WorldWideScience

Sample records for efficient phagocytosis requires

  1. The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape

    Directory of Open Access Journals (Sweden)

    Dart Anna E

    2010-11-01

    Full Text Available Abstract Background Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood. Results Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcγRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes. Conclusions This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.

  2. Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6.

    Science.gov (United States)

    Hall, M O; Prieto, A L; Obin, M S; Abrams, T A; Burgess, B L; Heeb, M J; Agnew, B J

    2001-10-01

    The function and viability of vertebrate photoreceptors requires the daily phagocytosis of photoreceptor outer segments (OS) by the adjacent retinal pigment epithelium (RPE). We demonstrate here a critical role in this process for Gas6 and by implication one of its receptor protein tyrosine kinases (RTKs), Mertk (Mer). Gas6 specifically and selectively stimulates the phagocytosis of OS by normal cultured rat RPE cells. The magnitude of the response is dose-dependent and shows an absolute requirement for calcium. By contrast the Royal College of Surgeons (RCS) rat RPE cells, in which a mutation in the gene Mertk results in the expression of a truncated, non-functional receptor, does not respond to Gas6. These data strongly suggest that activation of Mertk by its ligand, Gas6, is the specific signaling pathway responsible for initiating the ingestion of shed OS. Moreover, photoreceptor degeneration in the RCS rat retina, which lacks Mertk, and in humans with a mutation in Mertk, strongly suggests that the Gas6/Mertk signaling pathway is essential for photoreceptor viability. We believe that this is the first demonstration of a specific function for Gas6 in the eye. Copyright 2001 Academic Press.

  3. Depression of efficiency of neutrophils for Candida albicans phagocytosis in personnel working in radiation field

    International Nuclear Information System (INIS)

    Hassan, A.A.

    2000-01-01

    The neutrophil functions, chemotaxis (direct and random migration), phagocytosis using Candida albicans (percent, index), phagocytosis by NBT (percent, score) and adherence were studied on 55 persons working in radiation field (group I) and 40 persons as control (group II). The effect of radiation on blood picture of persons working in this field with special references to leucocytic counts and neutrophil functions was studied. White and red cells counts were 6.275 +- 1.723 and 5.475 +- 1.039 (group I) and 6.440 +- 1.556, 4.704 +- 0.734 for group II, respectively with no significant difference, while in neutrophil function there was a statistically significant difference in all functions between two groups (P < 0.01). This indicates the importance of neutrophil functions in following up persons working in radiation field

  4. ITAM-like signalling for efficient phagocytosis : The paradigm of the granulocyte receptor CEACAM3

    OpenAIRE

    Pils, Stefan

    2010-01-01

    Human CEACAM3 is a tailor-made receptor of the innate immune system to fight pathogens exploiting epithelial CEACAM-family members for colonisation and invasion of their host. Previous studies established CEACAM3 as the receptor facilitating rapid phagocytosis and elimination of N. gonorrhoeae by human granulocytes. The studies reported here set out to shed light on the evolution of this highly specialised receptor and the associated signalling machinery.CEACAM3 arose from exon shuffling afte...

  5. Activation-Inactivation Cycling of Rab35 and ARF6 Is Required for Phagocytosis of Zymosan in RAW264 Macrophages

    Directory of Open Access Journals (Sweden)

    Youhei Egami

    2015-01-01

    Full Text Available Phagocytosis of zymosan by phagocytes is a widely used model of microbial recognition by the innate immune system. Live-cell imaging showed that fluorescent protein-fused Rab35 accumulated in the membranes of phagocytic cups and then dissociated from the membranes of newly formed phagosomes. By our novel pull-down assay for Rab35 activity, we found that Rab35 is deactivated immediately after zymosan internalization into the cells. Phagosome formation was inhibited in cells expressing the GDP- or GTP-locked Rab35 mutant. Moreover, the simultaneous expression of ACAP2—a Rab35 effector protein—with GTP-locked Rab35 or the expression of plasma membrane-targeted ACAP2 showed a marked inhibitory effect on phagocytosis through ARF6 inactivation by the GAP activity of ACAP2. ARF6, a substrate for ACAP2, was also localized on the phagocytic cups and dissociated from the membranes of internalized phagosomes. In support of the microscopic observations, ARF6-GTP pull-down experiments showed that ARF6 is transiently activated during phagosome formation. Furthermore, the expression of GDP- or GTP-locked ARF6 mutants also suppresses the uptake of zymosan. These data suggest that the activation-inactivation cycles of Rab35 and ARF6 are required for the uptake of zymosan and that ACAP2 is an important component that links Rab35/ARF6 signaling during phagocytosis of zymosan.

  6. Stimulation of phagocytosis by sulforaphane

    International Nuclear Information System (INIS)

    Suganuma, Hiroyuki; Fahey, Jed W.; Bryan, Kelley E.; Healy, Zachary R.; Talalay, Paul

    2011-01-01

    Research highlights: → Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. → This effect does not require Nrf2-dependent induction of phase 2 genes. → Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-μm diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2 -/- mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

  7. Stimulation of phagocytosis by sulforaphane

    Energy Technology Data Exchange (ETDEWEB)

    Suganuma, Hiroyuki, E-mail: hsuganu1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Fahey, Jed W., E-mail: jfahey@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Bryan, Kelley E., E-mail: kbryanm1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Healy, Zachary R., E-mail: zhealy1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Talalay, Paul, E-mail: ptalalay@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States)

    2011-02-04

    Research highlights: {yields} Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. {yields} This effect does not require Nrf2-dependent induction of phase 2 genes. {yields} Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-{mu}m diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2{sup -/-} mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

  8. Syk-dependent tyrosine phosphorylation of 3BP2 is required for optimal FcRγ-mediated phagocytosis and chemokine expression in U937 cells.

    Science.gov (United States)

    Chihara, Kazuyasu; Kato, Yuji; Yoshiki, Hatsumi; Takeuchi, Kenji; Fujieda, Shigeharu; Sada, Kiyonao

    2017-09-13

    The adaptor protein c-Abl SH3 domain binding protein-2 (3BP2) is tyrosine phosphorylated by Syk in response to cross-linking of antigen receptors, which in turn activates various immune responses. Recently, a study using the mouse model of cherubism, a dominant inherited disorder caused by mutations in the gene encoding 3BP2, showed that 3BP2 is involved in the regulation of phagocytosis mediated by Fc receptor for IgG (FcγR) in macrophages. However, the molecular mechanisms underlying 3BP2-mediated regulation of phagocytosis and the physiological relevance of 3BP2 tyrosine phosphorylation remains elusive. In this study, we established various gene knockout U937 cell lines using the CRISPR/Cas9 system and found that 3BP2 is rapidly tyrosine phosphorylated by Syk in response to cross-linking of FcγRI. Depletion of 3BP2 caused significant reduction in the Fc receptor γ chain (FcRγ)-mediated phagocytosis in addition to the FcγRI-mediated induction of chemokine mRNA for IL-8, CCL3L3 and CCL4L2. Syk-dependent tyrosine phosphorylation of 3BP2 was required for overcoming these defects. Finally, we found that the PH and SH2 domains play important roles on FcγRI-mediated tyrosine phosphorylation of 3BP2 in HL-60 cells. Taken together, these results indicate that Syk-dependent tyrosine phosphorylation of 3BP2 is required for optimal FcRγ-mediated phagocytosis and chemokine expression.

  9. Commensal Bacteria-Induced Inflammasome Activation in Mouse and Human Macrophages Is Dependent on Potassium Efflux but Does Not Require Phagocytosis or Bacterial Viability.

    Directory of Open Access Journals (Sweden)

    Kejie Chen

    Full Text Available Gut commensal bacteria contribute to the pathogenesis of inflammatory bowel disease, in part by activating the inflammasome and inducing secretion of interleukin-1ß (IL-1ß. Although much has been learned about inflammasome activation by bacterial pathogens, little is known about how commensals carry out this process. Accordingly, we investigated the mechanism of inflammasome activation by representative commensal bacteria, the Gram-positive Bifidobacterium longum subspecies infantis and the Gram-negative Bacteroides fragilis. B. infantis and B. fragilis induced IL-1ß secretion by primary mouse bone marrow-derived macrophages after overnight incubation. IL-1ß secretion also occurred in response to heat-killed bacteria and was only partly reduced when phagocytosis was inhibited with cytochalasin D. Similar results were obtained with a wild-type immortalized mouse macrophage cell line but neither B. infantis nor B. fragilis induced IL-1ß secretion in a mouse macrophage line lacking the nucleotide-binding/leucine-rich repeat pyrin domain containing 3 (NLRP3 inflammasome. IL-1ß secretion in response to B. infantis and B. fragilis was significantly reduced when the wild-type macrophage line was treated with inhibitors of potassium efflux, either increased extracellular potassium concentrations or the channel blocker ruthenium red. Both live and heat-killed B. infantis and B. fragilis also induced IL-1ß secretion by human macrophages (differentiated THP-1 cells or primary monocyte-derived macrophages after 4 hours of infection, and the secretion was inhibited by raised extracellular potassium and ruthenium red but not by cytochalasin D. Taken together, our findings indicate that the commensal bacteria B. infantis and B. fragilis activate the NLRP3 inflammasome in both mouse and human macrophages by a mechanism that involves potassium efflux and that does not require bacterial viability or phagocytosis.

  10. Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages.

    Science.gov (United States)

    Kim, Jun Sub; Kim, Jae Gyu; Jeon, Chan Young; Won, Ha Young; Moon, Mi Young; Seo, Ji Yeon; Kim, Jong Il; Kim, Jaebong; Lee, Jae Yong; Choi, Soo Young; Park, Jinseu; Yoon Park, Jung Han; Ha, Kwon Soo; Kim, Pyeung Hyeun; Park, Jae Bong

    2005-12-31

    Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase. Tat-C3 blocked superoxide production, suggesting that RhoA is essentially involved in superoxide formation during phagocytosis of SOZ. Conversely SOZ activated both RhoA and Rac1/2. Inhibition of RhoA-activated kinase (ROCK), an important downstream effector of RhoA, by Y27632 and myosin light chain kinase (MLCK) by ML-7 abrogated superoxide production by SOZ. Extracellular signaling-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were activated during phagocytosis of SOZ, and Tat-C3 and SB203580 reduced ERK1/2 and p38 MAPK activation, suggesting that RhoA and p38 MAPK may be upstream regulators of ERK1/2. Inhibition of ERK1/2, p38 MAPK, phosphatidyl inositol 3-kinase did not block translocation of RhoA to membranes, suggesting that RhoA is upstream to these kinases. Inhibition of RhoA by Tat-C3 blocked phosphorylation of p47(PHOX). Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47(PHOX) may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide.

  11. Effects of microparticle size and Fc density on macrophage phagocytosis.

    Directory of Open Access Journals (Sweden)

    Patricia Pacheco

    Full Text Available Controlled induction of phagocytosis in macrophages offers the ability to therapeutically regulate the immune system as well as improve delivery of chemicals or biologicals for immune processing. Maximizing particle uptake by macrophages through Fc receptor-mediated phagocytosis could lead to new delivery mechanisms in drug or vaccine development. Fc ligand density and particle size were examined independently and in combination in order to optimize and tune the phagocytosis of opsonized microparticles. We show the internalization efficiency of small polystyrene particles (0.5 µm to 2 µm is significantly affected by changes in Fc ligand density, while particles greater than 2 µm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population. This study is the first to treat as independent variables the physical and biological properties of Fc density and microparticle size that initiate macrophage phagocytosis. Defining the physical and biological parameters that affect phagocytosis efficiency will lead to improved methods of microparticle delivery to macrophages.

  12. Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

    Directory of Open Access Journals (Sweden)

    Fikadu G Tafesse

    2015-10-01

    Full Text Available The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

  13. Teaching Phagocytosis Using Flow Cytometry

    Directory of Open Access Journals (Sweden)

    John Boothby

    2009-12-01

    Full Text Available Investigative microbiology on protists in a basic teaching laboratory environment is limited by student skill level, ease of microbial culture and manipulation, instrumentation, and time. The flow cytometer is gaining use as a mainstream instrument in research and clinical laboratories, but has had minimal application in teaching laboratories. Although the cost of a flow cytometer is currently prohibitive for many microbiology teaching environments and the number of trained instructors and teaching materials is limited, in many ways the flow cytometer is an ideal instrument for teaching basic microbiology. We report here on a laboratory module to study phagocytosis in Tetrahymena sp. using flow cytometry in a basic microbiology teaching laboratory. Students and instructors found the flow cytometry data analysis program, Paint-A-GatePRO-TM, to be very intuitive and easy to learn within a short period of time. Assessment of student learning about Tetrahymena sp., phagocytosis, flow cytometry, and investigative microbiology using an inquiry-based format demonstrated an overall positive response from students.

  14. CEACAM3-mediated phagocytosis of human-specific bacterial pathogens involves the adaptor molecule Nck

    OpenAIRE

    Peterson, Lisa

    2010-01-01

    Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are exploited by human-specific pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella and Haemophilus species. As opsonin-independent phagocytosis of CEACAM-binding Neisseria depends on Src-family protein tyrosine kinase (PTK) phosphorylation of the CEACAM3 ...

  15. CD14(hi)CD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so.

    Science.gov (United States)

    Zhou, Jingling; Feng, Gaoqian; Beeson, James; Hogarth, P Mark; Rogerson, Stephen J; Yan, Yan; Jaworowski, Anthony

    2015-07-07

    With more than 600,000 deaths from malaria, mainly of children under five years old and caused by infection with Plasmodium falciparum, comes an urgent need for an effective anti-malaria vaccine. Limited details on the mechanisms of protective immunity are a barrier to vaccine development. Antibodies play an important role in immunity to malaria and monocytes are key effectors in antibody-mediated protection by phagocytosing antibody-opsonised infected erythrocytes (IE). Eliciting antibodies that enhance phagocytosis of IE is therefore an important potential component of an effective vaccine, requiring robust assays to determine the ability of elicited antibodies to stimulate this in vivo. The mechanisms by which monocytes ingest IE and the nature of the monocytes which do so are unknown. Purified trophozoite-stage P. falciparum IE were stained with ethidium bromide, opsonised with anti-erythrocyte antibodies and incubated with fresh whole blood. Phagocytosis of IE and TNF production by individual monocyte subsets was measured by flow cytometry. Ingestion of IE was confirmed by imaging flow cytometry. CD14(hi)CD16+ monocytes phagocytosed antibody-opsonised IE and produced TNF more efficiently than CD14(hi)CD16- and CD14(lo)CD16+ monocytes. Blocking experiments showed that Fcγ receptor IIIa (CD16) but not Fcγ receptor IIa (CD32a) or Fcγ receptor I (CD64) was necessary for phagocytosis. CD14(hi)CD16+ monocytes ingested antibody-opsonised IE when peripheral blood mononuclear cells were reconstituted with autologous serum but not heat-inactivated autologous serum. Antibody-opsonised IE were rapidly opsonised with complement component C3 in serum (t1/2 = 2-3 minutes) and phagocytosis of antibody-opsonised IE was inhibited in a dose-dependent manner by an inhibitor of C3 activation, compstatin. Compared to other monocyte subsets, CD14(hi)CD16+ monocytes expressed the highest levels of complement receptor 4 (CD11c) and activated complement receptor 3 (CD11b) subunits

  16. Integrins and small GTPases as modulators of phagocytosis.

    Science.gov (United States)

    Sayedyahossein, Samar; Dagnino, Lina

    2013-01-01

    Phagocytosis is the mechanism whereby cells engulf large particles. This process has long been recognized as a critical component of the innate immune response, which constitutes the organism's defense against microorganisms. In addition, phagocytic internalization of apoptotic cells or cell fragments plays important roles in tissue homeostasis and remodeling. Phagocytosis requires target interactions with receptors on the plasma membrane of the phagocytic cell. Integrins have been identified as important mediators of particle clearance, in addition to their well-established roles in cell adhesion, migration and mechanotransduction. Indeed, these ubiquitously expressed proteins impart phagocytic capacity to epithelial, endothelial and mesenchymal cell types. The importance of integrins in particle internalization is emphasized by the ability of microbial and viral pathogens to exploit their signaling pathways to invade host cells, and by the wide variety of disorders that arise from abnormalities in integrin-dependent phagocytic uptake. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Rapamycin-based inducible translocation systems for studying phagocytosis.

    Science.gov (United States)

    Bohdanowicz, Michal; Fairn, Gregory D

    2011-01-01

    Phagocytosis is an immune receptor-mediated process whereby cells engulf large particles. The process is dynamic and requires several localized factors acting in concert with and sequentially after the engagement of immune receptors to envelope the particle. Once the particle is internalized, the nascent -phagosome undergoes a series of events leading to its maturation to the microbicidal phagolysosome. Investigating these dynamic and temporally controlled series of events in live cells requires noninvasive methods. The ability to rapidly recruit the proteins of interest to the sites of phagocytosis or to nascent phagosomes would help dissect the regulatory mechanisms involved during phagocytosis. Here, we describe a general approach to express in RAW264.7 murine macrophages, a genetically encoded rapamycin--induced heterodimerization system. In the presence of rapamycin, tight association between FK506-binding protein (FKBP) and FKBP rapamycin-binding protein (FRB) is observed. Based on this principle, a synthetic system consisting of a targeting domain attached to FKBP can recruit a protein of interest fused to FRB upon the addition of rapamycin. Previously, this technique has been used to target lipid-modifying enzymes and small GTPases to the phagosome or plasma membrane. The recruitment of the FRB module can be monitored by fluorescent microscopy if a fluorescent protein is fused to the FRB sequence. While the focus of this chapter is on phagocytic events, this method can be employed to study any organelle of interest when the appropriate targeting sequence is used.

  18. Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target

    Science.gov (United States)

    Beningo, Karen A.; Wang, Yu-li

    2002-01-01

    Phagocytosis is an actin-based process used by macrophages to clear particles greater than 0.5 microm in diameter. In addition to its role in immunological responses, phagocytosis is also necessary for tissue remodeling and repair. To prevent catastrophic autoimmune reactions, phagocytosis must be tightly regulated. It is commonly assumed that the recognition/selection of phagocytic targets is based solely upon receptor-ligand binding. Here we report an important new criterion, that mechanical parameters of the target can dramatically affect the efficiency of phagocytosis. When presented with particles of identical chemical properties but different rigidity, macrophages showed a strong preference to engulf rigid objects. Furthermore, phagocytosis of soft particles can be stimulated with the microinjection of constitutively active Rac1 but not RhoA, and with lysophosphatidic acid, an agent known to activate the small GTP-binding proteins of the Rho family. These data suggest a Rac1-dependent mechanosensory mechanism for phagocytosis, which probably plays an important role in a number of physiological and pathological processes from embryonic development to autoimmune diseases.

  19. Interaction between Mitochondrial Reactive Oxygen Species, Heme Oxygenase, and Nitric Oxide Synthase Stimulates Phagocytosis in Macrophages

    Directory of Open Access Journals (Sweden)

    Andrea Müllebner

    2018-01-01

    Full Text Available BackgroundMacrophages are cells of the innate immune system that populate every organ. They are required not only for defense against invading pathogens and tissue repair but also for maintenance of tissue homeostasis and iron homeostasis.AimThe aim of this study is to understand whether heme oxygenase (HO and nitric oxide synthase (NOS contribute to the regulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX activity and phagocytosis, two key components of macrophage function.MethodsThis study was carried out using resting J774A.1 macrophages treated with hemin or vehicle. Activity of NOS, HO, or NOX was inhibited using specific inhibitors. Reactive oxygen species (ROS formation was determined by Amplex® red assay, and phagocytosis was measured using fluorescein isothiocyanate-labeled bacteria. In addition, we analyzed the fate of the intracellular heme by using electron spin resonance.ResultsWe show that both enzymes NOS and HO are essential for phagocytic activity of macrophages. NOS does not directly affect phagocytosis, but stimulates NOX activity via nitric oxide-triggered ROS production of mitochondria. Treatment of macrophages with hemin results in intracellular accumulation of ferrous heme and an inhibition of phagocytosis. In contrast to NOS, HO products, including carbon monoxide, neither clearly affect NOX activity nor clearly affect phagocytosis, but phagocytosis is accelerated by HO-mediated degradation of heme.ConclusionBoth enzymes contribute to the bactericidal activity of macrophages independently, by controlling different pathways.

  20. Army Materiel Requirements Documents: Qualitative Analysis of Efficiency and Effectiveness

    Science.gov (United States)

    2013-06-01

    focuses on the program’s time to execute their mission based off the MRDs/MCDs. We measure efficiency based on two BPP initiatives: (1) Build...definitions of each BPP initiative during our interviews. A poor rating indicates the requirement documents did not sufficiently support the program...in terms of efficiency and effectiveness according to BPP initiatives. For efficiency, we assign a qualitative measure based on SME responses across

  1. Phagocytosis in phosphate chromium (III) suspensions

    International Nuclear Information System (INIS)

    Cruz-Arencibia, Jorge; Fano Machín, Yoiz; Cruz-Morales, Ahmed; Tamayo Fuente, Radamés; Morín-Zorrilla, José

    2015-01-01

    Phagocytosis in vivo and in vitro of a suspension of chromic phosphate (III) labeled with 51 Cr and 32 P is studied. The radioactive particles dispersed in a media of 2 % gelatin in acetate buffer pH 4-4.5 have a predominant size of 0.8 μm and 5 μm. According with biodistribution experiments in rats after 30 minutes near the 80 % of radioactivity is registered in the liver, probably associated with phagocytosis of the particles by liver Kupffer cells. Is also showed that the suspension particles are phagocytized in vitro by mouse peritoneal macrophages. This facts indicate that the studied suspension have appropriate characteristics to be used in radiosynoviorthesis according to the principal action mechanism described for this procedure, particles phagocytosis by cells present in the inflamed synovium. (author)

  2. Autophagy and phagocytosis converge for better vision.

    Science.gov (United States)

    Ferguson, Thomas A; Green, Douglas R

    2014-01-01

    The retinal pigment epithelium (RPE) is a single layer of nonregenerating cells essential to homeostasis in the retina and the preservation of vision. While the RPE perform a number of important functions, 2 essential processes are phagocytosis, which removes the most distal tips of the photoreceptors to support disk renewal, and the visual cycle, which maintains the supply of chromophore for regeneration of photo-bleached visual pigments. We recently reported that these processes are linked by a noncanonical form of autophagy termed LC3-associated phagocytosis (LAP) in which components of the autophagy pathway are co-opted by phagocytosis to recover vitamin A in support of optimal vision. Here we summarize these findings.

  3. Determination of phagocytosis in periodontitis postjuvenilis using 14C

    International Nuclear Information System (INIS)

    Zietek, M.

    1990-01-01

    In 20 patients with periodontitis and 10 healthy controls phagocytosis was determined using 14 C-labelled Staphylococcus aureus. The decrease of phagocytosis found in the diseased patients was significant

  4. Rat Neutrophil Phagocytosis Following Feed Restriction

    Czech Academy of Sciences Publication Activity Database

    Slapničková, Martina; Berger, J.

    2002-01-01

    Roč. 11, č. 3 (2002), s. 172-177 ISSN 0938-7714 Institutional research plan: CEZ:AV0Z5052915 Keywords : circulating neutrophil * diet restriction * phagocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.167, year: 2001

  5. Neisseria meningitidis and Escherichia coli are protected from leukocyte phagocytosis by binding to erythrocyte complement receptor 1 in human blood

    DEFF Research Database (Denmark)

    Brekke, O. L.; Hellerud, B. C.; Christiansen, D.

    2011-01-01

    The initial interaction of Gram-negative bacteria with erythrocytes and its implications on leukocyte phagocytosis and oxidative burst in human whole blood were examined. Alexa-labeled Escherichia coli, wild-type H44/76 N. meningitidis and the H44/76lpxA lipopolysaccharide (LPS)-deficient mutant...... antagonist (C5aRa) and a complement receptor 1 (CR1)-blocking antibody (3D9) were examined. Most bacteria (80%) immediately bound to erythrocytes. The binding gradually declined over time, with a parallel increase in phagocytosis. Complement inhibition with compstatin reduced erythrocyte binding...... and bacterial C3 opsonization. In contrast, the C5aRa efficiently reduced phagocytosis, but did not affect the binding of bacteria to erythrocytes. The anti-CR1 blocking mAb dose-dependently reduced bacterial binding to erythrocytes to nil, with subsequent increased phagocytosis and oxidative burst. LPS had...

  6. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma

    DEFF Research Database (Denmark)

    Overdijk, M. B.; Verploegen, S.; Bogels, M.

    2015-01-01

    Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical development for the treatment of multiple myeloma (MM). The potential for IgG1 antibodies to induce macrophage-mediated phagocytosis, in combination with the known presence of macrophages in the tumor microenvironment...... in MM and other hematological tumors, led us to investigate the contribution of antibody-dependent, macrophage-mediated phagocytosis to DARA's mechanism of action. Live cell imaging revealed that DARA efficiently induced macrophage-mediated phagocytosis, in which individual macrophages rapidly...... and sequentially engulfed multiple tumor cells. DARA-dependent phagocytosis by mouse and human macrophages was also observed in an in vitro flow cytometry assay, using a range of MM and Burkitt's lymphoma cell lines. Phagocytosis contributed to DARA's anti-tumor activity in vivo, in both a subcutaneous...

  7. Maintenance requirement and deposition efficiency of lysine in pigs

    Directory of Open Access Journals (Sweden)

    Marcos Speroni Ceron

    2013-09-01

    Full Text Available The objective of this work was to determine the maintenance requirement and the deposition efficiency of lysine in growing pigs. It was used the incomplete changeover experimental design, with replicates over time. Twelve castrated pigs with average body weight (BW of 52±2 kg were kept in metabolism crates with a controlled temperature of 22ºC. The diets were formulated to supply 30, 50, 60, and 70% of the expected requirements of standardized lysine, and provided at 2.6 times the energy requirements for maintenance. The trial lasted 24 days and was divided into two periods of 12 days: seven days for animal adaptation to the diet and five days for sample collection. The increasing content of lysine in the diet did not affect dry matter intake of the pigs. The amount of nitrogen excreted was 47% of the nitrogen intake, of which 35% was excreted through feces and 65% through urine. The estimated endogenous losses of lysine were 36.4 mg kg-1 BW0.75. The maintenance requirement of lysine for pigs weighing around 50 kg is 40.4 mg kg-1 BW0.75, and the deposition efficiency of lysine is 90%.

  8. Phagocytosis in Teleosts. Implications of the New Cells Involved

    Directory of Open Access Journals (Sweden)

    María Ángeles Esteban

    2015-12-01

    Full Text Available Phagocytosis is the process by which cells engulf some solid particles to form internal vesicles known as phagosomes. Phagocytosis is in fact a specific form of endocytosis involving the vesicular interiorization of particles. Phagocytosis is essentially a defensive reaction against infection and invasion of the body by foreign substances and, in the immune system, phagocytosis is a major mechanism used to remove pathogens and/or cell debris. For these reasons, phagocytosis in vertebrates has been recognized as a critical component of the innate and adaptive immune responses to pathogens. Furthermore, more recent studies have revealed that phagocytosis is also crucial for tissue homeostasis and remodeling. Professional phagocytes in teleosts are monocyte/macrophages, granulocytes and dendritic cells. Nevertheless, in recent years phagocytic properties have also been attributed to teleost lymphocytes and thrombocytes. The possible implications of such cells on this important biological process, new factors affecting phagocytosis, evasion of phagocytosis or new forms of phagocytosis will be considered and discussed.

  9. [Update views on the theory of phagocytosis].

    Science.gov (United States)

    Freĭdlin, I S

    2008-01-01

    Developer of the phagocytosis theory I.I Mechnikov forecasted the most fruitful directions of its development. Macrophages express on the plasma membranes broad spectrum of receptors, which mediate their interaction with altered organism's own components as well as with exogenous agents, including various microorganisms. Recognition leads to changes of expression of surface molecules, enhancement of phagocytic activity as well as production and secretion of cytokines, presentation functions, signaling and genes expression. This reflected on maintenance of homeostasis, as well as on host defense effectiveness, including mechanisms of innate and adaptive immunity.

  10. Hemocyte-mediated phagocytosis differs between honey bee (Apis mellifera worker castes.

    Directory of Open Access Journals (Sweden)

    Eva Marit Hystad

    Full Text Available Honey bees as other insects rely on the innate immune system for protection against diseases. The innate immune system includes the circulating hemocytes (immune cells that clear pathogens from hemolymph (blood by phagocytosis, nodulation or encapsulation. Honey bee hemocyte numbers have been linked to hemolymph levels of vitellogenin. Vitellogenin is a multifunctional protein with immune-supportive functions identified in a range of species, including the honey bee. Hemocyte numbers can increase via mitosis, and this recruitment process can be important for immune system function and maintenance. Here, we tested if hemocyte mediated phagocytosis differs among the physiologically different honey bee worker castes (nurses, foragers and winter bees, and study possible interactions with vitellogenin and hemocyte recruitment. To this end, we adapted phagocytosis assays, which-together with confocal microscopy and flow cytometry-allow qualitative and quantitative assessment of hemocyte performance. We found that nurses are more efficient in phagocytic uptake than both foragers and winter bees. We detected vitellogenin within the hemocytes, and found that winter bees have the highest numbers of vitellogenin-positive hemocytes. Connections between phagocytosis, hemocyte-vitellogenin and mitosis were worker caste dependent. Our results demonstrate that the phagocytic performance of immune cells differs significantly between honey bee worker castes, and support increased immune competence in nurses as compared to forager bees. Our data, moreover, provides support for roles of vitellogenin in hemocyte activity.

  11. Hemocyte-mediated phagocytosis differs between honey bee (Apis mellifera) worker castes.

    Science.gov (United States)

    Hystad, Eva Marit; Salmela, Heli; Amdam, Gro Vang; Münch, Daniel

    2017-01-01

    Honey bees as other insects rely on the innate immune system for protection against diseases. The innate immune system includes the circulating hemocytes (immune cells) that clear pathogens from hemolymph (blood) by phagocytosis, nodulation or encapsulation. Honey bee hemocyte numbers have been linked to hemolymph levels of vitellogenin. Vitellogenin is a multifunctional protein with immune-supportive functions identified in a range of species, including the honey bee. Hemocyte numbers can increase via mitosis, and this recruitment process can be important for immune system function and maintenance. Here, we tested if hemocyte mediated phagocytosis differs among the physiologically different honey bee worker castes (nurses, foragers and winter bees), and study possible interactions with vitellogenin and hemocyte recruitment. To this end, we adapted phagocytosis assays, which-together with confocal microscopy and flow cytometry-allow qualitative and quantitative assessment of hemocyte performance. We found that nurses are more efficient in phagocytic uptake than both foragers and winter bees. We detected vitellogenin within the hemocytes, and found that winter bees have the highest numbers of vitellogenin-positive hemocytes. Connections between phagocytosis, hemocyte-vitellogenin and mitosis were worker caste dependent. Our results demonstrate that the phagocytic performance of immune cells differs significantly between honey bee worker castes, and support increased immune competence in nurses as compared to forager bees. Our data, moreover, provides support for roles of vitellogenin in hemocyte activity.

