced killer (CIK) cells have significant killing effects on all cancer cells across many systems including the blood, digestive, respiratory, urinary and reproductive systems. However, whether DC-CIK cells can selectively kill OCSCs is currently unclear. In this study, we collected ovarian cancer patient menstrual blood (OCPMB) samples to acquire mononuclear cells and isolated DC-CIK cells in vitro. In addition, autologous CD44+/CD133+ OCSCs were isolated and used as target cells. The experimental results showed that when DC-CIK cells and OCSCs were mixed and cultured in vitro at ratios of 5:1, 10:1 and 50:1, the DC-CIK cells killed significant amounts of OCSCs, inhibited their invasion in vitro and promoted their apoptosis. The qPCR and Western blot results showed that DC-CIK cells stimulated high expression levels and phosphorylation of TNFR1, ASK1, AIP1 and JNK in OCSCs through the release of TNF-α. After the endogenous TNFR1 gene was knocked out in OCSCs using the CRISPR/Cas9 technology, the killing function of DC-CIK cells on target OCSCs was significantly attenuated. The results of the analyses of clinical samples suggested that the TNFR1 expression level was negatively correlated with ovarian cancer stage and prognosis. Therefore, we innovatively confirmed that DC-CIK cells derived from OCPMB could secret TNF-α to activate the expression of the TNFR1-ASK1-AIP1-JNK pathway in OCSCs and kill autologous OCSCs. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Cytotoxic components of Pereskia bleo (Kunth) DC. (Cactaceae) leaves.

Science.gov (United States)

Malek, Sri Nurestri Abdul; Shin, Sim Kae; Wahab, Norhanom Abdul; Yaacob, Hashim

2009-05-06

Dihydroactinidiolide (1) and a mixture of sterols [campesterol (2), stigmasterol (3) and beta-sitosterol (4)], together with the previously isolated individual compounds beta-sitosterol (4), 2,4-di-tert-butylphenol (5), alpha-tocopherol (6), phytol (7) were isolated from the active ethyl acetate fraction of Pereskia bleo (Kunth) DC. (Cactaceae) leaves. Cytotoxic activities of the above mentioned compounds against five human carcinoma cell lines, namely the human nasopharyngeal epidermoid carcinoma cell line (KB), human cervical carcinoma cell line (CasKi), human colon carcinoma cell line (HCT 116), human hormone-dependent breast carcinoma cell line (MCF7) and human lung carcinoma cell line (A549); and non-cancer human fibroblast cell line (MRC-5) were investigated. Compound 5 possessed very remarkable cytotoxic activity against KB cells, with an IC(50 )value of 0.81microg/mL. This is the first report on the cytotoxic activities of the compounds isolated from Pereskia bleo.

Cytotoxic Components of Pereskia bleo (Kunth DC. (Cactaceae Leaves

Directory of Open Access Journals (Sweden)

Sri Nurestri Abdul Malek

2009-05-01

Full Text Available Dihydroactinidiolide (1 and a mixture of sterols [campesterol (2, stigmasterol (3 and β-sitosterol (4], together with the previously isolated individual compounds β-sitosterol (4, 2,4-di-tert-butylphenol (5, α-tocopherol (6, phytol (7 were isolated from the active ethyl acetate fraction of Pereskia bleo (Kunth DC. (Cactaceae leaves. Cytotoxic activities of the above mentioned compounds against five human carcinoma cell lines, namely the human nasopharyngeal epidermoid carcinoma cell line (KB, human cervical carcinoma cell line (CasKi, human colon carcinoma cell line (HCT 116, human hormone-dependent breast carcinoma cell line (MCF7 and human lung carcinoma cell line (A549; and non-cancer human fibroblast cell line (MRC-5 were investigated. Compound 5 possessed very remarkable cytotoxic activity against KB cells, with an IC50 value of 0.81µg/mL. This is the first report on the cytotoxic activities of the compounds isolated from Pereskia bleo.

Distribution of dendritic cells expressing dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN, CD209): Morphological analysis using a novel Photoshop-aided multiple immunohistochemistry technique.

Science.gov (United States)

Masuda, Akihiro; Nishikawa, Toshio

2014-08-01

The distribution of dendritic cells (DCs) expressing DC-specific ICAM-3-grabbing non-integrin (DC-SIGN, CD209) and the morphological interaction of DC-SIGN⁺ DCs with other cells, especially B cells, in tonsillar and other lymphoid tissues were investigated by multiple immunohistochemistry (IHC) using the graphics editing program Photoshop, which enabled staining with 4 or more antibodies in formalin-fixed paraffin sections. Images obtained by repetition of conventional IHC using diaminobenzidine color development in a tissue section were processed on Photoshop for multiple staining. DC-SIGN⁺ DCs were present in the area around the lymphoid follicles and formed a DC-SIGN⁺ DC-rich area, and these cells contacted not only T cells, fascin⁺ DCs, and blood vessels but also several subsets of B cells simultaneously, including naïve and memory B cells. DC-SIGN⁺ DCs may play an important role in the regulation of the immune response mediated by not only T cells but also B cells. The multiple IHC method introduced in the present study is a simple and useful method for analyzing details of complex structures. Because this method can be applied to routinely processed paraffin sections with conventional IHC with diaminobenzidine, it can be applied to a wide variety of archival specimens.

Effects of mesenchymal stem cells from human induced pluripotent stem cells on differentiation, maturation, and function of dendritic cells.

Science.gov (United States)

Gao, Wen-Xiang; Sun, Yue-Qi; Shi, Jianbo; Li, Cheng-Lin; Fang, Shu-Bin; Wang, Dan; Deng, Xue-Quan; Wen, Weiping; Fu, Qing-Ling

2017-03-02

Mesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs. Human monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production. In this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism. Our results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases.

Highly efficient transduction of human plasmacytoid dendritic cells without phenotypic and functional maturation

Directory of Open Access Journals (Sweden)

Plumas Joel

2009-01-01

Full Text Available Abstract Background Gene modified dendritic cells (DC are able to modulate DC functions and induce therapeutic immunity or tolerance in an antigen-specific manner. Among the different DC subsets, plasmacytoid DC (pDC are well known for their ability to recognize and respond to a variety of viruses by secreting high levels of type I interferon. Methods We analyzed here, the transduction efficiency of a pDC cell line, GEN2.2, and of pDC derived from CD34+ progenitors, using lentiviral vectors (LV pseudotyped with different envelope glycoproteins such as the vesicular stomatitis virus envelope (VSVG, the gibbon ape leukaemia virus envelope (GaLV or the feline endogenous virus envelope (RD114. At the same time, we evaluated transgene expression (E-GFP reporter gene under the control of different promoters. Results We found that efficient gene transfer into pDC can be achieved with VSVG-pseudotyped lentiviral vectors (LV under the control of phoshoglycerate kinase (PGK and elongation factor-1 (EF1α promoters (28% to 90% of E-GFP+ cells, respectively in the absence of phenotypic and functional maturation. Surprisingly, promoters (desmin or synthetic C5–12 described as muscle-specific and which drive gene expression in single strand AAV vectors in gene therapy protocols were very highly active in pDC using VSVG-LV. Conclusion Taken together, our results indicate that LV vectors can serve to design pDC-based vaccines in humans, and they are also useful in vitro to evaluate the immunogenicity of the vector preparations, and the specificity and safety of given promoters used in gene therapy protocols.

The r.b.e. of different-energy neutrons as determined by human bone-marrow cell-culture techniques

International Nuclear Information System (INIS)

Boeyum, A.; Carsten, A.L.; Chikkappa, G.; Cook, L.; Bullis, J.; Honikel, L.; Cronkite, E.P.

1978-01-01

The effect of X-rays and different-energy neutrons on human bone-marrow cells was studied using two different cell-culture techniques - diffusion chamber (DC) growth and colony formation in vitro (CFU-C). Based on the survival and proliferative granulocytes in DC on day 13, the D 0 value was 80 rad with X-rays, and 117 rad as measured by the CFU-C assay. The D 0 values for neutrons depended on the radiation source and the energy level. The r.b.e. values, which dropped with increasing energy levels of mono-energetic neutrons, were (i) 0.44 MeV; DC 3.7, CFU-C 4.1; (ii) 6 MeV; DC 1.8, CFU-C 2.0; (iii) 15 MeV; DC 1.6, CFU-C 1.6; (iv) fission neutrons; DC 2.6, CFU-C 2.4. (author)

Allergy-Protective Arabinogalactan Modulates Human Dendritic Cells via C-Type Lectins and Inhibition of NF-κB.

Science.gov (United States)

Peters, Marcus; Guidato, Patrick M; Peters, Karin; Megger, Dominik A; Sitek, Barbara; Classen, Birgit; Heise, Esther M; Bufe, Albrecht

2016-02-15

Arabinogalactan (AG) isolated from dust of a traditional farm prevents disease in murine models of allergy. However, it is unclear whether this polysaccharide has immune regulatory properties in humans. The aim of this study was to test the influence of AG on the immune-stimulating properties of human dendritic cells (DCs). Moreover, we sought to identify the receptor to which AG binds. AG was produced from plant callus tissue under sterile conditions to avoid the influence of pathogen-associated molecular patterns in subsequent experiments. The influence of AG on the human immune system was investigated by analyzing its impact on monocyte-derived DCs. To analyze whether the T cell stimulatory capacity of AG-stimulated DCs is altered, an MLR with naive Th cells was performed. We revealed that AG reduced T cell proliferation in a human MLR. In the search for a molecular mechanism, we found that AG binds to the immune modulatory receptors DC-specific ICAM-3 -: grabbing non integrin (DC-SIGN) and macrophage mannose receptor 1 (MMR-1). Stimulation of these receptors with AG simultaneously with TLR4 stimulation with LPS increased the expression of the E3 ubiquitin-protein ligase tripartite motif -: containing protein 21 and decreased the phosphorylation of NF-κB p65 in DCs. This led to a reduced activation profile with reduced costimulatory molecules and proinflammatory cytokine production. Blocking of MMR-1 or DC-SIGN with neutralizing Abs partially inhibits this effect. We conclude that AG dampens the activation of human DCs by LPS via binding to DC-SIGN and MMR-1, leading to attenuated TLR signaling. This results in a reduced T cell activation capacity of DCs. Copyright © 2016 by The American Association of Immunologists, Inc.

C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis.

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available OBJECTIVE: It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs to stimulate adaptive immune cells such as Th1 and Th17 in sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP. CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+DC, IFNγ(+Th1, and IL-17(+Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA. RESULTS: Our studies here showed that C5a induced IL-12(+DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+DC cells induced the expansion of pathogenic IFNγ(+Th1 and IL-17(+Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis. CONCLUSION: Our data suggests that C5a regulates IL-12(+DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.

Multilevel DC link inverter

Science.gov (United States)

Su, Gui-Jia

2003-06-10

A multilevel DC link inverter and method for improving torque response and current regulation in permanent magnet motors and switched reluctance motors having a low inductance includes a plurality of voltage controlled cells connected in series for applying a resulting dc voltage comprised of one or more incremental dc voltages. The cells are provided with switches for increasing the resulting applied dc voltage as speed and back EMF increase, while limiting the voltage that is applied to the commutation switches to perform PWM or dc voltage stepping functions, so as to limit current ripple in the stator windings below an acceptable level, typically 5%. Several embodiments are disclosed including inverters using IGBT's, inverters using thyristors. All of the inverters are operable in both motoring and regenerating modes.

Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity.

Science.gov (United States)

Miah, Mohammad Alam; Byeon, Se Eun; Ahmed, Md Selim; Yoon, Cheol-Hee; Ha, Sang-Jun; Bae, Yong-Soo

2013-09-01

Early growth response gene 2 (Egr2), which encodes a zinc finger transcription factor, is rapidly and transiently induced in various cell types independently of de novo protein synthesis. Although a role for Egr2 is well established in T-cell development, Egr2 expression and its biological function in dendritic cells (DCs) have not yet been described. Here, we demonstrate Egr2 expression during DC development, and its role in DC-mediated immune responses. Egr2 is expressed in the later stage of DC development from BM precursor cells. Even at steady state, Egr2 is highly expressed in mouse splenic DCs. Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities. Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine. DC-mediated cytotoxic T lymphocyte (CTL) activation and antitumor immunity were significantly enhanced by Egr2-KD, and impaired by Egr2 overexpression in antigen-pulsed DC vaccines. These data suggest that Egr2 acts as an intrinsic negative regulator of DC immunogenicity and can be an attractive molecular target for DC vaccine development. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zero-voltage DC/DC converter with asymmetric pulse-width modulation for DC micro-grid system

Science.gov (United States)

Lin, Bor-Ren

2018-04-01

This paper presents a zero-voltage switching DC/DC converter for DC micro-grid system applications. The proposed circuit includes three half-bridge circuit cells connected in primary-series and secondary-parallel in order to lessen the voltage rating of power switches and current rating of rectifier diodes. Thus, low voltage stress of power MOSFETs can be adopted for high-voltage input applications with high switching frequency operation. In order to achieve low switching losses and high circuit efficiency, asymmetric pulse-width modulation is used to turn on power switches at zero voltage. Flying capacitors are used between each circuit cell to automatically balance input split voltages. Therefore, the voltage stress of each power switch is limited at Vin/3. Finally, a prototype is constructed and experiments are provided to demonstrate the circuit performance.

Culture of normal human blood cells in diffusion chamber systems. I. Granulocyte survival and proliferation. [X radiation, mice

Energy Technology Data Exchange (ETDEWEB)

Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Cronkite, E.P.

1978-01-01

Blood cells from four normal volunteers were cultured in diffusion chambers (DC), made of Millipore (MDC) or Nuclepore (NDC) filters, in the peritoneal cavities of whole body X-irradiated (700 rad) mice. The total nucleated cell recovery from the two types of DC over 18 days indicates that the cells in DC persist and proliferate. The mature neutrophilic cells, metamyelocytes (M/sub 5/) + band forms (M/sub 6/) + segmented forms (M/sub 7/), survived with T/sup 1///sub 2/ of 29 and 34 h in MDC and NDC, respectively. The reduction of the cells in the DC was surmised to be due to degeneration and death of the M/sub 7/. The /sup 3/H-diisopropylfluorophosphate (/sup 3/HDFP) labeled M/sub /sub 6/+/sub 7// survival in MDC was slightly shorter than that of unlabeled cells, which may be explained on the basis of the loss of /sup 3/HDFP (5.1%/day) from the cells. The eosinophils survived with an average T/sup 1///sub 2/ of 7.2 days (range 4.8 to 9.6), and the results were comparable in both types of DC. Formation of myeloblasts, promyelocytes, and neutrophilic, eosinophilic and basophilic myelocytes, occasional megakaryocytes and rare normoblasts in DC indicated that the normal human blood contains progenitors (pluripotent and/or committed stem cells) of hemopoietic cells. The neutrophilic cell recovery pattern was similar from both types of DC, but the total number recovered was always greater from NDC than from MDC.

Human embryonic stem cell (hES derived dendritic cells are functionally normal and are susceptible to HIV-1 infection

Directory of Open Access Journals (Sweden)

Bandi Sriram

2008-01-01

Full Text Available Abstract Background Human embryonic stem (hES cells hold considerable promise for cell replacement and gene therapies. Their remarkable properties of pluripotency, self-renewal, and tractability for genetic modification potentially allows for the production of sizeable quantities of therapeutic cells of the hematopoietic lineage. Dendritic cells (DC arise from CD34+ hematopoietic progenitor cells (HPCs and are important in many innate and adaptive immune functions. With respect to HIV-1 infection, DCs play an important role in the efficient capture and transfer of the virus to susceptible cells. With an aim of generating DCs from a renewable source for HIV-1 studies, here we evaluated the capacity of hES cell derived CD34+ cells to give rise to DCs which can support HIV-1 infection. Results Undifferentiated hES cells were cultured on S17 mouse bone marrow stromal cell layers to derive CD34+ HPCs which were subsequently grown in specific cytokine differentiation media to promote the development of DCs. The hES derived DCs (hES-DC were subjected to phenotypic and functional analyses and compared with DCs derived from fetal liver CD34+ HPC (FL-DC. The mature hES-DCs displayed typical DC morphology consisting of veiled stellate cells. The hES-DCs also displayed characteristic phenotypic surface markers CD1a, HLA-DR, B7.1, B7.2, and DC-SIGN. The hES-DCs were found to be capable of antigen uptake and stimulating naïve allogeneic CD4+ T cells in a mixed leukocyte reaction assay. Furthermore, the hES-DCs supported productive HIV-1 viral infection akin to standard DCs. Conclusion Phenotypically normal and functionally competent DCs that support HIV-1 infection can be derived from hES cells. hES-DCs can now be exploited in applied immunology and HIV-1 infection studies. Using gene therapy approaches, it is now possible to generate HIV-1 resistant DCs from anti-HIV gene transduced hES-CD34+ hematopoietic progenitor cells.

Study on Characteristics of Constricted DC Plasma Using Particle-In-Cell Simulator

International Nuclear Information System (INIS)

Jo, Jong Gap; Park, Yeong Shin; Hwang, Yong Seok

2010-01-01

In dc glow discharge, when anode size is smaller than cathode, very small and bright plasma ball occurs in front of anode. This plasma is called constricted dc plasma and characterized by a high plasma density in positive glow, so called plasma ball, compared to the conventional dc plasma. For the reason, this plasma is utilized to ion or electron beam sources since the beam currents are enhanced by the dense anode glow. However, correlations between characteristics of the plasma (plasma density, electron temperature and space potential) and discharge conditions (anode size, discharge voltage, discharge current, pressure) have been a little investigated definitely clear in previous study because of the trouble of a diagnosis. The plasma ball which is the most essential part of the constricted plasma is too small to diagnose precisely without disturbing plasma. Therefore, we tried to analyze the constricted plasma through computer simulation with Particle-In-Cell (PIC) code. In this study, simulation result of constricted dc plasma as well as conventional dc glow discharge will be addressed and compared with each others

Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.

Science.gov (United States)

Yamanegi, Koji; Kawabe, Mutsuki; Futani, Hiroyuki; Nishiura, Hiroshi; Yamada, Naoko; Kato-Kogoe, Nahoko; Kishimoto, Hiromitsu; Yoshiya, Shinichi; Nakasho, Keiji

2015-05-01

The level of vascular endothelial growth inhibitor (VEGI) has been reported to be negatively associated with neovascularization in malignant tumors. The soluble form of VEGI is a potent anti-angiogenic factor due to its effects in inhibiting endothelial cell proliferation. This inhibition is mediated by death receptor 3 (DR3), which contains a death domain in its cytoplasmic tail capable of inducing apoptosis that can be subsequently blocked by decoy receptor 3 (DcR3). We investigated the effects of sodium valproate (VPA) and trichostatin A (TSA), histone deacetylase inhibitors, on the expression of VEGI and its related receptors in human osteosarcoma (OS) cell lines and human microvascular endothelial (HMVE) cells. Consequently, treatment with VPA and TSA increased the VEGI and DR3 expression levels without inducing DcR3 production in the OS cell lines. In contrast, the effect on the HMVE cells was limited, with no evidence of growth inhibition or an increase in the DR3 and DcR3 expression. However, VPA-induced soluble VEGI in the OS cell culture medium markedly inhibited the vascular tube formation of HMVE cells, while VEGI overexpression resulted in enhanced OS cell death. Taken together, the HDAC inhibitor has anti-angiogenesis and antitumor activities that mediate soluble VEGI/DR3-induced apoptosis via both autocrine and paracrine pathways. This study indicates that the HDAC inhibitor may be exploited as a therapeutic strategy modulating the soluble VEGI/DR3 pathway in osteosarcoma patients.

Peripheral Blood CD4 T-Cell and Plasmacytoid Dendritic Cell (pDC) Reactivity to Herpes Simplex Virus 2 and pDC Number Do Not Correlate with the Clinical or Virologic Severity of Recurrent Genital Herpes

Science.gov (United States)

Moss, Nicholas J.; Magaret, Amalia; Laing, Kerry J.; Kask, Angela Shaulov; Wang, Minna; Mark, Karen E.; Schiffer, Joshua T.; Wald, Anna

2012-01-01

Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population. Circulating CD4 T-cell responses to HSV-2 were measured in specimens from 67 immunocompetent individuals with measured genital lesion and HSV shedding rates. Similarly, pDC number and functional responses to HSV-2 were analyzed in 40 persons. CD4 responses and pDC concentrations and responses ranged as much as 100-fold between persons while displaying moderate within-person consistency over time. No correlations were observed between these immune response parameters and genital HSV-2 severity. Cytomegalovirus (CMV) coinfection was not correlated with differences in HSV-2-specific CD4 T-cell responses. The CD4 T-cell response to HSV-2 was much more polyfunctional than was the response to CMV. These data suggest that other immune cell subsets with alternate phenotypes or anatomical locations may be responsible for genital herpes control in chronically infected individuals. PMID:22761381

Using super-capacitors in combination with Bi-directional DC/DC converters for active load management in residential fuel cell applications

Energy Technology Data Exchange (ETDEWEB)

Cacciato, M.; Giulii Capponi, F. [Rome Univ., ' La Sapienza' , Dept. of Electrical Engineering (Italy)

2004-07-01

Among innovative conversion systems for alternative energy, Fuel Cells (FCs) are ideal in applications as distributed power generation or automotive. The connection of FCs to domestic or industrial loads requires a DC/AC converter also acting as a energy buffer to match the different dynamics of FCs and loads. In the last years, a new type of electrolytic capacitors called Super- Capacitors (SCs), has been designed using double layers technology. Such components are able to store more energy than electrolytic capacitors maintaining the capability to swap it at high power levels. Firstly, different solution used to connect SCs to a FC based conversion system are considered. Then, a comparison of bi-directional DC/DC converters designed to manage SCs energy is performed. Finally, the converter design and a laboratory prototype of the adopted solution are reported. (authors)

Human dendritic cells sequentially matured with CD4(+) T cells as a secondary signal favor CTL and long-term T memory cell responses.

Science.gov (United States)

Simon, Thomas; Tanguy-Royer, Séverine; Royer, Pierre-Joseph; Boisgerault, Nicolas; Frikeche, Jihane; Fonteneau, Jean-François; Grégoire, Marc

2012-01-01

Dendritic cells (DCs) are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL) responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4(+) T lymphocytes

NARCIS (Netherlands)

Naarding, Marloes A.; Ludwig, Irene S.; Groot, Fedde; Berkhout, Ben; Geijtenbeek, Teunis B. H.; Pollakis, Georgios; Paxton, William A.

2005-01-01

DC-specific ICAM3-grabbing non-integrin (DC-SIGN), which is expressed on DCs, can interact with a variety of pathogens such as HIV-1, hepatitis C, Ebola, cytomegalovirus, Dengue virus, Mycobacterium, Leisbmania, and Candida albicans. We demonstrate that human milk can inhibit the DC-SIGN-mediated

Macrophage galactose-type C-type lectin receptor for DC targeting of antitumor glycopeptide vaccines

DEFF Research Database (Denmark)

Nuti, M; Zizzari, I; Napoletano, C

2011-01-01

e13528 Background: Dendritic cells (DCs) are the most potent antigen presenting cells and are employed in cancer vaccination. Several receptors are being studied in order to identif strategies to increase DCs activating capacity. The C-type lectin macrophage galactose type C-type lectin (MGL...... of IFNg and IL-2 secretion by both CD8 and CD4 T cells. CONCLUSIONS: These results demonstrate that MGL engagement profoundly affects DC plasticity inducing and directing a Th1 immune response. Moreover, MGL receptor expressed on human DC can be targeted by glycopeptide based vaccines with adjuvant...

S-layer proteins from Lactobacillus sp. inhibit bacterial infection by blockage of DC-SIGN cell receptor.

Science.gov (United States)

Prado Acosta, Mariano; Ruzal, Sandra M; Cordo, Sandra M

2016-11-01

Many species of Lactobacillus sp. possess Surface(s) layer proteins in their envelope. Among other important characteristics S-layer from Lactobacillus acidophilus binds to the cellular receptor DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; CD209), which is involved in adhesion and infection of several families of bacteria. In this report we investigate the activity of new S-layer proteins from the Lactobacillus family (Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus helveticus and Lactobacillus kefiri) over the infection of representative microorganisms important to human health. After the treatment of DC-SIGN expressing cells with these proteins, we were able to diminish bacterial infection by up to 79% in both gram negative and mycobacterial models. We discovered that pre-treatment of the bacteria with S-layers from Lactobacillus acidophilus and Lactobacillus brevis reduced bacteria viability but also prevent infection by the pathogenic bacteria. We also proved the importance of the glycosylation of the S-layer from Lactobacillus kefiri in the binding to the receptor and thus inhibition of infection. This novel characteristic of the S-layers proteins may contribute to the already reported pathogen exclusion activity for these Lactobacillus probiotic strains; and might be also considered as a novel enzymatic antimicrobial agents to inhibit bacterial infection and entry to host cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of low dose irradiation on differentiation, maturation and T-cell activation of human dendritic cells

Energy Technology Data Exchange (ETDEWEB)

Jahns, Jutta [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany); Anderegg, Ulf; Saalbach, Anja [Department for Dermatology, Venerology and Allergology, University of Leipzig, Johannisallee 30, 04103 Leipzig (Germany); Rosin, Britt; Patties, Ina; Glasow, Annegret [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany); Kamprad, Manja [Institute for Clinical Immunology and Transfusion Medicine, University of Leipzig, Johannisallee 30, 04103 Leipzig (Germany); Scholz, Markus [Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstr. 16-18, 04103 Leipzig (Germany); Hildebrandt, Guido, E-mail: Guido.Hildebrandt@uni-rostock.de [Department of Radiotherapy and Radiation Oncology, University of Rostock, Suedring 75, 18059 Rostock (Germany); Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany)

2011-05-10

Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded.