  12. Energy Efficiency Requirements in Building Codes, Energy Efficiency Policies for New Buildings. IEA Information Paper

    Energy Technology Data Exchange (ETDEWEB)

    Laustsen, Jens

    2008-03-15

    The aim of this paper is to describe and analyse current approaches to encourage energy efficiency in building codes for new buildings. Based on this analysis the paper enumerates policy recommendations for enhancing how energy efficiency is addressed in building codes and other policies for new buildings. This paper forms part of the IEA work for the G8 Gleneagles Plan of Action. These recommendations reflect the study of different policy options for increasing energy efficiency in new buildings and examination of other energy efficiency requirements in standards or building codes, such as energy efficiency requirements by major renovation or refurbishment. In many countries, energy efficiency of buildings falls under the jurisdiction of the federal states. Different standards cover different regions or climatic conditions and different types of buildings, such as residential or simple buildings, commercial buildings and more complicated high-rise buildings. There are many different building codes in the world and the intention of this paper is not to cover all codes on each level in all countries. Instead, the paper details different regions of the world and different ways of standards. In this paper we also evaluate good practices based on local traditions. This project does not seek to identify one best practice amongst the building codes and standards. Instead, different types of codes and different parts of the regulation have been illustrated together with examples on how they have been successfully addressed. To complement this discussion of efficiency standards, this study illustrates how energy efficiency can be improved through such initiatives as efficiency labelling or certification, very best practice buildings with extremely low- or no-energy consumption and other policies to raise buildings' energy efficiency beyond minimum requirements. When referring to the energy saving potentials for buildings, this study uses the analysis of recent IEA

  13. Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes.

    Science.gov (United States)

    Sayedyahossein, Samar; Nini, Lylia; Irvine, Timothy S; Dagnino, Lina

    2012-10-01

    Phagocytic melanosome uptake by epidermal keratinocytes is a central protective mechanism against damage induced by ultraviolet radiation. Phagocytosis requires formation of pseudopodia via actin cytoskeleton rearrangements. Integrin-linked kinase (ILK) is an important modulator of actin cytoskeletal dynamics. We have examined the role of ILK in regulation of phagocytosis, using epidermal keratinocytes isolated from mice with epidermis-restricted Ilk gene inactivation. ILK-deficient cells exhibited severely impaired capacity to engulf fluorescent microspheres in response to stimulation of the keratinocyte growth factor (KGF) receptor or the protease-activated receptor-2. KGF induced ERK phosphorylation in ILK-expressing and ILK-deficient cells, suggesting that ILK is not essential for KGF receptor signaling. In contrast, KGF promoted activation of Rac1 and formation of pseudopodia in ILK-expressing, but not in ILK-deficient cells. Rac1-deficient keratinocytes also showed substantially impaired phagocytic ability, underlining the importance of ILK-dependent Rac1 function for particle engulfment. Finally, cross-modulation of KGF receptors by integrins may be another important element, as integrin β1-deficient keratinocytes also fail to show significant phagocytosis in response to KGF. Thus, we have identified a novel signaling pathway essential for phagocytosis in keratinocytes, which involves ILK-dependent activation of Rac1 in response to KGF, resulting in the formation of pseudopodia and particle uptake.

  14. Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

    Directory of Open Access Journals (Sweden)

    Irune Diaz-Aparicio

    2016-01-01

    Full Text Available Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro. Nevertheless, these indirect methods present several limitations and, thus, direct observation and quantification of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. These parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inflammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to find and engulf apoptotic cells, resulting in accumulation of debris and inflammation. Herein, we advocate that the efficiency of microglial phagocytosis should be routinely tested in neurodegenerative and neurological disorders, in order to determine the extent to which it contributes to apoptosis and inflammation found in these conditions. Finally, our findings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inflammation, and accelerate recovery in brain diseases.

  15. Efficient protein production by yeast requires global tuning of metabolism

    DEFF Research Database (Denmark)

    Huang, Mingtao; Bao, Jichen; Hallstrom, Bjorn M.

    2017-01-01

    The biotech industry relies on cell factories for production of pharmaceutical proteins, of which several are among the top-selling medicines. There is, therefore, considerable interest in improving the efficiency of protein production by cell factories. Protein secretion involves numerous...... intracellular processes with many underlying mechanisms still remaining unclear. Here, we use RNA-seq to study the genome-wide transcriptional response to protein secretion in mutant yeast strains. We find that many cellular processes have to be attuned to support efficient protein secretion. In particular...... that by tuning metabolism cells are able to efficiently secrete recombinant proteins. Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion....

  16. The adaptor molecule Nck localizes the WAVE complex to promote actin polymerization during CEACAM3-mediated phagocytosis of bacteria.

    Directory of Open Access Journals (Sweden)

    Stefan Pils

    Full Text Available BACKGROUND: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. PRINCIPAL FINDINGS: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. CONCLUSIONS: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.

  17. Overexpression of Enterococcus faecalis elr operon protects from phagocytosis.

    Science.gov (United States)

    Cortes-Perez, Naima G; Dumoulin, Romain; Gaubert, Stéphane; Lacoux, Caroline; Bugli, Francesca; Martin, Rebeca; Chat, Sophie; Piquand, Kevin; Meylheuc, Thierry; Langella, Philippe; Sanguinetti, Maurizio; Posteraro, Brunella; Rigottier-Gois, Lionel; Serror, Pascale

    2015-05-25

    Mechanisms underlying the transition from commensalism to virulence in Enterococcus faecalis are not fully understood. We previously identified the enterococcal leucine-rich protein A (ElrA) as a virulence factor of E. faecalis. The elrA gene is part of an operon that comprises four other ORFs encoding putative surface proteins of unknown function. In this work, we compared the susceptibility to phagocytosis of three E. faecalis strains, including a wild-type (WT), a ΔelrA strain, and a strain overexpressing the whole elr operon in order to understand the role of this operon in E. faecalis virulence. While both WT and ΔelrA strains were efficiently phagocytized by RAW 264.7 mouse macrophages, the elr operon-overexpressing strain showed a decreased capability to be internalized by the phagocytic cells. Consistently, the strain overexpressing elr operon was less adherent to macrophages than the WT strain, suggesting that overexpression of the elr operon could confer E. faecalis with additional anti-adhesion properties. In addition, increased virulence of the elr operon-overexpressing strain was shown in a mouse peritonitis model. Altogether, our results indicate that overexpression of the elr operon facilitates the E. faecalis escape from host immune defenses.

  18. CD47 limits antibody dependent phagocytosis against non-malignant B cells.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Lekstrom, Kristen; Wilson, Susan; Herbst, Ronald; Wang, Yue

    2017-05-01

    Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Cortactin and phagocytosis in isolated Sertoli cells

    Directory of Open Access Journals (Sweden)

    Wolski Katja M

    2005-12-01

    Full Text Available Abstract Background Cortactin, an actin binding protein, has been associated with Sertoli cell ectoplasmic specializations in vivo, based on its immunolocalization around the heads of elongated spermatids, but not previously identified in isolated Sertoli cells. In an in vitro model of Sertoli cell-spermatid binding, cortactin was identified around debris and dead germ cells. Based on this observation, we hypothesized that this actin binding protein may be associated with a non-junction-related physiological function, such as phagocytosis. The purpose of this study was to identify the presence and distribution of cortactin in isolated rat Sertoli cells active in phagocytic activity following the addition of 0.8 μm latex beads. Results Sertoli cell monocultures were incubated with or without follicle stimulating hormone (FSH; 0.1 μg/ml in the presence or absence of cytochalasin D (2 μM, as an actin disrupter. Cortactin was identified by standard immunostaining with anti-cortactin, clone 4F11 (Upstate after incubation times of 15 min, 2 hr, and 24 hr with or without beads. Cells exposed to no hormone and no beads appeared to have a ubiquitous distribution of cortactin throughout the cytoplasm. In the presence of cytochalasin D, cortactin immunostaining was punctate and distributed in a pattern similar to that reported for actin in cells exposed to cytochalasin D. Sertoli cells not exposed to FSH, but activated with beads, did not show cortactin immunostaining around the phagocytized beads at any of the time periods. FSH exposure did not alter the distribution of cortactin within Sertoli cells, even when phagocytic activity was upregulated by the presence of beads. Conclusion Results of this study suggest cortactin is not associated with peripheralized actin at junctional or phagocytic sites. Further studies are necessary to clarify the role of cortactin in Sertoli cells.

  20. Experience with Energy Efficiency Requirements for Electrical Equipment

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    This publication has been produced as part of the work programme in support of the Gleneagles Plan of Action (GPOA), where the IEA was requested to 'undertake a study to review existing global appliance standards and codes'. In accordance with the G8 request, this study investigates the coverage and impact of forms of minimum energy performance standards (MEPS) and comparative energy labelling programmes; which comprise the cornerstone of most IEA countries national energy efficiency strategy. This scope also reflects governments' aspirations to achieve ambitious targets for reducing greenhouse gas emissions. As a result, this study does not address endorsement labelling and associated voluntary programmes, although these are also important policy tools for national energy efficiency strategies.

  1. Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes.

    Science.gov (United States)

    Pál, László; Árnyas, Ervin M; Bujdosó, Orsolya; Baranyi, Gergő; Rácz, Gábor; Ádány, Róza; McKee, Martin; Szűcs, Sándor

    2015-04-01

    A large volume of alcoholic beverages containing aliphatic alcohols is consumed worldwide. Previous studies have confirmed the presence of ethanol-induced immunosuppression in heavy drinkers, thereby increasing susceptibility to infectious diseases. However, the aliphatic alcohols contained in alcoholic beverages might also impair immune cell function, thereby contributing to a further decrease in microbicidal activity. Previous research has shown that aliphatic alcohols inhibit phagocytosis by granulocytes but their effect on human monocytes has not been studied. This is important as they play a crucial role in engulfment and killing of pathogenic microorganisms and a decrease in their phagocytic activity could lead to impaired antimicrobial defence in heavy drinkers. The aim of this study was to measure monocyte phagocytosis following their treatment with those aliphatic alcohols detected in alcoholic beverages. Monocytes were separated from human peripheral blood and phagocytosis of opsonized zymosan particles by monocytes treated with ethanol and aliphatic alcohols individually and in combination was determined. It was shown that these alcohols could suppress the phagocytic activity of monocytes in a concentration-dependent manner and when combined with ethanol, they caused a further decrease in phagocytosis. Due to their additive effects, it is possible that they may inhibit phagocytosis in a clinically meaningful way in alcoholics and episodic heavy drinkers thereby contribute to their increased susceptibility to infectious diseases. However, further research is needed to address this question.

  2. Progranulin increases phagocytosis by retinal pigment epithelial cells in culture.

    Science.gov (United States)

    Murase, Hiromi; Tsuruma, Kazuhiro; Kuse, Yoshiki; Shimazawa, Masamitsu; Hara, Hideaki

    2017-12-01

    Retinal pigment epithelium (RPE) cells take part in retinal preservation, such as phagocytizing the shed photoreceptor outer segments (POS), every day. The incomplete phagocytic function accelerates RPE degeneration and formation of the toxic by-product lipofuscin. Excessive lipofuscin accumulation is characteristic of various blinding diseases in the human eye. Progranulin is a cysteine-rich protein that has multiple biological activities, and it has a high presence in the retina. Progranulin has been recognized to be involved in macrophage phagocytosis in the brain. The purpose of this study is to determine whether progranulin influences phagocytosis by RPE cells. All experiments were performed on primary human RPE (hRPE) cells in culture. pHrodo was used to label the isolated porcine POS, and quantification of pHrodo fluorescence was used to determine the degree of phagocytosis. Western blotting and immunohistochemistry of key proteins involved in phagocytosis were used to clarify the mechanism of progranulin. Progranulin increased RPE phagocytosis in hydrogen peroxide-treated and nontreated RPE cells. The phosphorylated form of Mer tyrosine kinase, which is important for POS internalization, was significantly increased in the progranulin-exposed cells. This increase was attenuated by SU11274, an inhibitor of hepatic growth factor receptor. Under the oxidative stress condition, exposure to progranulin led to an approximately twofold increase in integrin alpha-v, which is associated with the first step in recognition of POS by RPE cells. These results suggest that progranulin could be an effective stimulator for RPE phagocytosis and could repair RPE function. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Energy-efficient Ship Operation – Training Requirements and Challenges

    Directory of Open Access Journals (Sweden)

    Michael Baldauf

    2013-06-01

    Full Text Available The International Maritime Organization (IMO, through its Maritime Environmental Protection Committee (MEPC, has been carrying out substantive work on the reduction and limitation of greenhouse gas emissions from international shipping since 1997, following the adoption of the Kyoto Protocol and the 1997 MARPOL Conference. While to date no mandatory GHG instrument for international shipping has been adopted, IMO has given significant consideration of the matter and has been working in accordance with an ambitious work plan with a view to adopting a package of technical provisions. Beside the efforts undertaken by IMO, it is assumed that e.g. optimized manoeuvring regimes have potential to contribute to a reduction of GHG emissions. Such procedures and supporting technologies can decrease the negative effects to the environment and also may reduce fuel consumption. However, related training has to be developed and to be integrated into existing course schemes accordingly. IMO intends to develop a Model Course aiming at promoting the energy-efficient operation of ships. This Course will contribute to the IMO’s environmental protection goals as set out in resolutions A.947(23 and A.998(25 by promulgating industry “best practices”, which reduce greenhouse gas emissions and the negative impact of global shipping on climate change. In this paper the outline of the research work will be introduced and the fundamental ideas and concepts are described. A concept for the overall structure and the development of suggested detailed content of the draft Model course will be exemplarily explained. Also, a developed draft module for the model course with samples of the suggested integrated practical exercises will be introduced and discussed. The materials and data in this publication have been obtained partly through capacity building research project of IAMU kindly supported by the International Association of Maritime Universities (IAMU and The Nippon

  4. Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface.

    Directory of Open Access Journals (Sweden)

    Ya-Ping Ko

    Full Text Available Upon contact with human plasma, bacteria are rapidly recognized by the complement system that labels their surface for uptake and clearance by phagocytic cells. Staphylococcus aureus secretes the 16 kD Extracellular fibrinogen binding protein (Efb that binds two different plasma proteins using separate domains: the Efb N-terminus binds to fibrinogen, while the C-terminus binds complement C3. In this study, we show that Efb blocks phagocytosis of S. aureus by human neutrophils. In vitro, we demonstrate that Efb blocks phagocytosis in plasma and in human whole blood. Using a mouse peritonitis model we show that Efb effectively blocks phagocytosis in vivo, either as a purified protein or when produced endogenously by S. aureus. Mutational analysis revealed that Efb requires both its fibrinogen and complement binding residues for phagocytic escape. Using confocal and transmission electron microscopy we show that Efb attracts fibrinogen to the surface of complement-labeled S. aureus generating a 'capsule'-like shield. This thick layer of fibrinogen shields both surface-bound C3b and antibodies from recognition by phagocytic receptors. This information is critical for future vaccination attempts, since opsonizing antibodies may not function in the presence of Efb. Altogether we discover that Efb from S. aureus uniquely escapes phagocytosis by forming a bridge between a complement and coagulation protein.

  5. Bovine-associated CNS species resist phagocytosis differently

    Science.gov (United States)

    2013-01-01

    Background Coagulase-negative staphylococci (CNS) cause usually subclinical or mild clinical bovine mastitis, which often remains persistent. Symptoms are usually mild, mostly only comprising slight changes in the appearance of milk and possibly slight swelling. However, clinical mastitis with severe signs has also been reported. The reasons for the differences in clinical expression are largely unknown. Macrophages play an important role in the innate immunity of the udder. This study examined phagocytosis and killing by mouse macrophage cells of three CNS species: Staphylococcus chromogenes (15 isolates), Staphylococcus agnetis (6 isolates) and Staphylococcus simulans (15 isolates). Staphylococcus aureus (7 isolates) was also included as a control. Results All the studied CNS species were phagocytosed by macrophages, but S. simulans resisted phagocytosis more effectively than the other CNS species. Only S. chromogenes was substantially killed by macrophages. Significant variations between isolates were seen in both phagocytosis and killing by macrophages and were more common in the killing assays. Significant differences between single CNS species and S. aureus were observed in both assays. Conclusion This study demonstrated that differences in the phagocytosis and killing of mastitis-causing staphylococci by macrophages exist at both the species and isolate level. PMID:24207012

  6. Multiple sclerosis : Mechanisms of myelin phagocytosis and lesion expansion

    NARCIS (Netherlands)

    Hendrickx, D.A.E.

    2018-01-01

    Multiple sclerosis (MS) is characterized by immune activation and focal demyelination in the central nervous system. The aim of this thesis was to gain more insight into the mechanisms of myelin phagocytosis by resident microglia and infiltrating macrophages. We first evaluated the expression of the

  7. DMPD: Complement-mediated phagocytosis--the role of Syk. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16754322 Complement-mediated phagocytosis--the role of Syk. Tohyama Y, Yamamura H. ...IUBMB Life. 2006 May-Jun;58(5-6):304-8. (.png) (.svg) (.html) (.csml) Show Complement-mediated phagocytosis-...-the role of Syk. PubmedID 16754322 Title Complement-mediated phagocytosis--the role of Syk. Authors Tohyama

  8. An Analysis of BIM Web Service Requirements and Design to Support Energy Efficient Building Lifecycle

    Directory of Open Access Journals (Sweden)

    Yufei Jiang

    2016-04-01

    Full Text Available Energy Efficient Building (EEB design, construction, and operations require the development and sharing of building information among different individuals, organizations, and computer applications. The Representational State Transfer (RESTful Building Information Modeling (BIM web service is a solution to enable an effective exchange of data. This paper presents an investigation into the core RESTful web service requirements needed to effectively support the EEB project lifecycle. The requirements include information exchange requirements, distributed collaboration requirements, internal data storage requirements, and partial model query requirements. We also propose a RESTful web service design model on different abstraction layers to enhance the BIM lifecycle in energy efficient building design. We have implemented a RESTful Application Program Interface (API prototype on a mock BIMserver to demonstrate our idea. We evaluate our design by conducting a user study based on the Technology Acceptance Model (TAM. The results show that our design can enhance the efficiency of data exchange in EEB design scenarios.

  9. Analysis of Valve Requirements for High-Efficiency Digital Displacement Fluid Power Motors

    DEFF Research Database (Denmark)

    Rømer, Daniel; Johansen, Per; Pedersen, Henrik C.

    2013-01-01

    Digital displacement fluid power motors have been shown to enable high-efficiency operation in a wide operation range, including the part load range where conventional fluid power motors suffers from poor efficiencies. The use of these digital displacement motors set new requirements for the valve...... transition time and flow-pressure coefficient are normalized, leading to a presentation of the general efficiency map of the digital displacement motor. Finally the performance of existing commercial valves with respect to digital motors is commented....

  10. Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin

    Directory of Open Access Journals (Sweden)

    Hadas Smadar

    2012-07-01

    Full Text Available Abstract Background Intact myelin, which normally surrounds axons, breaks down in Wallerian degeneration following axonal injury and during neurodegenerative diseases such as multiple sclerosis. Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3 is a principal phagocytic receptor in myelin phagocytosis. We studied how tyrosine kinase Syk (spleen tyrosine kinase and cofilin control phagocytosis of degenerated myelin by CR3 in microglia and macrophages. Syk is a non-receptor tyrosine kinase that CR3 recruits to convey cellular functions. Cofilin is an actin-depolymerizing protein that controls F-actin (filamentous actin remodeling (i.e., disassembly and reassembly by shifting between active unphosphorylated and inactive phosphorylated states. Results Syk was continuously activated during prolonged phagocytosis. Phagocytosis increased when Syk activity and expression were reduced, suggesting that normally Syk down regulates CR3-mediated myelin phagocytosis. Levels of inactive p-cofilin (phosphorylated cofilin decreased transiently during prolonged phagocytosis. In contrast, p-cofilin levels decreased continuously when Syk activity and expression were continuously reduced, suggesting that normally Syk advances the inactive state of cofilin. Observations also revealed inverse relationships between levels of phagocytosis and levels of inactive p-cofilin, suggesting that active unphosphorylated cofilin advances phagocytosis. Active cofilin could advance phagocytosis by promoting F-actin remodeling, which supports the production of membrane protrusions (e.g., filopodia, which, as we also revealed, are instrumental in myelin phagocytosis. Conclusions CR3 both activates and downregulates myelin phagocytosis at the same time. Activation was previously documented. We presently demonstrate that downregulation is mediated through Syk, which advances the inactive

  11. Phagocytosis-induced /sup 45/calcium efflux in polymorphonuclear leucocytes

    Energy Technology Data Exchange (ETDEWEB)

    Barthelemy, A; Schell-Frederick, E [Brussels Univ. (Belgium). Institut de Recherche Interdisciplinaire; Paridaens, R [Brussels Univ. (Belgium). Faculte de Medicine

    1977-10-15

    The role of calcium ions in regulating the structure and function of non-muscle cells is a subject of intense study. Several lines of evidence that calcium may be essential in the function of polymorphonuclear leuocytes (PMNL) and an important control element in the process of phagocytosis. Direct studies of calcium distribution and fluxes have only recently been undertaken. To our knowledge, no report of calcium movements during normal phagocytosis has been published. In the context of an overall study of calcium dynamics in the PMNL, we report here initial studies on /sup 45/Ca efflux in prelabelled guinea pig PMNL. The results demonstrate the energy-dependence of resting calcium efflux and an increased efflux upon addition of phagocytic particles which is not dependent on particle internalization.

  12. Phagocytosis by Thrombocytes is a Conserved Innate Immune Mechanism in Lower Vertebrates.

    Science.gov (United States)

    Nagasawa, Takahiro; Nakayasu, Chihaya; Rieger, Aja M; Barreda, Daniel R; Somamoto, Tomonori; Nakao, Miki

    2014-01-01

    Thrombocytes, nucleated hemostatic blood cells of non-mammalian vertebrates, are regarded as the functional equivalent of anucleated mammalian platelets. Additional immune functions, including phagocytosis, have also been suggested for thrombocytes, but no conclusive molecular or cellular experimental evidence for their potential ingestion and clearance of infiltrating microbes has been provided till date. In the present study, we demonstrate the active phagocytic ability of thrombocytes in lower vertebrates using teleost fishes and amphibian models. Ex vivo, common carp thrombocytes were able to ingest live bacteria as well as latex beads (0.5-3 μm in diameter) and kill the bacteria. In vivo, we found that thrombocytes represented nearly half of the phagocyte population in the common carp total peripheral blood leukocyte pool. Phagocytosis efficiency was further enhanced by serum opsonization. Particle internalization led to phagolysosome fusion and killing of internalized bacteria, pointing to a robust ability for microbe elimination. We find that this potent phagocytic activity is shared across teleost (Paralichthys olivaceus) and amphibian (Xenopus laevis) models examined, implying its conservation throughout the lower vertebrate lineage. Our results provide novel insights into the dual nature of thrombocytes in the immune and homeostatic response and further provide a deeper understanding of the potential immune function of mammalian platelets based on the conserved and vestigial functions.

  13. Phagocytosis by thrombocytes is a conserved innate immune mechanism in lower vertebrates

    Directory of Open Access Journals (Sweden)

    Takahiro eNagasawa

    2014-09-01

    Full Text Available Thrombocytes, nucleated hemostatic blood cells of nonmammalian vertebrates, are regarded as the functional equivalent of anucleated mammalian platelets. Additional immune functions, including phagocytosis, have also been suggested for thrombocytes, but no conclusive molecular or cellular experimental evidence for their potential ingestion and clearance of infiltrating microbes has been provided till date. In the present study, we demonstrate the active phagocytic ability of thrombocytes in lower vertebrates using teleost fishes and amphibian models. Ex vivo, common carp thrombocytes were able to ingest live bacteria as well as latex beads (0.5–3 μm in diameter and kill the bacteria. In vivo, we found that thrombocytes represented nearly half of the phagocyte population in the common carp total peripheral blood leukocyte pool. Phagocytosis efficiency was further enhanced by serum opsonization. Particle internalization led to phagolysosome fusion and killing of internalized bacteria, pointing to a robust ability for microbe elimination. We find that this potent phagocytic activity is shared across teleost (Paralichthys olivaceus and amphibian (Xenopus laevis models examined, implying its conservation throughout the lower vertebrate lineage. Our results provide novel insights into the dual nature of thrombocytes in the immune and homeostatic response and further provide a deeper understanding of the potential immune function of mammalian platelets based on the conserved and vestigial functions.

  14. Lipopolysaccharide O-antigen prevents phagocytosis of Vibrio anguillarum by rainbow trout (Oncorhynchus mykiss skin epithelial cells.

    Directory of Open Access Journals (Sweden)

    Kristoffer Lindell

    Full Text Available Colonization of host tissues is a first step taken by many pathogens during the initial stages of infection. Despite the impact of bacterial disease on wild and farmed fish, only a few direct studies have characterized bacterial factors required for colonization of fish tissues. In this study, using live-cell and confocal microscopy, rainbow trout skin epithelial cells, the main structural component of the skin epidermis, were demonstrated to phagocytize bacteria. Mutant analyses showed that the fish pathogen Vibrio anguillarum required the lipopolysaccharide O-antigen to evade phagocytosis and that O-antigen transport required the putative wzm-wzt-wbhA operon, which encodes two ABC polysaccharide transporter proteins and a methyltransferase. Pretreatment of the epithelial cells with mannose prevented phagocytosis of V. anguillarum suggesting that a mannose receptor is involved in the uptake process. In addition, the O-antigen transport mutants could not colonize the skin but they did colonize the intestines of rainbow trout. The O-antigen polysaccharides were also shown to aid resistance to the antimicrobial factors, lysozyme and polymyxin B. In summary, rainbow trout skin epithelial cells play a role in the fish innate immunity by clearing bacteria from the skin epidermis. In defense, V. anguillarum utilizes O-antigen polysaccharides to evade phagocytosis by the epithelial cells allowing it to colonize rapidly fish skin tissues.

  15. Lipopolysaccharide O-Antigen Prevents Phagocytosis of Vibrio anguillarum by Rainbow Trout (Oncorhynchus mykiss) Skin Epithelial Cells

    Science.gov (United States)

    Lindell, Kristoffer; Fahlgren, Anna; Hjerde, Erik; Willassen, Nils-Peder; Fällman, Maria; Milton, Debra L.

    2012-01-01

    Colonization of host tissues is a first step taken by many pathogens during the initial stages of infection. Despite the impact of bacterial disease on wild and farmed fish, only a few direct studies have characterized bacterial factors required for colonization of fish tissues. In this study, using live-cell and confocal microscopy, rainbow trout skin epithelial cells, the main structural component of the skin epidermis, were demonstrated to phagocytize bacteria. Mutant analyses showed that the fish pathogen Vibrio anguillarum required the lipopolysaccharide O-antigen to evade phagocytosis and that O-antigen transport required the putative wzm-wzt-wbhA operon, which encodes two ABC polysaccharide transporter proteins and a methyltransferase. Pretreatment of the epithelial cells with mannose prevented phagocytosis of V. anguillarum suggesting that a mannose receptor is involved in the uptake process. In addition, the O-antigen transport mutants could not colonize the skin but they did colonize the intestines of rainbow trout. The O-antigen polysaccharides were also shown to aid resistance to the antimicrobial factors, lysozyme and polymyxin B. In summary, rainbow trout skin epithelial cells play a role in the fish innate immunity by clearing bacteria from the skin epidermis. In defense, V. anguillarum utilizes O-antigen polysaccharides to evade phagocytosis by the epithelial cells allowing it to colonize rapidly fish skin tissues. PMID:22662189

  16. Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones.

    Science.gov (United States)

    Cornell, R P; McClellan, C C

    1982-12-01

    Experiments were conducted to determine the influence of the pancreatic hormones insulin, glucagon, and somatostatin on reticuloendothelial system (RES) phagocytosis both in vivo and in the isolated perfused livers of rats. Chronic pancreatic hormonal treatment consisted of twice daily injections SC of NPH insulin with doses ranging from 0.75 U on day 1 to 9.0 U on day 13 and unchanged doses of glucagon (200 micrograms) and somatostatin (50 micrograms). Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value. Acute treatment with the three pancreatic hormones at 30 min prior to carbon administration similarly produced insulin depression as well as glucagon and somatostatin stimulation of RES phagocytosis. Addition of the three hormones at near physiologic concentrations (20 ng/ml for insulin, 10 ng/ml for glucagon, and 5 ng/ml for somatostatin) to the recirculating perfusate of isolated perfused rat livers simultaneous with 24 mg of colloidal carbon likewise resulted in phagocytic reduction after insulin and enhancement after glucagon and somatostatin. Experiments involving insulin in vitro with isolated perfused livers as well as glucose replacement therapy concomitant with insulin in vivo demonstrated that hypoglycemia is not necessary for phagocytic depression by insulin while severe hypoglycemia in the perfusion medium is sufficient to depress carbon uptake by isolated perfused livers independent of insulin. Both pancreatic hormones and the level of glycemia seem to be important in modulating hepatic reticuloendothelial system phagocytosis.

  17. How cells engulf: a review of theoretical approaches to phagocytosis

    Science.gov (United States)

    Richards, David M.; Endres, Robert G.

    2017-12-01

    Phagocytosis is a fascinating process whereby a cell surrounds and engulfs particles such as bacteria and dead cells. This is crucial both for single-cell organisms (as a way of acquiring nutrients) and as part of the immune system (to destroy foreign invaders). This whole process is hugely complex and involves multiple coordinated events such as membrane remodelling, receptor motion, cytoskeleton reorganisation and intracellular signalling. Because of this, phagocytosis is an excellent system for theoretical study, benefiting from biophysical approaches combined with mathematical modelling. Here, we review these theoretical approaches and discuss the recent mathematical and computational models, including models based on receptors, models focusing on the forces involved, and models employing energetic considerations. Along the way, we highlight a beautiful connection to the physics of phase transitions, consider the role of stochasticity, and examine links between phagocytosis and other types of endocytosis. We cover the recently discovered multistage nature of phagocytosis, showing that the size of the phagocytic cup grows in distinct stages, with an initial slow stage followed by a much quicker second stage starting around half engulfment. We also address the issue of target shape dependence, which is relevant to both pathogen infection and drug delivery, covering both one-dimensional and two-dimensional results. Throughout, we pay particular attention to recent experimental techniques that continue to inform the theoretical studies and provide a means to test model predictions. Finally, we discuss population models, connections to other biological processes, and how physics and modelling will continue to play a key role in future work in this area.

  18. ON THE IMPACT OF FLIGHT SAFETY CERTIFICATION REQUIREMENTS ON THE AERODYNAMIC EFFICIENCY OF COMMERCIAL AIRPLANES

    Directory of Open Access Journals (Sweden)

    Vladimir I. Shevyakov

    2018-01-01

    Full Text Available The article considers the issue of aerodynamics efficiency implementation taking into account certification requirements for flight safety. Aerodynamics efficiency means high aerodynamic performance (depending on the airplane size, aerodynamic performance in cruise flight, high aerodynamic performance at takeoff, as well as lift performance at landing.The author estimated the impact on aerodynamics efficiency of both the requirements for aerodynamics performance and requirements for aircraft systems, noncompliance with which may result in significant change of expected operating conditions. It was shown that the use of supercritical wing profiles may result in flight mode limitations due to failure of the required buffeting capacities. It does not allow engaging all the advantages of aerodynamics layout and requires special design solutions to prevent such cases.There were reviewed certification requirements for flight level pressure altitude accuracy and icing conditions warning sysytem. The research presented the methods of aerodynamic efficiency increase by meeting the requirements for reduced vertical separation minima flights and in icing conditions, including requirements for air data probes. Reduced vertical separation minima flight requirements are met by means of efficient air data probes location. Theoretical methods of flow calculation determine areas on the airplane skin surface where static probes minimize errors depending on angle-of-attack and sideslip. It was shown that if certification requirements are not met and in case of flight out of reduced vertical separation minima area, aerodynamics efficiency is significantly reduced and fuel consumption can be increased by 10% and higher. Suggested approaches implementation allows increasing commercial airplanes competitiveness.

  19. Some Observations on Carbon Nano tubes Susceptibility to Cell Phagocytosis

    International Nuclear Information System (INIS)

    Fraczek-Szczypta, A.; Menaszek, E.; Blazewicz, S.; Menaszek, E.

    2011-01-01

    The aim of this study was to assess the influence of different types of carbon nano tubes (CNTs) on cell phagocytosis. Three kinds of carbon nano tubes: single-walled carbon nano horns (SWCNHs), multi walled carbon nano tubes (MWCNTs), and ultra-long single-walled carbon nano tubes (ULSWCNTs) before and after additional chemical functionalization were seeded with macrophage cell culture. Prior to biological testing, the CNTs were subjected to dispersion process with the use of phosphate buffered solution (PBS) and PBS containing surfactant (Tween 20) or dimethyl sulfoxide (DMSO). The results indicate that the cells interaction with an individual nano tube is entirely different as compared to CNTs in the form of aggregate. The presence of the surfactant favors the CNTs dispersion in culture media and facilitates phagocytosis process, while it has disadvantageous influence on cells morphology. The cells phagocytosis is a more effective for MWCNTs and SWCNHs after their chemical functionalization. Moreover, these nano tubes were well dispersed in culture media without using DMSO or surfactant. The functionalized carbon nano tubes were easily dispersed in pure PBS and seeded with cells

  20. Characterization of myosin light chain in shrimp hemocytic phagocytosis.

    Science.gov (United States)

    Han, Fang; Wang, Zhiyong; Wang, Xiaoqing

    2010-11-01

    Myosin light chain, a well-known cytoskeleton gene, regulates multiple processes that are involved in material transport, muscle shrink and cell division. However, its function in phagocytosis against invading pathogens in crustacean remains unknown. In this investigation, a myosin light chain gene was obtained from Marsupenaeus japonicus shrimp. The full-length cDNA of this gene was of 766 bp and an open reading frame (ORF) of 462 bp encoding a polypeptide of 153 amino acids. The myosin light chain protein was expressed in Escherichia coli and purified. Subsequently the specific antibody was raised using the purified GST fusion protein. As revealed by immuno-electron microscopy, the myosin light chain protein was only expressed in the dark bands of muscle. In the present study, the myosin light chain gene was up-regulated in the WSSV-resistant shrimp as revealed by real-time PCR and western blot. And the phagocytic percentage and phagocytic index using FITC-labeled Vibrio parahemolyticus were remarkably increased in the WSSV-resistant shrimp, suggesting that the myosin light chain protein was essential in hemocytic phagocytosis. On the other hand, RNAi assays indicated that the phagocytic percentage and phagocytic index were significantly decreased when the myosin light chain gene was silenced by sequence-specific siRNA. These findings suggested that myosin light chain protein was involved in the regulation of hemocytic phagocytosis of shrimp. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Collectin-11 Is an Important Modulator of Retinal Pigment Epithelial Cell Phagocytosis and Cytokine Production.

    Science.gov (United States)

    Dong, Xia; Wu, Weiju; Ma, Liang; Liu, Chengfei; Bhuckory, Mohajeet B; Wang, Liping; Nandrot, Emeline F; Xu, Heping; Li, Ke; Liu, Yizhi; Zhou, Wuding

    2017-01-01

    In this paper, we report previously unknown roles for collectin-11 (CL-11, a soluble C-type lectin) in modulating the retinal pigment epithelial (RPE) cell functions of phagocytosis and cytokine production. We found that CL-11 and its carbohydrate ligand are expressed in both the murine and human neural retina; these resemble each other in terms of RPE and photoreceptor cells. Functional analysis of murine RPE cells showed that CL-11 facilitates the opsonophagocytosis of photoreceptor outer segments and apoptotic cells, and also upregulates IL-10 production. Mechanistic analysis revealed that calreticulin on the RPE cells is required for CL-11-mediated opsonophagocytosis whereas signal-regulatory protein α and mannosyl residues on the cells are involved in the CL-11-mediated upregulation of IL-10 production. This study is the first to demonstrate the role of CL-11 and the molecular mechanisms involved in modulating RPE cell phagocytosis and cytokine production. It provides a new insight into retinal health and disease and has implications for other phagocytic cells. © 2017 S. Karger AG, Basel.

  2. EPPRD: An Efficient Privacy-Preserving Power Requirement and Distribution Aggregation Scheme for a Smart Grid.

    Science.gov (United States)

    Zhang, Lei; Zhang, Jing

    2017-08-07

    A Smart Grid (SG) facilitates bidirectional demand-response communication between individual users and power providers with high computation and communication performance but also brings about the risk of leaking users' private information. Therefore, improving the individual power requirement and distribution efficiency to ensure communication reliability while preserving user privacy is a new challenge for SG. Based on this issue, we propose an efficient and privacy-preserving power requirement and distribution aggregation scheme (EPPRD) based on a hierarchical communication architecture. In the proposed scheme, an efficient encryption and authentication mechanism is proposed for better fit to each individual demand-response situation. Through extensive analysis and experiment, we demonstrate how the EPPRD resists various security threats and preserves user privacy while satisfying the individual requirement in a semi-honest model; it involves less communication overhead and computation time than the existing competing schemes.

  3. The Army Materiel Requirements Documents: Qualitative Analysis of Efficiency and Effectiveness

    Science.gov (United States)

    2013-06-30

    65 - k~î~ä=mçëíÖê~Çì~íÉ=pÅÜççä= We measure efficiency based on two BPP initiatives: (1) Build Stronger Partnerships With the Requirements...poor,” “average,” or “excellent” based on comments received from SMEs in relation to the definitions of each BPP initiative during our interviews. A...M-ATV, and JLTV and how well they rank in terms of efficiency and effectiveness according to BPP initiatives. For efficiency, we assign a

  4. The kinetics of phagocytosis of 198Au colloids ''in vitro''

    International Nuclear Information System (INIS)

    Astorri, N.L.; Bergoc, R.M.; Bianchin, A.M.; Caro, R.A.; Ihlo, J.E.; Rivera, E.S.

    1982-01-01

    The kinetics of the phagocytosis of 198-Au colloids by macrophages ''in vitro'' was studied by incubating during 5 hours phagocytic cells from the liver and the spleen of Wistar rats with colloidal radiogold particles, in the presence of an adequate culture medium (TC-199 with 10 per cent of Bovine Fetal Serum). In each experiment, the number of colloidal gold particles offered to each phatocytic cell, (Au) 0 and the mean rate of phagocytosis v, were calculated. The latter value was determined by measuring the radioactivity incorporated into the phagocytic cells during the incubation; it was expressed as the number of phagocytized colloidal gold particles per cell per minute. The values of log v = f [log (Au) 0 ] were plotted. The Lineweaver-Burk analysis of the results demonstrates that the kinetics of the phagocytosis of colloidal radiogold particles ''in vitro'' follows a model similar to Michaelis-Menten equations for enzyme reactions. The values of the substratum constant Ks and maximun velocity Vm were obtained by the regression analysis of the 1/v vs. 1/(Au) 0 graph. Vm was equal to 9.44 x 10 and 1.63 x 10 phagocytized colloidal gold particles per cell per minute for liver and spleen macrophages, respectively. Ks was equal to 6.01 x 10 9 and 8.02 x 10 8 colloidal gold particles per cell for liver and spleen macrophages, respectively. The significance of these differences is discussed and attributed mainly to a change of the specific engulfment rate constant. (author) [es

  5. Influence of UV-radiation on granulocytic phagocytosis in vitro

    International Nuclear Information System (INIS)

    Walther, T.; Rytter, M.; Gast, W.; Haustein, U.F.

    1987-01-01

    The influence of UV radiation on the vitality, the performance of phagocytosis and the ability to reduce nitro-blue tetrazolium test (NBT) by human granulocytes was investigated in vitro. Already by low doses of UVA (8% UVB) the percentage of phagocytizing granulocytes was decreased more distinctly than their cell vitality. The number of ingested Candida albicans particles was 4.5 particles per granulocyte in the controls. It was reduced to about 1.4 particles per cell by UV radiation independent of the dosis applied. On the other hand the ability of granulocytes to reduce NBT intracellularly remained completely unchanged. (author)

  6. The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new mechanism involving activation of C-terminal Src kinase.

    Science.gov (United States)

    Dodd, Dana A; Worth, Randall G; Rosen, Michael K; Grinstein, Sergio; van Oers, Nicolai S C; Hansen, Eric J

    2014-05-20

    Haemophilus ducreyi causes chancroid, a sexually transmitted infection. A primary means by which this pathogen causes disease involves eluding phagocytosis; however, the molecular basis for this escape mechanism has been poorly understood. Here, we report that the LspA virulence factors of H. ducreyi inhibit phagocytosis by stimulating the catalytic activity of C-terminal Src kinase (Csk), which itself inhibits Src family protein tyrosine kinases (SFKs) that promote phagocytosis. Inhibitory activity could be localized to a 37-kDa domain (designated YL2) of the 456-kDa LspA1 protein. The YL2 domain impaired ingestion of IgG-opsonized targets and decreased levels of active SFKs when expressed in mammalian cells. YL2 contains tyrosine residues in two EPIYG motifs that are phosphorylated in mammalian cells. These tyrosine residues were essential for YL2-based inhibition of phagocytosis. Csk was identified as the predominant mammalian protein interacting with YL2, and a dominant-negative Csk rescued phagocytosis in the presence of YL2. Purified Csk phosphorylated the tyrosines in the YL2 EPIYG motifs. Phosphorylated YL2 increased Csk catalytic activity, resulting in positive feedback, such that YL2 can be phosphorylated by the same kinase that it activates. Finally, we found that the Helicobacter pylori CagA protein also inhibited phagocytosis in a Csk-dependent manner, raising the possibility that this may be a general mechanism among diverse bacteria. Harnessing Csk to subvert the Fcγ receptor (FcγR)-mediated phagocytic pathway represents a new bacterial mechanism for circumventing a crucial component of the innate immune response and may potentially affect other SFK-involved cellular pathways. Phagocytosis is a critical component of the immune system that enables pathogens to be contained and cleared. A number of bacterial pathogens have developed specific strategies to either physically evade phagocytosis or block the intracellular signaling required for

  7. 78 FR 27982 - U.S. Flag Compliance With MARPOL Annex VI International Energy Efficiency (IEE) Requirements

    Science.gov (United States)

    2013-05-13

    ... MARPOL Annex VI International Energy Efficiency (IEE) Requirements AGENCY: Coast Guard, DHS. ACTION... Efficiency Certificate and the preparation of a Ship Energy Efficiency Management Plan for both new and... extensive that it is regarded as a newly constructed ship, must first have an Attained Energy Efficiency...

  8. In vitro phagocytosis of several Candida berkhout species by murine leukocytes.

    Science.gov (United States)

    Fontenla de Petrino, S E; Bibas Bonet de Jorrat, M E; Sirena, A

    1985-03-01

    In vitro phagocytosis of thirteen Candida berkhout species by rat leukocytes was studied to assess a possible correlation between pathogenicity and phagocytosis Yeast-leukocyte suspensions were mixed up for 3 h and phagocytic index, germ-tube formation and leukocyte candidacidal activity were evaluated. Highest values for phagocytosis were reached in all cases at the end of the first hour. Leukocyte candidacidal activity was absent. Only C. albicans produced germ-tubes. The various phagocytosis indices were determined depending on the Candida species assayed. Under these conditions, the more pathogenic species presented the lower indices of phagocytosis. It is determined that the in vitro phagocytic index may bear a close relationship with the pathogenicity of the Candida berkhout.

  9. THE IMPLEMENTATION OF EFFICIENT TRADE MATRIX AND GOLD RESERVE REQUIREMENT FOR COMMODITY TRADE AMONG ASEAN COUNTRIES

    Directory of Open Access Journals (Sweden)

    nurul anisak

    2017-06-01

    Full Text Available Objective - This study attempts to implement the efficient trade matrix among five selected ASEAN countries and its settlement by the gold reserve requirements through Multi-Bilateral Payments Arrangement (MBPA.Methods – The study is a qualitative research with analytic description. The purpose of this qualitative-descriptive study is to simulate the implementation of gold in the Multi-Bilateral Payment Arrangement among ASEAN countries using the current trade data.Results – This paper argues that the Southeast Asian countries can solve the problem through their internal coordination, particularly in terms of trade. One of the efforts is to reduce even eliminate the market risk by using the efficient payment arrangement.Conclusions – The study implied that the quantity amount of gold required to settle the trade balance will be reduced from the early gross payment. However, the ASEAN countries need to strengthen the cooperation among them through maximizing the trade relationship.

  10. Efficient visual search from synchronized auditory signals requires transient audiovisual events.

    Directory of Open Access Journals (Sweden)

    Erik Van der Burg

    Full Text Available BACKGROUND: A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that temporal coincidence (i.e., synchrony of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. CONCLUSIONS/SIGNIFICANCE: Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time.

  11. THE IMPLEMENTATION OF EFFICIENT TRADE MATRIX AND GOLD RESERVE REQUIREMENT FOR COMMODITY TRADE AMONG ASEAN COUNTRIES

    OpenAIRE

    nurul anisak

    2017-01-01

    Objective - This study attempts to implement the efficient trade matrix among five selected ASEAN countries and its settlement by the gold reserve requirements through Multi-Bilateral Payments Arrangement (MBPA).Methods – The study is a qualitative research with analytic description. The purpose of this qualitative-descriptive study is to simulate the implementation of gold in the Multi-Bilateral Payment Arrangement among ASEAN countries using the current trade data.Results – This paper argue...

  12. Wip1-dependent modulation of macrophage migration and phagocytosis

    DEFF Research Database (Denmark)

    Tang, Yiting; Pan, Bing; Zhou, Xin

    2017-01-01

    Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. Controlling macrophage conversion into foam cells remains a major challenge for treatment of atherosclerotic diseases. Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates...... macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1-/- macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways. Elevated...... phagocytic ability of Wip1-/- macrophages is linked to CD36 plasma membrane recruitment that is regulated by AMPK activity. Our study identifies Wip1 as an intrinsic negative regulator of macrophage chemotaxis. We propose that Wip1-dependent control of macrophage function may provide avenues for preventing...

  13. Induction of Live Cell Phagocytosis by a Specific Combination of Inflammatory Stimuli

    Directory of Open Access Journals (Sweden)

    Takamasa Ishidome

    2017-08-01

    Full Text Available Conditions of severe hyper-inflammation can lead to uncontrolled activation of macrophages, and the ensuing phagocytosis of live cells. However, relationships between inflammatory stimuli and uncontrolled phagocytosis of live cells by macrophages are poorly understood. To identify mediators of this process, we established phagocytosis assays of live cells by stimulating macrophages with CpG DNA, interferon-γ, and anti-interleukin-10 receptor antibody. In this model, various cell surface receptors were upregulated on macrophages, and phagocytosis of live cells was induced in a Rac1-dependent manner. Subsequent inhibition of the ICAM-1, VCAM-1, and both of these receptors abolished in vitro and in vivo phagocytosis of live T cells, myeloid cells, and B cells, respectively. Specifically, the reduction in lymphocyte numbers due to in vivo activation of macrophages was ameliorated in Icam-1-deficient mice. In addition, overexpression of ICAM-1 or VCAM-1 in non-phagocytic NIH3T3 cells led to active phagocytosis of live cells. These data indicate molecular mechanisms underlying live cell phagocytosis induced by hyper-inflammation, and this experimental model will be useful to clarify the pathophysiological mechanisms of hemophagocytosis and to indicate therapeutic targets.

  14. Pathogen-Specific Binding Soluble Down Syndrome Cell Adhesion Molecule (Dscam Regulates Phagocytosis via Membrane-Bound Dscam in Crab

    Directory of Open Access Journals (Sweden)

    Xue-Jie Li

    2018-04-01

    Full Text Available The Down syndrome cell adhesion molecule (Dscam gene is an extraordinary example of diversity that can produce thousands of isoforms and has so far been found only in insects and crustaceans. Cumulative evidence indicates that Dscam may contribute to the mechanistic foundations of specific immune responses in insects. However, the mechanism and functions of Dscam in relation to pathogens and immunity remain largely unknown. In this study, we identified the genome organization and alternative Dscam exons from Chinese mitten crab, Eriocheir sinensis. These variants, designated EsDscam, potentially produce 30,600 isoforms due to three alternatively spliced immunoglobulin (Ig domains and a transmembrane domain. EsDscam was significantly upregulated after bacterial challenge at both mRNA and protein levels. Moreover, bacterial specific EsDscam isoforms were found to bind specifically with the original bacteria to facilitate efficient clearance. Furthermore, bacteria-specific binding of soluble EsDscam via the complete Ig1–Ig4 domain significantly enhanced elimination of the original bacteria via phagocytosis by hemocytes; this function was abolished by partial Ig1–Ig4 domain truncation. Further studies showed that knockdown of membrane-bound EsDscam inhibited the ability of EsDscam with the same extracellular region to promote bacterial phagocytosis. Immunocytochemistry indicated colocalization of the soluble and membrane-bound forms of EsDscam at the hemocyte surface. Far-Western and coimmunoprecipitation assays demonstrated homotypic interactions between EsDscam isoforms. This study provides insights into a mechanism by which soluble Dscam regulates hemocyte phagocytosis via bacteria-specific binding and specific interactions with membrane-bound Dscam as a phagocytic receptor.

  15. Using an improved phagocytosis assay to evaluate the effect of HIV on specific antibodies to pregnancy-associated malaria.

    Science.gov (United States)

    Ataíde, Ricardo; Hasang, Wina; Wilson, Danny W; Beeson, James G; Mwapasa, Victor; Molyneux, Malcolm E; Meshnick, Steven R; Rogerson, Stephen J

    2010-05-25

    Pregnant women residing in malaria endemic areas are highly susceptible to Plasmodium falciparum malaria, particularly during their first pregnancy, resulting in low birth weight babies and maternal anaemia. This susceptibility is associated with placental sequestration of parasitised red blood cells expressing pregnancy-specific variant surface antigens. Acquisition of antibodies against these variant surface antigens may protect women and their offspring. Functions of such antibodies may include prevention of placental sequestration or opsonisation of parasitised cells for phagocytic clearance. Here we report the development and optimisation of a new high-throughput flow cytometry-based phagocytosis assay using undifferentiated Thp-1 cells to quantitate the amount of opsonizing antibody in patient sera, and apply this assay to measure the impact of HIV on the levels of antibodies to a pregnancy malaria-associated parasite line in a cohort of Malawian primigravid women. The assay showed high reproducibility, with inter-experimental correlation of r(2) = 0.99. In primigravid women, concurrent malaria infection was associated with significantly increased antibodies, whereas HIV decreased the ability to acquire opsonising antibodies (Mann-Whitney ranksum: p = 0.013). This decrease was correlated with HIV-induced immunosuppression, with women with less than 350 x 10(6) CD4+ T- cells/L having less opsonising antibodies (coef: -11.95,P = 0.002). Levels of antibodies were not associated with protection from low birth weight or anaemia. This flow cytometry-based phagocytosis assay proved to be efficient and accurate for the measurement of Fc-receptor mediated phagocytosis-inducing antibodies in large cohorts. HIV was found to affect mainly the acquisition of antibodies to pregnancy-specific malaria in primigravidae. Further studies of the relationship between opsonising antibodies to malaria in pregnancy and HIV are indicated.

  16. Phagocytosis of gram-negative bacteria by a unique CD14-dependent mechanism.

    Science.gov (United States)

    Schiff, D E; Kline, L; Soldau, K; Lee, J D; Pugin, J; Tobias, P S; Ulevitch, R J

    1997-12-01

    THP-1-derived cell lines were stably transfected with constructs encoding glycophosphatidylinositol (GPI)-anchored or transmembrane forms of human CD14. CD14 expression was associated with enhanced phagocytosis of serum (heat-inactivated)-opsonized Escherichia coli (opEc). Both the GPI-anchored and transmembrane forms of CD14 supported phagocytosis of opEc equally well. Lipopolysaccharide-binding protein (LBP) played a role in CD14-dependent phagocytosis as evidenced by inhibition of CD14-dependent phagocytosis of opEc with anti-LBP monoclonal antibody (mAb) and by enhanced phagocytosis of E. coli opsonized with purified LBP. CD14-dependent phagocytosis was inhibited by a phosphatidylinositol (PI) 3-kinase inhibitor (wortmannin) and a protein tyrosine kinase inhibitor (tyrphostin 23) but not a protein kinase C inhibitor (bisindolyl-maleimide) or a divalent cation chelator (ethylenediaminetetraacetate). Anti-LBP mAb 18G4 and anti-CD14 mAb 18E12 were used to differentiate between the pathways involved in CD14-dependent phagocytosis and CD14-dependent cell activation. F(ab')2 fragments of 18G4, a mAb to LBP that does not block cell activation, inhibited ingestion of opEc by THP1-wtCD14 cells. 18E12 (an anti-CD14 mAb that does not block LPS binding to CD14 but does inhibit CD14-dependent cell activation) did not inhibit phagocytosis of LBP-opEc by THP1-wtCD14 cells. Furthermore, CD14-dependent phagocytosis was not inhibited by anti-CD18 (CR3 and CR4 beta-chain) or anti-Fcgamma receptor mAb.

  17. A versatile, high through-put, bead-based phagocytosis assay for Plasmodium falciparum

    DEFF Research Database (Denmark)

    Lloyd, Yukie M.; Ngati, Elise P.; Salanti, Ali

    2017-01-01

    Antibody-mediated phagocytosis is an important immune effector mechanism against Plasmodium falciparum-infected erythrocytes (IE); however, current phagocytosis assays use IE collected from infected individuals or from in vitro cultures of P. falciparum, making them prone to high variation....... A simple, high-throughput flow cytometric assay was developed that uses THP-1 cells and fluorescent beads covalently-coupled with the malarial antigen VAR2CSA. The assay is highly repeatable, provides both the overall percent phagocytosis and semi-quantitates the number of antigen-coupled beads...

  18. Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion

    Science.gov (United States)

    Townley, Anna K.; Schmidt, Katy; Hodgson, Lorna; Stephens, David J.

    2012-01-01

    Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture. PMID:22331354

  19. Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion.

    Science.gov (United States)

    Townley, Anna K; Schmidt, Katy; Hodgson, Lorna; Stephens, David J

    2012-02-01

    Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.

  20. The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway.

    Science.gov (United States)

    Roboti, Peristera; Sato, Keisuke; Lowe, Martin

    2015-04-15

    Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER-Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). © 2015. Published by The Company of Biologists Ltd.

  1. Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease is Enhanced by Nrf2 Agonists.

    NARCIS (Netherlands)

    Bewley, Martin A; Budd, Richard C; Ryan, Eilise; Cole, Joby; Collini, Paul; Marshall, Jennifer; Kolsum, Umme; Beech, Gussie; Emes, Richard D; Tcherniaeva, Irina; Berbers, Guy A M; Walmsley, Sarah R; Donaldson, Gavin; Wedzicha, Jadwiga A; Kilty, Iain; Rumsey, William; Sanchez, Yolanda; Brightling, Christopher E; Donnelly, Louise E; Barnes, Peter J; Singh, Dave; Whyte, Moira K B; Dockrell, David H

    2018-01-01

    Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined.

  2. Immunomodulation by gadolinium chloride-induced Kupffer cell phagocytosis blockade

    International Nuclear Information System (INIS)

    Lazar, G.; Husztik, E.; Kiss, I.; Szakacs, J.; Olah, J.

    1998-01-01

    Gadolinium chloride (GdCl 3 ), a rare earth metal salt, depresses macrophage activity, and is commonly used to study the physiology of the reticuloendothelial system. In the present work, the effect of GdCl 3 -induced Kupffer cell blockade on the humoral immune response in mice to sheep red blood cells (SRBC) was investigated. Kupffer cell phagocytosis blockade was found to increase both the primary and secondary immune responses to SRBC. The primary immune response was significantly augmented in animals injected intravenously with GdCl 3 2, 3 or 4 days before injection of the cellular antigen, but GdCl 3 injected 7 days before the antigen did not modify the immune response. Increased secondary humoral immune responses were also observed. When GdCl 3 was injected 2 days before the second dose of antigen, the numbers of both IgM and IgG-producing plaque forming cells were augmented. GdCl 3 injected 2 days before the first dose of SRBC did not modify the humoral immune response. Earlier studies with 51 Cr-labelled foreign red blood cells suggested that the augmentation of the humoral immune response in GdCl 3 -pretreated mice is a consequence of the spillover of the antigen from the liver into the spleen and other extrahepatic reticuloendothelial organs. (orig.)

  3. Phagocytosis and Inflammation: Exploring the effects of the components of E?cigarette vapor on macrophages

    OpenAIRE

    Ween, Miranda P.; Whittall, Jonathan J.; Hamon, Rhys; Reynolds, Paul N.; Hodge, Sandra J.

    2017-01-01

    Abstract E?cigarettes are perceived as harmless; however, evidence of their safety is lacking. New data suggests E?cigarettes discharge a range of compounds capable of physiological damage to users. We previously established that cigarette smoke caused defective alveolar macrophage phagocytosis. The present study compared the effect E?cigarette of components; E?liquid flavors, nicotine, vegetable glycerine, and propylene glycol on phagocytosis, proinflammatory cytokine secretion, and phagocyt...

  4. Alveolar macrophage phagocytosis is enhanced after blunt chest trauma and alters the posttraumatic mediator release.

    Science.gov (United States)

    Seitz, Daniel H; Palmer, Annette; Niesler, Ulrike; Fröba, Janine S; Heidemann, Vera; Rittlinger, Anne; Braumüller, Sonja T; Zhou, Shaoxia; Gebhard, Florian; Knöferl, Markus W

    2011-12-01

    Blunt chest trauma is known to induce a pulmonary invasion of short-lived polymorphonuclear neutrophils and apoptosis of alveolar epithelial type 2 (AT2) cells. Apoptotic cells are removed by alveolar macrophages (AMΦ). We hypothesized that chest trauma alters the phagocytic response of AMΦ as well as the mediator release of AMΦ during phagocytosis. To study this, male Sprague-Dawley rats were subjected to blunt chest trauma. Phagocytosis assays were performed in AMΦ isolated 2 or 24 h after trauma with apoptotic cells or opsonized beads. Phagocytosis of apoptotic AT2 cells by unstimulated AMΦ was significantly increased 2 h after trauma. At 24 h, AMΦ from traumatized animals, stimulated with phorbol-12-myristate-13-acetate, ingested significantly more apoptotic polymorphonuclear neutrophils than AMΦ from sham animals. Alveolar macrophages after trauma released significantly higher levels of tumor necrosis factor α, macrophage inflammatory protein 1α, and cytokine-induced neutrophil chemoattractant 1 when they incorporated latex beads, but significantly lower levels of interleukin 1β and macrophage inflammatory protein 1α when they ingested apoptotic cells. In vivo, phagocytosis of intratracheally instilled latex beads was decreased in traumatized rats. The bronchoalveolar lavage concentrations of the phagocytosis-supporting surfactant proteins A and D after blunt chest trauma were slightly decreased, whereas surfactant protein D mRNA expression in AT2 cells was significantly increased after 2 h. These findings indicate that chest trauma augments the phagocytosis of apoptotic cells by AMΦ. Phagocytosis of opsonized beads enhances and ingestion of apoptotic cells downregulates the immunologic response following lung contusion. Our data emphasize the important role of phagocytosis during posttraumatic inflammation after lung contusion.

  5. Antibiotic-Enhanced Phagocytosis of ’Borrelia recurrentis’ by Blood Polymorphonuclear Leukocytes.

    Science.gov (United States)

    1979-11-30

    hours after Butler 7 institution of antibiotic treatment. Polymorphonuclear leukocytes are known to release endogenous pyrogen after phagocytosis of...other bacteria (6), and endogenous pyrogen may be one of the mediators of the rigor and temperature rise in the Jarisch-Herxheimer reaction (2). Release...the pathogenesis of fever. XII. The effect of phagocytosis on the release of endogenous pyrogen by polymorphonuclear leukocytes. J. Exp. Med. 119:715

  6. SEBAL Model Using to Estimate Irrigation Water Efficiency & Water Requirement of Alfalfa Crop

    Science.gov (United States)

    Zeyliger, Anatoly; Ermolaeva, Olga

    2013-04-01

    The sustainability of irrigation is a complex and comprehensive undertaking, requiring an attention to much more than hydraulics, chemistry, and agronomy. A special combination of human, environmental, and economic factors exists in each irrigated region and must be recognized and evaluated. A way to evaluate the efficiency of irrigation water use for crop production is to consider the so-called crop-water production functions, which express the relation between the yield of a crop and the quantity of water applied to it or consumed by it. The term has been used in a somewhat ambiguous way. Some authors have defined the Crop-Water Production Functions between yield and the total amount of water applied, whereas others have defined it as a relation between yield and seasonal evapotranspiration (ET). In case of high efficiency of irrigation water use the volume of water applied is less than the potential evapotranspiration (PET), then - assuming no significant change of soil moisture storage from beginning of the growing season to its end-the volume of water may be roughly equal to ET. In other case of low efficiency of irrigation water use the volume of water applied exceeds PET, then the excess of volume of water applied over PET must go to either augmenting soil moisture storage (end-of-season moisture being greater than start-of-season soil moisture) or to runoff or/and deep percolation beyond the root zone. In presented contribution some results of a case study of estimation of biomass and leaf area index (LAI) for irrigated alfalfa by SEBAL algorithm will be discussed. The field study was conducted with aim to compare ground biomass of alfalfa at some irrigated fields (provided by agricultural farm) at Saratov and Volgograd Regions of Russia. The study was conducted during vegetation period of 2012 from April till September. All the operations from importing the data to calculation of the output data were carried by eLEAF company and uploaded in Fieldlook web

  7. Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast.

    Science.gov (United States)

    Matsuhara, Hirotada; Yamamoto, Ayumu

    2016-01-01

    Autophagy is a conserved intracellular degradation system, which contributes to development and differentiation of various organisms. Yeast cells undergo meiosis under nitrogen-starved conditions and require autophagy for meiosis initiation. However, the precise roles of autophagy in meiosis remain unclear. Here, we show that autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast. Autophagy-defective strains bearing a mutation in the autophagy core factor gene atg1, atg7, or atg14 exhibit deformed nuclear structures during meiosis. These mutant cells require an extracellular nitrogen supply for meiosis progression following their entry into meiosis and show delayed meiosis progression even with a nitrogen supply. In addition, they show frequent chromosome dissociation from the spindle together with spindle overextension, forming extra nuclei. Furthermore, Aurora kinase, which regulates chromosome segregation and spindle elongation, is significantly increased at the centromere and spindle in the mutant cells. Aurora kinase down-regulation eliminated delayed initiation of meiosis I and II, chromosome dissociation, and spindle overextension, indicating that increased Aurora kinase activity may cause these aberrances in the mutant cells. Our findings show a hitherto unrecognized relationship of autophagy with the nuclear structure, regulation of cell cycle progression, and chromosome segregation in meiosis. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  8. Aquaporins of the PIP2 class are required for efficient anther dehiscence in tobacco.

    Science.gov (United States)

    Bots, Marc; Vergeldt, Frank; Wolters-Arts, Mieke; Weterings, Koen; van As, Henk; Mariani, Celestina

    2005-03-01

    Several processes during sexual reproduction in higher plants involve the movement of water between cells or tissues. Before flower anthesis, anther and pollen dehydration takes place before the release of mature pollen at dehiscence. Aquaporins represent a class of proteins that mediates the movement of water over cellular membranes. Aquaporins of the plasmamembrane PIP2 family are expressed in tobacco (Nicotiana tabacum) anthers and may therefore be involved in the movement of water in this organ. To gain more insight into the role these proteins may play in this process, we have analyzed their localization using immunolocalizations and generated plants displaying RNA interference of PIP2 aquaporins. Our results indicate that PIP2 protein expression is modulated during anther development. Furthermore, in tobacco PIP2 RNA interference plants, anther dehydration was slower, and dehiscence occurred later when compared with control plants. Together, our results suggest that aquaporins of the PIP2 class are required for efficient anther dehydration prior to dehiscence.

  9. Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement.