Active pre-filters for dc/dc Boost regulators

Directory of Open Access Journals (Sweden)

Carlos Andrés Ramos-Paja

2014-05-01

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.

Maturation of human dendritic cells by monocyte-conditioned medium is dependent upon trace amounts of lipopolysaccharide inducing tumour necrosis factor alpha

DEFF Research Database (Denmark)

Nersting, Jacob; Svenson, Morten; Andersen, Vagn

2003-01-01

We investigated the ability of monocyte-conditioned medium (MCM), generated by monocytes cultured on plastic-immobilised immunoglobulin, to stimulate maturation of human monocyte-derived dendritic cells (DC). Earlier reports suggest that MCM is a strong inducer of irreversible DC maturation......, whereas we find, that adding a small amount of lipopolysaccharide (LPS) to the MCM-generating cultures is required for the production of a DC-stimulatory MCM. Moreover, compared with addition of LPS directly to the DC cultures, stimulation via MCM cultures increases by several fold the DC...

DC-DC Type High-Frequency Link DC for Improved Power Quality of Cascaded Multilevel Inverter

Science.gov (United States)

Sadikin, Muhammad; Senjyu, Tomonobu; Yona, Atsushi

2013-06-01

Multilevel inverters are emerging as a new breed of power converter options for power system applications. Recent advances in power switching devices enabled the suitability of multilevel inverters for high voltage and high power applications because they are connecting several devices in series without the need of component matching. Usually, a transformerless battery energy storage system, based on a cascaded multilevel inverter, is used as a measure for voltage and frequency deviations. System can be reduced in size, weight, and cost of energy storage system. High-frequency link circuit topology is advantageous in realizing compact and light-weight power converters for uninterruptible power supply systems, new energy systems using photovoltaic-cells, fuel-cells and so on. This paper presents a DC-DC type high-frequency link DC (HFLDC) cascaded multilevel inverter. Each converter cell is implemented a control strategy for two H-bridge inverters that are controlled with the same multicarrier pulse width modulation (PWM) technique. The proposed cascaded multilevel inverter generates lower voltage total harmonic distortion (THD) in comparison with conventional cascaded multilevel inverter. Digital simulations are carried out using PSCAD/EMTDC to validate the performance of the proposed cascaded multilevel inverter.

Human dendritic cells sequentially matured with CD4+ T cells as a secondary signal favor CTL and long-term T memory cell responses

Directory of Open Access Journals (Sweden)

Thomas Simon

2012-01-01

Full Text Available Dendritic cells (DCs are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

Integrating DC/DC Conversion with Possible Reconfiguration within Submodule Solar Photovoltaic Systems

Science.gov (United States)

Huang, Peter Jen-Hung

This research first proposes a method to merge photovoltaic (PV) cells or PV panels within the internal components DC-DC converters. The purpose of this merged structure is to reconfigure the PV modules between series and parallel connections using high switching frequencies (hundreds of kHz). This leads to multi-levels of voltages and currents that become applied to the output filter of the converter. Further, this research introduces a concept of a switching cell that utilizes the reconfiguration of series and parallel connections in DC-DC converters. The switching occurs at high switching frequency and the switches can be integrated to be within the solar panels or in between the solar cells. The concept is generalized and applied to basic buck and boost topologies. As examples of the new types of converters: reconfigurable PV-buck and PV-boost converter topologies are presented. It is also possible to create other reconfigurable power converters: non-isolated and isolated topologies. Analysis, simulation and experimental verification for the reconfigurable PV-buck and PV-boost converters are presented extensively to illustrate proof of concept. Benefits and drawbacks of the new approach are discussed. The second part of this research proposes to utilize the internal solar cell capacitance and internal solar module wire parasitic inductances to replace the input capacitor and filter inductor in boost derived DC-DC converters for energy harvesting applications. High switching frequency (MHz) hard switched and resonant boost converters are proposed. Their analysis, simulation and experimental prototypes are presented. A specific proof-of-concept application is especially tested for foldable PV panels, which are known for their high internal wire inductance. The experimental converters successfully boost solar module voltage without adding any external input capacitance or filter inductor. Benefits and drawbacks of new proposed PV submodule integrated boost

Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells.

Directory of Open Access Journals (Sweden)

Tina Zavašnik-Bergant

Full Text Available Dendritic cells (DC play a pivotal role as antigen presenting cells (APC and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70 during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii.

An overview of power electronics applications in fuel cell systems: DC and AC converters.

Science.gov (United States)

Ali, M S; Kamarudin, S K; Masdar, M S; Mohamed, A

2014-01-01

Power electronics and fuel cell technologies play an important role in the field of renewable energy. The demand for fuel cells will increase as fuel cells become the main power source for portable applications. In this application, a high-efficiency converter is an essential requirement and a key parameter of the overall system. This is because the size, cost, efficiency, and reliability of the overall system for portable applications primarily depend on the converter. Therefore, the selection of an appropriate converter topology is an important and fundamental aspect of designing a fuel cell system for portable applications as the converter alone plays a major role in determining the overall performance of the system. This paper presents a review of power electronics applications in fuel cell systems, which include various topology combinations of DC converters and AC inverters and which are primarily used in fuel cell systems for portable or stand-alone applications. This paper also reviews the switching techniques used in power conditioning for fuel cell systems. Finally, this paper addresses the current problem encountered with DC converters and AC inverter.

Staphylococcus aureus Esx Factors Control Human Dendritic Cell Functions Conditioning Th1/Th17 Response

Directory of Open Access Journals (Sweden)

Melania Cruciani

2017-07-01

Full Text Available The opportunistic pathogen Staphylococcus aureus (S. aureus is a major cause of nosocomial- and community-acquired infections. In addition, many antibiotic-resistant strains are emerging worldwide, thus, there is an urgent unmet need to pinpoint novel therapeutic and prophylactic strategies. In the present study, we characterized the impact of infection with the pandemic methicillin-resistant USA300 S. aureus strain on human primary dendritic cells (DC, key initiators and regulators of immune responses. In particular, among staphylococcal virulence factors, the function of EsxA and EsxB, two small acidic dimeric proteins secreted by the type VII-like secretion system Ess (ESAT-6-like secretion system, was investigated in human DC setting. A comparative analysis of bacterial entry, replication rate as well as DC maturation, apoptosis, signaling pathway activation and cytokine production was performed by using wild type (wt USA300 and three isogenic mutants carrying the deletion of esxA (ΔesxA, esxB (ΔesxB, or both genes (ΔesxAB. The S. aureus mutant lacking only the EsxA protein (ΔesxA stimulated a stronger pro-apoptotic phenotype in infected DC as compared to wt USA300, ΔesxAB, and ΔesxB strains. When the mutant carrying the esxB deletion (ΔesxB was analyzed, a higher production of both regulatory and pro-inflammatory mediators was found in the infected DC with respect to those challenged with the wt counterpart and the other esx mutants. In accordance with these data, supernatant derived from ΔesxB-infected DC promoted a stronger release of both IFN-γ and IL-17 from CD4+ T cells as compared with those conditioned with supernatants derived from wild type USA300-, ΔesxAB-, and ΔesxA-infected cultures. Although, the interaction of S. aureus with human DC is not yet fully understood, our data suggest that both cytokine production and apoptotic process are modulated by Esx factors, thus indicating a possible role of these proteins in the

DC-DC power converter research for Orbiter/Station power exchange

Science.gov (United States)

Ehsani, M.

1993-01-01

This project was to produce innovative DC-DC power converter concepts which are appropriate for the power exchange between the Orbiter and the Space Station Freedom (SSF). The new converters must interface three regulated power buses on SSF, which are at different voltages, with three fuel cell power buses on the Orbiter which can be at different voltages and should be tracked independently. Power exchange is to be bi-directional between the SSF and the Orbiter. The new converters must satisfy the above operational requirements with better weight, volume, efficiency, and reliability than is available from the present conventional technology. Two families of zero current DC-DC converters were developed and successfully adapted to this application. Most of the converters developed are new and are presented.

Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

Science.gov (United States)

Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

2017-11-01

In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Converter DC/AC Multilevel of Three Cells: Modeling and Simulation

Directory of Open Access Journals (Sweden)

Julián Peláez-Restrepo

2013-11-01

Full Text Available This paper presents a three-cell converter DC / AC. Multilevel topologies are attracting attention in the industry, obtained as a ripple on the state variables much smaller, and reduces stress on the switching devices. The topology used in this work is known in the technical literature as floating capacitor multilevel inverter, which imposes the challenge of balancing the voltage across each cell switching using floating capacitors, besides obtaining a sinusoidal signal regulated. The paper presents the averaged model of the inverter, and results obtained through simulation.

The role of cDC1s in vivo: CD8 T cell priming through cross-presentation [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Derek Theisen

2017-02-01

Full Text Available The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance on in vitro systems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells. We then discuss the role of cDC1s as a cellular platform to combine antigen processing for class I and class II MHC presentation to allow the integration of “help” from CD4 T cells during priming of CD8 T cell responses.

Impute DC link (IDCL) cell based power converters and control thereof

Science.gov (United States)

Divan, Deepakraj M.; Prasai, Anish; Hernendez, Jorge; Moghe, Rohit; Iyer, Amrit; Kandula, Rajendra Prasad

2016-04-26

Power flow controllers based on Imputed DC Link (IDCL) cells are provided. The IDCL cell is a self-contained power electronic building block (PEBB). The IDCL cell may be stacked in series and parallel to achieve power flow control at higher voltage and current levels. Each IDCL cell may comprise a gate drive, a voltage sharing module, and a thermal management component in order to facilitate easy integration of the cell into a variety of applications. By providing direct AC conversion, the IDCL cell based AC/AC converters reduce device count, eliminate the use of electrolytic capacitors that have life and reliability issues, and improve system efficiency compared with similarly rated back-to-back inverter system.

Floating high step-down stacked dc-dc converter based on buck-boost cells

NARCIS (Netherlands)

Tibola, G.; Duarte, J.L.; Blinov, A.

2015-01-01

In some high power dc-dc applications, where high voltage is present, a converter with high step-down ratio is required in order to provide an isolated low power auxiliary supply. This requirement represents a challenge and many topologies are currently being researched. The analysis of a

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

Science.gov (United States)

Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Appel, Silke

2012-01-01

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

Directory of Open Access Journals (Sweden)

Arnt-Ove Hovden

Full Text Available Dendritic cells (DC used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

Science.gov (United States)

Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

2016-01-01

Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.

Science.gov (United States)

Li, Jinyao; Geng, Shuang; Liu, Xiuping; Liu, Hu; Jin, Huali; Liu, Chang-Gong; Wang, Bin

2013-10-01

We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c(+)CD40(low)IL-10(+) regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway.

Antigen-specific IL-23/17 pathway activation by murine semi-mature DC-like cells

Energy Technology Data Exchange (ETDEWEB)

Nagasaka, Shinya; Iwasaki, Takumi; Okano, Tomoko [Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510 (Japan); Chiba, Joe, E-mail: chibaj@rs.noda.tus.ac.jp [Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510 (Japan)

2009-09-11

We analyzed the phenotype and function of bone marrow-derived dendritic cells (DCs) induced in vitro without using any serum during the late stage of cultivation. These 'serum-free' DCs (SF-DCs) possessed the ability to induce T cell proliferation as well as antibody responses, indicating that they were functional DCs. Surprisingly, the SF-DCs akin to semi-mature DCs in terms of both phenotypic and functional characteristics. The SF-DCs did not produce IL-12 but produced large amounts of IL-23 following lipopolysaccharide stimulation. The antigen-specific production of IL-17 by CD4{sup +} T cells co-cultured with OVA-loaded SF-DCs was significantly higher than that with OVA-loaded conventional DCs. These results suggest that SF-DCs tend to produce IL-23 and can consequently induce the IL-17 producing CD4{sup +} T cells. The semi-mature DC-like cells reported here will be useful vehicles for DC immunization and might contribute to studies on the possible involvement of semi-mature DCs in Th17 cell differentiation.

In vitro culture and characterization of human umbilical cord blood-derived plasmacytoid dendritic cell subsets

Directory of Open Access Journals (Sweden)

PENG Jianping

2015-11-01

Full Text Available ObjectiveTo establish a method for in vitro culture of plasmacytoid dendritic cell (pDC. MethodsUmbilical cord blood (40 ml was collected from healthy parturients in the First Affiliated Hospital of Hunan University of Chinese Medicine, and cord blood mononuclear cell (CBMC were isolated. The CBMC were cultured for 7 days with RPMI 1640 complete medium containing rh Flt3-ligand (Flt3-L (100 ng/ml and rh interleukin (IL-3 (10 ng/ml, and the medium was half changed every 2 days. On the eighth day, CpG ODN (2 μg/ml was added to the cells, and the attached cells and supernatant were collected 24 h later for flow cytometry and interferon (IFNα measurement, respectively. On days 1, 3, 5, 7, and 8 of cell culture, the morphological changes of pDC were observed. Results After 2 h of culture, the CBMC showed circular, flat morphology. Twenty-four hours later, the cells began to adhere to the wall, with extended cytoplasm and increased volumes, and they became round and translucent, with scattered small colonies. On days 3-4 of culture, the cell volume continued increasing; most cells were round, and some had small protrusions; few cells were spindle-, tadpole-, star- or irregularly shaped; the number and volumes of colonies increased substantially. On days 5-8 of culture, the number of colonies and the number of cells in colonies gradually decreased, and suspended cells that were round or had small protrusions gradually increased in the medium. The cells expressing CD123, BDCA-2, and BDCA-4, which were considered pDC, were detected by flow cytometry. Flow cytometry revealed that the proportion of pDC in CBMC increased during the culture: increasing from 1.08% at the beginning of culture to 5.32% on day 4, and finally reaching a peak of 19.8% on day 8. On day 8, the level of IFNα in pDC culture supernatant was(11 302.61±1745.31 pg/ml. ConclusionpDC can be successfully induced in vitro by rh Flt3-L combined with IL-3 from human umbilical CBMC.

Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro

NARCIS (Netherlands)

Jones, CA; Fernandez, M; Herc, K; Bosnjak, L; Miranda-Saksena, M; Boadle, RA; Cunningham, A

2003-01-01

Dendritic cells (DC) are critical for stimulation of naive T cells. Little is known about the effect of herpes simplex virus type 2 (HSV-2) infection on DC structure or function or if the observed effects of HSV-1 on human DC are reproduced in murine DC. Here, we demonstrate that by 12 h

Specific Intensity Direct Current (DC) Electric Field Improves Neural Stem Cell Migration and Enhances Differentiation towards βIII-Tubulin+ Neurons

Science.gov (United States)

Zhao, Huiping; Steiger, Amanda; Nohner, Mitch; Ye, Hui

2015-01-01

Control of stem cell migration and differentiation is vital for efficient stem cell therapy. Literature reporting electric field–guided migration and differentiation is emerging. However, it is unknown if a field that causes cell migration is also capable of guiding cell differentiation—and the mechanisms for these processes remain unclear. Here, we report that a 115 V/m direct current (DC) electric field can induce directional migration of neural precursor cells (NPCs). Whole cell patching revealed that the cell membrane depolarized in the electric field, and buffering of extracellular calcium via EGTA prevented cell migration under these conditions. Immunocytochemical staining indicated that the same electric intensity could also be used to enhance differentiation and increase the percentage of cell differentiation into neurons, but not astrocytes and oligodendrocytes. The results indicate that DC electric field of this specific intensity is capable of promoting cell directional migration and orchestrating functional differentiation, suggestively mediated by calcium influx during DC field exposure. PMID:26068466

Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells.

Science.gov (United States)

Zhang, Xiao-Fei; Weng, De-Sheng; Pan, Ke; Zhou, Zi-Qi; Pan, Qiu-Zhong; Zhao, Jing-Jing; Tang, Yan; Jiang, Shan-Shan; Chen, Chang-Long; Li, Yong-Qiang; Zhang, Hong-Xia; Chang, Alfred E; Wicha, Max S; Zeng, Yi-Xin; Li, Qiao; Xia, Jian-Chuan

2017-11-01

Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified "stem-like" characteristics of CD105+ cells in two human RCC cell lines: A498 and SK-RC-39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC-based immunotherapy for human RCC. © 2017 Wiley Periodicals, Inc.

DC electric springs with DC/DC converters

DEFF Research Database (Denmark)

Wang, Qingsong; Cheng, Ming; Jiang, Yunlei

2016-01-01

The concept of DC electric spring (DCES) was recently proposed to solve the stability issue caused by integrating intermittent renewable energy sources (RESs) to DC microgrids. In this paper, a new topology of DCES is proposed based on DC/DC converters. The proposed DCES consists of a bi-directio......The concept of DC electric spring (DCES) was recently proposed to solve the stability issue caused by integrating intermittent renewable energy sources (RESs) to DC microgrids. In this paper, a new topology of DCES is proposed based on DC/DC converters. The proposed DCES consists of a bi...... and/or constant discharging for batteries is adopted and four operating modes are analyzed as charging-positive, charging-negative, discharging-positive and discharging-negative modes. An additional mechanism for fast charging or fast discharging is also designed to secure normal operation...... of batteries. With the proposed DCES, the power fluctuations due to intermittent RESs can be passed to non-critical loads (NCLs) and batteries while power on critical loads (CLs) is kept stable. This is possibly the first attempt to design a DCES with only DC/DC converters. The performances of the proposed...

Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential.

Science.gov (United States)

Carrion, Julio; Scisci, Elizabeth; Miles, Brodie; Sabino, Gregory J; Zeituni, Amir E; Gu, Ying; Bear, Adam; Genco, Caroline A; Brown, David L; Cutler, Christopher W

2012-09-15

The low-grade oral infection chronic periodontitis (CP) has been implicated in coronary artery disease risk, but the mechanisms are unclear. In this study, a pathophysiological role for blood dendritic cells (DCs) in systemic dissemination of oral mucosal pathogens to atherosclerotic plaques was investigated in humans. The frequency and microbiome of CD19(-)BDCA-1(+)DC-SIGN(+) blood myeloid DCs (mDCs) were analyzed in CP subjects with or without existing acute coronary syndrome and in healthy controls. FACS analysis revealed a significant increase in blood mDCs in the following order: healthy controls < CP < acute coronary syndrome/CP. Analysis of the blood mDC microbiome by 16S rDNA sequencing showed Porphyromonas gingivalis and other species, including (cultivable) Burkholderia cepacia. The mDC carriage rate with P. gingivalis correlated with oral carriage rate and with serologic exposure to P. gingivalis in CP subjects. Intervention (local debridement) to elicit a bacteremia increased the mDC carriage rate and frequency in vivo. In vitro studies established that P. gingivalis enhanced by 28% the differentiation of monocytes into immature mDCs; moreover, mDCs secreted high levels of matrix metalloproteinase-9 and upregulated C1q, heat shock protein 60, heat shock protein 70, CCR2, and CXCL16 transcripts in response to P. gingivalis in a fimbriae-dependent manner. Moreover, the survival of the anaerobe P. gingivalis under aerobic conditions was enhanced when within mDCs. Immunofluorescence analysis of oral mucosa and atherosclerotic plaques demonstrate infiltration with mDCs, colocalized with P. gingivalis. Our results suggest a role for blood mDCs in harboring and disseminating pathogens from oral mucosa to atherosclerosis plaques, which may provide key signals for mDC differentiation and atherogenic conversion.

DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1

Directory of Open Access Journals (Sweden)

Connor Joseph P

2012-05-01

Full Text Available Abstract Background Overcoming platinum resistance is a major obstacle in the treatment of Epithelial Ovarian Cancer (EOC. In our previous work Decoy Receptor 3 (DcR3 was found to be related to platinum resistance. The major objective of this work was to define the cellular interaction of DcR3 with EOC and to explore its effects on platinum responsiveness. Methods We studied cell lines and primary cultures for the expression of and the cells ability to bind DcR3. Cells were cultured with DcR3 and then exposed to platinum. Cell viability was determined by MTT assay. Finally, the cells molecular response to DcR3 was studied using real time RT-PCR based differential expression arrays, standard RT-PCR, and Western blot. Results High DcR3 in the peritoneal cavity of women with EOC is associated with significantly shorter time to first recurrence after platinum based therapy (p = 0.02. None-malignant cells contribute DcR3 in the peritoneal cavity. The cell lines studied do not secrete DcR3; however they all bind exogenous DcR3 to their surface implying that they can be effected by DcR3 from other sources. DcR3s protein binding partners are minimally expressed or negative, however, all cells expressed the DcR3 binding Heparan Sulfate Proteoglycans (HSPGs Syndecans-2, and CD44v3. DcR3 binding was inhibited by heparin and heparinase. After DcR3 exposure both SKOV-3 and OVCAR-3 became more resistant to platinum with 15% more cells surviving at high doses. On the contrary CaOV3 became more sensitive to platinum with 20–25% more cell death. PCR array analysis showed increase expression of BRCA1 mRNA in SKOV-3 and OVCAR-3 and decreased BRCA1 expression in CaOV-3 after exposure to DcR3. This was confirmed by gene specific real time PCR and Western blot analysis. Conclusions Non-malignant cells contribute to the high levels of DcR3 in ovarian cancer. DcR3 binds readily to EOC cells via HSPGs and alter their responsiveness to platinum chemotherapy. The

Neuropeptide Y induces potent migration of human immature dendritic cells and promotes a Th2 polarization.

Science.gov (United States)

Buttari, Brigitta; Profumo, Elisabetta; Domenici, Giacomo; Tagliani, Angela; Ippoliti, Flora; Bonini, Sergio; Businaro, Rita; Elenkov, Ilia; Riganò, Rachele

2014-07-01

Neuropeptide Y (NPY), a major autonomic nervous system and stress mediator, is emerging as an important regulator of inflammation, implicated in autoimmunity, asthma, atherosclerosis, and cancer. Yet the role of NPY in regulating phenotype and functions of dendritic cells (DCs), the professional antigen-presenting cells, remains undefined. Here we investigated whether NPY could induce DCs to migrate, mature, and polarize naive T lymphocytes. We found that NPY induced a dose-dependent migration of human monocyte-derived immature DCs through the engagement of NPY Y1 receptor and the activation of ERK and p38 mitogen-activated protein kinases. NPY promoted DC adhesion to endothelial cells and transendothelial migration. It failed to induce phenotypic DC maturation, whereas it conferred a T helper 2 (Th2) polarizing profile to DCs through the up-regulation of interleukin (IL)-6 and IL-10 production. Thus, during an immune/inflammatory response NPY may exert proinflammatory effects through the recruitment of immature DCs, but it may exert antiinflammatory effects by promoting a Th2 polarization. Locally, at inflammatory sites, cell recruitment could be amplified in conditions of intense acute, chronic, or cold stress. Thus, altered or amplified signaling through the NPY-NPY-Y1 receptor-DC axis may have implications for the development of inflammatory conditions.-Buttari, B., Profumo, E., Domenici, G., Tagliani, A., Ippoliti, F., Bonini, S., Businaro, R., Elenkov, I., Riganò, R. Neuropeptide Y induces potent migration of human immature dendritic cells and promotes a Th2 polarization. © FASEB.

The Influence of Ouabain on Human Dendritic Cells Maturation

Directory of Open Access Journals (Sweden)

C. R. Nascimento

2014-01-01

Full Text Available Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua. Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate DC maturation under Ouabain influence. To generate immature DCs, human monocytes were cultured with IL-4 and GM-CSF (5 days. To investigate Ouabain role on DC activation, DCs were stimulated with TNF-α for 48 h in the presence or absence of Ouabain. TNF-induced CD83 expression and IL-12 production were abolished in DCs incubated with 100 nM Ouabain, though DC functional capacity concerning lymphocyte activation remained unaltered. Nevertheless, TNF-α-induced antigen capture downregulation, another maturation marker, occurred even in the presence of Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80 expression was maintained. Collectively, our results suggest that DCs respond to Ouabain maturating into a distinct category, possibly contributing to the balance between immunity and tolerance.

DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption.

Science.gov (United States)

Wisitrasameewong, W; Kajiya, M; Movila, A; Rittling, S; Ishii, T; Suzuki, M; Matsuda, S; Mazda, Y; Torruella, M R; Azuma, M M; Egashira, K; Freire, M O; Sasaki, H; Wang, C Y; Han, X; Taubman, M A; Kawai, T

2017-06-01

Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis ( n = 6-7/group) where Pasteurella pneumotropica ( Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis. DC-STAMP was expressed on the cell surface of mature multinuclear OCs, as well as immature mononuclear OCs, in primary cultures of RANKL-stimulated bone marrow cells. Anti-DC-STAMP-mAb suppressed the emergence of large, but not small, multinuclear OCs, suggesting that DC-STAMP is engaged in the late stage of cell fusion. Anti-DC-STAMP-mAb also inhibited pit formation caused by RANKL-stimulated bone marrow cells. Attachment of ligature to a second maxillary molar induced DC-STAMP messenger RNA and protein, along with elevated tartrate-resistant acid phosphatase-positive (TRAP+) OCs and alveolar bone loss. As we expected, systemic administration of anti-DC-STAMP-mAb downregulated the ligature-induced alveolar bone loss. Importantly, local injection of anti-DC-STAMP-mAb also suppressed alveolar bone loss and reduced the total number of multinucleated TRAP+ cells in mice that received ligature attachment. Attachment of ligature induced significantly elevated tumor necrosis factor-α, interleukin-1β, and RANKL in the gingival tissue compared with the control site without ligature ( P < 0.05), which was unaffected by local injection with either anti-DC-STAMP-mAb or control-mAb. Neither in vivo anti- Pp IgG antibody nor in vitro anti- Pp T-cell

Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway.