    Science.gov (United States)

    Wu, Junjun; Zhang, Xia; Zhou, Peng; Huang, Jiaying; Xia, Xiudong; Li, Wei; Zhou, Ziyu; Chen, Yue; Liu, Yinghao; Dong, Mingsheng

    2017-11-01

    Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C 6 -C 10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield. Furthermore, the introduction of formate dehydrogenase from Candida boidinii using fermentative inhibitor byproduct formate as a redox NADH sink improved MCFA titer from initial 1.2g/L to 3.1g/L. Moreover, coupling of increasing the supply of acetyl-CoA with NADH to achieve fermentative redox balance enabled product synthesis at maximum titers. To this end, the acetate re-assimilation pathway was further optimized to increase acetyl-CoA availability associated with the new supply of NADH. It was found that the acetyl-CoA synthetase activity and intracellular ATP levels constrained the activity of acetate re-assimilation pathway, and 4.7g/L of MCFA titer was finally achieved after alleviating these two limiting factors. To the best of our knowledge, this represented the highest titer reported to date. These results demonstrated that the key constraint of r-BOX was redox imbalance and redox engineering could further unleash the lipogenic potential of this cycle. The redox engineering strategies could be applied to acetyl-CoA-derived products or other bio-products requiring multiple redox cofactors for biosynthesis. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  10. Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells.

    Science.gov (United States)

    Panneerdoss, Subbarayalu; Viswanadhapalli, Suryavathi; Abdelfattah, Nourhan; Onyeagucha, Benjamin C; Timilsina, Santosh; Mohammad, Tabrez A; Chen, Yidong; Drake, Michael; Vuori, Kristiina; Kumar, T Rajendra; Rao, Manjeet K

    2017-09-19

    Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.

  11. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

    Directory of Open Access Journals (Sweden)

    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  12. Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells

    Directory of Open Access Journals (Sweden)

    Kimberly A. Wong

    2015-03-01

    Full Text Available Retina formation requires the correct spatiotemporal patterning of key regulatory factors. While it is known that repression of several signaling pathways lead to specification of retinal fates, addition of only Noggin, a known BMP antagonist, can convert pluripotent Xenopus laevis animal cap cells to functional retinal cells. The aim of this study is to determine the intracellular molecular events that occur during this conversion. Surprisingly, blocking BMP signaling alone failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells resulted in a concentration-dependent suppression of both Smad1 and Smad2 phosphorylation, which act downstream of BMP and Activin signaling, respectively. This caused a decrease in downstream targets: endothelial marker, xk81, and mesodermal marker, xbra. We treated pluripotent cells with dominant-negative receptors or the chemical inhibitors, dorsomorphin and SB431542, which each target either the BMP or Activin signaling pathway. We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT assay; in which treated pluripotent cells were transplanted into the eye field of host embryos. We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone. In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542. Future studies could translate these findings to a mammalian culture assay, in order to more efficiently produce retinal cells in culture.

  13. Integrity of the Linker of Nucleoskeleton and Cytoskeleton Is Required for Efficient Herpesvirus Nuclear Egress.

    Science.gov (United States)

    Klupp, Barbara G; Hellberg, Teresa; Granzow, Harald; Franzke, Kati; Dominguez Gonzalez, Beatriz; Goodchild, Rose E; Mettenleiter, Thomas C

    2017-10-01

    Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes. The linker of nucleoskeleton and cytoskeleton (LINC) complex consists of INM proteins with a luminal SUN (Sad1/UNC-84 homology) domain connected to ONM proteins with a KASH (Klarsicht, ANC-1, SYNE homology) domain and is thought to be responsible for spacing the nuclear membranes. To investigate the role of the LINC complex during herpesvirus infection, we generated cell lines constitutively expressing dominant negative (dn) forms of SUN1 and SUN2. Ultrastructural analyses revealed a significant expansion of the PNS and the contiguous intracytoplasmic lumen, most likely representing endoplasmic reticulum (ER), especially in cells expressing dn-SUN2. After infection, primary virions accumulated in these expanded luminal regions, also very distant from the nucleus. The importance of the LINC complex was also confirmed by reduced progeny virus titers in cells expressing dn-SUN2. These data show that the intact LINC complex is required for efficient nuclear egress of herpesviruses, likely acting to promote fusion of primary enveloped virions with the ONM. IMPORTANCE While the viral factors for primary envelopment of nucleocapsids at the inner nuclear membrane are known to the point of high-resolution structures, the roles of cellular components and regulators remain enigmatic. Furthermore, the machinery responsible for fusion with the outer nuclear membrane is unsolved. We show here

  14. Increased ATP generation in the host cell is required for efficient vaccinia virus production

    Directory of Open Access Journals (Sweden)

    Hsu Che-Fang

    2009-09-01

    Full Text Available Abstract To search for cellular genes up-regulated by vaccinia virus (VV infection, differential display-reverse transcription-polymerase chain reaction (ddRT-PCR assays were used to examine the expression of mRNAs from mock-infected and VV-infected HeLa cells. Two mitochondrial genes for proteins that are part of the electron transport chain that generates ATP, ND4 and CO II, were up-regulated after VV infection. Up-regulation of ND4 level by VV infection was confirmed by Western blotting analysis. Up-regulation of ND4 was reduced by the MAPK inhibitor, apigenin, which has been demonstrated elsewhere to inhibit VV replication. The induction of ND4 expression occurred after viral DNA replication since ara C, an inhibitor of poxviral DNA replication, could block this induction. ATP production was increased in the host cells after VV infection. Moreover, 4.5 μM oligomycin, an inhibitor of ATP production, reduced the ATP level 13 hr after virus infection to that of mock-infected cells and inhibited viral protein expression and virus production, suggesting that increased ATP production is required for efficient VV production. Our results further suggest that induction of ND4 expression is through a Bcl-2 independent pathway.

  15. Microglial Phagocytosis and Its Regulation: A Therapeutic Target in Parkinson’s Disease?

    Directory of Open Access Journals (Sweden)

    Elzbieta Janda

    2018-04-01

    Full Text Available The role of phagocytosis in the neuroprotective function of microglia has been appreciated for a long time, but only more recently a dysregulation of this process has been recognized in Parkinson’s disease (PD. Indeed, microglia play several critical roles in central nervous system (CNS, such as clearance of dying neurons and pathogens as well as immunomodulation, and to fulfill these complex tasks they engage distinct phenotypes. Regulation of phenotypic plasticity and phagocytosis in microglia can be impaired by defects in molecular machinery regulating critical homeostatic mechanisms, including autophagy. Here, we briefly summarize current knowledge on molecular mechanisms of microglia phagocytosis, and the neuro-pathological role of microglia in PD. Then we focus more in detail on the possible functional role of microglial phagocytosis in the pathogenesis and progression of PD. Evidence in support of either a beneficial or deleterious role of phagocytosis in dopaminergic degeneration is reported. Altered expression of target-recognizing receptors and lysosomal receptor CD68, as well as the emerging determinant role of α-synuclein (α-SYN in phagocytic function is discussed. We finally discuss the rationale to consider phagocytic processes as a therapeutic target to prevent or slow down dopaminergic degeneration.

  16. Overload training inhibits phagocytosis and ROS generation of peritoneal macrophages: role of IGF-1 and MGF.

    Science.gov (United States)

    Xiao, Weihua; Chen, Peijie; Wang, Ru; Dong, Jingmei

    2013-01-01

    We tested the hypothesis that overload training inhibits the phagocytosis and the reactive oxygen species (ROS) generation of peritoneal macrophages (Mϕs), and that insulin-like growth factor-1(IGF-1) and mechano-growth factor (MGF) produced by macrophages may contribute to this process. Rats were randomized to two groups, sedentary control group (n = 10) and overload training group (n = 10). The rats of overload training group were subjected to 11 weeks of experimental training protocol. Blood sample was used to determine the content of hemoglobin, testosterone, and corticosterone. The phagocytosis and the ROS generation of Mϕs were measured by the uptake of neutral red and the flow cytometry, respectively. IGF-1 and MGF mRNA levels in Mϕs were determined by real-time PCR. In addition, we evaluated the effects of IGF-1 and MGF peptide on phagocytosis and ROS generation of Mϕs in vitro. The data showed that overload training significantly decreased the body weight (19.3 %, P overload training significantly decreased the phagocytosis (27 %, P overload training group increased significantly compared with the control group (21-fold and 92-fold, respectively; P overload training inhibits the phagocytosis and the ROS generation of peritoneal macrophages, and that MGF produced by macrophages may play a key role in this process. This may represent a novel mechanism of immune suppression induced by overload training.

  17. Aliphatic alcohol contaminants of illegally produced spirits inhibit phagocytosis by human granulocytes.

    Science.gov (United States)

    Pál, László; Árnyas, Ervin M; Tóth, Béla; Ádám, Balázs; Rácz, Gábor; Ádány, Róza; McKee, Martin; Szűcs, Sándor

    2013-04-01

    Unregulated production of spirits in many countries leads to products containing appreciable levels of aliphatic alcohols (AAs) and is the main source of human exposure to these substances worldwide. Previous studies have confirmed that alcohol abuse can lead to ethanol-induced immunosuppression and thereby increased susceptibility to infectious diseases. Granulocytes, as professional phagocytic cells, play a crucial role in engulfment and killing of pathogenic microorganisms. Thus, a decrease in their phagocytic activity has been invoked as a factor in the impaired antimicrobial defense observed in alcoholics. However, AAs consumed as contaminants of illicit spirits may also influence phagocytosis, thereby contributing to a further decrease in microbicidal activity but, so far, this has not been studied. Therefore, the aim of this study was to measure granulocyte phagocytosis following treatment of granulocytes with those higher alcohols found in illegal spirits. Granulocytes were isolated from human peripheral blood. Then phagocytosis of opsonized zymosan particles by granulocytes treated with AAs individually and in combination was determined. These alcohols inhibited phagocytosis in a concentration-dependent manner and at lower concentrations when combined than when tested individually. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit phagocytosis in a clinically meaningful way in episodic heavy drinkers.

  18. Improvement of uranium production efficiency to meet China's nuclear power requirements

    International Nuclear Information System (INIS)

    Zhang, R.

    1997-01-01

    Recently China put the Qinshan Nuclear Power Plant, with an installed capacity of 300 MW, in the province of Zhejiang and the Daya Bay Nuclear Power Plant, with a total installed capacity of 2 x 900 MW, in commercial operation. China plans a rapid growth in nuclear power from 1995 to 2010. China's uranium production will therefore also enter a new period with nuclear power increasing. In order to meet the demand of nuclear power for uranium special attention has been paid to both technical progress improvement using management with the aim of reducing the cost of uranium production. The application of the trackless mining technique has enhanced the uranium mining productivity significantly. China has produced a radiometric sorter, model 5421-2 for pre-concentrating uranium run-of-mine ore. This effectively increases the uranium content in mill feed and decreases the operating cost of hydrometallurgical treatment. The in situ leach technique after blasting is applied underground in the Lantian Mine, in addition to the surface heap leaching, and has obtained a perfect result. The concentrated acid-curing, and ferric sulphate trickle leaching process, will soon be used in commercial operation for treating uranium ore grading -5 to -7 mm in size. The annual production capability of the Yining Mine will be extended to 100 tonnes U using improving in situ leaching technology. For the purpose of improving the uranium production efficiency much work has been done optimizing the distribution of production centres. China plans to expand its uranium production to meet the uranium requirements of the developing nuclear power plants. (author). 4 tabs

  19. Improved phosphorus use efficiency in agriculture: a key requirement for its sustainable use.

    Science.gov (United States)

    Schröder, J J; Smit, A L; Cordell, D; Rosemarin, A

    2011-08-01

    Mineral phosphorus (P) fertilizers processed from fossil reserves have enhanced food production over the past 50 years and, hence, the welfare of billions of people. Fertilizer P has, however, not only been used to lift the fertility level of formerly poor soils, but also allowed people to neglect the reuse of P that humans ingest in the form of food and excrete again as faeces and urine and also in other organic wastes. Consequently, P mainly moves in a linear direction from mines to distant locations for crop production, processing and consumption, where a large fraction eventually may become either agronomically inactive due to over-application, unsuitable for recycling due to fixation, contamination or dilution, and harmful as a polluting agent of surface water. This type of P use is not sustainable because fossil phosphate rock reserves are finite. Once the high quality phosphate rock reserves become depleted, too little P will be available for the soils of food-producing regions that still require P supplements to facilitate efficient utilization of resources other than P, including other nutrients. The paper shows that the amounts of P applied in agriculture could be considerably smaller by optimizing land use, improvement of fertilizer recommendations and application techniques, modified livestock diets, and adjustment of livestock densities to available land. Such a concerted set of measures is expected to reduce the use of P in agriculture whilst maintaining crop yields and minimizing the environmental impact of P losses. The paper also argues that compensation of the P exported from farms should eventually be fully based on P recovered from 'wastes', the recycling of which should be stimulated by policy measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. What Types of Policies Are Required for a Constitutionally Sound, Efficient Educational System of Common Schools?

    Science.gov (United States)

    La Brecque, Richard

    This paper clarifies core concepts in a Kentucky judge's decision that the State General Assembly has failed to provide an efficient system of common schools. Connecting "efficiency" of educational systems to "equality of educational opportunity," the paper argues that the realization of a constitutionally sound, efficient…

  1. A Simple Microscopy Assay to Teach the Processes of Phagocytosis and Exocytosis

    Science.gov (United States)

    Gray, Ross; Gray, Andrew; Fite, Jessica L.; Jordan, Renee; Stark, Sarah; Naylor, Kari

    2012-01-01

    Phagocytosis and exocytosis are two cellular processes involving membrane dynamics. While it is easy to understand the purpose of these processes, it can be extremely difficult for students to comprehend the actual mechanisms. As membrane dynamics play a significant role in many cellular processes ranging from cell signaling to cell division to…

  2. Phagocytosis and Inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages.

    Science.gov (United States)

    Ween, Miranda P; Whittall, Jonathan J; Hamon, Rhys; Reynolds, Paul N; Hodge, Sandra J

    2017-08-01

    E-cigarettes are perceived as harmless; however, evidence of their safety is lacking. New data suggests E-cigarettes discharge a range of compounds capable of physiological damage to users. We previously established that cigarette smoke caused defective alveolar macrophage phagocytosis. The present study compared the effect E-cigarette of components; E-liquid flavors, nicotine, vegetable glycerine, and propylene glycol on phagocytosis, proinflammatory cytokine secretion, and phagocytic recognition molecule expression using differentiated THP-1 macrophages. Similar to CSE, phagocytosis of NTHi bacteria was significantly decreased by E-liquid flavoring (11.65-15.75%) versus control (27.01%). Nicotine also decreased phagocytosis (15.26%). E-liquid, nicotine, and E-liquid+ nicotine reduced phagocytic recognition molecules; SR-A1 and TLR-2. IL-8 secretion increased with flavor and nicotine, while TNF α , IL-1 β , IL-6, MIP-1 α , MIP-1 β , and MCP-1 decreased after exposure to most flavors and nicotine. PG, VG, or PG:VG mix also induced a decrease in MIP-1 α and MIP-1 β We conclude that E-cigarettes can cause macrophage phagocytic dysfunction, expression of phagocytic recognition receptors and cytokine secretion pathways. As such, E-cigarettes should be treated with caution by users, especially those who are nonsmokers. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Toxoplasma gondii Requires Glycogen Phosphorylase for Balancing Amylopectin Storage and for Efficient Production of Brain Cysts.

    Science.gov (United States)

    Sugi, Tatsuki; Tu, Vincent; Ma, Yanfen; Tomita, Tadakimi; Weiss, Louis M

    2017-08-29

    In immunocompromised hosts, latent infection with Toxoplasma gondii can reactivate from tissue cysts, leading to encephalitis. A characteristic of T. gondii bradyzoites in tissue cysts is the presence of amylopectin granules. The regulatory mechanisms and role of amylopectin accumulation in this organism are not fully understood. The T. gondii genome encodes a putative glycogen phosphorylase (TgGP), and mutants were constructed to manipulate the activity of TgGP and to evaluate the function of TgGP in amylopectin storage. Both a stop codon mutant (Pru/TgGP S25stop [expressing a Ser-to-stop codon change at position 25 in TgGP]) and a phosphorylation null mutant (Pru/TgGP S25A [expressing a Ser-to-Ala change at position 25 in TgGp]) mutated at Ser25 displayed amylopectin accumulation, while the phosphorylation-mimetic mutant (Pru/TgGP S25E [expressing a Ser-to-Glu change at position 25 in TgGp]) had minimal amylopectin accumulation under both tachyzoite and bradyzoite growth conditions. The expression of active TgGP S25S or TgGP S25E restored amylopectin catabolism in Pru/TgGP S25A To understand the relation between GP and calcium-dependent protein kinase 2 (CDPK2), which was recently reported to regulate amylopectin consumption, we knocked out CDPK2 in these mutants. Pru Δcdpk2 /TgGP S25E had minimal amylopectin accumulation, whereas the Δcdpk2 phenotype in the other GP mutants and parental lines displayed amylopectin accumulation. Both the inactive S25A and hyperactive S25E mutant produced brain cysts in infected mice, but the numbers of cysts produced were significantly less than the number produced by the S25S wild-type GP parasite. Complementation that restored amylopectin regulation restored brain cyst production to the control levels seen in infected mice. These data suggest that T. gondii requires tight regulation of amylopectin expression for efficient production of cysts and persistent infections and that GP phosphorylation is a regulatory mechanism

  4. Current drive efficiency requirements for an attractive steady-state reactor

    Energy Technology Data Exchange (ETDEWEB)

    Tonon, G

    1994-12-31

    The expected values of the figure of merit and the electrical efficiency of various non-inductive current drive methods are considered. The main experimental results achieved today with neutral beams and radiofrequency systems are summarized. Taking into account the simplified energy flow diagram of a steady state reactor, the figure of merit and the electrical efficiency values which are necessary in order to envisage an attractive steady-state reactor are determined. These values are compared to the theoretical predictions. (author). 16 refs., 11 figs., 2 tabs.

  5. Current drive efficiency requirements for an attractive steady-state reactor

    International Nuclear Information System (INIS)

    Tonon, G.

    1994-01-01

    The expected values of the figure of merit and the electrical efficiency of various non-inductive current drive methods are considered. The main experimental results achieved today with neutral beams and radiofrequency systems are summarized. Taking into account the simplified energy flow diagram of a steady state reactor, the figure of merit and the electrical efficiency values which are necessary in order to envisage an attractive steady-state reactor are determined. These values are compared to the theoretical predictions. (author). 16 refs., 11 figs., 2 tabs

  6. STUDIES ON THE PATHOGENESIS OF FEVER. 13. THE EFFECT OF PHAGOCYTOSIS ON THE RELEASE OF ENDOGENOUS PYROGEN BY POLYMORPHONUCLEAR LEUKOCYTES.

    Science.gov (United States)

    BERLIN, R D; WOOD, W B

    1964-05-01

    1. Phagocytosis promotes the release of endogenous pyrogen from polymorphonuclear leucocytes. 2. The release of pyrogen, though initiated by the phagocytic event, is not synchronous with it. 3. The postphagocytic release mechanism is not inhibited by sodium fluoride and, therefore, appears not to require continued production of energy by the cell. 4. The release process, on the other hand, is inhibited by arsenite, suggesting the participation of one or more sulfhydryl-dependent enzymes in the over-all reaction. 5. Particle for particle, the ingestion of heat-killed rough pneumococci causes the release of approximately 100 times as much pyrogen as the ingestion of polystyrene beads of the same size. 6. The pyrogen release mechanism of polymorphonuclear leucocytes separated directly from blood, unlike that of granulocytes in acute inflammatory exudates, is not readily activated by incubation of the cells in K-free saline. Despite this difference, both blood and exudate leucocytes following phagocytosis release large amounts of pyrogen, even in the presence of K(+). The fact that the postphagocytic reaction is uninhibited by the concentrations of K(+) which are present in plasma and extracellular fluids, suggests that this mechanism of pyrogen release may well operate in vivo. 7. As might be expected from the foregoing observations, the intravenous injection of a sufficiently large number of heat-killed pneumococci causes fever in the intact host. Intravenously injected polystyrene beads, on the other hand, are significantly less pyrogenic. Evidence is presented to support the conclusion that the fever in both instances is caused by pyrogen released from the circulating leucocytes which have phagocyted the injected particles. 8. The possible relationships of these findings to the pathogenesis of fevers caused by acute bacterial infections are discussed.

  7. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Nagaya, Yoshiaki; Asai, Hayato; Hussein, Mohamed Hamed; Suzuki, Mieko; Kato, Shin; Saitoh, Shinji; Asai, Kiyofumi

    2013-01-01

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N G -monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for IAE

  8. LRRK2 kinase inhibition prevents pathological microglial phagocytosis in response to HIV-1 Tat protein

    Directory of Open Access Journals (Sweden)

    Marker Daniel F

    2012-11-01

    Full Text Available Abstract Background Human Immunodeficiency Virus-1 (HIV-1 associated neurocognitive disorders (HANDs are accompanied by significant morbidity, which persists despite the use of combined antiretroviral therapy (cART. While activated microglia play a role in pathogenesis, changes in their immune effector functions, including phagocytosis and proinflammatory signaling pathways, are not well understood. We have identified leucine-rich repeat kinase 2 (LRRK2 as a novel regulator of microglial phagocytosis and activation in an in vitro model of HANDs, and hypothesize that LRRK2 kinase inhibition will attenuate microglial activation during HANDs. Methods We treated BV-2 immortalized mouse microglia cells with the HIV-1 trans activator of transcription (Tat protein in the absence or presence of LRRK2 kinase inhibitor (LRRK2i. We used Western blot, qRT-PCR, immunocytochemistry and latex bead engulfment assays to analyze LRRK2 protein levels, proinflammatory cytokine and phagocytosis receptor expression, LRRK2 cellular distribution and phagocytosis, respectively. Finally, we utilized ex vivo microfluidic chambers containing primary hippocampal neurons and BV-2 microglia cells to investigate microglial phagocytosis of neuronal axons. Results We found that Tat-treatment of BV-2 cells induced kinase activity associated phosphorylation of serine 935 on LRRK2 and caused the formation of cytoplasmic LRRK2 inclusions. LRRK2i decreased Tat-induced phosphorylation of serine 935 on LRRK2 and inhibited the formation of Tat-induced cytoplasmic LRRK2 inclusions. LRRK2i also decreased Tat-induced process extension in BV-2 cells. Furthermore, LRRK2i attenuated Tat-induced cytokine expression and latex bead engulfment. We examined relevant cellular targets in microfluidic chambers and found that Tat-treated BV-2 microglia cells cleared axonal arbor and engulfed neuronal elements, whereas saline treated controls did not. LRRK2i was found to protect axons in the presence

  9. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Kakita, Hiroki [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aoyama, Mineyoshi, E-mail: ao.mine@med.nagoya-cu.ac.jp [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Nagaya, Yoshiaki; Asai, Hayato [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Hussein, Mohamed Hamed [Neonatal Intensive Care Unit, Pediatric Hospital, Cairo University, Cairo 11559 (Egypt); Maternal and Child Health Department, VACSERA, 51 Wizaret El-Zeraa-Agouza, Giza 22311 (Egypt); Suzuki, Mieko [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Kato, Shin [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Saitoh, Shinji [Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-04-15

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N{sup G}-monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for

  10. Transforming Functional Requirements from UML into BPEL to Efficiently Develop SOA-Based Systems

    Science.gov (United States)

    Vemulapalli, Anisha; Subramanian, Nary

    The intended behavior of any system such as services, tasks or functions can be captured by functional requirements of the system. As our dependence on online services has grown steadily, the web applications are being developed employing the SOA. BPEL4WS provides a means for expressing functional requirements of an SOA-based system by providing constructs to capture business goals and objectives for the system. In this paper we propose an approach for transforming user-centered requirements captured using UML into a corresponding BPEL specification, where the business processes are captured by means of use-cases from which UML sequence diagrams and activity diagrams are extracted. Subsequently these UML models are mapped to BPEL specifications that capture the essence of the initial business requirements to develop the SOA-based system by employing CASE tools. A student housing system is used as a case study to illustrate this approach and the system is validated using NetBeans.

  11. Efficient cellular release of Rift Valley fever virus requires genomic RNA.

    Directory of Open Access Journals (Sweden)

    Mary E Piper

    2011-03-01

    Full Text Available The Rift Valley fever virus is responsible for periodic, explosive epizootics throughout sub-Saharan Africa. The development of therapeutics targeting this virus is difficult due to a limited understanding of the viral replicative cycle. Utilizing a virus-like particle system, we have established roles for each of the viral structural components in assembly, release, and virus infectivity. The envelope glycoprotein, Gn, was discovered to be necessary and sufficient for packaging of the genome, nucleocapsid protein and the RNA-dependent RNA polymerase into virus particles. Additionally, packaging of the genome was found to be necessary for the efficient release of particles, revealing a novel mechanism for the efficient generation of infectious virus. Our results identify possible conserved targets for development of anti-phlebovirus therapies.

  12. Energy-efficient houses built according to the energy performance requirements introduced in Denmark in 2006

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Rose, Jørgen; Svendsen, Svend

    2007-01-01

    In order to meet new tighter building energy requirements introduced in Denmark in 2006 and prepare the way for future buildings with even lower energy consumption, single-family houses were built with the purpose to demonstrate that it is possible to build typical single-family houses with an en......% of the required and almost the level of typical passive houses.......In order to meet new tighter building energy requirements introduced in Denmark in 2006 and prepare the way for future buildings with even lower energy consumption, single-family houses were built with the purpose to demonstrate that it is possible to build typical single-family houses...... with an energy consumption that meets the demands without problems concerning building technology or economy. The paper gives a brief presentation of the houses and the applied energy-saving measures. The paper also presents results from measurements of the overall energy use, indoor climate and air tightness...

  13. National Energy Efficiency Evaluation, Measurement and Verification (EM&V) Standard: Scoping Study of Issues and Implementation Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Schiller Consulting, Inc.; Schiller, Steven R.; Goldman, Charles A.; Galawish, Elsia

    2011-02-04

    This report is a scoping study that identifies issues associated with developing a national evaluation, measurement and verification (EM&V) standard for end-use, non-transportation, energy efficiency activities. The objectives of this study are to identify the scope of such a standard and define EM&V requirements and issues that will need to be addressed in a standard. To explore these issues, we provide and discuss: (1) a set of definitions applicable to an EM&V standard; (2) a literature review of existing guidelines, standards, and 'initiatives' relating to EM&V standards as well as a review of 'bottom-up' versus 'top-down' evaluation approaches; (3) a summary of EM&V related provisions of two recent federal legislative proposals (Congressman Waxman's and Markey's American Clean Energy and Security Act of 2009 and Senator Bingaman's American Clean Energy Leadership Act of 2009) that include national efficiency resource requirements; (4) an annotated list of issues that that are likely to be central to, and need to be considered when, developing a national EM&V standard; and (5) a discussion of the implications of such issues. There are three primary reasons for developing a national efficiency EM&V standard. First, some policy makers, regulators and practitioners believe that a national standard would streamline EM&V implementation, reduce costs and complexity, and improve comparability of results across jurisdictions; although there are benefits associated with each jurisdiction setting its own EM&V requirements based on their specific portfolio and evaluation budgets and objectives. Secondly, if energy efficiency is determined by the US Environmental Protection Agency to be a Best Available Control Technology (BACT) for avoiding criteria pollutant and/or greenhouse gas emissions, then a standard can be required for documenting the emission reductions resulting from efficiency actions. The third reason for a national

  14. The base excision repair pathway is required for efficient lentivirus integration.

    Directory of Open Access Journals (Sweden)

    Kristine E Yoder

    Full Text Available An siRNA screen has identified several proteins throughout the base excision repair (BER pathway of oxidative DNA damage as important for efficient HIV infection. The proteins identified included early repair factors such as the base damage recognition glycosylases OGG1 and MYH and the late repair factor POLß, implicating the entire BER pathway. Murine cells with deletions of the genes Ogg1, Myh, Neil1 and Polß recapitulate the defect of HIV infection in the absence of BER. Defective infection in the absence of BER proteins was also seen with the lentivirus FIV, but not the gammaretrovirus MMLV. BER proteins do not affect HIV infection through its accessory genes nor the central polypurine tract. HIV reverse transcription and nuclear entry appear unaffected by the absence of BER proteins. However, HIV integration to the host chromosome is reduced in the absence of BER proteins. Pre-integration complexes from BER deficient cell lines show reduced integration activity in vitro. Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins.

  15. Changing the Army’s Weapon Training Strategies to Meet Operational Requirements More Efficiently and Effectively

    Science.gov (United States)

    2014-01-01

    psycho -motor skills. Other major weapon systems are more supported by technology and require crews or units collectively applying procedures rapidly and...Army can take to improve its train- ing and leader development management processes and architectures . The directions for improvement outlined in this...activity; (4) enhance ATLD and Army-wide information technology architectures to improve data collection and analysis; and (5) evolve emerging ATLD

  16. Cell Surface Glycosylation Is Required for Efficient Mating of Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Yarden Shalev

    2017-07-01

    Full Text Available Halophilic archaea use a fusion-based mating system for lateral gene transfer across cells, yet the molecular mechanisms involved remain unknown. Previous work implied that cell fusion involves cell–cell recognition since fusion occurs more efficiently between cells from the same species. Long believed to be restricted only to Eukarya, it is now known that cells of all three domains of life perform N-glycosylation, the covalent attachment of glycans to select target asparagine residues in proteins, and that this post-translational modification is common for archaeal cell surface proteins. Here, we show that differences in glycosylation of the Haloferax volcanii surface-layer glycoprotein, brought about either by changing medium salinity or by knocking out key glycosylation genes, reduced mating success. Thus, different glycosylation patterns are likely to underlie mating preference in halophilic archaea, contributing to speciation processes.

  17. LABOUR-USE EFFICIENCY BY SMALLHOLDER YAM FARMERS IN ABIA STATE NIGERIA: A LABOUR-USE REQUIREMENT FRONTIER APPROACH

    Directory of Open Access Journals (Sweden)

    Chidozie Onyedikachi Anyiro

    2013-07-01

    Full Text Available Production of yam is a labour intensive set of activities especially in the Tropics. In Eastern Nigeria this is done by small farmers at subsistent level due to inadequate and short supply of labour. This study examined labour-use efficiency by smallholder yam farmers in Abia State, Nigeria. A two-stage random sampling technique was used to select 120 smallholder yam farmers from Ikwuano and Umuahia North Local Government Areas of the state. Data were collected during a survey with a wellstructured questionnaire administered by personal interview method with the farmers. The result revealed that farm households provided an average of 336 man-days used in yam production activities, with 36.66% using hired labour while family labour, share croppers, and exchange labour provided the balance labour (63.34% required. The Cobb-Douglas functional form of labour-use frontier estimates shows that the quantity of harvested yam, size of cleared farm land and quantity of fertilizer applied significantly affected the amount of labour used in yam production at 10.0%, 5.0% and 1.0% level of significance respectively. The socio-economic determinants of labour use efficiency were age, education, farm size, gender, labour wage and household size which were statistically significant at 1.0% risk level except the coefficient of age which was significant at 5.0% risk level. The result showed that the estimated farm labour-use efficiency ranged from 0.20 to 0.97 with a mean labour-use efficiency value of 0.76. Policies aimed at increasing yam farmers’ scale of operation through improved access to production inputs like fertilizer, agrochemical and capital are required for increasing labour use efficiency in the area.

  18. Diversity and Versatility of Phagocytosis: Roles in Innate Immunity, Tissue Remodeling, and Homeostasis.

    Science.gov (United States)

    Lim, Justin J; Grinstein, Sergio; Roth, Ziv

    2017-01-01

    Phagocytosis, a critical early event in the microbicidal response of neutrophils, is now appreciated to serve multiple functions in a variety of cell types. Professional phagocytes play a central role in innate immunity by eliminating pathogenic bacteria, fungi and malignant cells, and contribute to adaptive immunity by presenting antigens to lymphocytes. In addition, phagocytes play a part in tissue remodeling and maintain overall homeostasis by disposing of apoptotic cells, a task shared by non-professional phagocytes, often of epithelial origin. This functional versatility is supported by a vast array of receptors capable of recognizing a striking variety of foreign and endogenous ligands. Here we present an abbreviated overview of the different types of phagocytes, their varied modes of signaling and particle engulfment, and the multiple physiological roles of phagocytosis.