Science.gov (United States)

Guzman, Efrain; Taylor, Geraldine; Hope, Jayne; Herbert, Rebecca; Cubillos-Zapata, Carolina; Charleston, Bryan

2016-10-01

Dendritic cells (DC) are central to the initiation of immune responses, and various approaches have been used to target vaccines to DC in order to improve immunogenicity. Cannulation of lymphatic vessels allows for the collection of DC that migrate from the skin. These migrating DC are involved in antigen uptake and presentation following vaccination. Human replication-deficient adenovirus (AdV) 5 is a promising vaccine vector for delivery of recombinant antigens. Although the mechanism of AdV attachment and penetration has been extensively studied in permissive cell lines, few studies have addressed the interaction of AdV with DC. In this study, we investigated the interaction of bovine skin-migrating DC and replication-deficient AdV-based vaccine vectors. We found that, despite lack of expression of Coxsackie B-Adenovirus Receptor and other known adenovirus receptors, AdV readily enters skin-draining DC via an actin-dependent endocytosis. Virus exit from endosomes was pH independent, and neutralizing antibodies did not prevent virus entry but did prevent virus translocation to the nucleus. We also show that combining adenovirus with adjuvant increases the absolute number of intracellular virus particles per DC but not the number of DC containing intracellular virus. This results in increased trans-gene expression and antigen presentation. We propose that, in the absence of Coxsackie B-Adenovirus Receptor and other known receptors, AdV5-based vectors enter skin-migrating DC using actin-dependent endocytosis which occurs in skin-migrating DC, and its relevance to vaccination strategies and vaccine vector targeting is discussed.

Characterization of CD8+ T-Cell Responses in the Peripheral Blood and Skin Injection Sites of Melanoma Patients Treated with mRNA Electroporated Autologous Dendritic Cells (TriMixDC-MEL

Directory of Open Access Journals (Sweden)

Daphné Benteyn

2013-01-01

Full Text Available Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL stimulates T-cell responses against the presented tumor-associated antigens (TAAs. In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8+ T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71% patients screened, CD8+ T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8+ T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8+ T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8+ T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.

Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL).

Science.gov (United States)

Benteyn, Daphné; Van Nuffel, An M T; Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; Neyns, Bart; Thielemans, Kris; Bonehill, Aude

2013-01-01

Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL) stimulates T-cell responses against the presented tumor-associated antigens (TAAs). In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8(+) T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs) and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71%) patients screened, CD8(+) T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8(+) T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8(+) T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8(+) T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.

Advanced DC/DC converters

CERN Document Server

Luo, Fang Lin

2003-01-01

DC/DC conversion techniques have undergone rapid development in recent decades. With the pioneering work of these authors, DC/DC converters have now moved into their sixth generation. This book offers a concise, practical presentation of DC/DC converters, summarizing the spectrum of conversion tecnologies and presentingmany new ideas and more than 100 new topologies. Nowhere else in the literature are DC/DC converters so logically sorted and systematically introduced, and nowhere else can readers find detailed information on prototype topologies that represent a major contribution to modern power engineering. More than 320 figures, 60 tables, and 500 formulae facilitate understand and provide precise data.

Multi-level cascaded DC/DC converters for PV applications

Directory of Open Access Journals (Sweden)

Ahmed A.A. Hafez

2015-12-01

Full Text Available A robust multi-level cascaded DC/DC system for Photovoltaic (PV application is advised in this article. There are three PV generators, each is coupled to a half-bridge buck cell. Each PV-generator–buck-converter channel is controlled such that maximum power is captured independently under different irradiation and temperature levels. The system operation under normal and abnormal conditions was comprehensively investigated. Internal Model Control (IMC technique was adopted for tuning the controllers. An elaborate switching modulation strategy was used to reduce the current ripple and inductor size, while maintaining high efficiency. Annotative, simple and robust remedial strategies were proposed to mitigate different anticipated faults. Comprehensive simulation results in Matlab environment were illustrated for corroborating the performance of the advised cascaded DC/DC system under normal/abnormal conditions. The proposed system enjoys the merits of independency, reduced volumetric dimensions and improved efficiency. Furthermore, the system is inherently fault-tolerant.

The cancer-immunity cycle as rational design for synthetic cancer drugs: Novel DC vaccines and CAR T-cells.

Science.gov (United States)

Ramachandran, Mohanraj; Dimberg, Anna; Essand, Magnus

2017-08-01

Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas. Although encouraging, CAR T-cells have not yet proven clinically effective for solid tumors. This is mainly due to the lack of specific and homogenously expressed targets to direct the T-cells against and a hostile immunosuppressive tumor microenvironment in solid tumors. Cancer vaccines based on dendritic cells (DC) are also making progress although clinical efficacy is still lacking. The likelihood of success is however increasing now when individual tumors can be sequences and patient-specific neoepitopes identified. Neoepitopes and/or neoantigens can then be included in patient-based DC vaccines. This review discusses recent advancements of DC vaccines and CAR T-cells with emphasis on the cancer-immunity cycle, and current efforts to design novel cell therapies. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A Novel Dual-input Isolated Current-Fed DC-DC Converter for Renewable Energy System

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

2010-01-01

In this paper, a novel isolated current-fed DC-DC converter (boost-type) with two input power sources based on multi-transformer structure, which is suitable for fuel cells and super-capacitors hybrid energy system, is proposed and designed. With particular transformer windings connection strategy...

A Unidirectional DC-DC Autotransformer for DC Grid Application

Directory of Open Access Journals (Sweden)

Meng Zhou

2018-03-01

Full Text Available Conventional unidirectional DC-DC converters for DC grid application employ DC-AC-DC two-stage conversion technology and suffer from high converter cost and power loss. To solve these issues, a unidirectional step-up DC-DC autotransformer (UUDAT and a unidirectional step-down DC-DC autotransformer (DUDAT are studied. The UUDAT and DUDAT are composed of a series connection of diode bridges and voltage source converters. Topologies of UUDAT and DUDAT are detailed. The harmonic and un-controllability issues are discussed. Control and possible application scenarios for UUDAT and DUDAT are depicted. DC fault isolation mechanism and the methods of dimensioning the voltage and power ratings of the components in UUDAT and DUDAT are studied. Extensive simulations on power system level and experiments on a UUDAT and DUDAT prototype verified their technical feasibility.

Soft switching bidirectional DC-DC converter for ultracapacitor-batteries interface

International Nuclear Information System (INIS)

Adib, Ehsan; Farzanehfard, Hosein

2009-01-01

In this paper a new soft switching bidirectional DC-DC converter is introduced which can be applied as the interface circuit between ultracapacitors and batteries or fuel cells. All semiconductor devices in the proposed converter are soft switched while the control circuit remains PWM. Due to achieved soft switching condition, the energy conversion through the proposed converter is highly efficient. The proposed converter is analyzed and a prototype converter is implemented. The presented experimental results confirm the theoretical analysis.

Design and implementation of a bidirectional current-controlled voltage-regulated DC-DC switched-mode converter

CSIR Research Space (South Africa)

Coetzer, A

2016-01-01

Full Text Available The design and implementation of a bidirectional current-controlled voltage-regulated DC-DC converter is presented. The converter is required to connect a battery of electrochemical cells (the battery) to an asynchronous motor-drive unit via a...

Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization.

Directory of Open Access Journals (Sweden)

Martina Müller

Full Text Available BACKGROUND: IL-2 deficient (IL-2(-/- mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/--mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP dendritic cells (DC. LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(loCD80(loMHC-II(hi whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/--mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/--DC in vitro. CONCLUSIONS/SIGNIFICANCE: From this data we conclude that the B. vulgatus triggered IL-6 secretion by LP DC in absence of proinflammatory cytokines such as IL-12 or TNF-alpha induces a semi-mature LP DC phenotype, which might prevent T-cell activation and thereby the induction of colitis in IL-2(-/--mice. The data provide new evidence that IL-6 might act as an immune regulatory cytokine in the mucosa by targeting intestinal DC.

Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses

Directory of Open Access Journals (Sweden)

Andoh Y

2013-01-01

Full Text Available Yoshiaki Andoh,1,2 Naohiko Makino,2 Mitsunori Yamakawa11Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanBackground: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL and CD4+CD25high regulatory T-cells (Tregs among dendritic cells (DCs fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs, were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.Results: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1 was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.Conclusion: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs

IRX-2, a novel immunotherapeutic, enhances functions of human dendritic cells.

Directory of Open Access Journals (Sweden)

Bastian Schilling

Full Text Available In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA-specific immunity by up-regulating functions of dendritic cells (DC.Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix". Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL. IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05 of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all. IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05 compared to the conv. mix-matured DC.Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy.

Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde

International Nuclear Information System (INIS)

Python, Francois; Goebel, Carsten; Aeby, Pierre

2009-01-01

The number of studies involved in the development of in vitro skin sensitization tests has increased since the adoption of the EU 7th amendment to the cosmetics directive proposing to ban animal testing for cosmetic ingredients by 2013. Several studies have recently demonstrated that sensitizers induce a relevant up-regulation of activation markers such as CD86, CD54, IL-8 or IL-1β in human myeloid cell lines (e.g., U937, MUTZ-3, THP-1) or in human peripheral blood monocyte-derived dendritic cells (PBMDCs). The present study aimed at the identification of new dendritic cell activation markers in order to further improve the in vitro evaluation of the sensitizing potential of chemicals. We have compared the gene expression profiles of PBMDCs and the human cell line MUTZ-3 after a 24-h exposure to the moderate sensitizer cinnamaldehyde. A list of 80 genes modulated in both cell types was obtained and a set of candidate marker genes was selected for further analysis. Cells were exposed to selected sensitizers and non-sensitizers for 24 h and gene expression was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. Results indicated that PIR, TRIM16 and two Nrf2-regulated genes, CES1 and NQO1, are modulated by most sensitizers. Up-regulation of these genes could also be observed in our recently published DC-activation test with U937 cells. Due to their role in DC activation, these new genes may help to further refine the in vitro approaches for the screening of the sensitizing properties of a chemical.

Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling.

Science.gov (United States)

Xiong, Hua; Chen, Zhao-Fei; Liang, Qin-Chuan; Du, Wan; Chen, Hui-Min; Su, Wen-Yu; Chen, Guo-Qiang; Han, Ze-Guang; Fang, Jing-Yuan

2009-09-01

DNA methyltransferase inhibitors (MTIs) have recently emerged as promising chemotherapeutic or preventive agents for cancer, despite their poorly characterized mechanisms of action. The present study shows that DNA methylation is integral to the regulation of SH2-containing protein tyrosine phosphatase 1 (SHP1) expression, but not for regulation of suppressors of cytokine signalling (SOCS)1 or SOCS3 in colorectal cancer (CRC) cells. SHP1 expression correlates with down-regulation of Janus kinase/signal transducers and activators of transcription (JAK2/STAT3/STAT5) signalling, which is mediated in part by tyrosine dephosphorylation events and modulation of the proteasome pathway. Up-regulation of SHP1 expression was achieved using a DNA MTI, 5-aza-2'-deoxycytidine (5-aza-dc), which also generated significant down-regulation of JAK2/STAT3/STAT5 signalling. We demonstrate that 5-aza-dc suppresses growth of CRC cells, and induces G2 cell cycle arrest and apoptosis through regulation of downstream targets of JAK2/STAT3/STAT5 signalling including Bcl-2, p16(ink4a), p21(waf1/cip1) and p27(kip1). Although 5-aza-dc did not significantly inhibit cell invasion, 5-aza-dc did down-regulate expression of focal adhesion kinase and vascular endothelial growth factor in CRC cells. Our results demonstrate that 5-aza-dc can induce SHP1 expression and inhibit JAK2/STAT3/STAT5 signalling. This study represents the first evidence towards establishing a mechanistic link between inhibition of JAK2/STAT3/STAT5 signalling and the anticancer action of 5-aza-dc in CRC cells that may lead to the use of MTIs as a therapeutic intervention for human colorectal cancer.

Soft switching bidirectional DC-DC converter for ultracapacitor-batteries interface

Energy Technology Data Exchange (ETDEWEB)

Adib, Ehsan; Farzanehfard, Hosein [Dept. of Electrical and Computer Engineering, Isfahan Univ. of Technology (Iran)

2009-12-15

In this paper a new soft switching bidirectional DC-DC converter is introduced which can be applied as the interface circuit between ultracapacitors and batteries or fuel cells. All semiconductor devices in the proposed converter are soft switched while the control circuit remains PWM. Due to achieved soft switching condition, the energy conversion through the proposed converter is highly efficient. The proposed converter is analyzed and a prototype converter is implemented. The presented experimental results confirm the theoretical analysis. (author)

High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.

Science.gov (United States)

Zahorchak, Alan F; Macedo, Camila; Hamm, David E; Butterfield, Lisa H; Metes, Diana M; Thomson, Angus W

2018-01-01

Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4 + and CD8 + T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8 + T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunomodulatory effects of aqueous and organic fractions from Petiveria alliacea on human dendritic cells.

Science.gov (United States)

Santander, Sandra Paola; Hernández, John Fredy; Barreto, Claudia Cifuentes; Cifuentes B, Claudia; Masayuki, Aoki; M, Aoki; Moins-Teisserenc, Hélène; H, Moins-Teisserenc; Fiorentino, Susana

2012-01-01

Petiveria alliacea is a plant traditionally known for its anti-inflammatory and anti-tumor activities; however, the molecular and cellular mechanisms of its immunomodulatory properties are still unknown. Dendritic cells (DC) promote adaptive immune response by activating T lymphocytes, inducing an effector response or tolerance depending on the DC differentiation level. Herein, we evaluated the immunomodulatory activity of aqueous and organic plant fractions from P. alliacea using human monocyte-derived dendritic cells. The phenotype, cytokine secretion and gene expression were estimated after treatment with the plant fractions. We found that P. alliacea aqueous fraction induced morphological changes and co-stimulatory expression of CD86, indicating partial DC maturation. In addition, pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α were secreted. The fraction also increased NF-κB gene expression while down-regulating TGFβ gene expression. These results suggest that the aqueous fraction can induce partial DC activation, a situation that can be relevant in tolerance induction. It is important to state that the organic fraction by itself does not show any immunomodulatory activity. This study provides evidence for possible immunomodulatory activity of P. alliacea extracts which has been used in traditional medicine in Colombia.

Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections

Directory of Open Access Journals (Sweden)

Marc eDALOD

2014-07-01

Full Text Available Infection of mice with murine cytomegalovirus (MCMV recapitulates many physiopathological characteristics of human CMV infection and enables studying the interactions between a virus and its natural host. Dendritic cells (DC are mononuclear phagocytes linking innate and adaptive immunity which are both necessary for MCMV control. DC are critical for the induction of cellular immunity because they are uniquely efficient for the activation of naïve T cells during their first encounter with a pathogen. DC are equipped with a variety of innate immune recognition receptors (I2R2 allowing them to detect pathogens or infections and to engulf molecules, microorganisms or cellular debris. The combinatorial engagement of I2R2 during infections controls DC maturation and shapes their response in terms of cytokine production, activation of natural killer (NK cells and functional polarization of T cells. Several DC subsets exist which express different arrays of I2R2 and are specialized in distinct functions. The study of MCMV infection helped deciphering the physiological roles of DC subsets and their molecular regulation. It allowed the identification and first in vivo studies of mouse plasmacytoid DC which produce high level of interferons-α/β early after infection. Despite its ability to infect DC and dampen their functions, MCMV induces very robust, efficient and long-lasting CD8 T cell responses. Their priming may rely on the unique ability of uninfected XCR1+ DC to cross-present engulfed viral antigens and thus to counter MCMV interference with antigen presentation. A balance appears to have been reached during co-evolution, allowing controlled replication of the virus for horizontal spread without pathological consequences for the immunocompetent host. We will discuss the role of the interplay between the virus and DC in setting this balance, and how advancing this knowledge further could help develop better vaccines against other intracellular

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 s......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...

Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults.

Science.gov (United States)

Szpakowski, Piotr; Biet, Franck; Locht, Camille; Paszkiewicz, Małgorzata; Rudnicka, Wiesława; Druszczyńska, Magdalena; Allain, Fabrice; Fol, Marek; Pestel, Joël; Kowalewicz-Kulbat, Magdalena

2015-01-01

Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4(+) T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults

Directory of Open Access Journals (Sweden)

Piotr Szpakowski

2015-01-01

Full Text Available Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG, the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18 and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+ T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

Targeting dendritic cells in vivo for cancer therapy

Directory of Open Access Journals (Sweden)

Irina eCaminschi

2012-02-01

Full Text Available Monoclonal antibodies that recognise cell surface molecules have been used deliver antigenic cargo to dendritic cells (DC for induction of immune responses. The encouraging anti-tumour immunity elicited using this immunisation strategy suggests its suitability for clinical trials. This review discusses the complex network of DC, the functional specialisation of DC-subsets, the immunological outcomes of targeting different DC-subsets and their cell surface receptors, and the requirements for the induction of effective anti-tumour immunity. Finally, we review preclinical experiments and the progress towards targeting human DC in vivo.

Yeast modulation of human dendritic cell cytokine secretion: an in vitro study.

Directory of Open Access Journals (Sweden)

Ida M Smith

Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications

Yeast Modulation of Human Dendritic Cell Cytokine Secretion: An In Vitro Study

Science.gov (United States)

Smith, Ida M.; Christensen, Jeffrey E.; Arneborg, Nils; Jespersen, Lene

2014-01-01

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs) appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications beyond the current

Curcumin prevents human dendritic cell response to immune stimulants

International Nuclear Information System (INIS)

Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

2008-01-01

Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14 + monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4 + T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

Step-Up DC-DC converters

DEFF Research Database (Denmark)

Forouzesh, Mojtaba; Siwakoti, Yam P.; Gorji, Saman A.

2017-01-01

on the general law and framework of the development of next-generation step-up dc-dc converters, this paper aims to comprehensively review and classify various step-up dc-dc converters based on their characteristics and voltage-boosting techniques. In addition, the advantages and disadvantages of these voltage......DC-DC converters with voltage boost capability are widely used in a large number of power conversion applications, from fraction-of-volt to tens of thousands of volts at power levels from milliwatts to megawatts. The literature has reported on various voltage-boosting techniques, in which......-boosting techniques and associated converters are discussed in detail. Finally, broad applications of dc-dc converters are presented and summarized with comparative study of different voltage-boosting techniques....

A resonant dc-dc power converter assembly

OpenAIRE

Madsen, Mickey Pierre

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 fo...

Dendritic Cells Activate and Mature after Infection with Mycobacterium tuberculosis

Directory of Open Access Journals (Sweden)

Mamo Gezahagne

2011-07-01

Full Text Available Abstract Background Dendritic cells (DCs can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood. Findings To analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation. Conclusion These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro.

Mesothelioma tumor cells modulate dendritic cell lipid content, phenotype and function.

Directory of Open Access Journals (Sweden)

Joanne K Gardner

Full Text Available Dendritic cells (DCs play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay, upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+ CD8α- DCs, CD4- CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses.

Expression of the dendritic cell-associated C-type lectin DC-SIGN by inflammatory matrix metalloproteinase-producing macrophages in rheumatoid arthritis synovium and interaction with intercellular adhesion molecule 3-positive T cells.

NARCIS (Netherlands)

Lent, P.L.E.M. van; Figdor, C.G.; Barrera Rico, P.; Ginkel, K. van; Sloetjes, A.W.; Berg, W.B. van den; Torensma, R.

2003-01-01

OBJECTIVE: To determine whether matrix metalloproteinase (MMP)-producing inflammatory macrophages in the synovium of rheumatoid arthritis (RA) patients express the novel dendritic cell (DC)-specific C-type lectin DC-SIGN and whether this expression is associated with the presence of naive T cells

Cell-Wall-Bound Proteinase of Lactobacillus delbrueckii subsp. lactis ACA-DC 178: Characterization and Specificity for β-Casein

Science.gov (United States)

Tsakalidou, E.; Anastasiou, R.; Vandenberghe, I.; van Beeumen, J.; Kalantzopoulos, G.

1999-01-01

Lactobacillus delbrueckii subsp. lactis ACA-DC 178, which was isolated from Greek Kasseri cheese, produces a cell-wall-bound proteinase. The proteinase was removed from the cell envelope by washing the cells with a Ca2+-free buffer. The crude proteinase extract shows its highest activity at pH 6.0 and 40°C. It is inhibited by phenylmethylsulfonyl fluoride, showing that the enzyme is a serine-type proteinase. Considering the substrate specificity, the enzyme is similar to the lactococcal PI-type proteinases, since it hydrolyzes β-casein mainly and α- and κ-caseins to a much lesser extent. The cell-wall-bound proteinase from L. delbrueckii subsp. lactis ACA-DC 178 liberates four main peptides from β-casein, which have been identified. PMID:10223997

Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis

Directory of Open Access Journals (Sweden)

Yanling Xiao

2015-06-01

Full Text Available Osteoclasts (OCs originate from the myeloid cell lineage, but the successive steps in their lineage commitment are ill-defined, especially in humans. To clarify OC origin, we sorted cell populations from pediatric bone marrow (BM by flow cytometry and assessed their differentiation potential in vitro. Within the CD11b−CD34+c-KIT+ BM cell population, OC-differentiation potential was restricted to FLT3+ cells and enriched in an IL3 receptor (Rαhigh subset that constituted less than 0.5% of total BM. These IL3Rαhigh cells also generated macrophages (MΦs and dendritic cells (DCs but lacked granulocyte (GR-differentiation potential, as demonstrated at the clonal level. The IL3Rαlow subset was re-defined as common progenitor of GR, MΦ, OC, and DC (GMODP and gave rise to the IL3Rαhigh subset that was identified as common progenitor of MΦ, OC, and DC (MODP. Unbiased transcriptome analysis of CD11b−CD34+c-KIT+FLT3+ IL3Rαlow and IL3Rαhigh subsets corroborated our definitions of the GMODP and MODP and their developmental relationship.

Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.

Directory of Open Access Journals (Sweden)

Carlos Alfaro

Full Text Available Dendritic cells (DC are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs as a result of being co-attracted by interleukin-8 (IL-8, for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA protein, were able to cross-present the antigen to CD8 (OT-1 and CD4 (OT-2 TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2(d mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2(d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2(b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2(d are coinjected in the footpad of mice with autologous DC (H-2(b. In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC.

Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1

International Nuclear Information System (INIS)

Moehler, Markus; Sieben, Maike; Roth, Susanne; Springsguth, Franziska; Leuchs, Barbara; Zeidler, Maja; Dinsart, Christiane; Rommelaere, Jean; Galle, Peter R

2011-01-01

Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric, colorectal, cervix and pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents or targeted agents could be combined with the oncolytic and immunostimmulatory properties of H-1PV. Using human ex vivo models we evaluated the biological and immunological effects of H-1PV-induced tumor cell lysis alone or in combination with chemotherapeutic or targeted agents in human melanoma cells +/- characterized human cytotoxic T-cells (CTL) and HLA-A2-restricted dendritic cells (DC). H-1PV-infected MZ7-Mel cells showed a clear reduction in cell viability of >50%, which appeared to occur primarily through apoptosis. This correlated with viral NS1 expression levels and was enhanced by combination with chemotherapeutic agents or sunitinib. Tumor cell preparations were phagocytosed by DC whose maturation was measured according to the treatment administered. Immature DC incubated with H-1PV-induced MZ7-Mel lysates significantly increased DC maturation compared with non-infected or necrotic MZ7-Mel cells. Tumor necrosis factor-α and interleukin-6 release was clearly increased by DC incubated with H-1PV-induced SK29-Mel tumor cell lysates (TCL) and was also high with DC-CTL co-cultures incubated with H-1PV-induced TCL. Similarly, DC co-cultures with TCL incubated with H-1PV combined with cytotoxic agents or sunitinib enhanced DC maturation to a greater extent than cytotoxic agents or sunitinib alone. Again, these combinations increased pro-inflammatory responses in DC-CTL co-cultures compared with chemotherapy or sunitinib alone. In our human models, chemotherapeutic or targeted agents did not only interfere with the pronounced immunomodulatory properties of H-1PV, but also reinforced drug-induced tumor cell killing. H-1PV combined with cisplatin, vincristine or sunitinib induced effective immunostimulation via a pronounced DC maturation, better cytokine

Step-Up DC-DC converters

DEFF Research Database (Denmark)

Forouzesh, Mojtaba; Siwakoti, Yam P.; Gorji, Saman A.

2017-01-01

on the general law and framework of the development of next-generation step-up dc-dc converters, this paper aims to comprehensively review and classify various step-up dc-dc converters based on their characteristics and voltage-boosting techniques. In addition, the advantages and disadvantages of these voltage...