  19. Influence of Corynebacterium parvum on the phagocytosis of /sup 198/Au colloids in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bergoc, R.M.; Bianchin, A.M.; Caro, R.A.; Ihlo, J.E.; Rivera, E.S. (Buenos Aires Univ. Nacional (Argentina). Facultad de Farmacia y Bioquimica)

    1982-07-01

    The kinetics of the phagocytosis of gelatin-protected /sup 198/Au colloids in Wistar rats treated with Corynebacterium Parvum (CBP), was studied in order to explain its mechanism of immunomodulation. A previously developed extracorporeal blood circulation technique was used. The changes in the rate of phagocytosis, v, after the administration of CBP, for a dose of the /sup 198/Au colloid smaller or higher than the substratum constant, were studied. In the first case, no significant changes of v were observed; in the second case, significant increases of v were determined, which reached a maximum 6 days after the CBP administration. The kinetic analysis of the obtained data indicates that the action of CBP is exerted on the stage of the entrance of the colloidal particle into the reticuloendothelial cell.

  20. Influence of Corynebacterium parvum on the phagocytosis of 198Au colloids in rats

    International Nuclear Information System (INIS)

    Bergoc, R.M.; Bianchin, A.M.; Caro, R.A.; Ihlo, J.E.; Rivera, E.S.

    1982-01-01

    The kinetics of the phagocytosis of gelatin-protected 198 Au colloids in Wistar rats treated with Corynebacterium Parvum (CBP), was studied in order to explain its mechanism of immunomodulation. A previously developed extracorporeal blood circulation technique was used. The changes in the rate of phagocytosis, v, after the administration of CBP, for a dose of the 198 Au colloid smaller or higher than the substratum constant, were studied. In the first case, no significant changes of v were observed; in the second case, significant increases of v were determined, which reached a maximum 6 days after the CBP administration. The kinetic analysis of the obtained data indicates that the action of CBP is exerted on the stage of the entrance of the colloidal particle into the reticuloendothelial cell. (author) [es

  1. Inhaled corticosteroid treatment for 6?months was not sufficient to normalize phagocytosis in asthmatic children

    OpenAIRE

    da Silva-Martins, Carmen L?via Faria; Couto, Shirley Claudino; Muniz-Junqueira, Maria Imaculada

    2013-01-01

    Background Corticosteroids are the first-line therapy for asthma; however, the effect of corticosteroids on the innate immune system remains unclear. This study?s objective was to evaluate the effect of inhaled corticosteroid therapy (ICT) on phagocytic functions. Methods To evaluate the impact of ICT, the phagocytosis of Saccharomyces cerevisiae by blood monocytes and neutrophils and the production of superoxide anions were assessed before and after three and six months of ICT treatment in 5...

  2. Phagocytosis by Thrombocytes is a Conserved Innate Immune Mechanism in Lower Vertebrates

    OpenAIRE

    Nagasawa, Takahiro; Nakayasu, Chihaya; Rieger, Aja M.; Barreda, Daniel R.; Somamoto, Tomonori; Nakao, Miki

    2014-01-01

    Thrombocytes, nucleated hemostatic blood cells of non-mammalian vertebrates, are regarded as the functional equivalent of anucleated mammalian platelets. Additional immune functions, including phagocytosis, have also been suggested for thrombocytes, but no conclusive molecular or cellular experimental evidence for their potential ingestion and clearance of infiltrating microbes has been provided till date. In the present study, we demonstrate the active phagocytic ability of thrombocytes in l...

  3. Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

    Directory of Open Access Journals (Sweden)

    Grace E Cooper

    Full Text Available Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function. Human monocyte-derived macrophages (MDM were exposed to H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV or UV-irradiated virus. No infection of MDM was seen upon exposure to UV-irradiated virus but incubation with live X31 or M37 resulted in significant levels of viral detection by flow cytometry or RT-PCR respectively. Infection resulted in significantly diminished uptake of S. pneumoniae by MDM and significantly decreased expression of CD36 at both the cell surface and mRNA level. Concurrently, there was a significant increase in IFNβ gene expression in response to infection and we observed a significant decrease in bacterial phagocytosis (p = 0.031 and CD36 gene expression (p = 0.031 by MDM cultured for 24 h in 50IU/ml IFNβ. Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was mimicked by transfection reagent alone. When MDM were incubated with CD36 blocking antibodies no effect on phagocytic ability was observed. These data indicate that autologous IFNβ production by virally-infected cells can inhibit bacterial phagocytosis, but that decreased CD36 expression by these cells does not play a major role in this functional deficiency.

  4. Microgrids: An emerging paradigm for meeting building electricityand heat requirements efficiently and with appropriate energyquality

    Energy Technology Data Exchange (ETDEWEB)

    Marnay, Chris; Firestone, Ryan

    2007-04-10

    The first major paradigm shift in electricity generation,delivery, and control is emerging in the developed world, notably Europe,North America, and Japan. This shift will move electricity supply awayfrom the highly centralised universal service quality model with which weare familiar today towards a more dispersed system with heterogeneousqualities of service. One element of dispersed control is the clusteringof sources and sinks into semi-autonomous mu grids (microgrids).Research, development, demonstration, and deployment (RD3) of mu gridsare advancing rapidly on at least three continents, and significantdemonstrations are currently in progress. This paradigm shift will resultin more electricity generation close to end-uses, often involvingcombined heat and power application for building heating and cooling,increased local integration of renewables, and the possible provision ofheterogeneous qualities of electrical service to match the requirementsof various end-uses. In Europe, mu grid RD3 is entering its third majorround under the 7th European Commission Framework Programme; in the U.S.,one specific mu grid concept is undergoing rigorous laboratory testing,and in Japan, where the most activity exists, four major publiclysponsored and two privately sponsored demonstrations are in progress.This evolution poses new challenges to the way buildings are designed,built, and operated. Traditional building energy supply systems willbecome much more complex in at least three ways: 1. one cannot simplyassume gas arrives at the gas meter, electricity at its meter, and thetwo systems are virtually independent of one another; rather, energyconversion, heat recovery and use, and renewable energy harvesting mayall be taking place simultaneously within the building energy system; 2.the structure of energy flows in the building must accommodate multipleenergy processes in a manner that permits high overall efficiency; and 3.multiple qualities of electricity may be supplied to

  5. Inertia may limit efficiency of slow flapping flight, but mayflies show a strategy for reducing the power requirements of loiter

    International Nuclear Information System (INIS)

    Usherwood, James R

    2009-01-01

    Predictions from aerodynamic theory often match biological observations very poorly. Many insects and several bird species habitually hover, frequently flying at low advance ratios. Taking helicopter-based aerodynamic theory, wings functioning predominantly for hovering, even for quite small insects, should operate at low angles of attack. However, insect wings operate at very high angles of attack during hovering; reduction in angle of attack should result in considerable energetic savings. Here, I consider the possibility that selection of kinematics is constrained from being aerodynamically optimal due to the inertial power requirements of flapping. Potential increases in aerodynamic efficiency with lower angles of attack during hovering may be outweighed by increases in inertial power due to the associated increases in flapping frequency. For simple hovering, traditional rotary-winged helicopter-like micro air vehicles would be more efficient than their flapping biomimetic counterparts. However, flapping may confer advantages in terms of top speed and manoeuvrability. If flapping-winged micro air vehicles are required to hover or loiter more efficiently, dragonflies and mayflies suggest biomimetic solutions

  6. Alginate-Derived Oligosaccharide Inhibits Neuroinflammation and Promotes Microglial Phagocytosis of β-Amyloid

    Directory of Open Access Journals (Sweden)

    Rui Zhou

    2015-09-01

    Full Text Available Alginate from marine brown algae has been widely applied in biotechnology. In this work, the effects of alginate-derived oligosaccharide (AdO on lipopolysaccharide (LPS/β-amyloid (Aβ-induced neuroinflammation and microglial phagocytosis of Aβ were studied. We found that pretreatment of BV2 microglia with AdO prior to LPS/Aβ stimulation led to a significant inhibition of production of nitric oxide (NO and prostaglandin E2 (PGE2, expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 and secretion of proinflammatory cytokines. We further demonstrated that AdO remarkably attenuated the LPS-activated overexpression of toll-like receptor 4 (TLR4 and nuclear factor (NF-κB in BV2 cells. In addition to the impressive inhibitory effect on neuroinflammation, we also found that AdO promoted the phagocytosis of Aβ through its interaction with TLR4 in microglia. Our results suggested that AdO exerted the inhibitory effect on neuroinflammation and the promotion effect on microglial phagocytosis, indicating its potential as a nutraceutical or therapeutic agent for neurodegenerative diseases, particularly Alzheimer’s disease (AD.

  7. Phagocytosis by macrophages mediated by receptors for denatured proteins - dependence on tyrosine protein kinases

    Directory of Open Access Journals (Sweden)

    M.R. Hespanhol

    2002-03-01

    Full Text Available Previous studies have demonstrated that some components of the leukocyte cell membrane, CR3 (Mac-1, CD11b/CD18 and p150/95, are able to bind to denatured proteins. Thus, it is of interest to know which effector functions of these cells can be triggered by these receptors when they interact with particles or surfaces covered with denatured proteins. In the present study we analyzed their possible role as mediators of phagocytosis of red cells covered with denatured bovine serum albumin (BSA by mouse peritoneal macrophages. We observed that a macrophages are able to recognize (bind to these red cells, b this interaction can be inhibited by denatured BSA in the fluid phase, c there is no phagocytosis of these particles by normal macrophages, d phagocytosis mediated by denatured BSA can be, however, effectively triggered in inflammatory macrophages induced by glycogen or in macrophages activated in vivo with LPS, and e this phagocytic capacity is strongly dependent on the activity of tyrosine protein kinases in its signal transduction pathway, as demonstrated by using three kinds of enzyme inhibitors (genistein, quercetin and herbimycin A.

  8. Rab20 regulates phagosome maturation in RAW264 macrophages during Fc gamma receptor-mediated phagocytosis.

    Directory of Open Access Journals (Sweden)

    Youhei Egami

    Full Text Available Rab20, a member of the Rab GTPase family, is known to be involved in membrane trafficking, however its implication in FcγR-mediated phagocytosis is unclear. We examined the spatiotemporal localization of Rab20 during phagocytosis of IgG-opsonized erythrocytes (IgG-Es in RAW264 macrophages. By the live-cell imaging of fluorescent protein-fused Rab20, it was shown that Rab20 was transiently associated with the phagosomal membranes. During the early stage of phagosome formation, Rab20 was not localized on the membranes of phagocytic cups, but was gradually recruited to the newly formed phagosomes. Although Rab20 was colocalized with Rab5 to some extent, the association of Rab20 with the phagosomes persisted even after the loss of Rab5 from the phagosomal membranes. Then, Rab20 was colocalized with Rab7 and Lamp1, late endosomal/lysosomal markers, on the internalized phagosomes. Moreover, our analysis of Rab20 mutant expression revealed that the maturation of phagosomes was significantly delayed in cells expressing the GDP-bound mutant Rab20-T19N. These data suggest that Rab20 is an important component of phagosome and regulates the phagosome maturation during FcγR-mediated phagocytosis.

  9. Effects of pentachlorophenol on survival of earthworms (Lumbricus terrestris) and phagocytosis by their immunoactive coelomocytes

    Energy Technology Data Exchange (ETDEWEB)

    Giggleman, M.A.; Fitzpatrick, L.C.; Goven, A.J. [Univ. of North Texas, Denton, TX (United States); Venables, B.J. [TRAC Labs., Denton, TX (United States)

    1998-12-01

    Earthworms, Lumbricus terrestris, exposed for 96 h to filter paper saturated with five nominal concentrations of pentachlorophenol, exhibited a 50% lethal concentration (LC50) of 25.0 {micro}g PCP/cm{sup 2} and corresponding whole worm body burden-based 50% lethal dose (LD50) of 877.7 {micro}g PCP/g dry mass. Linear regression modeling showed that worms increased body concentrations (BC = {micro}g PCP/g dry tissue mass) with increasing exposure concentrations (EC) according to BC = 113.5 + 29.5EC. Phagocytosis of yeast cells by immunoactive coelomocytes was suppressed only at body concentrations (863.3 {micro}g PCP/g dry mass) that approximated the calculated LD50 and overlapped those demonstrating lethality, indicating a sharp transition between sublethal and lethal toxicity. An exposure concentration of 15 {micro}g PCP/cm{sup 2} produced significant suppression of phagocytosis of yeast cells by immunoactive coelomocytes. However, the average measured body burden from this group approximated the estimated LD50, indicating a sharp toxic response slope. Exposure to 10 {micro}g PCP/cm{sup 2} with a corresponding body concentration of 501.3 {micro}g PCP/g dry mass did not affect phagocytosis. The importance of body burden data is emphasized.

  10. A novel flow cytometric assay for measurement of In Vivo pulmonary neutrophil phagocytosis

    Directory of Open Access Journals (Sweden)

    Gentry-Nielsen Martha J

    2006-07-01

    Full Text Available Abstract Background Phagocytosis assays are traditionally performed in vitro using polymorphonuclear leukocytes (PMNs isolated from peripheral blood or the peritoneum and heat-killed, pre-opsonized organisms. These assays may not adequately mimic the environment within the infected lung. Our laboratory therefore has developed a flow cytometric in vivo phagocytosis assay that enables quantification of PMN phagocytosis of viable bacteria within the lungs of rats. In these studies, rats are injected transtracheally with lipopolysaccharide (LPS to recruit PMNs to their lungs. They are then infected with live 5(-and 6 carboxyfluorescein diacetate succinimidyl ester (CFDA/SE labeled type 3 Streptococcus pneumoniae. Bronchoalveolar lavage is performed and resident alveolar macrophages and recruited PMNs are labeled with monoclonal antibodies specific for surface epitopes on each cell type. Three color flow cytometry is utilized to identify the cell types, quantify recruitment, and determine uptake of the labeled bacteria. Results The viability of the alveolar macrophages and PMNs isolated from the lavage fluid was >95%. The values of the percentage of PMNs in the lavage fluid as well as the percentage of PMNs associated with CFSE-labeled S. pneumoniae as measured through flow cytometry showed a high degree of correlation with the results from manual counting of cytospin slides. Conclusion This assay is suitable for measuring bacterial uptake within the infected lung. It can be adapted for use with other organisms and/or animal model systems.

  11. Epstein-Barr Virus BKRF4 Gene Product Is Required for Efficient Progeny Production.

    Science.gov (United States)

    Masud, H M Abdullah Al; Watanabe, Takahiro; Yoshida, Masahiro; Sato, Yoshitaka; Goshima, Fumi; Kimura, Hiroshi; Murata, Takayuki

    2017-12-01

    Epstein-Barr virus (EBV), a member of human gammaherpesvirus, infects mainly B cells. EBV has two alternative life cycles, latent and lytic, and is reactivated occasionally from the latent stage to the lytic cycle. To combat EBV-associated disorders, understanding the molecular mechanisms of the EBV lytic replication cycle is also important. Here, we focused on an EBV lytic gene, BKRF4. Using our anti-BKRF4 antibody, we revealed that the BKRF4 gene product is expressed during the lytic cycle with late kinetics. To characterize the role of BKRF4, we constructed BKRF4-knockout mutants using the bacterial artificial chromosome (BAC) and CRISPR/Cas9 systems. Although disruption of the BKRF4 gene had almost no effect on viral protein expression and DNA synthesis, it significantly decreased progeny virion levels in HEK293 and Akata cells. Furthermore, we show that BKRF4 is involved not only in production of progeny virions but also in increasing the infectivity of the virus particles. Immunoprecipitation assays revealed that BKRF4 interacted with a virion protein, BGLF2. We showed that the C-terminal region of BKRF4 was critical for this interaction and for efficient progeny production. Immunofluorescence analysis revealed that BKRF4 partially colocalized with BGLF2 in the nucleus and perinuclear region. Finally, we showed that BKRF4 is a phosphorylated, possible tegument protein and that the EBV protein kinase BGLF4 may be important for this phosphorylation. Taken together, our data suggest that BKRF4 is involved in the production of infectious virions. IMPORTANCE Although the latent genes of EBV have been studied extensively, the lytic genes are less well characterized. This study focused on one such lytic gene, BKRF4, which is conserved only among gammaherpesviruses (ORF45 of Kaposi's sarcoma-associated herpesvirus or murine herpesvirus 68). After preparing the BKRF4 knockout virus using B95-8 EBV-BAC, we demonstrated that the BKRF4 gene was involved in infectious

  12. Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins.

    Science.gov (United States)

    Aguilera, Cristina; Fernández-Majada, Vanessa; Inglés-Esteve, Julia; Rodilla, Verónica; Bigas, Anna; Espinosa, Lluís

    2006-09-01

    IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and IkappaBalpha proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of IkappaBalpha in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or IkappaBalpha results in a predominantly nuclear distribution of both proteins. TNFalpha treatment promotes recruitment of 14-3-3 and IkappaBalpha to NFkappaB-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-IkappaBalpha complexes and the constitutive association of p65 with the chromatin. In this situation, NFkappaB-dependent genes become unresponsive to TNFalpha stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of IkappaBalpha-p65 complexes and are required for the appropriate regulation of NFkappaB signaling.

  13. Efficient system modules to meet the communication requirements in the mining industry; Leistungsfaehige Systembausteine zur Erfuellung der Kommunikationsanforderungen des Bergbaus

    Energy Technology Data Exchange (ETDEWEB)

    Becker, F. [Becker Mining Systems GmbH, Friedrichsthal (Germany)

    2006-11-07

    Communication technology has become an important module of efficient operation of a mine. The exchange of information with technical aids takes place between man and machines as participants in communication. The diversity of the requirements associated with the need for communication in a mine can be mastered only by a wide portfolio of suitable technical components. In addition to the technical serviceability of the individual components the ergonomic handling and economic efficiency of the entire production operation must also be ensured. For this purpose it is necessary to design the individual technical modules in such a way that despite their different appearance they interact as a system and thus make available an integrated and transparent communication network to the mine. (orig.)

  14. Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.

    Science.gov (United States)

    Gray, Lawrence R; Sultana, Mst Rasheda; Rauckhorst, Adam J; Oonthonpan, Lalita; Tompkins, Sean C; Sharma, Arpit; Fu, Xiaorong; Miao, Ren; Pewa, Alvin D; Brown, Kathryn S; Lane, Erin E; Dohlman, Ashley; Zepeda-Orozco, Diana; Xie, Jianxin; Rutter, Jared; Norris, Andrew W; Cox, James E; Burgess, Shawn C; Potthoff, Matthew J; Taylor, Eric B

    2015-10-06

    Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. GIMAP6 is required for T cell maintenance and efficient autophagy in mice.

    Science.gov (United States)

    Pascall, John C; Webb, Louise M C; Eskelinen, Eeva-Liisa; Innocentin, Silvia; Attaf-Bouabdallah, Noudjoud; Butcher, Geoffrey W

    2018-01-01

    The GTPases of the immunity-associated proteins (GIMAP) GTPases are a family of proteins expressed strongly in the adaptive immune system. We have previously reported that in human cells one member of this family, GIMAP6, interacts with the ATG8 family member GABARAPL2, and is recruited to autophagosomes upon starvation, suggesting a role for GIMAP6 in the autophagic process. To study this possibility and the function of GIMAP6 in the immune system, we have established a mouse line in which the Gimap6 gene can be inactivated by Cre-mediated recombination. In mice bred to carry the CD2Cre transgene such that the Gimap6 gene was deleted within the T and B cell lineages there was a 50-70% reduction in peripheral CD4+ and CD8+ T cells. Analysis of splenocyte-derived proteins from these mice indicated increased levels of MAP1LC3B, particularly the lipidated LC3-II form, and S405-phosphorylation of SQSTM1. Electron microscopic measurements of Gimap6-/- CD4+ T cells indicated an increased mitochondrial/cytoplasmic volume ratio and increased numbers of autophagosomes. These results are consistent with autophagic disruption in the cells. However, Gimap6-/- T cells were largely normal in character, could be effectively activated in vitro and supported T cell-dependent antibody production. Treatment in vitro of CD4+ splenocytes from GIMAP6fl/flERT2Cre mice with 4-hydroxytamoxifen resulted in the disappearance of GIMAP6 within five days. In parallel, increased phosphorylation of SQSTM1 and TBK1 was observed. These results indicate a requirement for GIMAP6 in the maintenance of a normal peripheral adaptive immune system and a significant role for the protein in normal autophagic processes. Moreover, as GIMAP6 is expressed in a cell-selective manner, this indicates the potential existence of a cell-restricted mode of autophagic regulation.

  16. Urea kinetics during sustained low-efficiency dialysis in critically ill patients requiring renal replacement therapy.

    Science.gov (United States)

    Marshall, Mark R; Golper, Thomas A; Shaver, Mary J; Alam, Muhammad G; Chatoth, Dinesh K

    2002-03-01

    Continuous renal replacement therapies have practical and theoretical advantages compared with conventional intermittent hemodialysis in hemodynamically unstable or severely catabolic patients with acute renal failure (ARF). Sustained low-efficiency dialysis (SLED) is a hybrid modality introduced July 1998 at the University of Arkansas for Medical Sciences that involves the application of a conventional hemodialysis machine with reduced dialysate and blood flow rates for 12-hour nocturnal treatments. Nine critically ill patients with ARF were studied during a single SLED treatment to determine delivered dialysis dose and the most appropriate model for the description of urea kinetics during treatment. Five patients were men, mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 28.9 and mean weight was 92.5 kg. Kt/V was determined by the reference method of direct dialysate quantification (DDQ) combined with an equilibrated postdialysis plasma water urea nitrogen (PUN) concentration and four other methods that were either blood or dialysate based, single or double pool, or model independent (whole-body kinetic method). Solute removal indices (SRIs) were determined from net urea removal and urea distribution volume supplied from DDQ (reference method) and by mass balance using variables supplied from blood-based formal variable-volume single-pool (VVSP) urea kinetic modeling. Equivalent renal urea clearances (EKRs) were calculated from urea generation rates and time-averaged concentrations for PUN based on weekly mass balance with kinetic variables supplied by either DDQ (reference method) or formal blood-based VVSP modeling. Mean Kt/V determined by the reference method was 1.40 and not significantly different when determined by formal VVSP modeling, DDQ using an immediate postdialysis PUN, or the whole-body kinetic method. Correction of single-pool Kt/V by a Daugirdas rate equation did not yield plausible results. Mean SRI and EKR by the

  17. Long-term energy efficiency analysis requires solid energy statistics: The case of the German basic chemical industry

    International Nuclear Information System (INIS)

    Saygin, D.; Worrell, E.; Tam, C.; Trudeau, N.; Gielen, D.J.; Weiss, M.; Patel, M.K.

    2012-01-01

    Analyzing the chemical industry’s energy use is challenging because of the sector’s complexity and the prevailing uncertainty in energy use and production data. We develop an advanced bottom-up model (PIE-Plus) which encompasses the energy use of the 139 most important chemical processes. We apply this model in a case study to analyze the German basic chemical industry’s energy use and energy efficiency improvements in the period between 1995 and 2008. We compare our results with data from the German Energy Balances and with data published by the International Energy Agency (IEA). We find that our model covers 88% of the basic chemical industry’s total final energy use (including non-energy use) as reported in the German Energy Balances. The observed energy efficiency improvements range between 2.2 and 3.5% per year, i.e., they are on the higher side of the values typically reported in literature. Our results point to uncertainties in the basic chemical industry’s final energy use as reported in the energy statistics and the specific energy consumption values. More efforts are required to improve the quality of the national and international energy statistics to make them useable for reliable monitoring of energy efficiency improvements of the chemical industry. -- Highlights: ► An advanced model was developed to estimate German chemical industry’s energy use. ► For the base year (2000), model covers 88% of the sector’s total final energy use. ► Sector’s energy efficiency improved between 2.2 and 3.5%/yr between 1995 and 2008. ► Improved energy statistics are required for accurate monitoring of improvements.

  18. Relevance of splenic tissue preservation to bacteria phagocytosis

    International Nuclear Information System (INIS)

    Marques, Ruy Garcia; Petroianu, Andy; Oliveira, Marcia Betania Nunes de; Bernardo Filho, Mario

    2002-01-01

    Objective: Being the major lymphoid organ of human body, spleen performs critical immunological functions such as bacteria depuration from bloodstream and precocious antibody production against various antigenic particles. Spleen, liver and lung accounts for more than 95% of phagocytic activity in humans. Methods: We used intravenous inoculation of Escherichia coli AB 1157 in Wistar rats in order to evaluate this function. Young and adult rats of both sexes were submitted to total splenectomy and compared to animals not submitted to any surgical procedure. Sixteen weeks later, rats of both groups were challenged with a suspension of E. coli labeled with Tc- 99 m, and, after twenty minutes, they were killed. Liver, lung, spleen and a blood clot sample were removed for radioactivity determination. The statistical study was performed with Student.s t test. Results: There were no significant differences in the radioactivity uptake obtained from young and adult splenectomized rats. However, these rats were associated with higher levels of blood counts than animals of the control group (p<0.0001) due to a larger bacteria remnant in the bloodstream. Conclusion: This finding suggests that some failure in mononuclear phagocytic system occurs in spleen absence adaptation, ratifying the necessity of development of alternative surgical techniques to total splenectomy in patients requiring spleen removal. (author)

  19. Ubiquitin-specific protease 5 is required for the efficient repair of DNA double-strand breaks.

    Directory of Open Access Journals (Sweden)

    Satoshi Nakajima

    Full Text Available During the DNA damage response (DDR, ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiquitin-specific protease 5 (USP5, a deubiquitinating enzyme, is involved in the elimination of the ubiquitin signal from damaged sites and is required for efficient DNA double-strand break (DSB repair. Depletion of USP5 sensitizes cells to DNA damaging agents, produces DSBs, causes delayed disappearance of γH2AX foci after Bleocin treatment, and influences DSB repair efficiency in the homologous recombination pathway but not in the non-homologous end joining pathway. USP5 co-localizes to DSBs induced by laser micro-irradiation in a RAD18-dependent manner. Importantly, polyubiquitin chains at sites of DNA damage remained for longer periods in USP5-depleted cells. Our results show that disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair.

  20. Decoupling internalization, acidification and phagosomal-endosomal/lysosomal fusion during phagocytosis of InlA coated beads in epithelial cells.

    Directory of Open Access Journals (Sweden)

    Craig D Blanchette

    Full Text Available BACKGROUND: Phagocytosis has been extensively examined in 'professional' phagocytic cells using pH sensitive dyes. However, in many of the previous studies, a separation between the end of internalization, beginning of acidification and completion of phagosomal-endosomal/lysosomal fusion was not clearly established. In addition, very little work has been done to systematically examine phagosomal maturation in 'non-professional' phagocytic cells. Therefore, in this study, we developed a simple method to measure and decouple particle internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in Madin-Darby Canine Kidney (MDCK and Caco-2 epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Our method was developed using a pathogen mimetic system consisting of polystyrene beads coated with Internalin A (InlA, a membrane surface protein from Listeria monocytogenes known to trigger receptor-mediated phagocytosis. We were able to independently measure the rates of internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in epithelial cells by combining the InlA-coated beads (InlA-beads with antibody quenching, a pH sensitive dye and an endosomal/lysosomal dye. By performing these independent measurements under identical experimental conditions, we were able to decouple the three processes and establish time scales for each. In a separate set of experiments, we exploited the phagosomal acidification process to demonstrate an additional, real-time method for tracking bead binding, internalization and phagosomal acidification. CONCLUSIONS/SIGNIFICANCE: Using this method, we found that the time scales for internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion ranged from 23-32 min, 3-4 min and 74-120 min, respectively, for MDCK and Caco-2 epithelial cells. Both the static and real-time methods developed here are expected to be readily and broadly applicable, as they simply

  1. CD14-dependent monocyte isolation enhances phagocytosis of listeria monocytogenes by proinflammatory, GM-CSF-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Caroline Neu

    Full Text Available Macrophages are an important line of defence against invading pathogens. Human macrophages derived by different methods were tested for their suitability as models to investigate Listeria monocytogenes (Lm infection and compared to macrophage-like THP-1 cells. Human primary monocytes were isolated by either positive or negative immunomagnetic selection and differentiated in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF or macrophage colony-stimulating factor (M-CSF into pro- or anti-inflammatory macrophages, respectively. Regardless of the isolation method, GM-CSF-derived macrophages (GM-Mφ stained positive for CD206 and M-CSF-derived macrophages (M-Mφ for CD163. THP-1 cells did not express CD206 or CD163 following incubation with PMA, M- or GM-CSF alone or in combination. Upon infection with Lm, all primary macrophages showed good survival at high multiplicities of infection whereas viability of THP-1 was severely reduced even at lower bacterial numbers. M-Mφ generally showed high phagocytosis of Lm. Strikingly, phagocytosis of Lm by GM-Mφ was markedly influenced by the method used for isolation of monocytes. GM-Mφ derived from negatively isolated monocytes showed low phagocytosis of Lm whereas GM-Mφ generated from positively selected monocytes displayed high phagocytosis of Lm. Moreover, incubation with CD14 antibody was sufficient to enhance phagocytosis of Lm by GM-Mφ generated from negatively isolated monocytes. By contrast, non-specific phagocytosis of latex beads by GM-Mφ was not influenced by treatment with CD14 antibody. Furthermore, phagocytosis of Lactococcus lactis, Escherichia coli, human cytomegalovirus and the protozoan parasite Leishmania major by GM-Mφ was not enhanced upon treatment with CD14 antibody indicating that this effect is specific for Lm. Based on these observations, we propose macrophages derived by ex vivo differentiation of negatively selected human primary monocytes as the most

  2. The in vitro biocompatibility and macrophage phagocytosis of Mg17Al12 phase in Mg-Al-Zn alloys.

    Science.gov (United States)

    Liu, Chen; He, Peng; Wan, Peng; Li, Mei; Wang, Kehong; Tan, Lili; Zhang, Yu; Yang, Ke

    2015-07-01

    Mg alloys are gaining interest for applications as biodegradable medical implant, including Mg-Al-Zn series alloys with good combination of mechanical properties and reasonable corrosion resistance. However, whether the existence of second phase particles in the alloys exerts influence on the biocompatibility is still not clear. A deeper understanding of how the particles regulate specific biological responses is becoming a crucial requirement for their subsequent biomedical application. In this work, the in vitro biocompatibility of Mg17Al12 as a common second phase in biodegradable Mg-Al-Zn alloys was investigated via hemolysis, cytotoxicity, cell proliferation, and cell adhesion tests. Moreover, osteogenic differentiation was evaluated by the extracellular matrix mineralization assay. The Mg17Al12 particles were also prepared to simulate the real situation of second phase in the in vivo environment in order to estimate the cellular response in macrophages to the Mg17Al12 particles. The experimental results indicated that no hemolysis was found and an excellent cytocompatibility was also proved for the Mg17Al12 second phase when co-cultured with L929 cells, MC3T3-E1 cells and BMSCs. Macrophage phagocytosis co-culture test revealed that Mg17Al12 particles exerted no harmful effect on RAW264.7 macrophages and could be phagocytized by the RAW264.7 cells. Furthermore, the possible inflammatory reaction and metabolic way for Mg17Al12 phase were also discussed in detail. © 2014 Wiley Periodicals, Inc.

  3. Importance of considering riparian vegetation requirements for the long-term efficiency of environmental flows in aquatic microhabitats

    Directory of Open Access Journals (Sweden)

    R. Rivaes

    2017-11-01

    Full Text Available Environmental flows remain biased toward the traditional biological group of fish species. Consequently, these flows ignore the inter-annual flow variability that rules species with longer lifecycles and therefore disregard the long-term perspective of the riverine ecosystem. We analyzed the importance of considering riparian requirements for the long-term efficiency of environmental flows. For that analysis, we modeled the riparian vegetation development for a decade facing different environmental flows in two case studies. Next, we assessed the corresponding fish habitat availability of three common fish species in each of the resulting riparian landscape scenarios. Modeling results demonstrated that the environmental flows disregarding riparian vegetation requirements promoted riparian degradation, particularly vegetation encroachment. Such circumstance altered the hydraulic characteristics of the river channel where flow depths and velocities underwent local changes of up to 10 cm and 40 cm s−1, respectively. Accordingly, after a decade of this flow regime, the available habitat area for the considered fish species experienced modifications of up to 110 % when compared to the natural habitat. In turn, environmental flows regarding riparian vegetation requirements were able to maintain riparian vegetation near natural standards, thereby preserving the hydraulic characteristics of the river channel and sustaining the fish habitat close to the natural condition. As a result, fish habitat availability never changed more than 17 % from the natural habitat.

  4. Kinetic studies of Candida parapsilosis phagocytosis by macrophages and detection of intracellular survival mechanisms

    Directory of Open Access Journals (Sweden)

    Renata eToth

    2014-11-01

    Full Text Available Even though the number of Candida infections due to non-albicans species like C. parapsilosis has been increasing, little is known about their pathomechanisms. Certain aspects of C. parapsilosis and host interactions have already been investigated; however we lack information about the innate cellular responses towards this species. The aim of our project was to dissect and compare the phagocytosis of C. parapsilosis to C. albicans and to another Candida species C. glabrata by murine and human macrophages by live cell video microscopy. We broke down the phagocytic process into three stages: macrophage migration, engulfment of fungal cells and host cell killing after the uptake. Our results showed increased macrophage migration towards C. parapsilosis and we observed differences during the engulfment processes when comparing the three species. The engulfment time of C. parapsilosis was comparable to that of C. albicans regardless of the pseudohypha length and spatial orientation relative to phagocytes, while the rate of host cell killing and the overall uptake regarding C. parapsilosis showed similarities mainly with C. glabrata. Furthermore, we observed difference between human and murine phagocytes in the uptake of C. parapsilosis. UV-treatment of fungal cells had varied effects on phagocytosis dependent upon which Candida strain was used. Besides statistical analysis, live cell imaging videos showed that this species similarly to the other two also has the ability to survive in host cells via the following mechanisms: yeast replication, and pseudohypha growth inside of phagocytes, exocytosis of fungal cells and also abortion of host cell mitosis following the uptake. According to our knowledge this is the first study that provides a thorough examination of C. parapsilosis phagocytosis and reports intracellular survival mechanisms associated with this species.

  5. Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis.

    Directory of Open Access Journals (Sweden)

    Jeroen van Bergenhenegouwen

    Full Text Available Oral delivery of Gram positive bacteria, often derived from the genera Lactobacillus or Bifidobacterium, can modulate immune function. Although the exact mechanisms remain unclear, immunomodulatory effects may be elicited through the direct interaction of these bacteria with the intestinal epithelium or resident dendritic cell (DC populations. We analyzed the immune activation properties of Lactobacilli and Bifidobacterium species and made the surprising observation that cellular responses in vitro were differentially influenced by the presence of serum, specifically the extracellular vesicle (EV fraction. In contrast to the tested Lactobacilli species, tested Bifidobacterium species induce TLR2/6 activity which is inhibited by the presence of EVs. Using specific TLR ligands, EVs were found to enhance cellular TLR2/1 and TLR4 responses while TLR2/6 responses were suppressed. No effect could be observed on cellular TLR5 responses. We determined that EVs play a role in bacterial aggregation, suggesting that EVs interact with bacterial surfaces. EVs were found to slightly enhance DC phagocytosis of Bifidobacterium breve whereas phagocytosis of Lactobacillus rhamnosus was virtually absent upon serum EV depletion. DC uptake of a non-microbial substance (dextran was not affected by the different serum fractions suggesting that EVs do not interfere with DC phagocytic capacity but rather modify the DC-microbe interaction. Depending on the microbe, combined effects of EVs on TLR activity and phagocytosis result in a differential proinflammatory DC cytokine release. Overall, these data suggest that EVs play a yet unrecognized role in host-microbe responses, not by interfering in recipient cellular responses but via attachment to, or scavenging of, microbe-associated molecular patterns. EVs can be found in any tissue or bodily fluid, therefore insights into EV-microbe interactions are important in understanding the mechanism of action of potential

  6. Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy Impairment and Resulting Phagocytosis Defect

    Directory of Open Access Journals (Sweden)

    Garrett Pehote

    2017-01-01

    Full Text Available Introduction. Cigarette smoke (CS exposure is the leading risk factor for COPD-emphysema pathogenesis. A common characteristic of COPD is impaired phagocytosis that causes frequent exacerbations in patients leading to increased morbidity. However, the underlying mechanism is unclear. Hence, we investigated if CS exposure causes autophagy impairment as a mechanism for diminished bacterial clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells and Pseudomonas aeruginosa (PA01-GFP as an experimental model. Methods. Briefly, RAW cells were treated with cigarette smoke extract (CSE, chloroquine (autophagy inhibitor, TFEB-shRNA, CFTR(inh-172, and/or fisetin prior to bacterial infection for functional analysis. Results. Bacterial clearance of PA01-GFP was significantly impaired while its survival was promoted by CSE (p<0.01, autophagy inhibition (p<0.05; p<0.01, TFEB knockdown (p<0.01; p<0.001, and inhibition of CFTR function (p<0.001; p<0.01 in comparison to the control group(s that was significantly recovered by autophagy-inducing antioxidant drug, fisetin, treatment (p<0.05; p<0.01; and p<0.001. Moreover, investigations into other pharmacological properties of fisetin show that it has significant mucolytic and bactericidal activities (p<0.01; p<0.001, which warrants further investigation. Conclusions. Our data suggests that CS-mediated autophagy impairment as a critical mechanism involved in the resulting phagocytic defect, as well as the therapeutic potential of autophagy-inducing drugs in restoring is CS-impaired phagocytosis.

  7. Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response.

    Science.gov (United States)

    Cai, Qing; Li, Yuanyuan; Pei, Gang

    2017-03-24

    Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia. The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta 42 (Aβ 42 ) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain. Quantitative results revealed that GLP down-regulates LPS- or Aβ-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions. Overall, our study provides an insight into the GLP regulation of LPS- and Aβ-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

  8. Scavenger Receptor C Mediates Phagocytosis of White Spot Syndrome Virus and Restricts Virus Proliferation in Shrimp

    Science.gov (United States)

    Yang, Ming-Chong; Shi, Xiu-Zhen; Yang, Hui-Ting; Sun, Jie-Jie; Xu, Ling; Wang, Xian-Wei; Zhao, Xiao-Fan

    2016-01-01

    Scavenger receptors are an important class of pattern recognition receptors that play several important roles in host defense against pathogens. The class C scavenger receptors (SRCs) have only been identified in a few invertebrates, and their role in the immune response against viruses is seldom studied. In this study, we firstly identified an SRC from kuruma shrimp, Marsupenaeus japonicus, designated MjSRC, which was significantly upregulated after white spot syndrome virus (WSSV) challenge at the mRNA and protein levels in hemocytes. The quantity of WSSV increased in shrimp after knockdown of MjSRC, compared with the controls. Furthermore, overexpression of MjSRC led to enhanced WSSV elimination via phagocytosis by hemocytes. Pull-down and co-immunoprecipitation assays demonstrated the interaction between MjSRC and the WSSV envelope protein. Electron microscopy observation indicated that the colloidal gold-labeled extracellular domain of MjSRC was located on the outer surface of WSSV. MjSRC formed a trimer and was internalized into the cytoplasm after WSSV challenge, and the internalization was strongly inhibited after knockdown of Mjβ-arrestin2. Further studies found that Mjβ-arrestin2 interacted with the intracellular domain of MjSRC and induced the internalization of WSSV in a clathrin-dependent manner. WSSV were co-localized with lysosomes in hemocytes and the WSSV quantity in shrimp increased after injection of lysosome inhibitor, chloroquine. Collectively, this study demonstrated that MjSRC recognized WSSV via its extracellular domain and invoked hemocyte phagocytosis to restrict WSSV systemic infection. This is the first study to report an SRC as a pattern recognition receptor promoting phagocytosis of a virus. PMID:28027319

  9. Non-degradable contrast agent with selective phagocytosis for cellular and hepatic magnetic resonance imaging

    International Nuclear Information System (INIS)

    Chen, Fei-Yan; Gu, Zhe-Jia; Zhao, Dawen; Tang, Qun

    2015-01-01

    Degradation is the long-existing toxic issue of metal-containing inorganic medicine. In this paper, we fully investigated the degradation of dextran-coated KMnF 3 nanocube in the in vitro and in vivo surroundings. Different from the general decomposing and ion releasing events, this special agent is resistant to acidic environment, as well as ion exchange. Non-degradability was proved by simulated and real cellular experiments. Moreover, it can be engulfed in the macrophage cells and kept stable in the lysosome. Due to its stability and highly selective phagocytosis, implanted liver cancer can be clearly visualized after administration

  10. Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2

    Directory of Open Access Journals (Sweden)

    Ballinger Megan N

    2011-12-01

    Full Text Available Abstract Background Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM host defense and production of lipid mediators during the neonatal period compared to adult AMs. Methods AMs were harvested from young (day 7 and day 14 and adult (~10 week rats. The functionality of these cells was assessed by examining their ability to phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes and receptors essential for eicosanoid generation and phagocytosis measured by real time RT-PCR. Results AMs from young animals (day 7 and 14 were defective in their ability to phagocytose opsonized targets and produce tumor necrosis factor (TNF- α. In addition, young AMs produce more prostaglandin (PG E2, a suppressor of host defense, and less leukotriene (LT B4, a promoter of host defense. Young AMs express higher levels of enzymes responsible for the production of PGE2 and LTB4; however, there was no change in the expression of E prostanoid (EP receptors or LT receptors. Despite the similar EP profiles, young AMs are more responsive to PGE2 as evidenced by their increased production of the important second messenger, cyclic AMP. In addition, young AMs express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs. However, even though the young AMs produced a skewed eicosanoid profile, neither the inhibition of PGE2 by aspirin nor the addition of exogenous LTB4 rescued the defective opsonized phagocytosis. Examination of a receptor responsible for mediating opsonized phagocytosis showed a significant decrease in the gene expression levels of the Fcgamma receptor in young (day 7 AMs compared to adult AMs. Conclusion These

  11. Non-degradable contrast agent with selective phagocytosis for cellular and hepatic magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fei-Yan [Nanchang University, College of Chemistry (China); Gu, Zhe-Jia [Nanchang University, Institute for Advanced Study (China); Zhao, Dawen [UT Southwestern Medical Center, Department of Radiology (United States); Tang, Qun, E-mail: tangqun@ncu.edu.cn [Nanchang University, Institute for Advanced Study (China)

    2015-09-15

    Degradation is the long-existing toxic issue of metal-containing inorganic medicine. In this paper, we fully investigated the degradation of dextran-coated KMnF{sub 3} nanocube in the in vitro and in vivo surroundings. Different from the general decomposing and ion releasing events, this special agent is resistant to acidic environment, as well as ion exchange. Non-degradability was proved by simulated and real cellular experiments. Moreover, it can be engulfed in the macrophage cells and kept stable in the lysosome. Due to its stability and highly selective phagocytosis, implanted liver cancer can be clearly visualized after administration.

  12. Determination of phagocytosis of 32P-labeled Staphylococcus aureus by bovine polymorphonuclear leukocytes

    International Nuclear Information System (INIS)

    Dulin, A.M.; Paape, M.J.; Weinland, B.T.

    1984-01-01

    A procedure for the measurement of phagocytosis by bovine polymorphonuclear leukocytes (PMN) of 32 P-labeled Staphylococcus aureus was modified so that a larger number of samples could be compared in a single run, and smaller volumes of sample, PMN, and 32 P-labeled S aureus could be used. Results were highly reproducible, with a coefficient of variation between duplicate determinations of less than or equal to 2%. Lysostaphin was prepared from the supernatant of S staphylolyticus and was compared with a commercially available preparation. Effects of lysostaphin on PMN and influence of incubation media on release of 32 P from 32 P-labeled S aureus by lysostaphin were examined

  13. Ability of Staphylococcus aureus coagulase genotypes to resist neutrophil bactericidal activity and phagocytosis

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Scott, N. L.; Sordillo, L. M.

    1994-01-01

    This study investigated the functional capabilities of neutrophils against different Staphylococcus aureus genotypes isolated from cows with mastitis. Six strains of S. aureus were chosen for use in the study, two with a common genotype, two with an intermediate genotype, and two with a rare......; rare type, 10.5/cell). These findings suggest that one of the reasons for the variation in prevalence of different genotypes of S. aureus in the mammary gland is due to the superior ability of some types to resist phagocytosis and/or killing by bovine neutrophils...

  14. Octasaccharide is the minimal length unit required for efficient binding of cyclophilin B to heparin and cell surface heparan sulphate.

    Science.gov (United States)

    Vanpouille, Christophe; Denys, Agnès; Carpentier, Mathieu; Pakula, Rachel; Mazurier, Joël; Allain, Fabrice

    2004-09-01

    Cyclophilin B (CyPB) is a heparin-binding protein first identified as a receptor for cyclosporin A. In previous studies, we reported that CyPB triggers chemotaxis and integrin-mediated adhesion of T-lymphocytes by way of interaction with two types of binding sites. The first site corresponds to a signalling receptor; the second site has been identified as heparan sulphate (HS) and appears crucial to induce cell adhesion. Characterization of the HS-binding unit is critical to understand the requirement of HS in pro-adhesive activity of CyPB. By using a strategy based on gel mobility shift assays with fluorophore-labelled oligosaccharides, we demonstrated that the minimal heparin unit required for efficient binding of CyPB is an octasaccharide. The mutants CyPB(KKK-) [where KKK- refers to the substitutions K3A(Lys3-->Ala)/K4A/K5A] and CyPB(DeltaYFD) (where Tyr14-Phe-Asp16 has been deleted) failed to interact with octasaccharides, confirming that the Y14FD16 and K3KK5 clusters are required for CyPB binding. Molecular modelling revealed that both clusters are spatially arranged so that they may act synergistically to form a binding site for the octasaccharide. We then demonstrated that heparin-derived octasaccharides and higher degree of polymerization oligosaccharides inhibited the interaction between CyPB and fluorophore-labelled HS chains purified from T-lymphocytes, and strongly reduced the HS-dependent pro-adhesive activity of CyPB. However, oligosaccharides or heparin were unable to restore adhesion of heparinase-treated T-lymphocytes, indicating that HS has to be present on the cell membrane to support the pro-adhesive activity of CyPB. Altogether, these results demonstrate that the octasaccharide is likely to be the minimal length unit required for efficient binding of CyPB to cell surface HS and consequent HS-dependent cell responses.

  15. Equine herpesvirus type 1 (EHV-1) glycoprotein K is required for efficient cell-to-cell spread and virus egress

    International Nuclear Information System (INIS)

    Neubauer, Antonie; Osterrieder, Nikolaus

    2004-01-01

    The function of the equine herpesvirus type 1 (EHV-1) glycoprotein K (gK) homologue was investigated. Deletion of 88% of the UL53-homologous open reading frame in EHV-1 strain RacH resulted in a severe growth defect of the gK-negative virus (HΔgK) as reflected by a significant decrease in the production of infectious virus progeny on RK13 cells. The HΔgK virus induced only minute plaques, was unable to form syncytia, and its penetration efficiency into RK13 cells was reduced by approximately 40%. To further analyze gK function and intracellular trafficking, gK of strain RacH was replaced by a C-terminally truncated gK-green fluorescent protein fusion protein (gK-GFP). The generated recombinant virus was shown to replicate well on non-complementing cells, and virus penetration and syncytium formation were comparable to parental RacH. A reduction in plaque size and slightly decreased intra- and extracellular virus titers, however, were observed. The gK-GFP fusion protein was expressed with early-late kinetics, and multiple forms of the protein exhibiting M r s between 50,000 and 85,000 were detected by Western blot analysis. The various gK-GFP forms were shown to be N-glycosylated, associated with membranes of the Golgi apparatus, and were incorporated into extracellular virions. Complete processing of gK-GFP was only observed within the context of viral infection. From the results, we concluded that EHV-1 gK is required for efficient virus growth in vitro and that the carboxy-terminal amino acids are not required for its function, because the gK-GFP fusion protein was able to complement for EHV-1 growth in the absence of authentic gK

  16. Combinatorial Modulation of Signaling Pathways Reveals Cell-Type-Specific Requirements for Highly Efficient and Synchronous iPSC Reprogramming

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2014-10-01

    Full Text Available The differentiated state of somatic cells provides barriers for the derivation of induced pluripotent stem cells (iPSCs. To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. Surprisingly, inhibition of transforming growth factor β (TGF-β together with activation of Wnt signaling in the presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after 1 week of reprogramming factor expression. In contrast, hepatic and blood progenitors predominantly required only TGF-β inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner, and we demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF-β/mitogen-activated protein (MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Our observations define cell-type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

  17. Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α on phagocytes

    Directory of Open Access Journals (Sweden)

    Reichert Fanny

    2011-03-01

    Full Text Available Abstract Background Traumatic injury to axons produces breakdown of axons and myelin at the site of the lesion and then further distal to this where Wallerian degeneration develops. The rapid removal of degenerated myelin by phagocytosis is advantageous for repair since molecules in myelin impede regeneration of severed axons. Thus, revealing mechanisms that regulate myelin phagocytosis by macrophages and microglia is important. We hypothesize that myelin regulates its own phagocytosis by simultaneous activation and down-regulation of microglial and macrophage responses. Activation follows myelin binding to receptors that mediate its phagocytosis (e.g. complement receptor-3, which has been previously studied. Down-regulation, which we test here, follows binding of myelin CD47 to the immune inhibitory receptor SIRPα (signal regulatory protein-α on macrophages and microglia. Methods CD47 and SIRPα expression was studied by confocal immunofluorescence microscopy, and myelin phagocytosis by ELISA. Results We first document that myelin, oligodendrocytes and Schwann cells express CD47 without SIRPα and further confirm that microglia and macrophages express both CD47 and SIRPα. Thus, CD47 on myelin can bind to and subsequently activate SIRPα on phagocytes, a prerequisite for CD47/SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis by itself. We then demonstrate that phagocytosis of CD47+/+ myelin is augmented when binding between myelin CD47 and SIRPα on phagocytes is blocked by mAbs against CD47 and SIRPα, indicating that down-regulation of phagocytosis indeed depends on CD47-SIRPα binding. Further, phagocytosis in serum-free medium of CD47+/+ myelin is augmented after knocking down SIRPα levels (SIRPα-KD in phagocytes by lentiviral infection with SIRPα-shRNA, whereas phagocytosis of myelin that lacks CD47 (CD47-/- is not. Thus, myelin CD47 produces SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis in phagocytes

  18. Peripheral blood leukocyte phagocytosis and respiratory response to certain macromolecular substances in the ABCC-JNIH adult health study, Hiroshima

    Energy Technology Data Exchange (ETDEWEB)

    Barerras, R F; Finch, S C

    1974-01-01

    The functional integrity of the peripheral blood leukocytes of 10 heavily exposed subjects and 10 matched controls was evaluated by measuring oxygen consumption following the addition of latex particles and E. coli endotoxin, and measuring sensitized and unsensitized starch granule phagocytosis. There was no significant difference in the responses of leukocytes from exposed subjects and controls following the addition of latex particles. The ultimate response of leukocytes from exposed subjects to the stimulus of E. coli endotoxin was comparable to that of the controls. Depressed early response in 5 of 10 exposed and 1 of 10 control subjects was observed. Interpretation is unclear. No evidence of radiation-related impairment of starch granule phagocytosis was observed. Results fail to demonstrate any late radiation-related functional impairment of peripheral blood leukocytes during phagocytosis. The serum-related changes were inconstant and probably were of little significance. (auth)

  19. Intraocular pressure elevation precedes a phagocytosis decline in a model of pigmentary glaucoma [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Yalong Dang

    2018-04-01

    Full Text Available Background: Outflow regulation and phagocytosis are key functions of the trabecular meshwork (TM, but it is not clear how the two are related in secondary open angle glaucomas characterized by an increased particle load. We hypothesized that diminished TM phagocytosis is not the primary cause of early ocular hypertension and recreated pigment dispersion in a porcine ex vivo model. Methods: Sixteen porcine anterior chamber cultures received a continuous infusion of pigment granules (Pg, while 16 additional anterior chambers served as controls (C. Pressure transducers recorded the intraocular pressure (IOP. The phagocytic capacity of the trabecular meshwork was determined by fluorescent microspheres. Results: The baseline IOPs in Pg and C were similar (P=0.82. A significant IOP elevation occurred in Pg at 48, 120, and 180 hours (all P0.05. Conclusions: In this porcine model of pigmentary glaucoma, an IOP elevation occurs much earlier than when phagocytosis fails, suggesting that two separate mechanisms might be at work.

  20. Brucella abortus-activated microglia induce neuronal death through primary phagocytosis.

    Science.gov (United States)

    Rodríguez, Ana M; Delpino, M Victoria; Miraglia, M Cruz; Costa Franco, Miriam M; Barrionuevo, Paula; Dennis, Vida A; Oliveira, Sergio C; Giambartolomei, Guillermo H

    2017-07-01

    Inflammation has long been implicated as a contributor to pathogenesis in neurobrucellosis. Many of the associated neurocognitive symptoms of neurobrucellosis may be the result of neuronal dysfunction resulting from the inflammatory response induced by Brucella abortus infection in the central nervous system. In this manuscript, we describe an immune mechanism for inflammatory activation of microglia that leads to neuronal death upon B. abortus infection. B. abortus was unable to infect or harm primary cultures of mouse neurons. However, when neurons were co-cultured with microglia and infected with B. abortus significant neuronal loss occurred. This phenomenon was dependent on TLR2 activation by Brucella lipoproteins. Neuronal death was not due to apoptosis, but it was dependent on the microglial release of nitric oxide (NO). B. abortus infection stimulated microglial proliferation, phagocytic activity and engulfment of neurons. NO secreted by B. abortus-activated microglia induced neuronal exposure of the "eat-me" signal phosphatidylserine (PS). Blocking of PS-binding to protein milk fat globule epidermal growth factor-8 (MFG-E8) or microglial vitronectin receptor-MFG-E8 interaction was sufficient to prevent neuronal loss by inhibiting microglial phagocytosis without affecting their activation. Taken together, our results indicate that B. abortus is not directly toxic to neurons; rather, these cells become distressed and are killed by phagocytosis in the inflammatory surroundings generated by infected microglia. Neuronal loss induced by B. abortus-activated microglia may explain, in part, the neurological deficits observed during neurobrucellosis. © 2017 Wiley Periodicals, Inc.

  1. Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis.

    Science.gov (United States)

    Klettner, Alexa; Tahmaz, Nihat; Dithmer, Michaela; Richert, Elisabeth; Roider, Johann

    2014-10-01

    Anti-VEGF treatment is the therapy of choice in age-related macular degeneration, and is also applied in diabetic macular oedema or retinal vein occlusion. Recently, the fusion protein, aflibercept, has been approved for therapeutic use. In this study, we investigate the effects of aflibercept on primary RPE cells. Primary RPE cells were prepared from freshly slaughtered pigs' eyes. The impact of aflibercept on cell viability was investigated with MTT and trypan blue exclusion assay. The influence of aflibercept on wound healing was assessed with a scratch assay. Intracellular uptake of aflibercept was investigated in immunohistochemistry and its influence on phagocytosis with a phagocytosis assay using opsonised latex beads. Aflibercept displays no cytotoxicity on RPE cells but impairs its wound healing ability. It is taken up into RPE cells and can be intracellularly detected for at least 7 days. Intracellular aflibercept impairs the phagocytic capacity of RPE cells. Aflibercept interferes with the physiology of RPE cells, as it is taken up into RPE cells, which is accompanied by a reduction of the phagocytic ability. Additionally, it impairs the wound healing capacity of RPE cells. These effects on the physiology of RPE cells may indicate possible side effects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects

    Science.gov (United States)

    Nejadnik, Hossein; Lenkov, Olga; Gassert, Florian; Fretwell, Deborah; Lam, Isaac; Daldrup-Link, Heike E.

    2016-05-01

    Human mesenchymal stem cells (hMSCs) are a promising tool for cartilage regeneration in arthritic joints. hMSC labeling with iron oxide nanoparticles enables non-invasive in vivo monitoring of transplanted cells in cartilage defects with MR imaging. Since graft failure leads to macrophage phagocytosis of apoptotic cells, we evaluated in vitro and in vivo whether nanoparticle-labeled hMSCs show distinct MR signal characteristics before and after phagocytosis by macrophages. We found that apoptotic nanoparticle-labeled hMSCs were phagocytosed by macrophages while viable nanoparticle-labeled hMSCs were not. Serial MRI scans of hMSC transplants in arthritic joints of recipient rats showed that the iron signal of apoptotic, nanoparticle-labeled hMSCs engulfed by macrophages disappeared faster compared to viable hMSCs. This corresponded to poor cartilage repair outcomes of the apoptotic hMSC transplants. Therefore, rapid decline of iron MRI signal at the transplant site can indicate cell death and predict incomplete defect repair weeks later. Currently, hMSC graft failure can be only diagnosed by lack of cartilage defect repair several months after cell transplantation. The described imaging signs can diagnose hMSC transplant failure more readily, which could enable timely re-interventions and avoid unnecessary follow up studies of lost transplants.

  3. 10 CFR 905.17 - What are the requirements for the energy efficiency and/or renewable energy report (EE/RE report...

    Science.gov (United States)

    2010-01-01

    ... renewable energy report (EE/RE report) alternative? 905.17 Section 905.17 Energy DEPARTMENT OF ENERGY ENERGY... energy efficiency and/or renewable energy report (EE/RE report) alternative? (a) Requests to submit an EE..., including any requirements for documenting customer energy efficiency and renewable energy activities. (b...

  4. Identification of intracellular phospholipases A2 in the human eye: involvement in phagocytosis of photoreceptor outer segments

    DEFF Research Database (Denmark)

    Kolko, Miriam; Wang, Jinmei; Zhan, Chen

    2007-01-01

    PURPOSE: To identify intracellular phospholipases A(2) (PLA(2)) in the human retina and to explore the role of these enzymes in human retinal pigment epithelium (RPE) phagocytosis of photoreceptor outer segments (POS). METHODS: PCR amplification and Western blot analysis were used to identify m......)-VIA activity was found to be specifically increased 12 hours after ARPE-19 cells were fed with POS. Finally, RPE phagocytosis was inhibited by the iPLA(2)-VIA inhibitor bromoenol lactone. CONCLUSIONS: Various intracellular PLA(2) subtypes are present in the human retina. iPLA(2)-VIA may play...

  5. Involvement of Tiam1, RhoG and ELMO2/ILK in Rac1-mediated phagocytosis in human trabecular meshwork cells.

    Science.gov (United States)

    Peotter, Jennifer L; Phillips, Jenny; Tong, Tiegang; Dimeo, Kaylee; Gonzalez, Jose M; Peters, Donna M

    2016-10-01

    We previously demonstrated that an αvβ5 integrin/FAK- mediated pathway regulated the phagocytic properties of human trabecular meshwork (HTM) cells. Here we demonstrate that this process is mediated by Rac-1 and a previously unreported signaling pathway that utilizes the Tiam1 as well as a novel ILK/RhoG/ELMO2 signaling pathway. Phagocytosis in both a TM-1 cell line and normal HTM cells was mediated by Rac1 and could be significantly decreased by >75% using the Rac1 inhibitor EHop-016. Knockdown of Rac1 in TM-1 cells also inhibited phagocytosis by 40% whereas overexpression of a constitutively active Rac1 or stimulation with PDGF increased phagocytosis by 83% and 32% respectively. Tiam1 was involved in regulating phagocytosis. Knockdown of Tiam1 inhibited phagocytosis by 72% while overexpression of Tiam1 C1199 increased phagocytosis by 75%. Other upstream effectors of Rac1 found to be involved included ELMO2, RhoG, and ILK. Knockdowns of ELMO2, ILK, and RhoG caused a reduction in phagocytosis by 51%, 55% and 46% respectively. In contrast, knockdown of Vav2 and Dock1 or overexpression of Vav2 Y159/172F did not cause a significant change in phagocytosis. These data suggest a novel link between Tiam1 and RhoG/ILK /ELMO2 pathway as upstream effectors of the Rac1-mediated phagocytic process in TM cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. P2X receptor-dependent erythrocyte damage by α-hemolysin from Escherichia coli triggers phagocytosis by THP-1 cells

    DEFF Research Database (Denmark)

    Fagerberg, Steen Kåre; Skals, Marianne Gerberg; Leipziger, Jens Georg

    2013-01-01

    , which is known to be a keen trigger for phagocytosis. We hypothesize that exposure to HlyA elicits removal of the damaged erythrocytes by phagocytic cells. Cultured THP-1 cells as a model for erythrocytal phagocytosis was verified by a variety of methods, including live cell imaging. We consistently...

  7. The assessment of serum-mediated phagocytosis of necrotic material by polymorphonuclear leukocytes to diagnose and predict the clinical features of systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Compagno, Michele; Gullstrand, Birgitta; Jacobsen, Søren

    2016-01-01

    BACKGROUND: Serum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry-based assay. The phagocytosis of necrotic cell material (PNC) assay parallels the well-known lupus erythematosus c...

  8. The ABC transporter Tba of Amycolatopsis balhimycina is required for efficient export of the glycopeptide antibiotic balhimycin.

    Science.gov (United States)

    Menges, R; Muth, G; Wohlleben, W; Stegmann, E

    2007-11-01

    All known gene clusters for glycopeptide antibiotic biosynthesis contain a conserved gene supposed to encode an ABC-transporter. In the balhimycin-producer Amycolatopsis balhimycina this gene (tba) is localised between the prephenate dehydrogenase gene pdh and the peptide synthetase gene bpsA. Inactivation of tba in A. balhimycina by gene replacement did not interfere with growth and did not affect balhimycin resistance. However, in the supernatant of the tba mutant RM43 less balhimycin was accumulated compared to the wild type; and the intra-cellular balhimycin concentration was ten times higher in the tba mutant RM43 than in the wild type. These data suggest that the ABC transporter encoded in the balhimycin biosynthesis gene cluster is not involved in resistance but is required for the efficient export of the antibiotic. To elucidate the activity of Tba it was heterologously expressed in Escherichia coli with an N-terminal His-tag and purified by nickel chromatography. A photometric assay revealed that His(6)-Tba solubilised in dodecylmaltoside possesses ATPase activity, characteristic for ABC-transporters.

  9. Distributing and storing required data efficiently by means of specifically tailored data formats in the ATLAS collaboration

    CERN Document Server

    Koeneke, K; The ATLAS collaboration

    2011-01-01

    With the start of the LHC physics program, the ATLAS experiment started to record vast amounts of data. This data has to be distributed and stored on the world-wide computing grid in a smart way in order to enable an effective and efficient analysis by physicists. There are in principle two classes of analysis that are required. In the commissioning phase of the ATLAS experiment, low-level Event Summary Data (ESD), the result of the event reconstruction, has to be analyzed to evaluate the performance of the individual subdetectors, the performance of the reconstruction and particle identification algorithms, and to obtain calibration coefficients. For later physics analysis, it is usually sufficient to use the less detailed Analysis Object Data (AOD), which is a less-detailed version of the ESD. In the grid model of distributed analysis, these data must be transferred to Tier-2 sites before they can be analyzed. However, the large size of ESD (~1 MByte/event) constrains the amount of detailed data that can be...