The VNTR Polymorphism of the DC-SIGNR Gene and Susceptibility to HIV-1 Infection: A Meta-Analysis

OpenAIRE

Li, Hui; Yu, Xiao-Min; Wang, Jia-Xin; Hong, Ze-Hui; Tang, Nelson Leung-Sang

2012-01-01

BACKGROUND: Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin related (DC-SIGNR) can bind to the human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein and is thus important for the host-pathogen interaction in HIV-1 infection. Studies of the association between the variable number tandem repeat (VNTR) polymorphism of the DC-SIGNR gene and HIV-1 susceptibility have produced controversial results. METHODS AND FINDINGS: We conducted a meta-analysis of th...

A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system--battery not included.

Science.gov (United States)

Southcott, Mark; MacVittie, Kevin; Halámek, Jan; Halámková, Lenka; Jemison, William D; Lobel, Robert; Katz, Evgeny

2013-05-07

Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with serum solution mimicking the human blood circulatory system. The biofuel cell generated an open circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of 0.83 mA cm(-2)). The power generated by the implantable biofuel cell was used to activate a pacemaker connected to the cell via a charge pump and a DC-DC converter interface circuit to adjust the voltage produced by the biofuel cell to the value required by the pacemaker. The voltage-current dependencies were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of the interface circuit, or the power converter, and the pacemaker to study their operation. The correct pacemaker operation was confirmed using a medical device - an implantable loop recorder. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

Assessment of serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer after DC-CIK combined with intravenous chemotherapy

Directory of Open Access Journals (Sweden)

Lei-Fan Li

2016-12-01

Full Text Available Objective: To study the effect of DC-CIK combined with intravenous chemotherapy on serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer. Methods: A total of 79 patients with advanced colon cancer conservatively treated in our hospital between May 2012 and October 2015 were retrospectively studied and divided into DC-CIK group and intravenous chemotherapy group according to different therapeutic regimens, DC-CIK group received DC-CIK combined with intravenous chemotherapy and intravenous chemotherapy group received conventional intravenous chemotherapy. After three cycles of chemotherapy, the content of tumor markers in serum, expression levels of apoptotic molecules in tumor lesions as well as immune function indexes were determined. Results: After 3 cycles of chemotherapy, CEA, CA199, CA242, HIF-1α, IL-4, IL-5 and IL-10 content in serum of DC-CIK group were significantly lower than those of intravenous chemotherapy group; p53, FAM96B, PTEN, PHLPP, ASPP2 and RASSF10 mRNA content in tumor lesions of DC-CIK group were significantly higher than those of intravenous chemotherapy group; the fluorescence intensity of CD3, CD4 and CD56 on peripheral blood mononuclear cell surface of DC-CIK group were significantly higher than those of intravenous chemotherapy group while the fluorescence intensity of CD8 and CD25 were significantly lower than those of intravenous chemotherapy group; IL-2 and IFN-γ content in serum of DC-CIK group were significantly higher than those of intravenous chemotherapy group while IL-4, IL-5 and IL-10 content were significantly lower than those of intravenous chemotherapy group. Conclusions: DC-CIK combined with intravenous chemotherapy has better effect on killing colon cancer cells and inducing colon cancer cell apoptosis than conventional intravenous chemotherapy, and can also improve the body's anti-tumor immune response.

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...... by a voltage doubling output rectifier. The converter is well-suited to applications requiring a high voltage gain, especially renewable energy sources such as photovoltaic and fuel-cell power supplies. To demonstrate the converter's performance a prototype designed to output 400 V at 500 W was constructed...

Electroporation of DC-3F cells is a dual process.

Science.gov (United States)

Wegner, Lars H; Frey, Wolfgang; Silve, Aude

2015-04-07

Treatment of biological material by pulsed electric fields is a versatile technique in biotechnology and biomedicine used, for example, in delivering DNA into cells (transfection), ablation of tumors, and food processing. Field exposure is associated with a membrane permeability increase usually ascribed to electroporation, i.e., formation of aqueous membrane pores. Knowledge of the underlying processes at the membrane level is predominantly built on theoretical considerations and molecular dynamics (MD) simulations. However, experimental data needed to monitor these processes with sufficient temporal resolution are scarce. The whole-cell patch-clamp technique was employed to investigate the effect of millisecond pulsed electric fields on DC-3F cells. Cellular membrane permeabilization was monitored by a conductance increase. For the first time, to our knowledge, it could be established experimentally that electroporation consists of two clearly separate processes: a rapid membrane poration (transient electroporation) that occurs while the membrane is depolarized or hyperpolarized to voltages beyond so-called threshold potentials (here, +201 mV and -231 mV, respectively) and is reversible within ∼100 ms after the pulse, and a long-term, or persistent, permeabilization covering the whole voltage range. The latter prevailed after the pulse for at least 40 min, the postpulse time span tested experimentally. With mildly depolarizing or hyperpolarizing pulses just above threshold potentials, the two processes could be separated, since persistent (but not transient) permeabilization required repetitive pulse exposure. Conductance increased stepwise and gradually with depolarizing and hyperpolarizing pulses, respectively. Persistent permeabilization could also be elicited by single depolarizing/hyperpolarizing pulses of very high field strength. Experimental measurements of propidium iodide uptake provided evidence of a real membrane phenomenon, rather than a mere

Internalisation of hybrid titanium dioxide/para-amino benzoic acid nanoparticles in human dendritic cells did not induce toxicity and changes in their functions.

Science.gov (United States)

Migdal, Camille; Rahal, Raed; Rubod, Alain; Callejon, Sylvie; Colomb, Evelyne; Atrux-Tallau, Nicolas; Haftek, Marek; Vincent, Claude; Serres, Mireille; Daniele, Stéphane

2010-11-10

Nanoparticles (NPs) have been reported to penetrate into human skin through lesional skin or follicular structures. Therefore, their ability to interact with dendritic cell (DC) was investigated using DCs generated from monocytes (mono-DCs). Hybrid titanium dioxide/para-amino benzoic acid (TiO(2)/PABA) NPs did not induce any cell toxicity. NPs were internalised into DCs through macropinocytosis and not by a receptor-mediated mechanism. Confocal microscopy showed that NPs were not detected in the nucleus. These data are confirmed by electronic microscopy which demonstrated that hybrid NPs were rapidly in contact with cellular membrane and localised into cytoplasmic vesicles without colocalisation with clathrin-coated vesicles. Hybrid NPs did not induce CD86 or HLA-DR overexpression or cytokine secretion (IL-8 and TNF-α) indicating no DC activation. Internalisation of hybrid NPs did not modify DC response towards sensitisers such as nickel and thimerosal or LPS used as positive controls. Moreover, hybrid NPs did not induce any oxidative stress implicated in DC activation process. After mono-DC irradiation by ultraviolet A (UVA), hybrid NP-treated cells did not produce UVA-induced reactive oxygen species (ROS) and exhibited a better cell viability compared with UVA-irradiated control cells, suggesting a protecting effect of hybrid TiO(2)/PABA NPs against UVA-induced ROS. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Rapid, directed transport of DC-SIGN clusters in the plasma membrane.

Science.gov (United States)

Liu, Ping; Weinreb, Violetta; Ridilla, Marc; Betts, Laurie; Patel, Pratik; de Silva, Aravinda M; Thompson, Nancy L; Jacobson, Ken

2017-11-01

C-type lectins, including dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), are all-purpose pathogen receptors that exist in nanoclusters in plasma membranes of dendritic cells. A small fraction of these clusters, obvious from the videos, can undergo rapid, directed transport in the plane of the plasma membrane at average speeds of more than 1 μm/s in both dendritic cells and MX DC-SIGN murine fibroblasts ectopically expressing DC-SIGN. Surprisingly, instantaneous speeds can be considerably greater. In MX DC-SIGN cells, many cluster trajectories are colinear with microtubules that reside close to the ventral membrane, and the microtubule-depolymerizing drug, nocodazole, markedly reduced the areal density of directed movement trajectories, suggesting a microtubule motor-driven transport mechanism; by contrast, latrunculin A, which affects the actin network, did not depress this movement. Rapid, retrograde movement of DC-SIGN may be an efficient mechanism for bringing bound pathogen on the leading edge and projections of dendritic cells to the perinuclear region for internalization and processing. Dengue virus bound to DC-SIGN on dendritic projections was rapidly transported toward the cell center. The existence of this movement within the plasma membrane points to an unexpected lateral transport mechanism in mammalian cells and challenges our current concepts of cortex-membrane interactions.

Functional evaluation of bone marrow derived DC of tumor bearing mice after immunotherapy

International Nuclear Information System (INIS)

Li Min; Chen Cheng; Gu Tao; Zhou Huan; Zhang Feng; Zhu Yibei; Yu Gehua; Zhang Xueguang; Gu Zongjiang

2006-01-01

Objective: To evaluate the function of bone marrow derived DC of tumor bearing mice after immunotherapy. Methods: Tumor bearing mice were immunized with DC vaccine plus injection of agonistic anti-4-1BB monoclonal antibody. The proliferation of T cells primed with bone marrow derived DC of tumor bearing mice after immunotherapy was tested by 3 H-TdR incorporation. ELISA was employed to determine the levels of IL-2, IFN-γ and IL-10 secreted by DC primed T cells. Results: Bone marrow derived DC of tumor bearing mice was less efficient in stimulating the proliferation of T cells and IL-2 and IFN-γ secretion made by T cells. After immunotherapy, the proliferation of cells and IL-2 and IFN-γ secretionmade by T cells were enhanced. Conclusion: The function of bone marrow derived DC of tumor bearing mice after immunotherapy was ameliorated. (authors)

Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line.

Science.gov (United States)

Ruffa, M J; Ferraro, G; Wagner, M L; Calcagno, M L; Campos, R H; Cavallaro, L

2002-03-01

Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts.

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

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10... amends Sec. 39.13 by adding the following new AD: 2010-09-12 McDonnell Douglas Corporation: Amendment 39... to McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A...

Different Temporal Effects of Ebola Virus VP35 and VP24 Proteins on Global Gene Expression in Human Dendritic Cells.

Science.gov (United States)

Ilinykh, Philipp A; Lubaki, Ndongala M; Widen, Steven G; Renn, Lynnsey A; Theisen, Terence C; Rabin, Ronald L; Wood, Thomas G; Bukreyev, Alexander

2015-08-01

Ebola virus (EBOV) causes a severe hemorrhagic fever with a deficient immune response, lymphopenia, and lymphocyte apoptosis. Dendritic cells (DC), which trigger the adaptive response, do not mature despite EBOV infection. We recently demonstrated that DC maturation is unblocked by disabling the innate response antagonizing domains (IRADs) in EBOV VP35 and VP24 by the mutations R312A and K142A, respectively. Here we analyzed the effects of VP35 and VP24 with the IRADs disabled on global gene expression in human DC. Human monocyte-derived DC were infected by wild-type (wt) EBOV or EBOVs carrying the mutation in VP35 (EBOV/VP35m), VP24 (EBOV/VP24m), or both (EBOV/VP35m/VP24m). Global gene expression at 8 and 24 h was analyzed by deep sequencing, and the expression of interferon (IFN) subtypes up to 5 days postinfection was analyzed by quantitative reverse transcription-PCR (qRT-PCR). wt EBOV induced a weak global gene expression response, including markers of DC maturation, cytokines, chemokines, chemokine receptors, and multiple IFNs. The VP35 mutation unblocked the expression, resulting in a dramatic increase in expression of these transcripts at 8 and 24 h. Surprisingly, DC infected with EBOV/VP24m expressed lower levels of many of these transcripts at 8 h after infection, compared to wt EBOV. In contrast, at 24 h, expression of the transcripts increased in DC infected with any of the three mutants, compared to wt EBOV. Moreover, sets of genes affected by the two mutations only partially overlapped. Pathway analysis demonstrated that the VP35 mutation unblocked pathways involved in antigen processing and presentation and IFN signaling. These data suggest that EBOV IRADs have profound effects on the host adaptive immune response through massive transcriptional downregulation of DC. This study shows that infection of DC with EBOV, but not its mutant forms with the VP35 IRAD and/or VP24 IRAD disabled, causes a global block in expression of host genes. The temporal

In vitro analysis of cytotoxic T cell recruitment mediated by the DC-derived chemokine CCL17

OpenAIRE

sprotocols

2015-01-01

Dendritic cell (DC) licensing in cross-priming requires physical interaction of several rare immune cells, i.e. cytotoxic T cells (CTL), and cross-presenting DCs. Here we describe a novel in vitro method of analyzing chemokine effects on complex recruitment events in a multi-cellular system. To study CTL recruitment towards CCL17-producing DCs, we established a co-culture system of murine splenic DCs with polyclonal splenic CTL from donor mice, which enables visualization of cell motility and...

Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells.

Science.gov (United States)

Van Tendeloo, V F; Ponsaerts, P; Lardon, F; Nijs, G; Lenjou, M; Van Broeckhoven, C; Van Bockstaele, D R; Berneman, Z N

2001-07-01

Designing effective strategies to load human dendritic cells (DCs) with tumor antigens is a challenging approach for DC-based tumor vaccines. Here, a cytoplasmic expression system based on mRNA electroporation to efficiently introduce tumor antigens into DCs is described. Preliminary experiments in K562 cells using an enhanced green fluorescent protein (EGFP) reporter gene revealed that mRNA electroporation as compared with plasmid DNA electroporation showed a markedly improved transfection efficiency (89% versus 40% EGFP(+) cells, respectively) and induced a strikingly lower cell toxicity (15% death rate with mRNA versus 51% with plasmid DNA). Next, mRNA electroporation was applied for nonviral transfection of different types of human DCs, including monocyte-derived DCs (Mo-DCs), CD34(+) progenitor-derived DCs (34-DCs) and Langerhans cells (34-LCs). High-level transgene expression by mRNA electroporation was obtained in more than 50% of all DC types. mRNA-electroporated DCs retained their phenotype and maturational potential. Importantly, DCs electroporated with mRNA-encoding Melan-A strongly activated a Melan-A-specific cytotoxic T lymphocyte (CTL) clone in an HLA-restricted manner and were superior to mRNA-lipofected or -pulsed DCs. Optimal stimulation of the CTL occurred when Mo-DCs underwent maturation following mRNA transfection. Strikingly, a nonspecific stimulation of CTL was observed when DCs were transfected with plasmid DNA. The data clearly demonstrate that Mo-DCs electroporated with mRNA efficiently present functional antigenic peptides to cytotoxic T cells. Therefore, electroporation of mRNA-encoding tumor antigens is a powerful technique to charge human dendritic cells with tumor antigens and could serve applications in future DC-based tumor vaccines.

Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients.

Directory of Open Access Journals (Sweden)

Brendan Fong

Full Text Available PURPOSE: Dendritic cell (DC vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+CD4(+CD25(+CD127(low frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623 after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+CD4(+ T cells (p = 0.0191; hazard ratio = 2.840 and CD3(+CD8(+ T cells (p = 0.0273; hazard ratio = 2.690, while that of activation markers (CD25, CD69 was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future

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

and the voltage transfer gain is obtained. It is also demonstrated that the voltage stress on all semiconductor devices is restricted to input voltage which allows the utilization of a power switch with lower drain source resistance. In order to further increase the voltage gain another switched capacitor voltage......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...

Optimizing parameters for clinical-scale production of high IL-12 secreting dendritic cells pulsed with oxidized whole tumor cell lysate

Directory of Open Access Journals (Sweden)

Chiang Cheryl L-L

2011-11-01

Full Text Available Abstract Background Dendritic cells (DCs are the most potent antigen-presenting cell population for activating tumor-specific T cells. Due to the wide range of methods for generating DCs, there is no common protocol or defined set of criteria to validate the immunogenicity and function of DC vaccines. Methods Monocyte-derived DCs were generated during 4 days of culture with recombinant granulocyte-macrophage colony stimulating factor and interleukin-4, and pulsed with tumor lysate produced by hypochlorous acid oxidation of tumor cells. Different culture parameters for clinical-scale DC preparation were investigated, including: 1 culture media; 2 culture surface; 3 duration of activating DCs with lipopolysaccharide (LPS and interferon (IFN-gamma; 4 method of DC harvest; and 5 cryomedia and final DC product formulation. Results DCs cultured in CellGenix DC media containing 2% human AB serum expressed higher levels of maturation markers following lysate-loading and maturation compared to culturing with serum-free CellGenix DC media or AIM-V media, or 2% AB serum supplemented AIM-V media. Nunclon™Δ surface, but not Corning® tissue-culture treated surface and Corning® ultra-low attachment surface, were suitable for generating an optimal DC phenotype. Recombinant trypsin resulted in reduced major histocompatibility complex (MHC Class I and II expression on mature lysate-loaded DCs, however presentation of MHC Class I peptides by DCs was not impaired and cell viability was higher compared to cell scraping. Preservation of DCs with an infusible cryomedia containing Plasma-Lyte A, dextrose, sodium chloride injection, human serum albumin, and DMSO yielded higher cell viability compared to using human AB serum containing 10% DMSO. Finally, activating DCs for 16 hours with LPS and IFN-γ stimulated robust mixed leukocyte reactions (MLRs, and high IL-12p70 production in vitro that continued for 24 hours after the cryopreserved DCs were thawed and

Family of multiport bidirectional DC-DC converters

NARCIS (Netherlands)

Tao, H.; Kotsopoulos, A.; Duarte, J.L.; Hendrix, M.A.M.

2006-01-01

Multiport DC-DC converters are of potential interest in applications such as generation systems utilising multiple sustainable energy sources. A family of multiport bidirectional DC-DC converters derived from a general topology is presented. The topology shows a combination of DC-link and magnetic

POWER CONTROL OF A BIDIRECTIONAL DC BUS FOR FUEL CELLS APPLICATIONS CONTROL DE POTENCIA DE UN BUS DC BIDIRECCIONAL PARA APLICACIONES DE PILAS DE COMBUSTIBLE CONTROLE DE POTÊNCIA DE UM ÔNIBUS DC BIDIRECIONAL PARA APLICAÇÕES DE PILHAS DE COMBUSTÍVE

Directory of Open Access Journals (Sweden)

Andrés Fernando Restrepo

2012-12-01

Full Text Available This paper proposes a power system for fuel cell applications able to transfer energy from the power source to the load, and to charge an auxiliary storage device using regenerative power flows generated by the load. The solution is based on a closed loop bidirectional DC/DC converter, where additional devices have been also designed to experimentally test the solution in a safe and realistic environment: a fuel cell emulator and an electronic load.Este artículo propone un sistema de potencia para aplicaciones de pilas de combustible capaz de transferir energía de la fuente de potencia a la carga y de cargar un sistema de almacenamiento con flujos regenerativos de potencia desde la carga. La solución está basada en un convertidor bidireccional DC/DC en lazo cerrado. Además, se presentan dispositivos auxiliares diseñados para evaluar experimentalmente la solución en un entorno seguro y realista: un emulador de pila de combustible y una carga electrónica.Este artigo propõe um sistema de potência para aplicações de pilhas de combustível capaz de transferir energia da fonte de potência à carga e de carregar um sistema de armazenamento com fluxos regenerativos de potência desde a carga. A solução está baseada em um conversor bidirecional DC/DC em laço fechado. Ademais, apresentam-se dispositivos auxiliares desenhados para avaliar experimentalmente a solução em um meio seguro e realista: um emulador de pilha de combustível e uma carga eletrônica.

N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN

Science.gov (United States)

Phoenix, Inaia; Nishiyama, Shoko; Lokugamage, Nandadeva; Hill, Terence E.; Huante, Matthew B.; Slack, Olga A.L.; Carpio, Victor H.; Freiberg, Alexander N.; Ikegami, Tetsuro

2016-01-01

Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)–any amino acid (X)–serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: “Gc-large” and “Gc-small”, and N1077 was responsible for “Gc-large” band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN. PMID:27223297

Phenotype and Function of CD209+ Bovine Blood Dendritic Cells, Monocyte-Derived-Dendritic Cells and Monocyte-Derived Macrophages.

Directory of Open Access Journals (Sweden)

Kun Taek Park

Full Text Available Phylogenic comparisons of the mononuclear phagocyte system (MPS of humans and mice demonstrate phenotypic divergence of dendritic cell (DC subsets that play similar roles in innate and adaptive immunity. Although differing in phenotype, DC can be classified into four groups according to ontogeny and function: conventional DC (cDC1 and cDC2, plasmacytoid DC (pDC, and monocyte derived DC (MoDC. DC of Artiodactyla (pigs and ruminants can also be sub-classified using this system, allowing direct functional and phenotypic comparison of MoDC and other DC subsets trafficking in blood (bDC. Because of the high volume of blood collections required to study DC, cattle offer the best opportunity to further our understanding of bDC and MoDC function in an outbred large animal species. As reported here, phenotyping DC using a monoclonal antibody (mAb to CD209 revealed CD209 is expressed on the major myeloid population of DC present in blood and MoDC, providing a phenotypic link between these two subsets. Additionally, the present study demonstrates that CD209 is also expressed on monocyte derived macrophages (MoΦ. Functional analysis revealed each of these populations can take up and process antigens (Ags, present them to CD4 and CD8 T cells, and elicit a T-cell recall response. Thus, bDC, MoDC, and MoΦ pulsed with pathogens or candidate vaccine antigens can be used to study factors that modulate DC-driven T-cell priming and differentiation ex vivo.

Washington DC Metropolitan Area Drug Study Homeless and Transient Population (DC-MADST-1991)

Data.gov (United States)

U.S. Department of Health & Human Services — The DC Metropolitan Area Drug Study (DCMADS) was conducted in 1991, and included special analyses of homeless and transient populations and of women delivering live...

RF-superimposed DC and pulsed DC sputtering for deposition of transparent conductive oxides

International Nuclear Information System (INIS)

Stowell, Michael; Mueller, Joachim; Ruske, Manfred; Lutz, Mark; Linz, Thomas

2007-01-01

Transparent conductive oxide films are widely used materials for electronic applications such as flat panel displays and solar cells. The superposition of DC and pulsed DC power by a certain fraction of RF power was applied to deposit indium tin oxide films. This technique allows an additional tuning of different parameters relevant to film growth, and yields high quality films even under kinetically limited conditions. A long-term stable RF/DC process could be realized by using different combinations of standard power supply components, which includes a fully reliable arc handling system for both the RF and DC generators. The effectiveness of the arc handling system is illustrated by the current and voltage behavior recorded for actual arcing events. The resistivity of indium tin oxide films is strongly influenced by the respective sputtering mode. The best resistivity values of 145-148 μΩ cm were obtained by RF-superimposed pulsed DC sputtering at a pulse frequency between 100 and 200 kHz and a substrate temperature as low as 140 deg. C. In addition, the films were extremely smooth with a surface roughness of 1-2.5 nm

Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity.

Science.gov (United States)

Tacken, Paul J; Zeelenberg, Ingrid S; Cruz, Luis J; van Hout-Kuijer, Maaike A; van de Glind, Gerline; Fokkink, Remco G; Lambeck, Annechien J A; Figdor, Carl G

2011-12-22

Effective vaccines consist of 2 components: immunodominant antigens and effective adjuvants. Whereas it has been demonstrated that targeted delivery of antigens to dendritic cells (DCs) improves vaccine efficacy, we report here that co-targeting of TLR ligands (TLRLs) to DCs strongly enhances adjuvanticity and immunity. We encapsulated ligands for intracellular TLRs within biodegradable nanoparticles coated with Abs recognizing DC-specific receptors. Targeted delivery of TLRLs to human DCs enhanced the maturation and production of immune stimulatory cytokines and the Ag-specific activation of naive CD8(+) T cells. In vivo studies demonstrated that nanoparticles carrying Ag induced cytotoxic T-lymphocyte responses at 100-fold lower adjuvant dose when TLRLs were co-encapsulated instead of administered in soluble form. Moreover, the efficacy of these targeted TLRLs reduced the serum cytokine storm and related toxicity that is associated with administration of soluble TLRLs. We conclude that the targeted delivery of adjuvants may improve the efficacy and safety of DC-based vaccines.

Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a cell- and gene-based study.

Science.gov (United States)

Wang, Chien-Yu; Chiao, Ming-Tsang; Yen, Po-Jen; Huang, Wei-Chou; Hou, Chia-Chung; Chien, Shih-Chang; Yeh, Kuo-Chen; Yang, Wen-Ching; Shyur, Lie-Fen; Yang, Ning-Sun

2006-12-01

Echinacea spp. are popularly used as an herbal medicine or food supplement for enhancing the immune system. This study shows that plant extracts from root [R] and stem plus leaf [S+L] tissues of E. purpurea exhibit opposite (enhancing vs inhibitory) modulatory effects on the expression of the CD83 marker in human dendritic cells (DCs), which are known as professional antigen-presenting cells. We developed a function-targeted DNA microarray system to characterize the effects of phytocompounds on human DCs. Down-regulation of mRNA expression of specific chemokines (e.g., CCL3 and CCL8) and their receptors (e.g., CCR1 and CCR9) was observed in [S+L]-treated DCs. Other chemokines and regulatory molecules (e.g., CCL4 and CCL2) involved in the c-Jun pathway were found to be up-regulated in [R]-treated DCs. This study, for the first time, demonstrates that E. purpurea extracts can modulate DC differentiation and expression of specific immune-related genes in DCs.

β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

Directory of Open Access Journals (Sweden)

Matthew J. Elder

2017-07-01

Full Text Available Dectin-1/CLEC7A is a pattern recognition receptor that recognizes β-1,3 glucans, and its stimulation initiates signaling events characterized by the production of inflammatory cytokines from human dendritic cells (DCs required for antifungal immunity. β-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate β-glucans are thought to be poor activators of innate immunity. We show that β-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large β-glucan-stimulated DC generate significantly more IL-1β, IL-6, and IL-23 compared to those stimulated with the smaller β-glucans. In marked contrast, the secretion of TSLP and CCL22 were found to be insensitive to β-glucan particle size. Furthermore, we show that the capacity to induce phagocytosis, and the relative IL-1β production determined by β-glucan size, regulates the composition of the cytokine milieu generated from DC. This suggests that β-glucan particle size is critically important in orchestrating the nature of the immune response to fungi.

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

Directory of Open Access Journals (Sweden)

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.

Design and Testing of Boost Type DC/DC Converter for DC Motor Control Applications

OpenAIRE

Samman, Faizal Arya; Akil, Yusri Syam; Noor, Nirwan A.

2017-01-01

in The Proceeding of The 2nd International Symposium on Smart Material and Mechatronics 2015 This paper presents the design and testing of a boost type DC/DC converter circuit, which can be used for DC motor control applications. The Boost converter is designed using DC chopper and DC chopper cascade configurations. The experimental setup was made by connecting the boost converter circuit with four types of DC motor, i.e. self-excited DC motor shunt, series, compound and separately exci...

Reprogramming tumor-infiltrating dendritic cells for CD103+CD8+ mucosal T cell differentiation and breast cancer rejection

Science.gov (United States)

Wu, Te-Chia; Xu, Kangling; Banchereau, Romain; Marches, Florentina; Yu, Chun I; Martinek, Jan; Anguiano, Esperanza; Pedroza-Gonzalez, Alexander; Snipes, G. Jackson; O’Shaughnessy, Joyce; Nishimura, Stephen; Liu, Yong-Jun; Pascual, Virginia; Banchereau, Jacques; Oh, Sangkon; Palucka, Karolina

2014-01-01

Our studies showed that tumor-infiltrating dendritic cells (DC) in breast cancer drive inflammatory T helper 2 (iTh2) cells and protumor inflammation. Here we show that intratumoral delivery of the β-glucan curdlan, a ligand of dectin-1, blocks the generation of iTh2 cells, and prevents breast cancer progression in vivo. Curdlan reprograms tumor-infiltrating DC via the ligation of dectin-1, enabling the DC to become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), to produce IL12p70, and to favor the generation of T helper 1 (Th1) cells. DC activated via dectin-1, but not those activated with TLR-7/8 ligand or poly IC, induce CD8+ T cells to express CD103 (αE integrin), a ligand for cancer cells E-cadherin. Generation of these mucosal CD8+ T cells is regulated by DC-derived integrin αvβ8 and TGF-β activation in a dectin-1-dependent fashion. These CD103+CD8+ mucosal T cells accumulate in the tumors thereby increasing cancer necrosis and inhibiting cancer progression in vivo in a humanized mouse model of breast cancer. Importantly, CD103+CD8+ mucosal T cells elicited by reprogrammed DC can reject established cancer. Thus, reprogramming tumor-infiltrating DC represents a new strategy for cancer rejection. PMID:24795361

Clinical efficacy of sunitinib combined with autologous DC and CIK for patients with metastatic renal cell carcinoma

Directory of Open Access Journals (Sweden)

Liang ZHANG

2014-01-01

Full Text Available Objective　To analyze the clinical efficacy and safety of sunitinib combined with autologous dentritic cell (DC and cytokine induced killer cell (CIK for patients suffering from metastatic renal cell carcinoma (mRCC. Methods　Clinical data of 27 mRCC patients treated with sunitinib combined with autologous DC and CIK were reviewed retrospectively. Efficacy, quality of life, immunology and safety of this treatment were evaluated. Results　Follow-up time ranged from 4 to 25 months. Out of all the patients, sunitinib was reduced in 1 and discontinued in 2 due to side effects; 1 patient quit for personal reasons; 14 patients developed progressive disease. The progression-free survival (PFS was 4 to 19.5 months. Ten patients died from tumor, the overall survival time (OS was 6 to 21 months. The median PFS was 16 months (95%CI 12.5-19.5. The OS was not achieved. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST. All the patients received treatment over 1 cycle. After one course of treatment, among 27 patients, 0 had complete remission (CR, 4 had partial remission (PR, 17 had stable disease (SD, and 6 had progressive disease (PD. The overall objective remission rate (ORR and disease control rate (DCR were 14.8% (4/27 and 77.8% (21/27, respectively. Sunitinib and autologous transfusion of DC and CIK improved the immune function and quality of life. The major adverse events were fatigue, hand-foot syndrome, hypertension, hypothyroidism, thrombocytopenia, neutropenia and fever. Most of the adverse events were ameliorated by supportive treatment or dose reduction. Conclusions　 Sunitinib combined with autologous DC and CIK may be beneficial in the treatment of mRCC with acceptable toxic reactions, and it may be considered as a new approach for the comprehensive treatment of RCC. DOI: 10.11855/j.issn.0577-7402.2013.12.06

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

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...... 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...

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation.

Science.gov (United States)

Chu, Chung-Ching; Ali, Niwa; Karagiannis, Panagiotis; Di Meglio, Paola; Skowera, Ania; Napolitano, Luca; Barinaga, Guillermo; Grys, Katarzyna; Sharif-Paghaleh, Ehsan; Karagiannis, Sophia N; Peakman, Mark; Lombardi, Giovanna; Nestle, Frank O

2012-05-07

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.

Role of Nuclear Factor (Erythroid-Derived 2-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells

Directory of Open Access Journals (Sweden)

Anna Hammer

2017-12-01

Full Text Available To date, the intracellular signaling pathways involved in dendritic cell (DC function are poorly understood. The antioxidative transcription factor nuclear factor (erythroid-derived 2-like 2 (Nrf2 has been shown to affect maturation, function, and subsequent DC-mediated T cell responses of murine and human DCs. In experimental autoimmune encephalomyelitis (EAE, as prototype animal model for a T helper cell-mediated autoimmune disease, antigen presentation, cytokine production, and costimulation by DCs play a major role. We explore the role of Nrf2 in DC function, and DC-mediated T cell responses during T cell-mediated autoimmunity of the central nervous system using genetic ablation and pharmacological activation in mice and men to corroborate our data in a translational setting. In murine and human DCs, monomethyl fumarate induced Nrf2 signaling inhibits DC maturation and DC-mediated T cell proliferation by reducing inflammatory cytokine production and expression of costimulatory molecules. In contrast, Nrf2-deficient DCs generate more activated T helper cells (Th1/Th17 but fewer regulatory T cells and foster T cell proliferation. Transfer of DCs with Nrf2 activation during active EAE reduces disease severity and T cell infiltration. Our data demonstrate that Nrf2 signaling modulates autoimmunity in murine and human systems via inhibiting DC maturation and function thus shedding further light on the mechanism of action of antioxidative stress pathways in antigen-presenting cells.

Washington DC Metropolitan Area Drug Study Household and Non-Household Populations (DC-MADSH-1991)

Data.gov (United States)

U.S. Department of Health & Human Services — The DC Metropolitan Area Drug Study (DCMADS) was conducted in 1991, and included special analyses of homeless and transient populations and of women delivering live...

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...

IGBT Based DC/DC Converter

Directory of Open Access Journals (Sweden)

M. Akherraz

1997-12-01

Full Text Available This paper presents an in-depth analytical and experimental investigation of an indirect DC-DC converter. The DC-AC conversion is a full bridge based on IGBT power modules, and the AC-DC conversion is done via a high  frequency AC link and a first diode bridge. The AC link, which consists of snubbing capacitors and a variable air-gap transformer, is analytically designed to fulfill Zero Voltage commutation requirement. The proposed converter is simulated using PSPICE and a prototype is designed built and tested in the laboratory. PSPICE simulation and experimental results are presented and compared.

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...

Three new DC-to-DC Single-Switch Converters

Directory of Open Access Journals (Sweden)

Barry W. Williams

2017-06-01

Full Text Available This paper presents a new family of three previously unidentified dc-to-dc converters, buck, boost, and buck-boost voltage-transfer-function topologies, which offer advantageous transformer coupling features and low capacitor dc voltage stressing. The three single-switch, single-diode, converters offer the same features as basic dc-to-dc converters, such as the buck function with continuous output current and the boost function with continuous input current. Converter time-domain simulations and experimental results (including transformer coupling support and extol the dc-to-dc converter concepts and analysis presented.

Impact of lactic Acid bacteria on dendritic cells from allergic patients in an experimental model of intestinal epithelium.

Science.gov (United States)

Ratajczak, Céline; Duez, Catherine; Grangette, Corinne; Pochard, Pierre; Tonnel, André-Bernard; Pestel, Joël

2007-01-01

Lactic acid bacteria (LAB) are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC) by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393) on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model. Confocal and flow cytometer analyses showed that immature DC efficiently captured FITC-labelled L. casei through the epithelial layer. After interaction with L. casei, DC acquired a partial maturation status (i.e., CD86 and CD54 increase) and increased their interleukin (IL)-10 and IL-12 production. Interestingly, after activation by L. casei in the presence of experimental epithelium, DC from allergic patients instructed autologous naïve CD4(+) T cells to produce more interferon-gamma than without the epithelium. Thus by modulating human DC reactivity, LAB and intestinal epithelium might modify T cell immune response and regulate the development of allergic reaction.

Impact of Lactic Acid Bacteria on Dendritic Cells from Allergic Patients in an Experimental Model of Intestinal Epithelium

Directory of Open Access Journals (Sweden)

Céline Ratajczak

2007-01-01

Full Text Available Lactic acid bacteria (LAB are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393 on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model. Confocal and flow cytometer analyses showed that immature DC efficiently captured FITC-labelled L. casei through the epithelial layer. After interaction with L. casei, DC acquired a partial maturation status (i.e., CD86 and CD54 increase and increased their interleukin (IL-10 and IL-12 production. Interestingly, after activation by L. casei in the presence of experimental epithelium, DC from allergic patients instructed autologous naïve CD4+ T cells to produce more interferon-γ than without the epithelium. Thus by modulating human DC reactivity, LAB and intestinal epithelium might modify T cell immune response and regulate the development of allergic reaction.

Comparison of solar panel cooling system by using dc brushless fan and dc water

International Nuclear Information System (INIS)

Irwan, Y M; Leow, W Z; Irwanto, M; M, Fareq; Hassan, S I S; Amelia, A R; Safwati, I

2015-01-01

The purpose of this article is to discuss comparison of solar panel cooling system by using DC brushless fan and DC water pump. Solar photovoltaic (PV) power generation is an interesting technique to reduce non-renewable energy consumption and as a renewable energy. The temperature of PV modules increases when it absorbs solar radiation, causing a decrease in efficiency. A solar cooling system is design, construct and experimentally researched within this work. To make an effort to cool the PV module, Direct Current (DC) brushless fan and DC water pump with inlet/outlet manifold are designed for constant air movement and water flow circulation at the back side and front side of PV module representatively. Temperature sensors were installed on the PV module to detect temperature of PV. PIC microcontroller was used to control the DC brushless fan and water pump for switch ON or OFF depend on the temperature of PV module automatically. The performance with and without cooling system are shown in this experiment. The PV module with DC water pump cooling system increase 3.52%, 36.27%, 38.98%in term of output voltage, output current, output power respectively. It decrease 6.36 °C compare than to PV module without DC water pump cooling system. While DC brushless fan cooling system increase 3.47%, 29.55%, 32.23%in term of output voltage, output current, and output power respectively. It decrease 6.1 °C compare than to PV module without DC brushless fan cooling system. The efficiency of PV module with cooling system was increasing compared to PV module without cooling system; this is because the ambient temperature dropped significantly. The higher efficiency of PV cell, the payback period of the system can be shorted and the lifespan of PV module can also be longer. (paper)

Controller design and stability analysis of grid connected DC microgrid

DEFF Research Database (Denmark)

Chauhan, Rajeev Kumar; Chauhan, Kalpana; Guerrero, Josep M.

2018-01-01

DC microgrids are desired to provide the electricity for the remote areas which are far from the main grid. The microgrid gets popularity because DC power sources such as photovoltaics (PVs), battery banks, and fuel cells can be interconnected without AC/DC converters. The stochastic nature of PV...

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...

Plastic downregulation of the transcriptional repressor BCL6 during maturation of human dendritic cells

International Nuclear Information System (INIS)

Pantano, Serafino; Jarrossay, David; Saccani, Simona; Bosisio, Daniela; Natoli, Gioacchino

2006-01-01

Dendritic cell (DC) maturation links peripheral events initiated by the encounter with pathogens to the activation and expansion of antigen-specific T lymphocytes in secondary lymphoid organs. Here, we describe an as yet unrecognized modulator of human DC maturation, the transcriptional repressor BCL6. We found that both myeloid and plasmacytoid DCs constitutively express BCL6, which is rapidly downregulated following maturation triggered by selected stimuli. Both in unstimulated and maturing DCs, control of BCL6 protein levels reflects the convergence of several mechanisms regulating BCL6 stability, mRNA transcription and nuclear export. By regulating the induction of several genes implicated in the immune response, including inflammatory cytokines, chemokines and survival genes, BCL6 may represent a pivotal modulator of the afferent branch of the immune response

A full scale comparative study of methods for generation of functional Dendritic cells for use as cancer vaccines

Directory of Open Access Journals (Sweden)

Kvalheim Gunnar

2007-07-01

Full Text Available Background Dendritic cells (DCs are professional antigen-presenting cells with the ability to induce primary T-cell responses and are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF for 5–7 days (Standard DC. Recently, Dauer and co-workers presented a modified protocol for differentiation of human monocytes into mature DCs within 48 hours (Fast DC. Here we report a functional comparison of the two strategies for generation of DCs from human monocytes with adaptions for large-scale clinical use. Methods The Elutra Cell Selection System was used to isolate monocytes after collection of leukapheresis product. The enriched monocytes were cultured in gas permeable Teflon bags with IL-4 and GM-CSF for 24 hours (Fast DC or 5 days (Standard DC to obtain immature DCs. The cells were then transfected with mRNA from the leukemia cell line Jurkat E6 by electroporation and incubated for additional 24 h or 2 days in the presence of pro-inflammatory cytokines (TNFα, IL-1β, IL-6 and PGE2 to obtain mature DCs. Results Mature Fast DC and Standard DC displayed comparable levels of many markers expressed on DC, including HLA-DR, CD83, CD86, CD208 and CCR7. However, compared to Standard DC, mature Fast DC was CD14high CD209low. Fast DC and Standard DC transfected with Jurkat E6-cell mRNA were equally able to elicit T cell specifically recognizing transfected DCs in vitro. IFNγ-secreting T cells were observed in both the CD4+ and CD8+ subsets. Conclusion Our results indicate that mature Fast DC are functional antigen presenting cells (APCs capable of inducing primary T-cell responses, and suggest that these cells may be valuable for generation of anti-tumor vaccines.

A full scale comparative study of methods for generation of functional Dendritic cells for use as cancer vaccines.

Science.gov (United States)

Jarnjak-Jankovic, Silvija; Hammerstad, Hege; Saebøe-Larssen, Stein; Kvalheim, Gunnar; Gaudernack, Gustav

2007-07-03

Dendritic cells (DCs) are professional antigen-presenting cells with the ability to induce primary T-cell responses and are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF for 5-7 days (Standard DC). Recently, Dauer and co-workers presented a modified protocol for differentiation of human monocytes into mature DCs within 48 hours (Fast DC). Here we report a functional comparison of the two strategies for generation of DCs from human monocytes with adaptions for large-scale clinical use. The Elutra Cell Selection System was used to isolate monocytes after collection of leukapheresis product. The enriched monocytes were cultured in gas permeable Teflon bags with IL-4 and GM-CSF for 24 hours (Fast DC) or 5 days (Standard DC) to obtain immature DCs. The cells were then transfected with mRNA from the leukemia cell line Jurkat E6 by electroporation and incubated for additional 24 h or 2 days in the presence of pro-inflammatory cytokines (TNFalpha, IL-1beta, IL-6 and PGE2) to obtain mature DCs. Mature Fast DC and Standard DC displayed comparable levels of many markers expressed on DC, including HLA-DR, CD83, CD86, CD208 and CCR7. However, compared to Standard DC, mature Fast DC was CD14high CD209low. Fast DC and Standard DC transfected with Jurkat E6-cell mRNA were equally able to elicit T cell specifically recognizing transfected DCs in vitro. IFNgamma-secreting T cells were observed in both the CD4+ and CD8+ subsets. Our results indicate that mature Fast DC are functional antigen presenting cells (APCs) capable of inducing primary T-cell responses, and suggest that these cells may be valuable for generation of anti-tumor vaccines.

Regulatory dendritic cell therapy: from rodents to clinical application.

Science.gov (United States)

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W

2014-10-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or "tolerogenic" DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

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

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10... adding the following new AD: 2010-20-14 McDonnell Douglas Corporation: Amendment 39-16449. Docket No. FAA... the airplanes identified in paragraphs (c)(1) and (c)(2) of this AD. (1) McDonnell Douglas Corporation...

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

...-0672; Directorate Identifier 2010-NM-047-AD] RIN 2120-AA64 Airworthiness Directives; McDonnell Douglas...: McDonnell Douglas Corporation: Docket No. FAA-2010-0672; Directorate Identifier 2010-NM-047-AD. Comments Due... applies to McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-30, DC-10-30F (KDC-10), DC-10...

Three-Phase Multistage System (DC-AC-DC-AC for Connecting Solar Cells to the Grid

Directory of Open Access Journals (Sweden)

Mahmudreza Changizian

2017-11-01

Full Text Available Inverter systems that feed electrical power from photovoltaic (PV system into the grid must convert the direct current of the PV array into the alternating current of the grid. In many applications, it is important for a converter to be lightweight, highly reliable, input/output isolated, flexible and operable in a boost mode. These features can be achieved by using a High-Frequency inverter which involves an isolated DC-DC stage and DC-AC section, which provides AC output. This paper proposes a new three phase topology, based on multi stage converter and PV system in order to use in medium and high power applications. The Perturb and Observe (P&O method is used for maximum power point tracking (MPPT control of PV array. The switching control signals for three-phase inverter are provided by hysteresis control method. Also, the comparison between the proposed topology and traditional structures has been conducted and finally the simulation researches are performed in a closed-loop control system by MATLAB/Simulink software to verify the operation of the proposed structure. The results represent better performance of the introduced system over traditional topologies.

Memory CD8+ T cells protect dendritic cells from CTL killing

NARCIS (Netherlands)

Watchmaker, Payal B.; Urban, Julie A.; Berk, Erik; Nakamura, Yutaro; Mailliard, Robbie B.; Watkins, Simon C.; van Ham, S. Marieke; Kalinski, Pawel

2008-01-01

CD8(+) T cells have been shown to be capable of either suppressing or promoting immune responses. To reconcile these contrasting regulatory functions, we compared the ability of human effector and memory CD8(+) T cells to regulate survival and functions of dendritic cells (DC). We report that, in

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.

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. PMID:25816321

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.

Aspergillus fumigatus Cell Wall α-(1,3)-Glucan Stimulates Regulatory T-Cell Polarization by Inducing PD-L1 Expression on Human Dendritic Cells.

Science.gov (United States)

Stephen-Victor, Emmanuel; Karnam, Anupama; Fontaine, Thierry; Beauvais, Anne; Das, Mrinmoy; Hegde, Pushpa; Prakhar, Praveen; Holla, Sahana; Balaji, Kithiganahalli N; Kaveri, Srini V; Latgé, Jean-Paul; Aimanianda, Vishukumar; Bayry, Jagadeesh

2017-12-05

Human dendritic cell (DC) response to α-(1,3)-glucan polysaccharide of Aspergillus fumigatus and ensuing CD4+ T-cell polarization are poorly characterized. α-(1,3)-Glucan was isolated from A. fumigatus conidia and mycelia cell wall. For the analysis of polarization, DCs and autologous naive CD4+ T cells were cocultured. Phenotype of immune cells was analyzed by flow cytometry, and cytokines by enzyme-linked immunosorbent assay (ELISA). Blocking antibodies were used to dissect the role of Toll-like receptor 2 (TLR2) and programmed death-ligand 1 (PD-L1) in regulating α-(1,3)-glucan-mediated DC activation and T-cell responses. DCs from TLR2-deficient mice were additionally used to consolidate the findings. α-(1,3)-Glucan induced the maturation of DCs and was dependent in part on TLR2. "α-(1,3)-Glucan-educated" DCs stimulated the activation of naive T cells and polarized a subset of these cells into CD4+CD25+FoxP3+ regulatory T cells (Tregs). Mechanistically, Treg stimulation by α-(1,3)-glucan was dependent on the PD-L1 pathway that negatively regulated interferon-gamma (IFN-γ) secretion. Short α-(1,3)-oligosaccharides lacked the capacity to induce maturation of DCs but significantly blocked α-(1,3)-glucan-induced Treg polarization. PD-L1 dictates the balance between Treg and IFN-γ responses induced by α-(1,3)-glucan. Our data provide a rationale for the exploitation of immunotherapeutic approaches that target PD-1-PD-L1 to enhance protective immune responses to A. fumigatus infections. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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

...-0032; Directorate Identifier 2009-NM-213-AD] RIN 2120-AA64 Airworthiness Directives; McDonnell Douglas...: McDonnell Douglas Corporation: Docket No. FAA-2010-0032; Directorate Identifier 2009-NM-213-AD. Comments Due... applies to McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A...

The Biomineralization of a Bioactive Glass-Incorporated Light-Curable Pulp Capping Material Using Human Dental Pulp Stem Cells

Directory of Open Access Journals (Sweden)

Soo-Kyung Jun

2017-01-01

Full Text Available The aim of this study was to investigate the biomineralization of a newly introduced bioactive glass-incorporated light-curable pulp capping material using human dental pulp stem cells (hDPSCs. The product (Bioactive® [BA] was compared with a conventional calcium hydroxide-incorporated (Dycal [DC] and a light-curable (Theracal® [TC] counterpart. Eluates from set specimens were used for investigating the cytotoxicity and biomineralization ability, determined by alkaline phosphatase (ALP activity and alizarin red staining (ARS. Cations and hydroxide ions in the extracts were measured. An hDPSC viability of less than 70% was observed with 50% diluted extract in all groups and with 25% diluted extract in the DC. Culturing with 12.5% diluted BA extract statistically lowered ALP activity and biomineralization compared to DC (p0.05. Ca (~110 ppm and hydroxide ions (pH 11 were only detected in DC and TC. Ionic supplement-added BA, which contained similar ion concentrations as TC, showed similar ARS mineralization compared to TC. In conclusion, the BA was similar to, yet more cytotoxic to hDPSCs than, its DC and TC. The BA was considered to stimulate biomineralization similar to DC and TC only when it released a similar amount of Ca and hydroxide ions.

The neck region of the C-type lectin DC-SIGN regulates its surface spatiotemporal organization and virus-binding capacity on antigen presenting cells

NARCIS (Netherlands)

Manzo, C.; Torreno-Pina, J.A.; Joosten, B.; Reinieren-Beeren, I.; Gualda, E.J.; Loza-Alvarez, P.; Figdor, Carl; Garcia Parajo, M.F.; Cambi, A.

2012-01-01

The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and

The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells

NARCIS (Netherlands)

Manzo, C.; Torreno-Pina, J.A.; Joosten, B.; Reinieren-Beeren, I.; Gualda, E.J.; Loza-Alvarez, P.; Figdor, C.G.; Garcia-Parajo, M.F.; Cambi, A.

2012-01-01

The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and

Brugia malayi Antigen (BmA Inhibits HIV-1 Trans-Infection but Neither BmA nor ES-62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells.

Directory of Open Access Journals (Sweden)

Emily E I M Mouser

Full Text Available One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA and excretory-secretory product 62 (ES-62 from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs.

Efficiency Analyses of a DC Residential Power Distribution System for the Modern Home

Directory of Open Access Journals (Sweden)

GELANI, H. E.

2015-02-01

Full Text Available The electric power system started as DC back in the nineteenth century. However, the DC paradigm was soon ousted by AC due to inability of DC to change its voltage level. Now, after many years, with the development of power electronic converters capable of stepping-up and down DC voltage and converting it to-and-from AC, DC appears to be challenging AC and attempting a comeback. We now have DC power generation by solar cells, fuel cells and wind farms, DC power transmission in the form of HVDC (High Voltage DC transmission, DC power utilization by various modern electronic loads and DC power distribution that maybe regarded as still in research phase. This paper is an attempt to investigate feasibility of DC in the distribution portion of electrical power system. Specifically, the efficiency of a DC distribution system for residential localities is determined while keeping in view the concept of daily load variation. The aim is to bring out a more practical value of system efficiency as the efficiencies of DC/DC converters making up the system vary with load variation. This paper presents the modeling and simulation of a DC distribution system and efficiency results for various scenarios are presented.

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

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 8-31, DC-8-32, DC-8-33, DC-8-41, DC-8-42, and... to all of the McDonnell Douglas Corporation airplanes identified above. The existing AD currently... the following new airworthiness directive (AD): 2010-21-03 McDonnell Douglas Corporation: Amendment 39...

Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma.