  10. Tick Thioester-Containing Proteins and Phagocytosis Do Not Affect Transmission of Borrelia afzelii from the Competent Vector Ixodes ricinus

    Czech Academy of Sciences Publication Activity Database

    Urbanová, V.; Hajdušek, O.; Hönig Mondeková, Helena; Šíma, R.; Kopáček, P.

    2017-01-01

    Roč. 7, MAR 16 (2017), s. 1-16, č. článku 73. ISSN 2235-2988 Institutional support: RVO:61388971 Keywords : Borrelia * complement * phagocytosis Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.300, year: 2016

  11. Effects of early-life lead exposure on oxidative status and phagocytosis activity in great tits (Parus major)

    NARCIS (Netherlands)

    Rainio, Miia J.; Eeva, Tapio; Lilley, Thomas; Stauffer, Janina; Ruuskanen, Suvi

    2015-01-01

    Abstract Lead is a highly poisonous metal with a very long half-life, distributing throughout the body in blood and accumulating primarily in bones and kidney. We studied the short and long-term effects of early-life lead exposure on antioxidant defense and phagocytosis activity in a small passerine

  12. Cryptococcus neoformans Is Internalized by Receptor-Mediated or ‘Triggered’ Phagocytosis, Dependent on Actin Recruitment

    Science.gov (United States)

    Guerra, Caroline Rezende; Seabra, Sergio Henrique; de Souza, Wanderley; Rozental, Sonia

    2014-01-01

    Cryptococcosis by the encapsulated yeast Cryptococcus neoformans affects mostly immunocompromised individuals and is a frequent neurological complication in AIDS patients. Recent studies support the idea that intracellular survival of Cryptococcus yeast cells is important for the pathogenesis of cryptococcosis. However, the initial steps of Cryptococcus internalization by host cells remain poorly understood. Here, we investigate the mechanism of Cryptococcus neoformans phagocytosis by peritoneal macrophages using confocal and electron microscopy techniques, as well as flow cytometry quantification, evaluating the importance of fungal capsule production and of host cell cytoskeletal elements for fungal phagocytosis. Electron microscopy analyses revealed that capsular and acapsular strains of C. neoformans are internalized by macrophages via both ‘zipper’ (receptor-mediated) and ‘trigger’ (membrane ruffle-dependent) phagocytosis mechanisms. Actin filaments surrounded phagosomes of capsular and acapsular yeasts, and the actin depolymerizing drugs cytochalasin D and latrunculin B inhibited yeast internalization and actin recruitment to the phagosome area. In contrast, nocodazole and paclitaxel, inhibitors of microtubule dynamics decreased internalization but did not prevent actin recruitment to the site of phagocytosis. Our results show that different uptake mechanisms, dependent on both actin and tubulin dynamics occur during yeast internalization by macrophages, and that capsule production does not affect the mode of Cryptococcus uptake by host cells. PMID:24586631

  13. Protein C Inhibitor (PCI) Binds to Phosphatidylserine Exposing Cells with Implications in the Phagocytosis of Apoptotic Cells and Activated Platelets

    Science.gov (United States)

    Rieger, Daniela; Assinger, Alice; Einfinger, Katrin; Sokolikova, Barbora; Geiger, Margarethe

    2014-01-01

    Protein C Inhibitor (PCI) is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS) is exposed on the surface of apoptotic cells and known as a phagocytosis marker. We hypothesized that PCI might bind to PS exposed on apoptotic cells and thereby influence their removal by phagocytosis. Using Jurkat T-lymphocytes and U937 myeloid cells, we show here that PCI binds to apoptotic cells to a similar extent at the same sites as Annexin V, but in a different manner as compared to live cells (defined spots on ∼10–30% of cells). PCI dose dependently decreased phagocytosis of apoptotic Jurkat cells by U937 macrophages. Moreover, the phagocytosis of PS exposing, activated platelets by human blood derived monocytes declined in the presence of PCI. In U937 cells the expression of PCI as well as the surface binding of PCI increased with time of phorbol ester treatment/macrophage differentiation. The results of this study suggest a role of PCI not only for the function and/or maturation of macrophages, but also as a negative regulator of apoptotic cell and activated platelets removal. PMID:25000564

  14. Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.

    Science.gov (United States)

    Chamilos, Georgios; Akoumianaki, Tonia; Kyrmizi, Irene; Brakhage, Axel; Beauvais, Anne; Latge, Jean-Paul

    2016-05-03

    Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.

  15. Intravenous immunglobulin binds beta amyloid and modifies its aggregation, neurotoxicity and microglial phagocytosis in vitro.

    Directory of Open Access Journals (Sweden)

    Susann Cattepoel

    Full Text Available Intravenous Immunoglobulin (IVIG has been proposed as a potential therapeutic for Alzheimer's disease (AD and its efficacy is currently being tested in mild-to-moderate AD. Earlier studies reported the presence of anti-amyloid beta (Aβ antibodies in IVIG. These observations led to clinical studies investigating the potential role of IVIG as a therapeutic agent in AD. Also, IVIG is known to mediate beneficial effects in chronic inflammatory and autoimmune conditions by interfering with various pathological processes. Therefore, we investigated the effects of IVIG and purified polyclonal Aβ-specific antibodies (pAbs-Aβ on aggregation, toxicity and phagocytosis of Aβ in vitro, thus elucidating some of the potential mechanisms of action of IVIG in AD patients. We report that both IVIG and pAbs-Aβ specifically bound to Aβ and inhibited its aggregation in a dose-dependent manner as measured by Thioflavin T assay. Additionally, IVIG and the purified pAbs-Aβ inhibited Aβ-induced neurotoxicity in the SH-SY5Y human neuroblastoma cell line and prevented Aβ binding to rat primary cortical neurons. Interestingly, IVIG and pAbs-Aβ also increased the number of phagocytosing cells as well as the amount of phagocytosed fibrillar Aβ by BV-2 microglia. Phagocytosis of Aβ depended on receptor-mediated endocytosis and was accompanied by upregulation of CD11b expression. Importantly, we could also show that Privigen dose-dependently reversed Aβ-mediated LTP inhibition in mouse hippocampal slices. Therefore, our in vitro results suggest that IVIG may have an impact on different processes involved in AD pathogenesis, thereby promoting further understanding of the effects of IVIG observed in clinical studies.

  16. Microgrids: An emerging paradigm for meeting building electricity and heat requirements efficiently and with appropriate energy quality

    Energy Technology Data Exchange (ETDEWEB)

    Marnay, Chris; Firestone, Ryan [Berkeley Lab MS 90R4000 (United States)

    2007-07-01

    The first major paradigm shift in electricity generation, delivery, and control is emerging in the developed world, notably Europe, North America, and Japan. This shift will move electricity supply away from the highly centralised universal service quality model with which we are familiar today towards a more dispersed system with heterogeneous qualities of service. One element of dispersed control is the clustering of sources and sinks into semi-autonomous {mu}grids (microgrids). Research, development, demonstration, and deployment (RD3) of {mu}grids are advancing rapidly on at least three continents, and significant demonstrations are currently in progress. This paradigm shift will result in more electricity generation close to end-uses, often involving combined heat and power application for building heating and cooling, increased local integration of renewables, and the possible provision of heterogeneous qualities of electrical service to match the requirements of various end-uses. In Europe, microgrid RD3 is entering its third major round under the 7th European Commission Framework Programme; in the U.S., one specific microgrid concept is undergoing rigorous laboratory testing, and in Japan, where the most activity exists, four major publicly sponsored and two privately sponsored demonstrations are in progress. This evolution poses new challenges to the way buildings are designed, built, and operated. Traditional building energy supply systems will become much more complex in at least three ways: 1. one cannot simply assume gas arrives at the gas meter, electricity at its meter, and the two systems are virtually independent of one another; rather, energy conversion, heat recovery and use, and renewable energy harvesting may all be taking place simultaneously within the building energy system; 2. the structure of energy flows in the building must accommodate multiple energy processes in a manner that permits high overall efficiency; and 3. multiple qualities

  17. Efficient overproduction of membrane proteins in Lactococcus lactis requires the cell envelope stress sensor/regulator couple CesSR

    NARCIS (Netherlands)

    Pinto, Joao P C; Kuipers, Oscar P; Marreddy, Ravi K R; Poolman, Bert; Kok, Jan

    2011-01-01

    BACKGROUND: Membrane proteins comprise an important class of molecules whose study is largely frustrated by several intrinsic constraints, such as their hydrophobicity and added requirements for correct folding. Additionally, the complexity of the cellular mechanisms that are required to insert

  18. CO{sub 2} capture efficiency and energy requirement analysis of power plant using modified calcium-based sorbent looping cycle

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.J.; Zhao, C.S.; Chen, H.C.; Ren, Q.Q.; Duan, L.B. [Southeast University, Nanjing (China). School of Energy & Environment

    2011-03-15

    This paper examines the average carbonation conversion, CO{sub 2} capture efficiency and energy requirement for post-combustion CO{sub 2} capture system during the modified calcium-based sorbent looping cycle. The limestone modified with acetic acid solution, i.e. calcium acetate is taken as an example of the modified calcium-based sorbents. The modified limestone exhibits much higher average carbonation conversion than the natural sorbent under the same condition. The CO{sub 2} capture efficiency increases with the sorbent flow ratios. Compared with the natural limestone, much less makeup mass flow of the recycled and the fresh sorbent is needed for the system when using the modified limestone at the same CO{sub 2} capture efficiency. Achieving 0.95 of CO{sub 2} capture efficiency without sulfation, 272 kJ/mol CO{sub 2} is required in the calciner for the natural limestone, whereas only 223 kJ/mol CO{sub 2} for the modified sorbent. The modified limestone possesses greater advantages in CO{sub 2} capture efficiency and energy consumption than the natural sorbent. When the sulfation and carbonation of the sorbents take place simultaneously, more energy is required. It is significantly necessary to remove SO{sub 2} from the flue gas before it enters the carbonator in order to reduce energy consumption in the calciner.

  19. Effect of near-infrared-radiation reflective screen materials on ventilation requirement, crop transpiration and water use efficiency of a greenhouse rose crop

    NARCIS (Netherlands)

    Stanghellini, C.; Jianfeng, D.; Kempkes, F.L.K.

    2011-01-01

    The effect of Near Infrared (NIR)-reflective screen material on ventilation requirement, crop transpiration and water use efficiency of a greenhouse rose crop was investigated in an experiment whereby identical climate was ensured in greenhouse compartments installed with either NIR-reflective or

  20. Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

    Science.gov (United States)

    Barresi, Valeria; Branca, Giovanni; Ieni, Antonio; Rigoli, Luciana; Tuccari, Giovanni; Caruso, Rosario Alberto

    2015-05-14

    cytoplasmic vacuoles of tumor cells. These data suggest phagocytosis (cannibalism) of apoptotic neutrophils by micropapillary tumor cells. Tumor cell cannibalism is usually found in aggressive tumors with anaplastic morphology. Our data extend these observations to gastric micropapillary carcinoma: a tumor histotype analogously characterized by aggressive behavior and poor prognosis. The results are of interest because they raise the intriguing possibility that neutrophil cannibalism by tumor cells may be one of the mechanisms favoring tumor growth in gastric micropapillary carcinomas. This is the first study showing phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

  1. The ED-inpatient dashboard: Uniting emergency and inpatient clinicians to improve the efficiency and quality of care for patients requiring emergency admission to hospital.

    Science.gov (United States)

    Staib, Andrew; Sullivan, Clair; Jones, Matt; Griffin, Bronwyn; Bell, Anthony; Scott, Ian

    2017-06-01

    Patients who require emergency admission to hospital require complex care that can be fragmented, occurring in the ED, across the ED-inpatient interface (EDii) and subsequently, in their destination inpatient ward. Our hospital had poor process efficiency with slow transit times for patients requiring emergency care. ED clinicians alone were able to improve the processes and length of stay for the patients discharged directly from the ED. However, improving the efficiency of care for patients requiring emergency admission to true inpatient wards required collaboration with reluctant inpatient clinicians. The inpatient teams were uninterested in improving time-based measures of care in isolation, but they were motivated by improving patient outcomes. We developed a dashboard showing process measures such as 4 h rule compliance rate coupled with clinically important outcome measures such as inpatient mortality. The EDii dashboard helped unite both ED and inpatient teams in clinical redesign to improve both efficiencies of care and patient outcomes. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  2. Microglial phagocytosis induced by fibrillar β-amyloid is attenuated by oligomeric β-amyloid: implications for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lin Nan

    2011-06-01

    Full Text Available Abstract Background Reactive microglia are associated with β-amyloid (Aβ deposit and clearance in Alzhiemer's Disease (AD. Paradoxically, entocranial resident microglia fail to trigger an effective phagocytic response to clear Aβ deposits although they mainly exist in an "activated" state. Oligomeric Aβ (oAβ, a recent target in the pathogenesis of AD, can induce more potent neurotoxicity when compared with fibrillar Aβ (fAβ. However, the role of the different Aβ forms in microglial phagocytosis, induction of inflammation and oxidation, and subsequent regulation of phagocytic receptor system, remain unclear. Results We demonstrated that Aβ(1-42 fibrils, not Aβ(1-42 oligomers, increased the microglial phagocytosis. Intriguingly, the pretreatment of microglia with oAβ(1-42 not only attenuated fAβ(1-42-triggered classical phagocytic response to fluorescent microspheres but also significantly inhibited phagocytosis of fluorescent labeled fAβ(1-42. Compared with the fAβ(1-42 treatment, the oAβ(1-42 treatment resulted in a rapid and transient increase in interleukin 1β (IL-1β level and produced higher levels of tumor necrosis factor-α (TNF-α, nitric oxide (NO, prostaglandin E2 (PGE2 and intracellular superoxide anion (SOA. The further results demonstrated that microglial phagocytosis was negatively correlated with inflammatory mediators in this process and that the capacity of phagocytosis in fAβ(1-42-induced microglia was decreased by IL-1β, lippolysaccharide (LPS and tert-butyl hydroperoxide (t-BHP. The decreased phagocytosis could be relieved by pyrrolidone dithiocarbamate (PDTC, a nuclear factor-κB (NF-κB inhibitor, and N-acetyl-L-cysteine (NAC, a free radical scavenger. These results suggest that the oAβ-impaired phagocytosis is mediated through inflammation and oxidative stress-mediated mechanism in microglial cells. Furthermore, oAβ(1-42 stimulation reduced the mRNA expression of CD36, integrin β1 (Itgb1, and Ig

  3. Effect of Bothrops alternatus snake venom on macrophage phagocytosis and superoxide production: participation of protein kinase C

    Directory of Open Access Journals (Sweden)

    SS Setubal

    2011-01-01

    Full Text Available Envenomations caused by different species of Bothrops snakes result in severe local tissue damage, hemorrhage, pain, myonecrosis, and inflammation with a significant leukocyte accumulation at the bite site. However, the activation state of leukocytes is still unclear. According to clinical cases and experimental work, the local effects observed in envenenomation by Bothrops alternatus are mainly the appearance of edema, hemorrhage, and necrosis. In this study we investigated the ability of Bothrops alternatus crude venom to induce macrophage activation. At 6 to 100 ¼g/mL, BaV is not toxic to thioglycollate-elicited macrophages; at 3 and 6 ¼g/mL, it did not interfere in macrophage adhesion or detachment. Moreover, at concentrations of 1.5, 3, and 6 ¼g/mL the venom induced an increase in phagocytosis via complement receptor one hour after incubation. Pharmacological treatment of thioglycollate-elicited macrophages with staurosporine, a protein kinase (PKC inhibitor, abolished phagocytosis, suggesting that PKC may be involved in the increase of serum-opsonized zymosan phagocytosis induced by BaV. Moreover, BaV also induced the production of anion superoxide (O2_ by thioglycollate-elicited macrophages. This BaV stimulated superoxide production was abolished after treating the cells with staurosporine, indicating that PKC is an important signaling pathway for the production of this radical. Based on these results, we suggest that phagocytosis and reactive oxygen species are involved in the pathogenesis of local tissue damage characteristic of Bothrops spp. envenomations.

  4. Impaired phagocytosis in localized aggressive periodontitis: rescue by Resolvin E1.

    Directory of Open Access Journals (Sweden)

    Gabrielle Fredman

    Full Text Available Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18 surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A(4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1-100 nM, rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression.

  5. Elasticity of nanoparticles influences their blood circulation, phagocytosis, endocytosis, and targeting.

    Science.gov (United States)

    Anselmo, Aaron C; Zhang, Mengwen; Kumar, Sunny; Vogus, Douglas R; Menegatti, Stefano; Helgeson, Matthew E; Mitragotri, Samir

    2015-03-24

    The impact of physical and chemical modifications of nanoparticles on their biological function has been systemically investigated and exploited to improve their circulation and targeting. However, the impact of nanoparticles' flexibility (i.e., elastic modulus) on their function has been explored to a far lesser extent, and the potential benefits of tuning nanoparticle elasticity are not clear. Here, we describe a method to synthesize polyethylene glycol (PEG)-based hydrogel nanoparticles of uniform size (200 nm) with elastic moduli ranging from 0.255 to 3000 kPa. These particles are used to investigate the role of particle elasticity on key functions including blood circulation time, biodistribution, antibody-mediated targeting, endocytosis, and phagocytosis. Our results demonstrate that softer nanoparticles (10 kPa) offer enhanced circulation and subsequently enhanced targeting compared to harder nanoparticles (3000 kPa) in vivo. Furthermore, in vitro experiments show that softer nanoparticles exhibit significantly reduced cellular uptake in immune cells (J774 macrophages), endothelial cells (bEnd.3), and cancer cells (4T1). Tuning nanoparticle elasticity potentially offers a method to improve the biological fate of nanoparticles by offering enhanced circulation, reduced immune system uptake, and improved targeting.

  6. Flow cytometric quantitation of phagocytosis in heparinized complete blood with latex particles and Candida albicans

    Directory of Open Access Journals (Sweden)

    Jesús M. Egido

    1997-12-01

    Full Text Available We report a rapid method for the flow cytometric quantitation of phagocytosis in heparinized complete peripherial blood (HCPB, using commercially available phycoerythrin-conjugated latex particles of 1µm diameter. The method is faster and shows greater reproducibility than Bjerknes' (1984 standard technique using propidium iodide-stained Candida albicans, conventionally applied to the leukocytic layer of peripherial blood but here modified for HCPB. We also report a modification of Bjerknes' Intracellular Killing Test to allow its application to HCPB.Se da cuenta de un método rápido para la cuantización del flujo citométrico de la fagocitosis en sangre periférica completamente heparinizada (HCPB, mediante la utilización de partículas de látex phycoerythrin-conjugadas de 1µm de diámetro disponibles comercialmente. El método es más rápido y presenta mayor reproducibilidad que la técnica estandar de Bjerknes' (1984 utilizando propidium iodide-teñida Candida albicans, aplicada convencionalmente a la capa leucocitica de sangre periférica pero modificada por HCPB. Tambien damos cuenta de una modificación de Bjerknes' Intracellular Killing Test para permitir su aplicación a HCPB.

  7. Stage-specific sampling by pattern recognition receptors during Candida albicans phagocytosis.

    Directory of Open Access Journals (Sweden)

    Sigrid E M Heinsbroek

    2008-11-01

    Full Text Available Candida albicans is a medically important pathogen, and recognition by innate immune cells is critical for its clearance. Although a number of pattern recognition receptors have been shown to be involved in recognition and phagocytosis of this fungus, the relative role of these receptors has not been formally examined. In this paper, we have investigated the contribution of the mannose receptor, Dectin-1, and complement receptor 3; and we have demonstrated that Dectin-1 is the main non-opsonic receptor involved in fungal uptake. However, both Dectin-1 and complement receptor 3 were found to accumulate at the site of uptake, while mannose receptor accumulated on C. albicans phagosomes at later stages. These results suggest a potential role for MR in phagosome sampling; and, accordingly, MR deficiency led to a reduction in TNF-alpha and MCP-1 production in response to C. albicans uptake. Our data suggest that pattern recognition receptors sample the fungal phagosome in a sequential fashion.

  8. Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing

    Science.gov (United States)

    Goh, Yun Shan; Armour, Kathryn L; Clark, Michael R; Grant, Andrew J; Mastroeni, Pietro

    2016-01-01

    Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte-like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease. PMID:27366588

  9. Roles of phagocytosis activating protein (PAP) in Aeromonas hydrophila infected Cyprinus carpio.

    Science.gov (United States)

    Wonglapsuwan, Monwadee; Kongmee, Pataraporn; Suanyuk, Naraid; Chotigeat, Wilaiwan

    2016-06-01

    Cyprinus carpio (koi) is one of the most popular ornamental fish. A major problem for C. carpio farming is bacterial infections especially by Aeromonas hydrophila. Previously studies had shown that the Phagocytosis Activating Protein (PAP) gene was involved in the innate immune response of animals. Therefore, we attempted to identify a role for the PAP gene in the immunology of C. carpio. The expression of the PAP was found in C. carpio whole blood and increased when the fish were stimulated by inactivated A. hydrophila. In addition, PAP-phMGFP DNA was injected as an immunostimulant. The survival rate and the phagocytic index were significantly increased in the A. hydrophila infected fish that received the PAP-phMGFP DNA immunostimulant. A chitosan-PAP-phMGFP nanoparticle was then developed and feeded into fish which infected with A. hydrophila. These fish had a significantly lower mortality rate than the control. Therefore, this research confirmed a key role for PAP in protection fish from bacterial infection and the chitosan-PAP-phMGFP nanoparticle could be a good prototype for fish immunostimulant in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Antibody dependent cellular phagocytosis by macrophages is a novel mechanism of action of elotuzumab.

    Science.gov (United States)

    Kurdi, Ahmed T; Glavey, Siobhan V; Bezman, Natalie A; Jhatakia, Amy; Guerriero, Jennifer L; Manier, Salomon; Moschetta, Michele; Mishima, Yuji; Roccaro, Aldo; Detappe, Alexandre; Liu, Chia-Jen; Sacco, Antonio; Huynh, Daisy; Tai, Yu-Tzu; Robbins, Michael D; Azzi, Jamil; Ghobrial, Irene M

    2018-04-13

    Elotuzumab, a recently approved antibody for the treatment of multiple myeloma (MM), has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells towards myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to anti-tumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor associated macrophages (TAMs) using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant anti-tumor efficacy of single agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in-vivo and mediates ADCP of myeloma cells though a FcγR dependent manner in-vitro. Together, these findings propose a novel immune mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. Copyright ©2018, American Association for Cancer Research.

  11. Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity.

    Science.gov (United States)

    Herter, Sylvia; Birk, Martina C; Klein, Christian; Gerdes, Christian; Umana, Pablo; Bacac, Marina

    2014-03-01

    Therapeutic Abs possess several clinically relevant mechanisms of action including perturbation of tumor cell signaling, activation of complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cellular phagocytosis (ADCP), and induction of adaptive immunity. In view of the important role of phagocytic lineage cells in the mechanism of action of therapeutic Abs, we analyzed FcγR receptor-dependent effector functions of monocytes and macrophages triggered by glycoengineered (GE) Abs (having enhanced FcγRIIIa [CD16a] binding affinity) versus their wild-type (WT) counterparts under different experimental conditions. We first defined the precise FcγR repertoire on classical and nonclassical intermediate monocytes--M1 and M2c macrophage populations. We further show that WT and GE Abs display comparable binding and induce similar effector functions (ADCC and ADCP) in the absence of nonspecific, endogenous IgGs. However, in the presence of these IgGs (i.e., in a situation that more closely mimics physiologic conditions), GE Abs display significantly superior binding and promote stronger monocyte and macrophage activity. These data show that in addition to enhancing CD16a-dependent NK cell cytotoxicity, glycoengineering also enhances monocyte and macrophage phagocytic and cytotoxic activities through enhanced binding to CD16a under conditions that more closely resemble the physiologic setting.

  12. Enhanced antibody-dependent cellular phagocytosis by chimeric monoclonal antibodies with tandemly repeated Fc domains.

    Science.gov (United States)

    Nagashima, Hiroaki; Ootsubo, Michiko; Fukazawa, Mizuki; Motoi, Sotaro; Konakahara, Shu; Masuho, Yasuhiko

    2011-04-01

    We previously reported that chimeric monoclonal antibodies (mAbs) with tandemly repeated Fc domains, which were developed by introducing tandem repeats of Fc domains downstream of 2 Fab domains, augmented binding avidities for all Fcγ receptors, resulting in enhanced antibody (Ab)-dependent cellular cytotoxicity. Here we investigated regarding Ab-dependent cellular phagocytosis (ADCP) mediated by these chimeric mAbs, which is considered one of the most important mechanisms that kills tumor cells, using two-color flow cytometric methods. ADCP mediated by T3-Ab, a chimeric mAb with 3 tandemly repeated Fc domains, was 5 times more potent than that by native anti-CD20 M-Ab (M-Ab hereafter). Furthermore, T3-Ab-mediated ADCP was resistant to competitive inhibition by intravenous Ig (IVIG), although M-Ab-mediated ADCP decreased in the presence of IVIG. An Fcγ receptor-blocking study demonstrated that T3-Ab mediated ADCP via both FcγRIA and FcγRIIA, whereas M-Ab mediated ADCP exclusively via FcγRIA. These results suggest that chimeric mAbs with tandemly repeated Fc domains enhance ADCP as well as ADCC, and that Fc multimerization may significantly enhance the efficacy of therapeutic Abs. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. Phagocytosis, bacterial killing, and cytokine activation of circulating blood neutrophils in horses with severe equine asthma and control horses.

    Science.gov (United States)

    Vanderstock, Johanne M; Lecours, Marie-Pier; Lavoie-Lamoureux, Annouck; Gottschalk, Marcelo; Segura, Mariela; Lavoie, Jean-Pierre; Jean, Daniel

    2018-04-01

    OBJECTIVE To evaluate in vitro phagocytosis and bactericidal activity of circulating blood neutrophils in horses with severe equine asthma and control horses and to determine whether circulating blood neutrophils in horses with severe equine asthma have an increase in expression of the proinflammatory cytokine tumor necrosis factor (TNF)-α and the chemokine interleukin (IL)-8 and a decrease in expression of the anti-inflammatory cytokine IL-10 in response to bacteria. ANIMALS 6 horses with severe equine asthma and 6 control horses. PROCEDURES Circulating blood neutrophils were isolated from horses with severe equine asthma and control horses. Phagocytosis was evaluated by use of flow cytometry. Bactericidal activity of circulating blood neutrophils was assessed by use of Streptococcus equi and Streptococcus zooepidemicus as targets, whereas the cytokine mRNA response was assessed by use of a quantitative PCR assay. RESULTS Circulating blood neutrophils from horses with severe equine asthma had significantly lower bactericidal activity toward S zooepidemicus but not toward S equi, compared with results for control horses. Phagocytosis and mRNA expression of TNF-α, IL-8, and IL-10 were not different between groups. CONCLUSIONS AND CLINCAL RELEVANCE Impairment of bactericidal activity of circulating blood neutrophils in horses with severe equine asthma could contribute to an increased susceptibility to infections.

  14. Source and role of diacylglycerol formed during phagocytosis of opsonized yeast particles and associated respiratory burst in human neutrophils

    International Nuclear Information System (INIS)

    Della Bianca, V.; Grzeskowiak, M.; Lissandrini, D.; Rossi, F.

    1991-01-01

    The results presented in this paper demonstrate that in human neutrophils phagocytosis of C3b/bi and IgG-opsonized yeast particles is associated with activation of phospholipase D and that this reaction is the main source of diglycerides. The demonstration is based upon the following findings: (1) the challenge of neutrophils with these opsonized particles was followed by a rapid formation of [3H]alkyl-phosphatidic acid [( 3H]alkyl-PA) and [3H]alkyl-diglyceride [( 3H]alkyl-DG) in cells labeled with [3H]alkyl-lyso-phosphatidylcholine; (2) in the presence of ethanol [3H]alkyl-phosphatidylethanol was formed, and accumulation of [3H]alkyl-PA and [3H]alkyl-DG was depressed; (3) propranolol, by inhibiting the dephosphorylation of [3H]alkyl-PA, completely inhibited the accumulation of [3H]alkyl-DG and depressed by about 75% the formation of diglyceride mass. Evidence is also presented that phagocytosis of C3b/bi and IgG-opsonized yeast particles and associated respiratory burst can take place independently of diglyceride formation and of the activity of this second messenger on protein kinase C. In fact: (a) propranolol while completely inhibited the formation of diglyceride mass did not modify either the phagocytosis or respiratory burst; (b) these two processes were insensitive to staurosporine

  15. Inter-domain synergism is required for efficient feeding of cellulose chain into active site of cellobiohydrolase Cel7A

    DEFF Research Database (Denmark)

    Kont, Riin; Kari, Jeppe; Borch, Kim

    2016-01-01

    systems. TrCel7A consists of catalytic domain (CD) and a smaller carbohydrate binding module (CBM) connected through the glycosylated linker peptide. A tunnel shaped active site rests in the CD and contains 10 glucose unit binding sites. The active site of TrCel7A is lined with four Trp residues with two...... to Ala substitution on on-rates was strongly dependent on the presence of the CBM-linker. This compensation between CBM-linker and Trp-38 indicates synergism between CBM-linker and CD in feeding the cellulose chain into the active site. The inter-domain synergism was pre-requisite for the efficient......Structural polysaccharides like cellulose and chitin are abundant and their enzymatic degradation to soluble sugars is an important route in green chemistry. Processive glycoside hydrolases (GHs), like cellobiohydrolase Cel7A of Trichoderma reesei (TrCel7A) are key components of efficient enzyme...

  16. Inter-domain Synergism Is Required for Efficient Feeding of Cellulose Chain into Active Site of Cellobiohydrolase Cel7A*

    OpenAIRE

    Kont, Riin; Kari, Jeppe; Borch, Kim; Westh, Peter; Väljamäe, Priit

    2016-01-01

    Structural polysaccharides like cellulose and chitin are abundant and their enzymatic degradation to soluble sugars is an important route in green chemistry. Processive glycoside hydrolases (GHs), like cellobiohydrolase Cel7A of Trichoderma reesei (TrCel7A) are key components of efficient enzyme systems. TrCel7A consists of a catalytic domain (CD) and a smaller carbohydrate-binding module (CBM) connected through the glycosylated linker peptide. A tunnel-shaped active site rests in the CD and ...

  17. Identification of a novel NLS of herpes simplex virus type 1 (HSV-1) VP19C and its nuclear localization is required for efficient production of HSV-1.

    Science.gov (United States)

    Li, You; Zhao, Lei; Wang, Shuai; Xing, Junji; Zheng, Chunfu

    2012-09-01

    Herpes simplex virus type 1 (HSV-1) triplex is a complex of three protein subunits, consisting of two copies of VP23 and one copy of VP19C. Here, we identified a non-classical NLS of VP19C between aa 50 and 61, and the nuclear import of VP19C was mediated by RanGTP and importin β1-, but not importin α5-, dependent pathway. Additionally, recombinant virus harbouring this NLS mutation (NLSm) replicates less efficiently as wild-type. These data strongly suggested that the nuclear import of VP19C is required for efficient HSV-1 production.

  18. Requirement, balance and energy efficiency under two models of cropping systems in the center-south of Buenos Aires, Argentina.