Science.gov (United States)

Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; van Baren, Nicolas; Lucas, Sophie; Kvistborg, Pia; Thielemans, Kris; Neyns, Bart

2016-04-20

Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma. Thirty-nine patients were treated with TriMixDC-MEL (4 × 10(6) cells administered intradermally and 20 × 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point. The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post-DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event. The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma. © 2016 by American Society of Clinical Oncology.

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...

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.

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.

High hydrostatic pressure affects antigenic pool in tumor cells: Implication for dendritic cell-based cancer immunotherapy.

Science.gov (United States)

Urbanova, Linda; Hradilova, Nada; Moserova, Irena; Vosahlikova, Sarka; Sadilkova, Lenka; Hensler, Michal; Spisek, Radek; Adkins, Irena

2017-07-01

High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time. On the other hand, quick reduction of tumor antigen-coding mRNA was observed at HHP 200MPa immediately after treatment in all cell lines tested. To optimize the DC-based active cellular therapy protocol for HHP-sensitive cell lines the immunogenicity of HHP-treated lung cancer cells at 150, 200 and 250MPa was compared. Lung cancer cells treated with HHP 150MPa display characteristics of immunogenic cell death, however cells are not efficiently phagocytosed by DC. Despite induction of the highest number of antigen-specific CD8 + T cells, 150 MPa-treated lung cancer cells survive in high numbers. This excludes their use in DC vaccine manufacturing. HHP of 200MPa treatment of lung cancer cells ensures the optimal ratio of efficient immunogenic killing and delivery of protein antigens in DC. These results represent an important pre-clinical data for generation of immunogenic killed lung cancer cells in ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa). Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Unimpaired dendritic cell functions in MVP/LRP knockout mice.

Science.gov (United States)

Mossink, Marieke H; de Groot, Jan; van Zon, Arend; Fränzel-Luiten, Erna; Schoester, Martijn; Scheffer, George L; Sonneveld, Pieter; Scheper, Rik J; Wiemer, Erik A C

2003-09-01

Dendritic cells (DCs) act as mobile sentinels of the immune system. By stimulating T lymphocytes, DCs are pivotal for the initiation of both T- and B-cell-mediated immune responses. Recently, ribonucleoprotein particles (vaults) were found to be involved in the development and/or function of human DCs. To further investigate the role of vaults in DCs, we examined the effects of disruption of the major vault protein (MVP/LRP) on the development and antigen-presenting capacity of DCs, using our MVP/LRP knockout mouse model. Mononuclear bone marrow cells were isolated from wild-type and knockout mice and stimulated to differentiate to DCs. Like human DCs, the wild-type murine DC cultures strongly expressed MVP/LRP. Nevertheless, the MVP/LRP-deficient DCs developed normally and showed similar expression levels of several DC surface markers. No differences were observed in in vitro studies on the antigen uptake and presenting capacities of the wild-type and MVP/LRP knockout DCs. Moreover, immunization of the MVP/LRP-deficient mice with several T-cell antigens led to responses similar to those observed in the wild-type mice, indicating that the in vivo DC migration and antigen-presentation capacities are intact. Moreover, no differences were observed in the induction of the T cell-dependent humoral responses and orally induced peripheral T-cell tolerance. In conclusion, vaults are not required for primary DC functions. Their abundance in DCs may, however, still reflect basic roles in myeloid cell proliferation and DC development.

dc Arc Fault Effect on Hybrid ac/dc Microgrid

Science.gov (United States)

Fatima, Zahra

The advent of distributed energy resources (DER) and reliability and stability problems of the conventional grid system has given rise to the wide spread deployment of microgrids. Microgrids provide many advantages by incorporating renewable energy sources and increasing the reliability of the grid by isolating from the main grid in case of an outage. AC microgrids have been installed all over the world, but dc microgrids have been gaining interest due to the advantages they provide over ac microgrids. However the entire power network backbone is still ac and dc microgrids require expensive converters to connect to the ac power network. As a result hybrid ac/dc microgrids are gaining more attention as it combines the advantages of both ac and dc microgrids such as direct integration of ac and dc systems with minimum number of conversions which increases the efficiency by reducing energy losses. Although dc electric systems offer many advantages such as no synchronization and no reactive power, successful implementation of dc systems requires appropriate protection strategies. One unique protection challenge brought by the dc systems is dc arc faults. A dc arc fault is generated when there is a gap in the conductor due to insulation degradation and current is used to bridge the gap, resulting in an arc with very high temperature. Such a fault if it goes undetected and is not extinguished can cause damage to the entire system and cause fires. The purpose of the research is to study the effect of the dc arc fault at different locations in the hybrid ac/dc microgrid and provide insight on the reliability of the grid components when it is impacted by arc faults at various locations in the grid. The impact of dc arc fault at different locations on the performance of the PV array, wind generation, and constant power loads (CPL) interfaced with dc/dc converters is studied. MATLAB/Simulink is used to model the hybrid ac/dc microgrid and arc fault.

Energy Management Strategy Based on Multiple Operating States for a Photovoltaic/Fuel Cell/Energy Storage DC Microgrid

Directory of Open Access Journals (Sweden)

Ying Han

2017-01-01

Full Text Available It is a great challenge for DC microgrids with stochastic renewable sources and volatility loads to achieve better operation performance. This study proposes an energy management strategy based on multiple operating states for a DC microgrid, which is comprised of a photovoltaic (PV array, a proton exchange membrane fuel cell (PEMFC system, and a battery bank. This proposed strategy can share the power properly and keep the bus voltage steady under different operating states (the state of charge (SOC of the battery bank, loading conditions, and PV array output power. In addition, a microgrids test platform is established. In order to verify the effectiveness of the proposed energy management strategy, the strategy is implemented in a hardware system and experimentally tested under different operating states. The experimental results illustrate the good performance of the proposed control strategy for the DC microgrid under different scenarios of power generation and load demand.

Milliwatt dc/dc Inverter

Science.gov (United States)

Mclyman, C. W.

1983-01-01

Compact dc/dc inverter uses single integrated-circuit package containing six inverter gates that generate and amplify 100-kHz square-wave switching signal. Square-wave switching inverts 10-volt local power to isolated voltage at another desired level. Relatively high operating frequency reduces size of filter capacitors required, resulting in small package unit.

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

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-30, DC-10-30F (KDC-10... following new airworthiness directive (AD): 2010-21-13 McDonnell Douglas Corporation: Amendment 39-16473... November 18, 2010. Affected ADs (b) None. Applicability (c) This AD applies to McDonnell Douglas...

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

...-1044; Directorate Identifier 2010-NM-033-AD] RIN 2120-AA64 Airworthiness Directives; McDonnell Douglas..., 2007) and adding the following new AD: McDonnell Douglas Corporation: Docket No. FAA-2010-1044.... Applicability (c) This AD applies to all McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

Directory of Open Access Journals (Sweden)

Ida M Smith

Full Text Available Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

Science.gov (United States)

Smith, Ida M; Baker, Adam; Christensen, Jeffrey E; Boekhout, Teun; Frøkiær, Hanne; Arneborg, Nils; Jespersen, Lene

2016-01-01

Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC) function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV+ status in head and neck cancer.

Science.gov (United States)

Lu, Shanhong; Concha-Benavente, Fernando; Shayan, Gulidanna; Srivastava, Raghvendra M; Gibson, Sandra P; Wang, Lin; Gooding, William E; Ferris, Robert L

2018-03-01

The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab. We correlated STING protein expression with clinical parameters by immunohistochemistry (n = 106) and its mRNA expression from The Cancer Genome Atlas (TCGA) in HNSCC tissue specimens. STING protein expression was tested for association with cancer-specific survival (CSS). We further examined the impact of STING activation on cetuximab-mediated immunity using an in vitro NK:DC:tumor cells co-culture system. In this study, we found that expression of STING both at the protein and mRNA level was higher in HPV positive (HPV + ) specimens but unrelated to TNM stage or cancer-specific survival. Our in vitro studies verified that STING activation enhanced cetuximab mediated NK cell activation and DC maturation. Our findings suggest a novel role of STING in HPV-related carcinogenesis, in which activation of the STING signaling pathway may facilitate anti-tumor response in HNSCC patients, particularly in combination with therapeutic monoclonal antibodies (mAbs) such as cetuximab, an epidermal growth factor receptor (EGFR) inhibitor. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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....

Uncarinic Acid C Isolated from Uncaria rhynchophylla Induces Differentiation of Th1-Promoting Dendritic Cells Through TLR4 Signaling

OpenAIRE

Kim, Kyu Sik; Pham, Thanh Nhan Nguyen; Jin, Chun-Ji; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

2011-01-01

Uncarinic acid C (URC) is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cells (DC) is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. DC might be a potential target for URC. We demonstrate that URC activates human DC as documented by phenotypic and functional maturation, and altered cytokine production. The expression ...

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.

Characterization of dendritic cells subpopulations in skin and afferent lymph in the swine model.

Directory of Open Access Journals (Sweden)

Florian Marquet

Full Text Available Transcutaneous delivery of vaccines to specific skin dendritic cells (DC subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC and dermal DC (DDC that could be divided in 3 subsets according to their phenotypes: (1 the CD163(neg/CD172a(neg, (2 the CD163(highCD172a(pos and (3 the CD163(lowCD172a(pos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163(high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163(negCD172(low DDC share properties with the CD8(+ T cell response-inducing murine skin CD103(pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.

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.

Application of Multi-Objective Human Learning Optimization Method to Solve AC/DC Multi-Objective Optimal Power Flow Problem

Science.gov (United States)

Cao, Jia; Yan, Zheng; He, Guangyu

2016-06-01

This paper introduces an efficient algorithm, multi-objective human learning optimization method (MOHLO), to solve AC/DC multi-objective optimal power flow problem (MOPF). Firstly, the model of AC/DC MOPF including wind farms is constructed, where includes three objective functions, operating cost, power loss, and pollutant emission. Combining the non-dominated sorting technique and the crowding distance index, the MOHLO method can be derived, which involves individual learning operator, social learning operator, random exploration learning operator and adaptive strategies. Both the proposed MOHLO method and non-dominated sorting genetic algorithm II (NSGAII) are tested on an improved IEEE 30-bus AC/DC hybrid system. Simulation results show that MOHLO method has excellent search efficiency and the powerful ability of searching optimal. Above all, MOHLO method can obtain more complete pareto front than that by NSGAII method. However, how to choose the optimal solution from pareto front depends mainly on the decision makers who stand from the economic point of view or from the energy saving and emission reduction point of view.

Effect of DC-CIK treatment on tumor markers and T cell subsets in patients with advanced ovarian cancer

Directory of Open Access Journals (Sweden)

Jie-Qun Guo

2016-10-01

Full Text Available Objective: To investigate the effects of dendritic cells (DC and cytokine induced killer cells (CIK on tumor markers and T cell subsets in peripheral blood of patients with advanced ovarian cancer. Methods: A total of 100 cases of patients with advanced ovarian cancer who were proved by operation and pathology in the department of gynecologic oncology in our hospital were selected from April 2013 to April 20l6, and randomly divided into experimental group and control group, the control group was treated with TC (Taxinol+Cisplat chemotherapy alone, the experimental group was treated with DC-CIK combined with chemotherapy. Before and after treatment, the changes of CD3+, CD4+, CD8+, CD4+/CD8+, CD4+/CD25+, NK cells in peripheral blood and serum tumor markers (CA125, CA19-9, HE4 were detected. Results: Before treatment, the phenotypes of T cell subsets in the two groups were not significantly different; in the experimental group after treatment, the levels of CD3+, CD4+, CD4+/CD8+, and NK cells were increased,while the levels of CD4+/CD25+ and CD8+ were decreased, compared with before treatment, the differences were statistically significant; the phenotype changes of T cells were not statistically significant before and after treatment in the control group; after treatment, there were significant differences in the levels of CD4+, CD8+, CD4+/CD8+, CD4+/CD25+ and NK cells between the two groups. Before treatment, there were no significant differences in HE4 value, CA125 value and CA19-9 value between the two groups; after treatment, the tumor markers in the two groups were all decreased, and the difference was significant as compared with those before treatment; after treatment, the CA125 value, CA19-9 value and HE4 value were (73.68±79.46 U/mL, (54.32±32.85 U/mL and (69.57±39.85 pmol/L respectively, the values of three tumor markers were compared with the control group, with a statistical difference. Conclusion: DC-CIK treatment can improve the

Mycobacterium tuberculosis promotes Th17 expansion via regulation of human dendritic cells toward a high CD14 and low IL-12p70 phenotype that reprograms upon exogenous IFN-γ

DEFF Research Database (Denmark)

Søndergaard, Jonas Nørskov; Laursen, Janne Marie; Rosholm, Lisbeth Buus

2014-01-01

) are some of the first cells to interact with Mtb and they play an essential role in development of protective immunity against Mtb. Given that Mtb-infected macrophages have difficulties in degrading Mtb, they need help from IFN-γ-producing CD4+ T cells propagated via IL-12p70-producing DCs. Here we report...... that Mtb modifies human DC plasticity by expanding a CD14+ DC subset with weak IL-12p70-producing capacity. The CD14+ Mtb-promoted subset was furthermore poor inducers of IFN-γ by naive CD4+ T cells, but instead prompted IL-17A-producing RORγT+ CD4+ T cells. Mtb-derived peptidoglycan and mannosylated...... conclude that Mtb exploits DC plasticity to reduce production of IL-12p70, and that this process is entirely divertible by exogenous IFN-γ. These data suggest that strategies to increase local IFN-γ production in the lungs of tuberculosis patients may boost host immunity toward Mtb....

Inefficient HIV-1 trans infection of CD4+ T cells by macrophages from HIV-1 nonprogressors is associated with altered membrane cholesterol and DC-SIGN.

Science.gov (United States)

DeLucia, Diana C; Rinaldo, Charles R; Rappocciolo, Giovanna

2018-04-11

Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4 + T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4 + T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes and lipid rafting was significantly lower in NP than PR, as well as virus internalization in early endosomes. Furthermore, simvastatin (SIMV), decreased the subpopulation of DC-SIGN + MΦ, as well as MΦ cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Targeting the ability of MΦ to drive HIV-1 dissemination in trans could enhance HIV-1 therapeutic strategies. IMPORTANCE Despite the success of combination anti-retroviral therapy, neither a vaccine nor a cure for HIV infection has been developed, demonstrating a need for novel prophylactic and therapeutic strategies. Here we show that efficiency of macrophage (M�

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

OpenAIRE

Liwen Pan; Chengning Zhang

2016-01-01

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 m...

PENGGUNAAN FUZZY LOGIC UNTUK KONTROL PARALLEL CONVERTER DC-DC

Directory of Open Access Journals (Sweden)

Bambang Prio Hartono

2012-09-01

Full Text Available Abstract: Using system fuzzy logic as control  technology have been used on low load dc-dc converter with combined parallel compiled  dc-dc converter can  obtain big load.   With existence of differrence of component parameter and each parallel compiled converter can obtained different current  and voltage output.  Function of controller  for to do adjustment, so that current which is applied  to  load by each converter  can be obtained  difference error as small as possible or same. The object of research is developing design of large signal dc-dc converter which is  combined with using  FLC so that  obtain  better performance.  To get better performance have been made plant model and simulation with CDE method.  The more systematic  system and design is needed to overcome bigger load  on dc-dc converter, so that parallel  compiled current master slave control system on dc-dc converter with using fuzzy logic  controller is used. Result of  research showed that error or difference of  current  which is applied to load can handled by fuzzy logic  controller.  Technic of current and voltage controller co to do adjustment current and voltage distribution  equally to load.  Distribution of iL1,iL2 and  output voltage Vo on dc-dc  converter with load 2,25 until  7,875 and voltage  100  until 120 volt,  load current beetwen  12 until 48, % relatif  error  Vo  0,4% until  0,9%.

DC-SIGN activation mediates the differential effects of SAP and CRP on the innate immune system and inhibits fibrosis in mice.

Science.gov (United States)

Cox, Nehemiah; Pilling, Darrell; Gomer, Richard H

2015-07-07

Fibrosis is caused by scar tissue formation in internal organs and is associated with 45% of deaths in the United States. Two closely related human serum proteins, serum amyloid P (SAP) and C-reactive protein (CRP), strongly affect fibrosis. In multiple animal models, and in Phase 1 and Phase 2 clinical trials, SAP affects several aspects of the innate immune system to reduce fibrosis, whereas CRP appears to potentiate fibrosis. However, SAP and CRP bind the same Fcγ receptors (FcγR) with similar affinities, and why SAP and CRP have opposing effects is unknown. Here, we report that SAP but not CRP binds the receptor DC-SIGN (SIGN-R1) to affect the innate immune system, and that FcγR are not necessary for SAP function. A polycyclic aminothiazole DC-SIGN ligand and anti-DC-SIGN antibodies mimic SAP effects in vitro. In mice, the aminothiazole reduces neutrophil accumulation in a model of acute lung inflammation and, at 0.001 mg/kg, alleviates pulmonary fibrosis by increasing levels of the immunosuppressant IL-10. DC-SIGN (SIGN-R1) is present on mouse lung epithelial cells, and SAP and the aminothiazole potentiate IL-10 production from these cells. Our data suggest that SAP activates DC-SIGN to regulate the innate immune system differently from CRP, and that DC-SIGN is a target for antifibrotics.

Radiation detection from phase-locked serial dc SQUID arrays

DEFF Research Database (Denmark)

Kaplunenko, V. K.; Mygind, Jesper; Pedersen, Niels Falsig

1993-01-01

We report on synchronous operation of series arrays of inductively coupled superconducting quantum interference devices (SQUIDs). Each array consisted of N=3 or 11 dc SQUIDs with common inductances providing a strong interaction between neighboring cells. Externally shunted (betac[approximately-e......We report on synchronous operation of series arrays of inductively coupled superconducting quantum interference devices (SQUIDs). Each array consisted of N=3 or 11 dc SQUIDs with common inductances providing a strong interaction between neighboring cells. Externally shunted (betac...

Full range ZVS DC-DC converter

International Nuclear Information System (INIS)

Upadhyay, Rinki; Badapanda, M.K.; Hannurkar, P.R.

2011-01-01

A 500 V, 24 Amp DC-DC converter with digital signal processor (DSP) based control and protection has been designed, fabricated and tested. Its power circuit consists of IGBT based single phase inverter bridge, ferrite transformer and diode rectifier. All IGBTs in the inverter bridge are operated in zero voltage switching (ZVS) mode to minimize switching losses thereby increasing the efficiency of the converter significantly. The efficiency of this converter is measured to be greater than 97% at full load. In a conventional full bridge inverter, typically ZVS is achieved under full load condition while at light load ZVS is lost. An auxiliary LC circuit has been intentionally incorporated in this converter to achieve ZVS even at light loaded conditions. Detailed simulation of the converter circuit is carried out and crucial waveforms have been presented in this paper. Microchip make dsPIC30F2020 DSP is employed to provide phase shifted PWMs to IGBTs in the inverter bridge. All the crucial parameters are also monitored by this DSP and in case of any unfavorable conditions, the converter is tripped off. Suitable experiments were carried out in this DC-DC converter under different loaded conditions and a close match between the simulated and experimental results were obtained. Such DC-DC converters can be connected in series or parallel for the development of solid state modular power supplies for various applications. (author)

Role of fatty-acid synthesis in dendritic cell generation and function.

Science.gov (United States)

Rehman, Adeel; Hemmert, Keith C; Ochi, Atsuo; Jamal, Mohsin; Henning, Justin R; Barilla, Rocky; Quesada, Juan P; Zambirinis, Constantinos P; Tang, Kerry; Ego-Osuala, Melvin; Rao, Raghavendra S; Greco, Stephanie; Deutsch, Michael; Narayan, Suchithra; Pachter, H Leon; Graffeo, Christopher S; Acehan, Devrim; Miller, George

2013-05-01

Dendritic cells (DC) are professional APCs that regulate innate and adaptive immunity. The role of fatty-acid synthesis in DC development and function is uncertain. We found that blockade of fatty-acid synthesis markedly decreases dendropoiesis in the liver and in primary and secondary lymphoid organs in mice. Human DC development from PBMC precursors was also diminished by blockade of fatty-acid synthesis. This was associated with higher rates of apoptosis in precursor cells and increased expression of cleaved caspase-3 and BCL-xL and downregulation of cyclin B1. Further, blockade of fatty-acid synthesis decreased DC expression of MHC class II, ICAM-1, B7-1, and B7-2 but increased their production of selected proinflammatory cytokines including IL-12 and MCP-1. Accordingly, inhibition of fatty-acid synthesis enhanced DC capacity to activate allogeneic as well as Ag-restricted CD4(+) and CD8(+) T cells and induce CTL responses. Further, blockade of fatty-acid synthesis increased DC expression of Notch ligands and enhanced their ability to activate NK cell immune phenotype and IFN-γ production. Because endoplasmic reticulum (ER) stress can augment the immunogenic function of APC, we postulated that this may account for the higher DC immunogenicity. We found that inhibition of fatty-acid synthesis resulted in elevated expression of numerous markers of ER stress in humans and mice and was associated with increased MAPK and Akt signaling. Further, lowering ER stress by 4-phenylbutyrate mitigated the enhanced immune stimulation associated with fatty-acid synthesis blockade. Our findings elucidate the role of fatty-acid synthesis in DC development and function and have implications to the design of DC vaccines for immunotherapy.

HMGB1-dependent triggering of HIV-1 replication and persistence in dendritic cells as a consequence of NK-DC cross-talk.

Directory of Open Access Journals (Sweden)

Héla Saïdi

Full Text Available HIV-1 has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. Recently, the fate of DCs has been found to be extremely dependent on the interaction with autologous NK cells, but the mechanisms by which NK-DC interaction controls viral infections remain unclear. Here, we investigate the impact of NK-DC cross-talk on maturation and functions of HIV-infected immature DCs.Immature DCs were derived from primary monocytes, cultured in the presence of IL-4 and GM-CSF. In some experiments, DCs were infected with R5-HIV-1(BaL or X4-HIV-1(NDK, and viral replication, proviral HIV-DNA and the frequency of infected DCs were measured. Autologous NK cells were sorted and either kept unstimulated in the presence of suboptimal concentration of IL-2, or activated by a combination of PHA and IL-2. The impact of 24 h NK-DC cross-talk on the fate of HIV-1-infected DCs was analyzed. We report that activated NK cells were required for the induction of maturation of DCs, whether uninfected or HIV-1-infected, and this process involved HMGB1. However, the cross-talk between HIV-1-infected DCs and activated NK cells was functionally defective, as demonstrated by the strong impairment of DCs to induce Th1 polarization of naïve CD4 T cells. This was associated with the defective production of IL-12 and IL-18 by infected DCs. Moreover, the crosstalk between activated NK cells and HIV-infected DCs resulted in a dramatic increase in viral replication and proviral DNA expression in DCs. HMGB1, produced both by NK cells and DCs, was found to play a pivotal role in this process, and inhibition of HMGB1 activity by glycyrrhizin, known to bind specifically to HMGB1, or blocking anti-HMGB1 antibodies, abrogated NK-dependent HIV-1 replication in DCs.These observations provide evidence for the crucial role of NK-DC cross-talk in promoting viral dissemination, and challenge the question of the in vivo involvement of HMGB1

TOPOLOGICAL REVIEW AND ANALYSIS OF DC-DC BOOST CONVERTERS

Directory of Open Access Journals (Sweden)

V. INDRA GANDHI

2017-06-01

Full Text Available DC voltage boost up is essential in numerous applications; especially considering Photovoltaic (PV based renewable power generation system. The conventional DC-DC boost converter is the most admired configuration for this scheme, even if the converter efficiency is restricted at duty cycle near to maximum value. In order to find solution to the problem and improve its conversion capability, many converter configurations have been implemented so far. With this circumstance, this research work proposes to give overview of a few most imperative research works related to DC-DC boost converters. Some configurations are covered and classified basically based on the application. The major benefits and disadvantages related to the available techniques are also briefly conveyed. At last, a proper evaluation is recognized among the important types of DC-DC boost converters in terms of efficiency, number of components, and stability.

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

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.

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

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.

Practical Design Guidelines of qZSI Based Step-Up DC/DC Converter

Science.gov (United States)

Zakis, Janis; Vinnikov, Dmitri; Roasto, Indrek; Jalakas, Tanel

2010-01-01

This paper presents some design guidelines for a new voltage fed step-up DC/DC isolated converter. The most significant advantage of proposed converter is voltage buck-boost operation on single stage. The most promising application for proposed converter is in the field of distributed power generation e.g. fuel cells or photovoltaic. The most sensitive issues - such as power losses caused by high currents in the input side of converter and high transient overvoltages across the inverter bridge caused by stray inductances were discussed and solved. The proposals and recommendations to overcome these issues are given in the paper. The Selection and design guidelines of converter elements are proposed and explained. The prototype of proposed converter was built and experimentally tested. Some results are presented and evaluated.

Uncarinic Acid C Isolated from Uncaria rhynchophylla Induces Differentiation of Th1-Promoting Dendritic Cells Through TLR4 Signaling.

Science.gov (United States)

Kim, Kyu Sik; Pham, Thanh Nhan Nguyen; Jin, Chun-Ji; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

2011-02-28

Uncarinic acid C (URC) is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cells (DC) is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. DC might be a potential target for URC. We demonstrate that URC activates human DC as documented by phenotypic and functional maturation, and altered cytokine production. The expression of CD1a, CD38, CD40, CD54, CD80, CD83, CD86, HLA-DR and CCR7 on URC-primed DC was enhanced. The production of IL-12p70 by URC-primed DC was higher than that of lipopolysaccharide (LPS)-primed DC. The production of IL-12p70 by URC-primed DC was inhibited by the anti-Toll-like receptor 4 (TLR4) monoclonal antibody (mAb), but partially abolished by anti-TLR2 mAb. mRNA coding for TLR2 and TLR4 was expressed in URC-primed DC. URC-primed DC induced the NF-κB transcription factor. Naïve T cells co-cultured with URC-primed DC turned into typical Th1 cells that produced large quantities of IFN-γ depending on IL-12 secretion. URC enhanced the T cell stimulatory capacity in an allo MLR. In the cytotoxic T-lymphocyte assay (CTL) assay, DNA fragmentation assay and (51)Cr release on URC-primed DC were more augmented than that of TNF-α-primed DC. DC matured with URC had an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that URC modulates DC function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR4 signaling, and may be used on DC-based vaccine for cancer immunotherapy.

Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.

Science.gov (United States)

Mahanty, Siddhartha; Hutchinson, Karen; Agarwal, Sudhanshu; McRae, Michael; Rollin, Pierre E; Pulendran, Bali

2003-03-15

Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.

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

Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.

Science.gov (United States)

Liebetanz, David; Nitsche, Michael A; Tergau, Frithjof; Paulus, Walter

2002-10-01

Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.

Millivolt-scale DC shifts in the human scalp EEG: evidence for a nonneuronal generator.

Science.gov (United States)

Voipio, Juha; Tallgren, Pekka; Heinonen, Erkki; Vanhatalo, Sampsa; Kaila, Kai

2003-04-01

Slow shifts in the human scalp-recorded EEG, including those related to changes in brain CO(2) levels, have been generally assumed to result from changes in the level of tonic excitation of apical dendrites of cortical pyramidal neurons. We readdressed this issue using DC-EEG shifts elicited in healthy adult subjects by hypo- or hypercapnia. A 3-min period of hyperventilation resulted in a prompt negative shift with a rate of up to 10 microV/s at the vertex (Cz) and an extremely steep dependence (up to 100 microV/mmHg) on the end-tidal Pco(2). This shift had a maximum of up to -2 mV at Cz versus the temporal derivations (T3/T4). Hyperventilation-like breathing of 5% CO(2)-95% O(2), which does not lead to a significant hypocapnia, resulted in a near-complete block of the negative DC shift at Cz. Hypoventilation, or breathing 5% CO(2) in air at normal respiratory rate, induced a positive shift. The high amplitude of the voltage gradients on the scalp induced by hyperventilation is not consistent with a neuronal origin. Instead, the present data suggest that they are generated by extracortical volume currents driven by a Pco(2)-dependent potential difference across epithelia separating the cerebrospinal fluid and blood. Since changes in respiratory patterns and, hence, in the level of brain Pco(2), are likely to occur under a number of experimental conditions in which slow EEG responses have been reported (e.g., attention shifts, preparatory states, epileptic seizures, and hypoxic episodes), the present results call for a thorough reexamination of the mechanisms underlying scalp-recorded DC-EEG responses.

Targeted knock down of CCL22 and CCL17 by siRNA during DC differentiation and maturation affects the recruitment of T subsets.

Science.gov (United States)

Kang, Shijun; Xie, Jianmin; Ma, Shudong; Liao, Wangjun; Zhang, Junyi; Luo, Rongcheng

2010-01-01

Chemokines secreted by DC are instrumental for DC to regulate their own migratory capacities and to recruit T lymphocytes during local tumour immune response. Using the recently developed chemokine protein arrays, we analyzed 38 chemokines associated with monocyte-derived DC (MoDC), including the CC family (CCL2, CCL3, CCL4, CCL17, CCL18, CCL22, CCL23, CCL24, CCL27) and the CXC family (CXCL3, CXCL5, CXCL7, CXCL8, CXCL16) chemokines. Our results indicate that MoDC largely inherit the chemokines constitutively expressed by monocytes, with a significant induction of CCL17, CCL22 and CCL23. Spent culture supernatant collected from MoDC exhibited chemotatic abilities to activate CD4(+), CD8(+), and CD25(+) Foxp3(+) regulatory T cells (Tregs). Selective knock down of CCL22 and CCL17 expression by siRNA decreased the ratios of CD4(+) to CD8(+), as well as the frequency of Tregs recruited by MoDC. Intratumoural injection of MoDC transfected with siCCL22 and siCCL17, significantly reduced the number of Tregs while increasing the number of infiltrating CD8(+) T cells in human tumour xenografts in athymic nude mice. This study demonstrates that chemokine expression of MoDC is complex and may change dynamically. Using siRNA to selectively knock down chemokines which are highly chemoattractive to Tregs may consequentially alter the lymphocyte populations recruited into the tumour microenvironment, therefore has the potency to provide insight into cellular interactions in cancer immunology. This may lead to a new strategy for DC vaccine development to improve cancer immunobiotherapy.

Intrinsic ZnO films fabricated by DC sputtering from oxygen-deficient targets for Cu(In,Ga)Se2 solar cell application

Institute of Scientific and Technical Information of China (English)

Chongyin Yang; DongyunWan; Zhou Wang; Fuqiang Huang

2011-01-01

Intrinsic zinc oxide films, normally deposited by radio frequency (RF) sputtering, are fabricated by direct current (DC) sputtering. The oxygen-deficient targets are prepared via a newly developed double crucible method. The 800-nm-thick film obtaines significantly higher carrier mobility compareing with that of the 800-nm-thick ZnO film. This is achieved by the widely used RF sputtering, which favors the prevention of carrier recombination at the interfaces and reduction of the series resistance of solar cells. The optimal ZnO film is used in a Cu (In, Ga) Se2 (CIGS) solar cell with a high efficiency of 11.57%. This letter demonstrates that the insulating ZnO films can be deposited by DC sputtering from oxygen-deficient ZnO targets to lower the cost of thin film solar cells.%Intrinsic zinc oxide films,normally deposited by radio frequency (RF) sputtering,are fabricated by direct current (DC) sputtering.The oxygen-deficient targets are prepared via a newly developed double crucible method.The 800-nm-thick film obtaines significantly higher carrier mobility compareing with that of the 800-nm-thick ZnO film.This is achieved by the widely used RF sputtering,which favors the prevention of carrier recombination at the interfaces and reduction of the series resistance of solar cells.The optimal ZnO film is used in a Cu (In,Ga) Se2 (C1GS) solar cell with a high efficiency of 11.57％.This letter demonstrates that the insulating ZnO films can be deposited by DC sputtering from oxygen-deficient ZnO targets to lower the cost of thin film solar cells.High resistance transparent intrinsic zinc oxide (i-ZnO)thin film has been widely nsed as the front electrode in transparent electronics and photovoltaic devices because of its low cost and nontoxicity.Owing to its unique characteristics of high transparency and adjustable resistivity in a certain range,the use of i-ZnO thin films as diffusion barrier layers of a-Si/μc-Si,CdTe,and CIGS thin-film solar cells has been advantageous

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.

Biotin deficiency enhances the inflammatory response of human dendritic cells.

Science.gov (United States)

Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

2016-09-01

The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

Interaction of Mycoplasma hominis PG21 with Human Dendritic Cells: Interleukin-23-Inducing Mycoplasmal Lipoproteins and Inflammasome Activation of the Cell.

Science.gov (United States)

Goret, J; Béven, L; Faustin, B; Contin-Bordes, C; Le Roy, C; Claverol, S; Renaudin, H; Bébéar, C; Pereyre, S

2017-08-01

Mycoplasma hominis lacks a cell wall, and lipoproteins anchored to the extracellular side of the plasma membrane are in direct contact with the host components. A Triton X-114 extract of M. hominis enriched with lipoproteins was shown to stimulate the production of interleukin-23 (IL-23) by human dendritic cells (hDCs). The inflammasome activation of the host cell has never been reported upon M. hominis infection. We studied here the interaction between M. hominis PG21 and hDCs by analyzing both the inflammation-inducing mycoplasmal lipoproteins and the inflammasome activation of the host cell. IL-23-inducing lipoproteins were determined using a sequential extraction strategy with two nondenaturing detergents, Sarkosyl and Triton X-114, followed by SDS-PAGE separation and mass spectrometry identification. The activation of the hDC inflammasome was assessed using PCR array and enzyme-linked immunosorbent assay (ELISA). We defined a list of 24 lipoproteins that could induce the secretion of IL-23 by hDCs, 5 with a molecular mass between 20 and 35 kDa and 19 with a molecular mass between 40 and 100 kDa. Among them, lipoprotein MHO_4720 was identified as potentially bioactive, and a synthetic lipopeptide corresponding to the N-terminal part of the lipoprotein was subsequently shown to induce IL-23 release by hDCs. Regarding the hDC innate immune response, inflammasome activation with caspase-dependent production of IL-1β was observed. After 24 h of coincubation of hDCs with M. homini s, downregulation of the NLRP3-encoding gene and of the adaptor PYCARD-encoding gene was noticed. Overall, this study provides insight into both protagonists of the interaction of M. hominis and hDCs. IMPORTANCE Mycoplasma hominis is a human urogenital pathogen involved in gynecologic and opportunistic infections. M. hominis lacks a cell wall, and its membrane contains many lipoproteins that are anchored to the extracellular side of the plasma membrane. In the present study, we focused on

Economical hydrogen production by electrolysis using nano pulsed DC

Energy Technology Data Exchange (ETDEWEB)

Dharmaraj, C.H. [Tangedco, Tirunelveli, ME Environmental Engineering (India); Adshkumar, S. [Department of Civil Engineering, Anna University of Technology Tirunelveli, Tirunelveli - 627007 (India)

2012-07-01

Hydrogen is an alternate renewable eco fuel. The environmental friendly hydrogen production method is electrolysis. The cost of electrical energy input is major role while fixing hydrogen cost in the conventional direct current Electrolysis. Using nano pulse DC input makes the input power less and economical hydrogen production can be established. In this investigation, a lab scale electrolytic cell developed and 0.58 mL/sec hydrogen/oxygen output is obtained using conventional and nano pulsed DC. The result shows that the nano pulsed DC gives 96.8 % energy saving.

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.

The performance of the DC motor by the PID controlling PWM DC-DC boost converter

OpenAIRE

Can, Erol; Sayan, Hasan Hüseyin

2017-01-01

This paper presents the PID controlling direct current (DC) to the direct current boost converter feds DC motor which has a 3.68 kW and 240 V of DC voltage input on its characteristics. What is first formed is the boost converter mathematical model at the design stage. Secondly, a mathematical model of the DC motor is created so that the boost converter with the machine can be established and modeled at the Matlab Simulink. The PID controller is considered for arranging a pulse width modulati...

On and off controlled resonant dc-dc power converter

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to a resonant DC-DC power converter comprising an input side circuit comprising a positive and a negative input terminal for receipt of an input voltage or current and an output side circuit comprising positive and negative output terminals for supply of a converter...... output voltage and connection to a converter load. The resonant DC-DC power converter further comprises a rectification circuit connected between an output of a resonant network and the output side circuit. The resonant network is configured for alternatingly being charged from the input voltage...... or current and discharged through the rectification circuit by a first controllable switch arrangement in accordance with a first switch control signal. A second controllable switch arrangement of the resonant DC-DC power converter is configured to select a first impedance characteristic of the resonant...

Design And Simulation Of A PV System With Battery Storage Using Bidirectional DC-DC Converter Using Matlab Simulink

Directory of Open Access Journals (Sweden)

Mirza Mursalin Iqbal

2017-07-01

Full Text Available PV Photovoltaic systems are one of the most renowned renewable green and clean sources of energy where power is generated from sunlight converting into electricity by the use of PV solar cells. Unlike fossil fuels solar energy has great environmental advantages as they have no harmful emissions during power generation. In this paper a PV system with battery storage using bidirectional DC-DC converter has been designed and simulated on MATLAB Simulink. The simulation outcomes verify the PV systems performance under standard testing conditions.

75 FR 27401 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-30, DC-9-40, and DC-9-50...

Science.gov (United States)

2010-05-17

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 9-30, DC-9-40, and DC-9-50 Series Airplanes... airworthiness directive (AD) for certain Model DC-9-30, DC-9-40, and DC-9-50 series airplanes. This AD requires... this AD to detect and correct the potential for an arc/spark condition to occur within the fuel boost...

HIV-derived vectors for gene therapy targeting dendritic cells.

Science.gov (United States)

Rossetti, Maura; Cavarelli, Mariangela; Gregori, Silvia; Scarlatti, Gabriella

2013-01-01

Human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LV) have the potential to mediate stable therapeutic gene transfer. However, similarly to other viral vectors, their benefit is compromised by the induction of an immune response toward transgene-expressing cells that closely mimics antiviral immunity. LV share with the parental HIV the ability to activate dendritic cells (DC), while lack the peculiar ability of subverting DC functions, which is responsible for HIV immune escape. Understanding the interaction between LV and DC, with plasmacytoid and myeloid DC playing fundamental and distinct roles, has paved the way to novel approaches aimed at regulating transgene-specific immune responses. Thanks to the ability to target either DC subsets LV might be a powerful tool to induce immunity (i.e., gene therapy of cancer), cell death (i.e., in HIV/AIDS infection), or tolerance (i.e., gene therapy strategies for monogenic diseases). In this chapter, similarities and differences between the LV-mediated and HIV-mediated induction of immune responses, with specific focus on their interactions with DC, are discussed.

Toll-like receptor activation enhances cell-mediated immunity induced by an antibody vaccine targeting human dendritic cells

Directory of Open Access Journals (Sweden)

Berger Marc A

2007-01-01

Full Text Available Abstract Previously, we have successfully targeted the mannose receptor (MR expressed on monocyte-derived dendritic cells (DCs using a fully human MR-specific antibody, B11, as a vehicle to deliver whole protein tumor antigens such as the human chorionic gonadotropin hormone (hCGβ. Since MRs play a role in bridging innate immunity with adaptive immunity we have explored several toll-like receptor (TLR-specific ligands that may synergize with MR targeting and be applicable as adjuvants in the clinic. We demonstrate that antigen-specific helper and cytolytic T cells from both healthy donors and cancer patients were effectively primed with B11-hCGβ-treated autologous DCs when a combination of one or several TLR ligands is used. Specifically, concomitant signaling of DCs via TLR3 with dsRNA (poly I:C and DC TLR 7/8 with Resiquimod (R-848, respectively, elicited efficient antigen presentation-mediated by MR-targeting. We demonstrate that MR and TLRs contribute towards maturation and activation of DCs by a mechanism that may be driven by a combination of adjuvant and antibody vaccines that specifically deliver antigenic targets to DCs.

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.

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 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....

Cysticerci drive dendritic cells to promote in vitro and in vivo Tregs differentiation.

Science.gov (United States)

Adalid-Peralta, Laura; Arce-Sillas, Asiel; Fragoso, Gladis; Cárdenas, Graciela; Rosetti, Marcos; Casanova-Hernández, Didier; Rangel-Escareño, Claudia; Uribe-Figueroa, Laura; Fleury, Agnes; Sciutto, Edda

2013-01-01

Regulatory T cells (Tregs) play a crucial role in immune homeostasis. Treg induction is a strategy that parasites have evolved to modulate the host's inflammatory environment, facilitating their establishment and permanence. In human Taenia solium neurocysticercosis (NC), the concurrence of increased peripheral and central Treg levels and their capacity to inhibit T cell activation and proliferation support their role in controlling neuroinflammation. This study is aimed at identifing possible mechanisms of Treg induction in human NC. Monocyte-derived dendritic cells (DC) from healthy human donors, cocultivated with autologous CD4(+) naïve cells either in the presence or absence of cysticerci, promoted CD25(high)Foxp3+ Treg differentiation. An increased Treg induction was observed when cysticerci were present. Moreover, an augmentation of suppressive-related molecules (SLAMF1, B7-H1, and CD205) was found in parasite-induced DC differentiation. Increased Tregs and a higher in vivo DC expression of the regulatory molecules SLAMF1 and CD205 in NC patients were also found. SLAMF1 gene was downregulated in NC patients with extraparenchymal cysticerci, exhibiting higher inflammation levels than patients with parenchymal parasites. Our findings suggest that cysticerci may modulate DC to favor a suppressive environment, which may help parasite establishment, minimizing the excessive inflammation, which may lead to tissue damage.

Dendritic cell activation and maturation induced by recombinant calreticulin fragment 39-272.

Science.gov (United States)

Li, Yue; Zeng, Xiaoli; He, Lijuan; Yuan, Hui

2015-01-01

Dendritic cells (DC) are the most potent antigen-presenting cells for initiating immune responses. DC maturation can be induced by exposing of immature DC to pathogen products or pro-inflammatory factor, which dramatically enhances the ability of DC to activate Ag-specific T cells. In this study, a recombinant calreticulin fragment 39-272 (rCRT/39-272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed and purified in Escherichia coli. Functional analysis studies revealed that rCRT/39-272 has potent immunostimulatory activities in both activating human monocytes and B cells to secrete cytokines. rCRT/39-272 can drive the activation of bone marrow derived DC in TLR4/CD14 dependent way, as indicated by secretion of cytokines IL-12/IL-23 (p40) and IL-1β. Exposure of DC to rCRT/39-272 induces P-Akt, suggesting that rCRT/39-272 induces maturation of DC through PI3K/Akt signaling pathway. The results suggest that soluble rCRT/39-272 is a potent stimulatory agent to DC maturation in TLR4/CD14 and PI3K/Akt dependent pathway. It may play important roles in initiating cellular immunity in vivo and the T cell response in vitro. Thus it could be used for study of DC-based tumor vaccines.

Using PBL to Improve Educational Outcomes and Student Satisfaction in the Teaching of DC/DC and DC/AC Converters

Science.gov (United States)

Martinez-Rodrigo, Fernando; Herrero-De Lucas, Luis Carlos; de Pablo, Santiago; Rey-Boue, Alexis B.

2017-01-01

This paper examines the question of how to use project-based learning to increase student performance and satisfaction in a power electronics course addressing the topics of dc/dc and dc/ac converters, the assembly of a dc/dc converter, and the use of a commercial speed drive. A detailed presentation of the methodology is shown, and the results…

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...

Factors influencing the drug sensitization of human tumor cells for in situ lipofection.

Science.gov (United States)

Son, K; Huang, L

1996-07-01

The cisplatin induced enhancement of in situ lipofection was optimized by considering the factors that can increase the degree of sensitization. Two other anticancer drugs, mechlorethamine (nitrogen mustard) and taxol, enhanced CAT gene expression but the degree of sensitization was not as great as cisplatin. Besides human 2008 ovarian cancer cells we also found that human lung (A549) and head and neck cancer cells (SCC 25) were transiently sensitized by cisplatin. The transfectability of the two commercially available cationic liposomes, Lipofectin and LipofectAmine, was either weak or not consistent among tumors tested. In vivo transfection efficiency of 2008 cells was the highest at 1 microgram DNA per nmol or microgram liposome with all three cationic liposomes. In vitro transfection efficiency of 2008 cells at 1:1 (microgram of DNA:nmole of DC-chol/DOPE liposome) increased in a dose-dependent manner while at 1:10, an optimal ratio for in vitro lipofection, rapidly decreased with an increase in dose. This result indicated that there was a correlation between in vivo and in vitro lipofection at 1:1 ratio for delivering liposomal DNA. Most of the DNA injected into the tumor was concentrated in the tumor and in the skin above the tumor whether cisplatin was preinjected or liposomes were used as carriers.

BaltDC: purification, characterization and infrared spectroscopy of an antiplatelet DC protein isolated from Bothrops alternatus snake venom.

Science.gov (United States)

Matias, Mariana Santos; de Sousa, Bruna Barbosa; da Cunha Pereira, Déborah Fernanda; Dias, Edigar Henrique Vaz; Mamede, Carla Cristine Neves; de Queiroz, Mayara Ribeiro; Silva, Anielle Christine Almeida; Dantas, Noelio Oliveira; Soares, Andreimar Martins; de Oliveira Costa, Júnia; de Oliveira, Fábio

2017-01-01

Snake venoms are a complex mixture of proteins, organic and inorganic compounds. Some of these proteins, enzymatic or non-enzymatic ones, are able to interact with platelet receptors, causing hemostatic disorders. The possible therapeutic potential of toxins with antiplatelet properties may arouse interest in the pharmacological areas. The present study aimed to purify and characterize an antiplatelet DC protein from Bothrops alternatus snake venom. The protein, called BaltDC (DC protein from B. alternatus snake venom), was purified by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. The molecular mass was estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). The amino acid sequence of the N-terminal region was carried out by Edman degradation method. Platelet aggregation assays were performed in human platelet-rich plasma (PRP). Infrared (IR) spectroscopy was used in order to elucidate the interactions between BaltDC and platelet membrane. BaltDC ran as a single protein band on SDS-PAGE and showed apparent molecular mass of 32 kDa under reducing or non-reducing conditions. The N-terminal region of the purified protein revealed the amino acid sequence IISPPVCGNELLEVGEECDCGTPENCQNECCDA, which showed identity with other snake venom metalloproteinases (SVMPs). BaltDC was devoid of proteolytic, hemorrhagic, defibrinating or coagulant activities, but it showed a specific inhibitory effect on platelet aggregation induced by ristocetin and epinephrine in PRP. IR analysis spectra strongly suggests that PO 3 2- groups, present in BaltDC, form hydrogen bonds with the PO 2 - groups present in the non-lipid portion of the membrane platelets. BaltDC may be of medical interest since it was able to inhibit platelet aggregation.

The Human Cell Atlas.

Science.gov (United States)

Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

2017-12-05

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

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.

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.

Evaluation of selected biomarkers for the detection of chemical sensitization in human skin: a comparative study applying THP-1, MUTZ-3 and primary dendritic cells in culture.

Science.gov (United States)

Hitzler, Manuel; Bergert, Antje; Luch, Andreas; Peiser, Matthias

2013-09-01

Dendritic cells (DCs) exhibit the unique capacity to induce T cell differentiation and proliferation, two processes that are crucially involved in allergic reactions. By combining the exclusive potential of DCs as the only professional antigen-presenting cells of the human body with the well known handling advantages of cell lines, cell-based alternative methods aimed at detecting chemical sensitization in vitro commonly apply DC-like cells derived from myeloid cell lines. Here, we present the new biomarkers programmed death-ligand 1 (PD-L1), DC immunoreceptor (DCIR), IL-16, and neutrophil-activating protein-2 (NAP-2), all of which have been detectable in primary human DCs upon exposure to chemical contact allergens. To evaluate the applicability of DC-like cells in the prediction of a chemical's sensitization potential, the expression of cell surface PD-L1 and DCIR was analyzed. In contrast to primary DCs, only minor subpopulations of MUTZ-3 and THP-1 cells presented PD-L1 or DCIR at their surface. After exposure to increasing concentrations of nickel and cinnamic aldehyde, the expression level of PD-L1 and DCIR revealed much stronger affected on monocyte-derived DCs (MoDCs) or Langerhans cells (MoLCs) when compared to THP-1 and MUTZ-3 cells. Applying protein profiler arrays we further identified the soluble factors NAP-2, IL-16, IL-8 and MIP-1α as sensitive biomarkers showing the capacity to discriminate sensitizing from non-sensitizing chemicals or irritants. An allergen-specific release of IL-8 and MIP-1α could be detected in the supernatants of MoDCs and MoLCs and also in MUTZ-3 and THP-1 cells, though at much lower levels. On the protein and transcriptional level, NAP-2 and IL-16 indicated sensitizers most sensitively and specifically in MoDCs. Altogether, we have proven the reciprocal regulated surface molecules PD-L1 and DCIR and the soluble factors MIP-1α, NAP-2 and IL-16 as reliable biomarkers for chemical sensitization. We further show that primary

Dendritic cell-tumor cell hybrids and immunotherapy

DEFF Research Database (Denmark)

Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

2011-01-01

Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

A full scale comparative study of methods for generation of functional Dendritic cells for use as cancer vaccines

OpenAIRE

Jarnjak-Jankovic, Silvija; Hammerstad, Hege; S?b?e-Larssen, Stein; Kvalheim, Gunnar; Gaudernack, Gustav

2007-01-01

Background Dendritic cells (DCs) are professional antigen-presenting cells with the ability to induce primary T-cell responses and are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF for 5–7 days (Standard DC). Recently, Dauer and co-workers presented a modified protocol for differentiation of human monocytes into mature DCs within 48 hours (Fast DC). Here we report a functional comparison of the two strategies for generation of DCs from human monocytes with adapt...

Two photon microscopy intravital study of DC-mediated anti-tumor response of NK cells

Science.gov (United States)

Caccia, Michele; Gorletta, Tatiana; Sironi, Laura; Zanoni, Ivan; Salvetti, Cristina; Collini, Maddalena; Granucci, Francesca; Chirico, Giuseppe

2010-02-01

Recent studies have demonstrated that dendritic cells (DCs) play a crucial role in the activation of Natural Killer cells (NKs) that are responsible for anti-tumor innate immune responses. The focus of this report is on the role of pathogen associated molecular pattern (PAMP) activated-DCs in inducing NK cell-mediated anti-tumor responses. Mice transplanted sub-cute (s.c.) with AK7 cells, a mesothelioma cell line sensitive to NK cell responses, are injected with fluorescent NK cells and DC activation is then induced by s.c. injection of Lipopolysaccharide (LPS). Using 4 dimensional tracking we follow the kinetic behavior of NK cells at the Draining Lymph-Node (DLN). As control, noninflammatory conditions are also evaluated. Our data suggest that NK cells are recruited to the DLN where they can interact with activated-DCs with a peculiar kinetic behavior: short lived interactions interleaved by rarer longer ones. We also found that the changes in the NK dynamic behavior in inflammatory conditions clearly affect relevant motility parameters such as the instantaneous and average velocity and the effective diffusion coefficient. This observation suggests that NK cells and activated-DCs might efficiently interact in the DLN, where cells could be activated. Therefore the interaction between activated-DCs and NK cells in DLN is not only a reality but it may be also crucial for the start of the immune response of the NKs.

Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

Science.gov (United States)

Ishola, I O; Chaturvedi, J P; Rai, S; Rajasekar, N; Adeyemi, O O; Shukla, R; Narender, T

2013-03-27

Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-α production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. Rat astrocytoma cells (C6) were stimulated with LPS (10μg/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3μg/ml) for 24h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-α level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test. LPS (10μg/ml) significantly (PTHP-1 cells. Amentoflavone (6.25-50mg/kg) significantly (Ptest. It produced time course significant (P<0.05) decrease in oedema formation in rodents. Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in neuroinflammation associated disorders. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Differential induction from X-irradiated human peripheral blood monocytes to dendritic cells

International Nuclear Information System (INIS)

Yoshino, Hironori; Takahashi, Kenji; Monzen, Satoru; Kashiwakura, Ikuo

2008-01-01

Dendritic cells (DCs) are a type of antigen-presenting cell which plays an essential role in the immune system. To clarify the influences of ionizing radiation on the differentiation to DCs, we focused on human peripheral blood monocytes and investigated whether X-irradiated monocytes can differentiate into DCs. The non-irradiated monocytes and 5 Gy-irradiated monocytes were induced into immature DCs (iDCs) and mature DCs (mDCs) with appropriate cytokine stimulation, and the induced cells from each monocyte expressed each DC-expressing surface antigen such as CD40, CD86 and HLA-DR. However, the expression levels of CD40 and CD86 on the iDCs derived from the 5 Gy-irradiated monocytes were higher than those of iDCs derived from non-irradiated monocytes. Furthermore, the mDCs derived from 5 Gy-irradiated monocytes had significantly less ability to stimulate allogeneic T cells in comparison to the mDCs derived from non-irradiated monocytes. There were no significant differences in the phagocytotic activity of the iDCs and cytokines detected in the supernatants conditioned by the DCs from the non-irradiated and irradiated monocytes. These results suggest that human monocytes which are exposed to ionizing radiation can thus differentiate into DCs, but there is a tendency that X-irradiation leads to an impairment of the function of DCs. (author)

Generation of blood-derived dendritic cells in dogs with oral malignant melanoma.

Science.gov (United States)

Catchpole, B; Stell, A J; Dobson, J M

2002-01-01

Advances in treatment of human melanoma indicate that immunotherapy, particularly dendritic cell (DC) immunization, may prove useful. The aim of this study was to investigate whether blood-derived DCs could be generated from canine melanoma patients. Peripheral blood mononuclear cells were isolated from three such dogs and cultured with recombinant canine granulocyte-macrophage colony stimulating factor (GM-CSF), canine interleukin 4 and human Flt3-ligand for 7 days. The resulting cells demonstrated a typical dendritic morphology, and were enriched for cells expressing CD1a, CD11c and MHC II by flow cytometric analysis. Thus, canine blood-derived DCs can be generated in vitro and DC immunization should be feasible in dogs. Copyright Harcourt Publishers Ltd.

RESONANT STEP-DOWN DC-DC POWER CONVERTERS

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to a resonant step-down 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...... 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......-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...

Atmel Microcontroller Based Soft Switched PWM ZVS Full Bridge DC to DC Converter

Directory of Open Access Journals (Sweden)

DEEPAK KUMAR NAYAK

2010-12-01

Full Text Available This paper deals with the simulation and implementation of soft switched PWM ZVS full bridge DC to DC converter. The 48V DC is efficiently reduced to 12V DC using a DC to DC converter. This converter has advantages like reduced switching losses, stresses and EMI. Input DC is converted into high frequency AC and it is stepped down to 12V level. Later it is rectified using a full wave rectifier. Laboratory model of microcontroller based DC to DC converter is fabricated and tested. The experimental results are compared with the simulation results.

Interaction of rotavirus with human peripheral blood mononuclear cells: plasmacytoid dendritic cells play a role in stimulating memory rotavirus specific T cells in vitro.

Science.gov (United States)

Mesa, Martha C; Rodríguez, Luz-Stella; Franco, Manuel A; Angel, Juana

2007-09-15

We studied the interaction of RV with human peripheral blood mononuclear cells (PBMC) from adult volunteers. After exposure of PBMC to rhesus RV (RRV), T and B lymphocytes, NK cells, monocytes, and myeloid and plasmacytoid dendritic cells expressed RV non-structural proteins, at variable levels. Expression of these RV proteins was abolished if infection was done in the presence of anti-VP7 neutralizing antibodies or 10% autologous serum. Supernatants of RRV exposed PBMC contained TNF-alpha, IL-6, IFN-alpha, IFN-gamma, IL-2 and IL-10. Plasmacytoid DC were found to be the main source of IFN-alpha production, and in their absence the production of IFN-gamma and the frequency of RV specific T cells that secrete IFN-gamma diminished. Finally, we could not detect RV-antigen associated with the PBMC or expression of RV non-structural proteins in PBMC of acutely RV-infected children. Thus, although PBMC are susceptible to the initial steps of RV infection, most PBMC of children with RV-gastroenteritis are not infected.

Quasi-Z-Source Half-Bridge DC-DC Converter for Photovoltaic Applications

OpenAIRE

Vinnikov, D; Chub, A; Husev, O; Zaķis, J

2015-01-01

This paper presents a novel quasi-Z-source halfbridge galvanically isolated DC-DC converter intended for the photovoltaic applications. The topology could be envisioned as an alternative to the boost half-bridge DC-DC converter but the benefit of its symmetric structure reduces the threat of transformer saturation due to the dc flux. The proposed converter features the continuous input current and could be used either with one or two input voltage sources.

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.

Frequency analysis of DC tolerant current transformers

International Nuclear Information System (INIS)

Mlejnek, P; Kaspar, P

2013-01-01

This article deals with wide frequency range behaviour of DC tolerant current transformers that are usually used in modern static energy meters. In this application current transformers must comply with European and International Standards in their accuracy and DC tolerance. Therefore, the linear DC tolerant current transformers and double core current transformers are used in this field. More details about the problems of these particular types of transformers can be found in our previous works. Although these transformers are designed mainly for power distribution network frequency (50/60 Hz), it can be interesting to understand their behaviour in wider frequency range. Based on this knowledge the new generations of energy meters with measuring quality of electric energy will be produced. This solution brings better measurement of consumption of nonlinear loads or measurement of non-sinusoidal voltage and current sources such as solar cells or fuel cells. The determination of actual power consumption in such energy meters is done using particular harmonics component of current and voltage. We measured the phase and ratio errors that are the most important parameters of current transformers, to characterize several samples of current transformers of both types

Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells

Science.gov (United States)

Reihl, Alec M.

2016-01-01

Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with multiple tissue manifestations. In this review, we summarize recent studies on the roles of conventional DC and plasmacytoid DC in the development of both murine lupus and human SLE. In the past decade, studies using selective DC depletions have demonstrated critical roles of DC in lupus progression. Comprehensive in vitro and in vivo studies suggest activation of DC by self-antigens in lupus pathogenesis, followed by breakdown of immune tolerance to self. Potential treatment strategies targeting DC have been developed. However, many questions remain regarding the mechanisms by which DC modulate lupus pathogenesis that require further investigations. PMID:27034965

Epstein Barr virus Latent Membrane Protein-1 enhances dendritic cell therapy lymph node migration, activation, and IL-12 secretion.

Directory of Open Access Journals (Sweden)

James M Termini

Full Text Available Dendritic cells (DC are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1 of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5 expressing LMP1 under the control of a Tet-inducible promoter. Ad5-LMP1 was found to mature and activate both human and mouse DC. LMP1 enhanced in vitro migration of DC toward CCL19, as well as in vivo migration of DC to the inguinal lymph nodes of mice following intradermal injection. LMP1-transduced DC increased T cell proliferation in a Pmel-1 adoptive transfer model and enhanced survival in B16-F10 melanoma models. LMP1-DC also enhanced protection in a vaccinia-Gag viral challenge assay. LMP1 induced high levels of IL-12p70 secretion in mouse DC when compared to standard maturation protocols. Importantly, LMP1-transduced human DC retained the capacity to secrete IL-12p70 and TNF in response to DC restimulation. In contrast, DC matured with Monocyte Conditioned Media-Mimic cocktail (Mimic were impaired in IL-12p70 secretion following restimulation. Overall, LMP1 matured and activated DC, induced migration to the lymph node, and generated high levels of IL-12p70 in a murine model. We propose LMP1 as a promising molecular adjuvant for DC vaccines.

Myrcia splendens (Sw. DC. (syn. M. fallax (Rich. DC. (Myrtaceae Essential Oil from Amazonian Ecuador: A Chemical Characterization and Bioactivity Profile

Directory of Open Access Journals (Sweden)

Laura Scalvenzi

2017-07-01

Full Text Available In this study, we performed the chemical characterization of Myrcia splendens (Sw. DC. (Myrtaceae essential oil from Amazonian Ecuador and the assessment of its bioactivity in terms of cytotoxic, antibacterial, and antioxidant activity as starting point for possible applicative uses. M. splendens essential oil, obtained by hydro-distillation, was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS and Gas Chromatography-Flame Ionization Detector (GC-FID: the major components were found to be trans-nerolidol (67.81% and α-bisabolol (17.51%. Furthermore, we assessed the cytotoxic activity against MCF-7 (breast, A549 (lung human tumor cell lines, and HaCaT (human keratinocytes non-tumor cell line through 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT test: promising results in terms of selectivity and efficacy against the MCF-7 cell line (IC50 of 5.59 ± 0.13 μg/mL at 48 h were obtained, mainly due to α-bisabolol. Furthermore, antibacterial activity against Gram positive and negative bacteria were performed through High Performance Thin Layer Chromatography (HPTLC bioautographic assay and microdilution method: trans-nerolidol and β-cedren-9-one were the main molecules responsible for the low antibacterial effects against human pathogens. Nevertheless, interesting values of Minimum Inhibitory Concentration (MIC were noticeable against phytopathogen strains. Radical scavenging activity performed by HPTLC bioautographic and spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH approaches were negligible. In conclusion, the essential oil revealed a good potential for plant defense and anti-cancer applications.

Mannosyl Glycodendritic Structure Inhibits DC-SIGN-Mediated Ebola Virus Infection in cis and in trans

OpenAIRE

Lasala, Fátima; Arce, Eva; Otero, Joaquín R.; Rojo, Javier; Delgado, Rafael

2003-01-01

We have designed a glycodendritic structure, BH30sucMan, that blocks the interaction between dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and Ebola virus (EBOV) envelope. BH30sucMan inhibits DC-SIGN-mediated EBOV infection at nanomolar concentrations. BH30sucMan may counteract important steps of the infective process of EBOV and, potentially, of microorganisms shown to exploit DC-SIGN for cell entry and infection.

Mannosyl Glycodendritic Structure Inhibits DC-SIGN-Mediated Ebola Virus Infection in cis and in trans

Science.gov (United States)

Lasala, Fátima; Arce, Eva; Otero, Joaquín R.; Rojo, Javier; Delgado, Rafael

2003-01-01

We have designed a glycodendritic structure, BH30sucMan, that blocks the interaction between dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and Ebola virus (EBOV) envelope. BH30sucMan inhibits DC-SIGN-mediated EBOV infection at nanomolar concentrations. BH30sucMan may counteract important steps of the infective process of EBOV and, potentially, of microorganisms shown to exploit DC-SIGN for cell entry and infection. PMID:14638512

The human cell atlas

DEFF Research Database (Denmark)

Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.

2017-01-01

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international...... collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells...... in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early...

Control of the DC-DC Converter used into Energy Generation System

International Nuclear Information System (INIS)

Bizon, Nicu; Oproescu, Mihai

2006-01-01

This paper presents an investigation of the DC-DC Converter controller used into Energy Generation System. The full bridge is used into an Energy Generation System (EGS) as second power interface between the energy source and the high DC bus. The simulation results show that the DC-DC Converter behavior can be improved using a well designed PI control surface. The used Simulink models for the EGS blocks and some design considerations are presented, too. (authors)

Langerin+ dermal dendritic cells are critical for CD8+ T cell activation and IgH γ-1 class switching in response to gene gun vaccines.

Science.gov (United States)

Stoecklinger, Angelika; Eticha, Tekalign D; Mesdaghi, Mehrnaz; Kissenpfennig, Adrien; Malissen, Bernard; Thalhamer, Josef; Hammerl, Peter

2011-02-01

The C-type lectin langerin/CD207 was originally discovered as a specific marker for epidermal Langerhans cells (LC). Recently, additional and distinct subsets of langerin(+) dendritic cells (DC) have been identified in lymph nodes and peripheral tissues of mice. Although the role of LC for immune activation or modulation is now being discussed controversially, other langerin(+) DC appear crucial for protective immunity in a growing set of infection and vaccination models. In knock-in mice that express the human diphtheria toxin receptor under control of the langerin promoter, injection of diphtheria toxin ablates LC for several weeks whereas other langerin(+) DC subsets are replenished within just a few days. Thus, by careful timing of diphtheria toxin injections selective states of deficiency in either LC only or all langerin(+) cells can be established. Taking advantage of this system, we found that, unlike selective LC deficiency, ablation of all langerin(+) DC abrogated the activation of IFN-γ-producing and cytolytic CD8(+) T cells after gene gun vaccination. Moreover, we identified migratory langerin(+) dermal DC as the subset that directly activated CD8(+) T cells in lymph nodes. Langerin(+) DC were also critical for IgG1 but not IgG2a Ab induction, suggesting differential polarization of CD4(+) T helper cells by langerin(+) or langerin-negative DC, respectively. In contrast, protein vaccines administered with various adjuvants induced IgG1 independently of langerin(+) DC. Taken together, these findings reflect a highly specialized division of labor between different DC subsets both with respect to Ag encounter as well as downstream processes of immune activation.

Multiphase soft switched DC/DC converter and active control technique for fuel cell ripple current elimination

Science.gov (United States)

Lai, Jih-Sheng; Liu, Changrong; Ridenour, Amy

2009-04-14

DC/DC converter has a transformer having primary coils connected to an input side and secondary coils connected to an output side. Each primary coil connects a full-bridge circuit comprising two switches on two legs, the primary coil being connected between the switches on each leg, each full-bridge circuit being connected in parallel wherein each leg is disposed parallel to one another, and the secondary coils connected to a rectifying circuit. An outer loop control circuit that reduces ripple in a voltage reference has a first resistor connected in series with a second resistor connected in series with a first capacitor which are connected in parallel with a second capacitor. An inner loop control circuit that reduces ripple in a current reference has a third resistor connected in series with a fourth resistor connected in series with a third capacitor which are connected in parallel with a fourth capacitor.

Electric response of an electrolytic cell to a periodic excitation in the dc limit

International Nuclear Information System (INIS)

Alexe-Ionescu, A.L.; Barbero, G.; Duarte, A.R.; Saracco, G.

2014-01-01

We evaluate the electrical impedance of an electrolytic cell submitted to a low frequency external voltage. We show that in the limit where the circular frequency of the applied voltage, ω, is small with respect to Debye relaxation circular frequency, ω D , the response of the cell can be evaluated by means of a perturbational calculation, where the expansion parameter is x=ω/ω D . Simple expressions for the reactance and resistance in the dc limit of the electrolytic cell are obtained in the case where the electrodes are blocking and the diffusion coefficients of the negative and positive ions are equal. The case where the diffusion coefficients are different is also considered. In this framework, our analysis indicates that in the considered frequency range the effective diffusion coefficient coincides with the ambipolar diffusion coefficient. A possible extension of our approach to the case where the electrodes are not blocking is discussed too.

New non-linear control strategy for non-isolated DC/DC converter with high voltage ratio

Energy Technology Data Exchange (ETDEWEB)

Shahin, A.; Huang, B.; Martin, J.P.; Pierfederici, S.; Davat, B. [Groupe de Recherche en Electronique et en Electrotechnique de Nancy - INPL - Nancy Universite, 2, Avenue de la Foret de Haye, 54516 Vandoeuvre-les-Nancy Cedex (France)

2010-01-15

In this paper, a non-isolated DC/DC converter with high voltage ratio is proposed to allow the interface between a low voltage power source like fuel cell and a high voltage DC bus. To take into account the low voltage-high density characteristics of power sources, a cascaded structure composed of two sub-converters has been chosen and allows obtaining a high voltage ratio. The choice of each sub-converter is based on the requirements of the source and its performances. Consequently, we have chosen a three-interleaved boost converter as the 1st sub-converter whereas the 2nd sub-converter is a three-level boost converter. The control of the whole system is realized thanks to energetic trajectories planning based on flatness properties of the system. The control of both the current and the balance of voltage across the output serial capacitors of the three-level boost converter is ensured by non-linear controllers based on a new non-linear model. Experimental results allow validating the proposed power architecture and its associated control. (author)

New non-linear control strategy for non-isolated DC/DC converter with high voltage ratio

International Nuclear Information System (INIS)

Shahin, A.; Huang, B.; Martin, J.P.; Pierfederici, S.; Davat, B.

2010-01-01

In this paper, a non-isolated DC/DC converter with high voltage ratio is proposed to allow the interface between a low voltage power source like fuel cell and a high voltage DC bus. To take into account the low voltage-high density characteristics of power sources, a cascaded structure composed of two sub-converters has been chosen and allows obtaining a high voltage ratio. The choice of each sub-converter is based on the requirements of the source and its performances. Consequently, we have chosen a three-interleaved boost converter as the 1st sub-converter whereas the 2nd sub-converter is a three-level boost converter. The control of the whole system is realized thanks to energetic trajectories planning based on flatness properties of the system. The control of both the current and the balance of voltage across the output serial capacitors of the three-level boost converter is ensured by non-linear controllers based on a new non-linear model. Experimental results allow validating the proposed power architecture and its associated control.

Investigation of silicon heterojunction solar cells by photoluminescence under DC-bias

Directory of Open Access Journals (Sweden)

Courtois Guillaume

2013-09-01

Full Text Available Photoluminescence measurements on solar cells are usually carried out under open-circuit conditions. We report here on an innovative approach, in which the samples are simultaneously illuminated and DC-biased, so that the luminescence can be monitored under several operating points, that is to say several injection levels, ranging from short-circuit conditions to the light-emitting regime of the device. The experiments were performed on in-house made c-Si/a-Si:H heterojunction solar cells illuminated by a continuous green laser diode and positively biased. The luminescence spectra obtained this way were compared to those obtained with no light excitation source, which corresponds to usual electroluminescence mode and dark J(V. Firstly, the obtained luminescence spectra have shown the expected exponential dependence on the applied voltage. Furthermore, given that the amplitude of the emitted luminescence is proportional to the radiative recombination rate, this approach enables to indirectly characterise the non-radiative recombination phenomena. In the case of HJ solar cells with intrinsic thin layers processed on high quality FZ-wafers, non-radiative recombination is dominated by the defects at the c-Si/a-Si:H interface. The luminescence measurements presented here therefore give information on the quality of the surface passivation. An estimation of the interface defect density was achieved by comparing our experimental results with modelling.

Antigen Presenting Cells and Stromal Cells Trigger Human Natural Killer Lymphocytes to Autoreactivity: Evidence for the Involvement of Natural Cytotoxicity Receptors (NCR and NKG2D

Directory of Open Access Journals (Sweden)

Alessandro Poggi

2006-01-01

Full Text Available Human natural killer (NK lymphocytes should not damage autologous cells due to the engagement of inhibitory receptor superfamily (IRS members by HLA-I. Nevertheless, NK cells kill self cells expressing low levels or lacking HLA-I, as it may occur during viral infections (missing-self hypothesis. Herein, we show that human NK cells can be activated upon binding with self antigen presenting cells or stromal cells despite the expression of HLA-I. Indeed, NK cells can kill and produce pro-inflammatory and regulating cytokines as IFN-γ, TNF-α and IL10 during interaction with autologous dendritic cells or bone marrow stromal cells or skin fibroblasts. The killing of antigen presenting and stromal cells is dependent on LFA1/ICAM1 interaction. Further, the natural cytotoxicity receptors (NCR NKp30 and NKp46 are responsible for the delivery of lethal hit to DC, whereas NKG2D activating receptor, the ligand of the MHC-related molecule MIC-A and the UL16 binding protein, is involved in stromal cell killing. These findings indicate that different activating receptors are involved in cell to self cell interaction. Finally, NK cells can revert the veto effect of stromal cells on mixed lymphocyte reaction further supporting the idea that NK cells may alter the interaction between T lymphocytes and microenvironment leading to autoreactivity.

Novel composite resonance DC-DC converter with voltage doubler rectifier

OpenAIRE

Kato, Hisatsugu; Matsuo, Hirohumi; Eguchi, Masaki; Sakamoto, Yukitaka; Nakaishi, Masaki

2009-01-01

This paper deals with a novel composite resonance DC-DC converter with the voltage doubler rectifier, which is developed to be applied to the power conditioner of the photovoltaic generation system. The proposed DC-DC converter has the current and voltage resonance functions. Therefore, the output voltage regulation can be achieved for the large variations of the input voltage and load. Also, this converter has the high power efficiency. The maximum power efficiency 96.1% can be realized.

Ultra-high Efficiency DC-DC Converter using GaN Devices

DEFF Research Database (Denmark)

Ramachandran, Rakesh

2016-01-01

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...... for many decades. However, the rate of improvement slowed as the silicon power materials asymptotically approached its theoretical bounds. Compared to Si, wideband gap materials such as Silicon Carbide (SiC) and Gallium Nitride (GaN) are promising semiconductors for power devices due to their superior...... in this thesis. Efficiency measurements from the hardware prototype of both the topologies are also presented in this thesis. Finally, the bidirectional operation of an optimized isolated dc-dc converter is presented. The optimized converter has achieved an ultra-high efficiency of 98.8% in both directions...

Cysticerci Drive Dendritic Cells to Promote In Vitro and In Vivo Tregs Differentiation

Directory of Open Access Journals (Sweden)

Laura Adalid-Peralta

2013-01-01

Full Text Available Regulatory T cells (Tregs play a crucial role in immune homeostasis. Treg induction is a strategy that parasites have evolved to modulate the host’s inflammatory environment, facilitating their establishment and permanence. In human Taenia solium neurocysticercosis (NC, the concurrence of increased peripheral and central Treg levels and their capacity to inhibit T cell activation and proliferation support their role in controlling neuroinflammation. This study is aimed at identifing possible mechanisms of Treg induction in human NC. Monocyte-derived dendritic cells (DC from healthy human donors, cocultivated with autologous CD4+ naïve cells either in the presence or absence of cysticerci, promoted CD25highFoxp3+ Treg differentiation. An increased Treg induction was observed when cysticerci were present. Moreover, an augmentation of suppressive-related molecules (SLAMF1, B7-H1, and CD205 was found in parasite-induced DC differentiation. Increased Tregs and a higher in vivo DC expression of the regulatory molecules SLAMF1 and CD205 in NC patients were also found. SLAMF1 gene was downregulated in NC patients with extraparenchymal cysticerci, exhibiting higher inflammation levels than patients with parenchymal parasites. Our findings suggest that cysticerci may modulate DC to favor a suppressive environment, which may help parasite establishment, minimizing the excessive inflammation, which may lead to tissue damage.

T cell reactivity with allergoids: influence of the type of APC.

Science.gov (United States)

Kahlert, H; Grage-Griebenow, E; Stüwe, H T; Cromwell, O; Fiebig, H

2000-08-15

The use of allergoids for allergen-specific immunotherapy has been established for many years. The characteristic features of these chemically modified allergens are their strongly reduced IgE binding activity compared with the native form and the retained immunogenicity. T cell reactivity of chemically modified allergens is documented in animals, but in humans indirect evidence of reactivity has been concluded from the induction of allergen-specific IgG during immunotherapy. Direct evidence of T cell reactivity was obtained recently using isolated human T cells. To obtain further insight into the mechanism of action of allergoids, we compared the Ag-presenting capacity of different APC types, including DC and macrophages, generated from CD14+ precursor cells from the blood of grass pollen allergic subjects, autologous PBMC, and B cells. These APC were used in experiments together with Phl p 5-specific T cell clones under stimulation with grass pollen allergen extract, rPhl p 5b, and the respective allergoids. Using DC and macrophages, allergoids exhibited a pronounced and reproducible T cell-stimulating capacity. Responses were superior to those with PBMC, and isolated B cells failed to present allergoids. Considerable IL-12 production was observed only when using the DC for Ag presentation of both allergens and allergoids. The amount of IL-10 in supernatants was dependent on the phenotype of the respective T cell clone. High IL-10 production was associated with suppressed IL-12 production from the DC in most cases. In conclusion, the reactivity of Th cells with allergoids is dependent on the type of the APC.

Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection▿

OpenAIRE