    Science.gov (United States)

    Zamora, Martin; Barbera, Agustin; Hansson, Alejandro; Carrasco, Natalia; Domenech, Marisa

    2017-04-01

    In a natural ecosystem, the solar energy is the main source. However, in the agro ecosystem we should use others in order to sustain specific processes or to avoid some interactions. This energy is introduced in the agro-system not only as fossil fuel but also as inputs like fertilizers and pesticides or for agricultural machines. Since February 2011, two adjacent fields were set at Barrow Experimental Station (Lat:-38.322844, Lon:-60.25572): one of them adopting agro-ecology principles (AGROE), as biodiversity increase, polyculture with legumes, less use of agrochemicals; while the other one is based on industrial model of agriculture (ACTUAL). This model is defined by its capital intensity and dependence on massive inputs like seeds, fertilizer, and pesticides. In both fields, beef cattle and agriculture production have been implemented with different intensity. The aim of this study was to compare the demand, production, balance and energy efficiency between these two agro-systems. To do this, we use tables of energy associated with different processes and inputs. For both systems, we estimate the energetic demand used in seeds, pesticides, fertilizers and labor during the crop sequence from February 2011 to December 2015; the energy production according to grains and meat yield achieved; the energetic balance calculated as the difference between inputs and outputs of energy in the system and finally, the energy efficiency which is the ratio between the energy produced and consumed. Inputs-outputs ratios of energy were transformed into equivalent units = GJ (Gigajoules). After a sequence of seven crops, ACTUAL consumed 60 GJ, which represents 158% more energy than AGROE. Particularly, ACTUAL consumed a 72% more energy in cultivation labor, 372% more in herbicides and 10 times more energy used in fertilizers than AGROE. Even though ACTUAL produced 37% more energy than AGROE (187 GJ vs 127 GJ) in grain and meat, the energetic balance was only 12% higher. However

  19. Far beyond Phagocytosis: Phagocyte-Derived Extracellular Traps Act Efficiently against Protozoan Parasites In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Liliana M. R. Silva

    2016-01-01

    Full Text Available Professional mononuclear phagocytes such as polymorphonuclear neutrophils (PMN, monocytes, and macrophages are considered as the first line of defence against invasive pathogens. The formation of extracellular traps (ETs by activated mononuclear phagocytes is meanwhile well accepted as an effector mechanism of the early host innate immune response acting against microbial infections. Recent investigations showed evidence that ETosis is a widely spread effector mechanism in vertebrates and invertebrates being utilized to entrap and kill bacteria, fungi, viruses, and protozoan parasites. ETs are released in response to intact protozoan parasites or to parasite-specific antigens in a controlled cell death process. Released ETs consist of nuclear DNA as backbone adorned with histones, antimicrobial peptides, and phagocyte-specific granular enzymes thereby producing a sticky extracellular matrix capable of entrapping and killing pathogens. This review summarizes recent data on protozoa-induced ETosis. Special attention will be given to molecular mechanisms of protozoa-induced ETosis and on its consequences for the parasites successful reproduction and life cycle accomplishment.

  20. Elements Required for an Efficient NADP-Malic Enzyme Type C4 Photosynthesis1[C][W][OPEN

    Science.gov (United States)

    Wang, Yu; Long, Stephen P.; Zhu, Xin-Guang

    2014-01-01

    C4 photosynthesis has higher light, nitrogen, and water use efficiencies than C3 photosynthesis. Although the basic anatomical, cellular, and biochemical features of C4 photosynthesis are well understood, the quantitative significance of each element of C4 photosynthesis to the high photosynthetic efficiency are not well defined. Here, we addressed this question by developing and using a systems model of C4 photosynthesis, which includes not only the Calvin-Benson cycle, starch synthesis, sucrose synthesis, C4 shuttle, and CO2 leakage, but also photorespiration and metabolite transport between the bundle sheath cells and mesophyll cells. The model effectively simulated the CO2 uptake rates, and the changes of metabolite concentrations under varied CO2 and light levels. Analyses show that triose phosphate transport and CO2 leakage can help maintain a high photosynthetic rate by balancing ATP and NADPH amounts in bundle sheath cells and mesophyll cells. Finally, we used the model to define the optimal enzyme properties and a blueprint for C4 engineering. As such, this model provides a theoretical framework for guiding C4 engineering and studying C4 photosynthesis in general. PMID:24521879

  1. Inter-domain Synergism Is Required for Efficient Feeding of Cellulose Chain into Active Site of Cellobiohydrolase Cel7A.

    Science.gov (United States)

    Kont, Riin; Kari, Jeppe; Borch, Kim; Westh, Peter; Väljamäe, Priit

    2016-12-09

    Structural polysaccharides like cellulose and chitin are abundant and their enzymatic degradation to soluble sugars is an important route in green chemistry. Processive glycoside hydrolases (GHs), like cellobiohydrolase Cel7A of Trichoderma reesei (TrCel7A) are key components of efficient enzyme systems. TrCel7A consists of a catalytic domain (CD) and a smaller carbohydrate-binding module (CBM) connected through the glycosylated linker peptide. A tunnel-shaped active site rests in the CD and contains 10 glucose unit binding sites. The active site of TrCel7A is lined with four Trp residues with two of them, Trp-40 and Trp-38, in the substrate binding sites near the tunnel entrance. Although addressed in numerous studies the elucidation of the role of CBM and active site aromatics has been obscured by a complex multistep mechanism of processive GHs. Here we studied the role of the CBM-linker and Trp-38 of TrCel7A with respect to binding affinity, on- and off-rates, processivity, and synergism with endoglucanase. The CBM-linker increased the on-rate and substrate affinity of the enzyme. The Trp-38 to Ala substitution resulted in increased off-rates and decreased processivity. The effect of the Trp-38 to Ala substitution on on-rates was strongly dependent on the presence of the CBM-linker. This compensation between CBM-linker and Trp-38 indicates synergism between CBM-linker and CD in feeding the cellulose chain into the active site. The inter-domain synergism was pre-requisite for the efficient degradation of cellulose in the presence of endoglucanase. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

    Science.gov (United States)

    Kober, P M; Filkins, J P

    1981-01-01

    Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

  3. Non-opsonic phagocytosis of Legionella pneumophila by macrophages is mediated by phosphatidylinositol 3-kinase.

    Directory of Open Access Journals (Sweden)

    Souvenir D Tachado

    Full Text Available BACKGROUND: Legionella pneumophila, is an intracellular pathogen that causes Legionnaires' disease in humans, a potentially lethal pneumonia. L. pneumophila has the ability to enter and replicate in the host and is essential for pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Phagocytosis was measured by cell invasion assays. Construction of PI3K mutant by PCR cloning and expression of dominant negative mutant was detected by Western blot. PI3K activity was measured by 32P labeling and detection of phospholipids products by thin layer chromatography. Infection of macrophages with virulent L. pneumophila stimulated the formation of phosphatidylinositol 3-phosphate (PIP3, a phosphorylated lipid product of PI3K whereas two structurally distinct phosphatidylinositol 3 kinase (PI3K inhibitors, wortmannin and LY294002, reduced L. pneumophila entry into macrophages in a dose-dependent fashion. Furthermore, PI3K activation led to Akt stimulation, a serine/threonine kinase, which was also inhibited by wortmannin and LY294002. In contrast, PI3K and protein kinase B (PKB/Akt activities were lower in macrophages infected with an avirulent bacterial strain. Only virulent L. pneumophila increased lipid kinase activity present in immunoprecipitates of the p85alpha subunit of class I PI3K and tyrosine phosphorylated proteins. In addition, macrophages expressing a specific dominant negative mutant of PI3K reduced L. pneumophila entry into these cells. CONCLUSION/SIGNIFICANCE: Entry of L. pneumophila is mediated by PI3K/Akt signaling pathway. These results suggest an important role for PI3K and Akt in the L. pneumophila infection process. They point to possible novel strategies for undermining L. pneumophila host uptake and reducing pathogenesis of Legionnaires' disease.

  4. Cyclic GMP-dependent protein kinase II is necessary for macrophage M1 polarization and phagocytosis via toll-like receptor 2.

    Science.gov (United States)

    Liao, Wei-Ting; You, Huey-Ling; Li, Changgui; Chang, Jan-Gowth; Chang, Shun-Jen; Chen, Chung-Jen

    2015-05-01

    Cyclic GMP-dependent protein kinase II (cGKII; PRKG2) phosphorylates a variety of biological targets and has been identified as a gout-susceptible gene. However, the regulatory role of cGKII in triggering gout disease has yet to be clarified. Thus, we plan to explore the specific function of cGKII in macrophages related to gout disease. By using cGKII gene knockdown method, we detected macrophage M1/M2 polarization, phagocytosis, and their responses to stimulation by monosodium urate (MSU). cGKII was highly expressed in M1 phenotype, but not in M2, and cGKII knockdown significantly inhibited macrophage M1 polarization by decreasing M1 chemokine markers (CXCL10 and CCL2) and downregulating phagocytosis function. We further identified that cGKII-associated phagocytosis was mediated by upregulating toll-like receptor 2 (TLR2) expression, but not by TLR4. Mimicking gout condition by MSU treatments, we found that MSU alone induced cGKII and TLR2 expression with increased M1 polarization markers and phagocytosis activity. It means that cGKII knockdown significantly inhibited this MSU-induced cGKII-TLR2-phagocytosis axis. Our study showed that cGKII plays a key role in M1 polarization, especially in TLR2-mediated phagocytosis under MSU exposure. The findings provide evidence for the possible role of cGKII as an inflammation exciter in gout disease. Gout-susceptible gene cGKII is necessary for macrophage M1 polarization. cGKII regulates M1 phagocytosis function via TLR2. Monosodium urate treatments increase cGKII expression and related function. This study reveals the role of cGKII in enhancing gouty inflammatory responses.

  5. A Coordinated Patient Transport System for ICU Patients Requiring Surgery: Impact on Operating Room Efficiency and ICU Workflow.

    Science.gov (United States)

    Brown, Michael J; Kor, Daryl J; Curry, Timothy B; Marmor, Yariv; Rohleder, Thomas R

    2015-01-01

    Transfer of intensive care unit (ICU) patients to the operating room (OR) is a resource-intensive, time-consuming process that often results in patient throughput inefficiencies, deficiencies in information transfer, and suboptimal nurse to patient ratios. This study evaluates the implementation of a coordinated patient transport system (CPTS) designed to address these issues. Using data from 1,557 patient transfers covering the 2006-2010 period, interrupted time series and before and after designs were used to analyze the effect of implementing a CPTS at Mayo Clinic, Rochester. Using a segmented regression for the interrupted time series, on-time OR start time deviations were found to be significantly lower after the implementation of CPTS (p < .0001). The implementation resulted in a fourfold improvement in on-time OR starts (p < .01) while significantly reducing idle OR time (p < .01). A coordinated patient transfer process for moving patient from ICUs to ORs can significantly improve OR efficiency, reduce nonvalue added time, and ensure quality of care by preserving appropriate care provider to patient ratios.

  6. Empirical Selection of Informative Microsatellite Markers within Co-ancestry Pig Populations Is Required for Improving the Individual Assignment Efficiency

    Directory of Open Access Journals (Sweden)

    Y. H. Li

    2014-05-01

    Full Text Available The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is distantly related to Asian and European pig breeds. It has been inbred to generate two breeds and crossed with Landrace and Duroc to produce two hybrids for laboratory use. Selecting sets of informative genetic markers to track the genetic qualities of laboratory animals and stud stock is an important function of genetic databases. For more than two decades, Lanyu derived breeds of common ancestry and crossbreeds have been used to examine the effectiveness of genetic marker selection and optimal approaches for individual assignment. In this paper, these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire, Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation Station Black pig are studied to build a genetic reference database. Nineteen microsatellite markers (loci provide information on genetic variation and differentiation among studied breeds. High differentiation index (FST and Cavalli-Sforza chord distances give genetic differentiation among breeds, including Lanyu’s inbred populations. Inbreeding values (FIS show that Lanyu and its derived inbred breeds have significant loss of heterozygosity. Individual assignment testing of 352 animals was done with different numbers of microsatellite markers in this study. The testing assigned 99% of the animals successfully into their correct reference populations based on 9 to 14 markers ranking D-scores, allelic number, expected heterozygosity (HE or FST, respectively. All miss-assigned individuals came from close lineage Lanyu breeds. To improve individual assignment among close lineage breeds, microsatellite markers selected from Lanyu populations with high polymorphic, heterozygosity, FST and D-scores were used. Only 6 to 8 markers ranking HE, FST or allelic number were required to obtain 99% assignment accuracy. This result suggests empirical examination of assignment-error rates

  7. Efficient Overproduction of Membrane Proteins in Lactococcus lactis Requires the Cell Envelope Stress Sensor/Regulator Couple CesSR

    Science.gov (United States)

    Pinto, Joao P. C.; Kuipers, Oscar P.; Marreddy, Ravi K. R.; Poolman, Bert; Kok, Jan

    2011-01-01

    Background Membrane proteins comprise an important class of molecules whose study is largely frustrated by several intrinsic constraints, such as their hydrophobicity and added requirements for correct folding. Additionally, the complexity of the cellular mechanisms that are required to insert membrane proteins functionally in the membrane and to monitor their folding state makes it difficult to foresee the yields at which one can obtain them or to predict which would be the optimal production host for a given protein. Methods and Findings We describe a rational design approach to improve the lactic acid bacterium Lactococcus lactis as a producer of membrane proteins. Our transcriptome data shows that the two-component system CesSR, which senses cell envelope stresses of different origins, is one of the major players when L. lactis is forced to overproduce the endogenous membrane protein BcaP, a branched-chain amino acid permease. Growth of the BcaP-producing L. lactis strain and its capability to produce membrane proteins are severely hampered when the CesSR system itself or particular members of the CesSR regulon are knocked out, notably the genes ftsH, oxaA2, llmg_2163 and rmaB. Overexpressing cesSR reduced the growth defect, thus directly improving the production yield of BcaP. Applying this rationale to eukaryotic proteins, some of which are notoriously more difficult to produce, such as the medically-important presenilin complex, we were able to significantly diminish the growth defect seen in the wild-type strain and improve the production yield of the presenilin variant PS1Δ9-H6 more than 4-fold. Conclusions The results shed light into a key, and perhaps central, membrane protein quality control mechanism in L. lactis. Modulating the expression of CesSR benefited the production yields of membrane proteins from different origins. These findings reinforce L. lactis as a legitimate alternative host for the production of membrane proteins. PMID:21818275

  8. Effect of UVB irradiation of the blood on cellular volume adherence and phagocytosis in probands and patients with multiple sclerosis

    International Nuclear Information System (INIS)

    Mix, E.; Jenssen, H.L.; Lehmitz, R.; Buddenhagen, F.; Hitzschke, B.; Richter, M.

    1988-01-01

    UVB-induced changes of blood cell properties were investigated in 12 multiple sclerosis (MS) patients and in 10 healthy volunteers. The mean cell volume (MCV) was determined by electronic sizing, the granulocyte and lymphocyte adherence was estimated in a capillary assay, and the phagocytic activity of granulocytes was measured in a test system based on the incorporation of opsonized baker's yeast. In MS patients the MCV of red cells and lymphocytes decreased rapidly within 6 UVB treatments. In contrast, the reduction of the granulocyte volume was delayed (between the 6th and 12th UVB). In the control group the mean value of the red cell and lymphocyte MCV remained rather unaffected. There was a slight rise of the granulocyte volume after the 6th UVB. The only significant change of adherence was an increase of granulocyte adherence in MS patients. Untreated patients had a significantly enhanced phagocytic activity in comparison to the control group. 6 UVB treatments induced a singificant reduction of the phagocytic activity in MS patients. However, subsequently the percentage of phagocytizing cells increased again, whereas the particle uptake per cell continued to decrease. In the control group only minor UVB-induced changes of phagocytosis were observed. The in vitro UV irradiation caused an enhanced phagocytosis in the majority of cases in both controls and MS patients. In general, under the UVB treatment all parameters examined changed in the sense of a normalisation, in that the measured values reached a new level lying between the extreme pretreatment values accompanied by a reduced standard deviation. The effect of UVB was more pronounced in MS patients when compared with normal control. This could result from an enhanced sensitivity to the influence of UVB of pathologically altered cells in MS patients. The monitoring of the MCV of red cells and lymphocytes as well as the repeated testing of granulocyte phagocytosis are recommended for supportion of therapy

  9. Tick thioester-containing proteins and phagocytosis do not affect transmission of Borrelia afzelii from the competent vector ixodes ricinus

    Czech Academy of Sciences Publication Activity Database

    Urbanová, Veronika; Hajdušek, Ondřej; Hönig Mondeková, Helena; Šíma, Radek; Kopáček, Petr

    2017-01-01

    Roč. 7, MAR (2017), č. článku 73. ISSN 2235-2988 R&D Projects: GA ČR GJ15-12006Y; GA ČR GA13-11043S; GA ČR GA17-27386S; GA ČR GA17-27393S EU Projects: European Commission(XE) 602272 - ANTIDotE Institutional support: RVO:60077344 Keywords : Borrelia * complement * Ixodes * phagocytosis * thioester-containing proteins Subject RIV: EC - Immunology OBOR OECD: Immunology Impact factor: 4.300, year: 2016

  10. Simultaneous determination of phagocytosis of Plasmodium falciparum-parasitized and non-parasitized red blood cells by flow cytometry

    Directory of Open Access Journals (Sweden)

    Gallo Valentina

    2012-12-01

    Full Text Available Abstract Background Severe falciparum malaria anaemia (SMA is a frequent cause of mortality in children and pregnant women. The most important determinant of SMA appears to be the loss of non-parasitized red blood cells (np-RBCs in excess of loss of parasitized (p- RBCs at schizogony. Based on data from acute SMA where excretion of haemoglobin in urine and increased plasma haemoglobin represented respectively less than 1% and 0.5% of total Hb loss, phagocytosis appears to be the predominant mechanism of removal of np- and p-RBC. Estimates indicate that np-RBCs are cleared in approximately 10-fold excess compared to p-RBCs. An even larger removal of np-RBCs has been described in vivax malaria anaemia. Estimates were based on two single studies both performed on neurosyphilitic patients who underwent malaria therapy. As the share of np-RBC removal is likely to vary between wide limits, it is important to assess the contribution of both np- and p-RBC populations to overall RBC loss, and disclose the mechanism of such variability. As available methods do not discriminate between the removal of np- vs p-RBCs, the purpose of this study was to set up a system allowing the simultaneous determination of phagocytosis of p- and np-RBC in the same sample. Methods and Results Phagocytosis of p- and np-RBCs was quantified in the same sample using double-labelled target cells and the human phagocytic cell-line THP-1, pre-activated by TNF and IFNγ to enhance their phagocytic activity. Target RBCs were double-labelled with fluorescent carboxyfluorescein-succinimidyl ester (CF-SE and the DNA label ethidium bromide (EB. EB, a DNA label, allowed to discriminate p-RBCs that contain parasitic DNA from the np-RBCs devoid of DNA. FACS analysis of THP-1 cells fed with double-labelled RBCs showed that p- and np-RBCs were phagocytosed in different proportions in relation to parasitaemia. Conclusions The assay allowed the analysis of phagocytosis rapidly and with low

  11. Neuro-immune relationships at patients with chronic pyelonephrite and cholecystite. Communication 2. Correlations between parameters EEG, HRV and Phagocytosis

    OpenAIRE

    Kul’chyns’kyi, Andriy B; Kovbasnyuk, Marta M; Korolyshyn, Tetyana A; Kyjenko, Valeriy M; Zukow, Walery; Popovych, Igor L

    2016-01-01

    Kul’chyns’kyi Andriy B, Kovbasnyuk Marta M, Korolyshyn Tetyana A, Kyjenko Valeriy M, Zukow Walery, Popovych Igor L. Neuro-immune relationships at patients with chronic pyelonephrite and cholecystite. Communication 2. Correlations between parameters EEG, HRV and Phagocytosis. Journal of Education, Health and Sport. 2016;6(10):377-401. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.163221 http://ojs.ukw.edu.pl/index.php/johs/article/view/3957 The journal h...

  12. Interaction between Salmonella typhimurium and phagocytic cells in pigs - Phagocytosis, oxidative burst and killing in polymorphonuclear leukocytes and monocytes

    DEFF Research Database (Denmark)

    Riber, Ulla; Lind, Peter

    1999-01-01

    Interactions between Salmonella typhimurium and peripheral blood leucocytes from healthy, Salmonella-free pigs were investigated in vitro. Both granulocytes and monocytes phagocytized FITC-labelled heat-killed Salmonella bacteria as shown by flow cytometry. Phagocytosis in whole blood and isolated...... with the exhaustion of oxidative burst in non-adherent monocytes were performed by prestimulation with PMA, heat-killed Salmonella or buffer. Prestimulation with PMA led to a strong reduction in oxidative burst induced by living opsonized Salmonella bacteria, whereas prestimulation with heat-killed bacteria gave rise...

  13. Diverse regulation of retinal pigment epithelium phagocytosis of photoreceptor outer segments by calcium-independent phospholipase A₂, group VIA and secretory phospholipase A₂, group IB

    DEFF Research Database (Denmark)

    Zhan, Chen; Wang, Jinmei; Kolko, Miriam

    2012-01-01

    PURPOSE: To investigate the roles of the phospholipases A(2) (PLA(2)) subtypes, iPLA(2)-VIA and sPLA(2)-IB in retinal pigment epithelium (RPE) phagocytosis of photoreceptor outer segments (POS) and to explore a possible interaction between sPLA(2)-IB and iPLA(2)-VIA in the RPE. METHODS: To explore...... the role of iPLA(2)-VIA in RPE phagocytosis of POS, experiments with iPLA(2)-VIA vector transfection, iPLA(2)-VIA(-/-) knockout (KO) mice, and iPLA(2)-VIA inhibition by bromoenol lactone (BEL) were done. Exogenous addition of sPLA(2)-IB was used to investigate the role of sPLA(2)-IB in RPE phagocytosis....... A Luciferase Reporter Vector containing the iPLA(2)-VIA promoter was used to study the effects of sPLA(2)-IB on the iPLA(2)-VIA promoter. RESULTS: ARPE-19 and primary mouse RPE cells transfected with iPLA(2)-VIA showed increased phagocytosis. Phagocytosis was reduced in primary mouse RPE inhibited with BEL...

  14. Decoupling Internalization, Acidification and Phagosmal-Endosomal/Iysosomal Phagocytosis of Internalin A coated Beads in epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Blanchette, C D; Woo, Y; Thomas, C; Shen, N; Sulchek, T A; Hiddessen, A L

    2008-12-22

    Phagocytosis has been extensively examined in 'professional' phagocytic cells using pH sensitive dyes. However, in many of the previous studies, a separation between the end of internalization, beginning of acidification and completion of phagosomal-endosomal/lysosomal fusion was not clearly established, and in several cases, it was treated as a one-step process. In addition, very little work has been done to systematically examine phagosomal maturation in 'non-professional' phagocytic cells, such as epithelial cells. Therefore, in this study, we developed a simple and novel method to decouple and accurately measure particle internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in Madin-Darby Canine Kidney (MDCK) and Caco-2 epithelial cells. Our method was developed using a pathogen mimetic system consisting of polystyrene beads coated with Internalin A (InlA), a membrane surface protein from Listeria monocytogenes known to trigger receptor-mediated internalization. We achieved independent measurements of the rates of internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in epithelial cells by combining the InlA-coated beads (InlA-beads) with antibody quenching, pH sensitive dyes and endosomal/lysosomal dyes, as follows: the rate of InlA bead internalization was measured via antibody quenching of a pH independent dye (Alexa488) conjugated to InlA-beads, the rate at which phagosomes containing internalized InlA beads became acidified was measured using a pH dependent dye (FITC) conjugated to the beads and the rate of phagosomal-endosomal/lysosomal fusion was measured using a combination of unlabeled InlA-beads and an endosomal/lysosomal dye. By performing these independent measurements under identical experimental conditions, we were able to decouple the three processes and establish time scales for each. In a separate set of experiments, we also exploited the phagosomal acidification

  15. Actin-binding protein regulation by microRNAs as a novel microbial strategy to modulate phagocytosis by host cells: the case of N-Wasp and miR-142-3p.

    Science.gov (United States)

    Bettencourt, Paulo; Marion, Sabrina; Pires, David; Santos, Leonor F; Lastrucci, Claire; Carmo, Nuno; Blake, Jonathon; Benes, Vladimir; Griffiths, Gareth; Neyrolles, Olivier; Lugo-Villarino, Geanncarlo; Anes, Elsa

    2013-01-01

    Mycobacterium tuberculosis (Mtb) is a successful intracellular pathogen that thrives in macrophages (Mφs). There is a need to better understand how Mtb alters cellular processes like phagolysosome biogenesis, a classical determinant of its pathogenesis. A central feature of this bacteria's strategy is the manipulation of Mφ actin. Here, we examined the role of microRNAs (miRNAs) as a potential mechanism in the regulation of actin-mediated events leading to phagocytosis in the context of mycobacteria infection. Given that non-virulent Mycobacterium smegmatis also controls actin filament assembly to prolong its intracellular survival inside host cells, we performed a global transcriptomic analysis to assess the modulation of miRNAs upon M. smegmatis infection of the murine Mφ cell line, J774A.1. This approach identified miR-142-3p as a key candidate to be involved in the regulation of actin dynamics required in phagocytosis. We unequivocally demonstrate that miR-142-3p targets N-Wasp, an actin-binding protein required during microbial challenge. A gain-of-function approach for miR-142-3p revealed a down-regulation of N-Wasp expression accompanied by a decrease of mycobacteria intake, while a loss-of-function approach yielded the reciprocal increase of the phagocytosis process. Equally important, we show Mtb induces the early expression of miR-142-3p and partially down-regulates N-Wasp protein levels in both the murine J774A.1 cell line and primary human Mφs. As proof of principle, the partial siRNA-mediated knock down of N-Wasp resulted in a decrease of Mtb intake by human Mφs, reflected in lower levels of colony-forming units (CFU) counts over time. We therefore propose the modulation of miRNAs as a novel strategy in mycobacterial infection to control factors involved in actin filament assembly and other early events of phagolysosome biogenesis.

  16. A ‘Carbon Saving Multiplier’ as an alternative to rebound in considering reduced energy supply chain requirements from energy efficiency?

    International Nuclear Information System (INIS)

    Turner, Karen; Katris, Antonios

    2017-01-01

    A growing area of research into rebound effects from increased energy efficiency involves application of demand-driven input-output models to consider indirect energy consumption effects associated with re-spending decisions by households with reduced energy spending requirements. However, there is often a lack of clarity in applied studies as to how indirect effects involving energy use and/or carbon emissions in supply chains of both energy and non-energy goods and services have been calculated. We propose that more transparency for policymakers may be introduced by replacing consideration of what are often referred to as ‘indirect rebound’ effects with a simple Carbon Saving Multiplier metric. We illustrate using results from a demand-driven input-output model that tracks supply chain activity at national and/or global level. We argue that this captures and conveys the same information on quantity adjustments in energy used in supply chain activity but does so in a manner that is more positive, transparent, understandable and useful for a policy audience. This is achieved by focusing (here via carbon emissions) on the net benefits of changes in different types of energy use at both household and supply chain levels when energy efficiency improves in households. - Highlights: • Considers energy supply adjustments when household energy efficiency improves. • Focuses on energy supply chain impacts that may offset direct rebound effects. • Carbon Saving Multiplier proposed as a useful indicator of net energy use benefits.

  17. Inhaled corticosteroid treatment for 6 months was not sufficient to normalize phagocytosis in asthmatic children.

    Science.gov (United States)

    da Silva-Martins, Carmen Lívia Faria; Couto, Shirley Claudino; Muniz-Junqueira, Maria Imaculada

    2013-08-30

    Corticosteroids are the first-line therapy for asthma; however, the effect of corticosteroids on the innate immune system remains unclear. This study's objective was to evaluate the effect of inhaled corticosteroid therapy (ICT) on phagocytic functions. To evaluate the impact of ICT, the phagocytosis of Saccharomyces cerevisiae by blood monocytes and neutrophils and the production of superoxide anions were assessed before and after three and six months of ICT treatment in 58 children with persistent asthma and 21 healthy controls. We showed that the phagocytic capacity of monocytes and neutrophils that occurred via pattern recognition receptors or was mediated by complement and immunoglobulin receptors in asthmatic children before treatment was significantly lower than in healthy controls (pICT for 6 months was not sufficient to normalize phagocytosis by the phagocytes. Superoxide anion production was also decreased in the asthmatic children before treatment, and ICT normalized the O- production only for children with mild persistent asthma when assessed at baseline but caused this function to decrease after stimulation (p<0.05, Kruskal-Wallis test). Our data suggest that an immunodeficiency in phagocytes remained even after treatment. However, this immunodeficiency does not appear to correspond with the clinical evolution of asthma because an improvement in clinical parameters occurred.

  18. Cromolyn Reduces Levels of the Alzheimer's Disease-Associated Amyloid β-Protein by Promoting Microglial Phagocytosis.

    Science.gov (United States)

    Zhang, Can; Griciuc, Ana; Hudry, Eloise; Wan, Yu; Quinti, Luisa; Ward, Joseph; Forte, Angela M; Shen, Xunuo; Ran, ChongZhao; Elmaleh, David R; Tanzi, Rudolph E

    2018-01-18

    Amyloid-beta protein (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). Aβ deposition triggers both pro-neuroinflammatory microglial activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma therapeutic agent previously shown to reduce Aβ levels in transgenic AD mouse brains after one-week of treatment. Here, we further explored these effects as well as the mechanism of action of cromolyn, alone, and in combination with ibuprofen in APP Swedish -expressing Tg2576 mice. Mice were treated for 3 months starting at 5 months of age, when the earliest stages of β-amyloid deposition begin. Cromolyn, alone, or in combination with ibuprofen, almost completely abolished longer insoluble Aβ species, i.e. Aβ40 and Aβ42, but increased insoluble Aβ38 levels. In addition to its anti-aggregation effects on Aβ, cromolyn, alone, or plus ibuprofen, but not ibuprofen alone, increased microglial recruitment to, and phagocytosis of β-amyloid deposits in AD mice. Cromolyn also promoted Aβ42 uptake in microglial cell-based assays. Collectively, our data reveal robust effects of cromolyn, alone, or in combination with ibuprofen, in reducing aggregation-prone Aβ levels and inducing a neuroprotective microglial activation state favoring Aβ phagocytosis versus a pro-neuroinflammatory state. These findings support the use of cromolyn, alone, or with ibuprofen, as a potential AD therapeutic.

  19. Phagocytosis-induced 51Cr release from activated macrophages and blood mononuclears. Effect of colchicine and antioxidants

    International Nuclear Information System (INIS)

    McGee, M.P.; Hale, A.H.

    1981-01-01

    The chromium-release test was adapted to the measurement of the cellular injury induced when activated macrophages phagocytose particulates. Macrophages obtained from rabbit lungs undergoing BCG-induced chronic inflammation released more chromium when incubated in the presence of phagocytosable particles than when incubated under resting conditions. Blood mononuclear cells, 40-60% monocytes, procured from the same BCG-injected animals, were less susceptible to phagocytosis-induced injury than the macrophages obtained from the lungs. The amount of chromium released by the activated macrophages was proportional to the number of particles present during incubation. In the presence of catalase, the amounts of chromium released by phagocytosing and resting macrophages were similar; in the presence of superoxide dismutase and cytochrome c, the amount of chromium released by phagocytosing macrophages was 13-35% less than the amount of chromium released by macrophages incubated without the antioxidants. In addition, colchicine, an inhibitor of degranulation also exerted partial inhibition of the chromium release. These results suggest that oxygen radicals and lysosomal contents contribute to the cellular injury that results from phagocytosis

  20. Shrimp miR-12 Suppresses White Spot Syndrome Virus Infection by Synchronously Triggering Antiviral Phagocytosis and Apoptosis Pathways

    Science.gov (United States)

    Shu, Le; Zhang, Xiaobo

    2017-01-01

    Growing evidence has indicated that the innate immune system can be regulated by microRNAs (miRNAs). However, the mechanism underlying miRNA-mediated simultaneous activation of multiple immune pathways remains unknown. To address this issue, the role of host miR-12 in shrimp (Marsupenaeus japonicus) antiviral immune responses was characterized in the present study. The results indicated that miR-12 participated in virus infection, host phagocytosis, and apoptosis in defense against white spot syndrome virus invasion. miR-12 could simultaneously trigger phagocytosis, apoptosis, and antiviral immunity through the synchronous downregulation of the expression of shrimp genes [PTEN (phosphatase and tensin homolog) and BI-1(transmembrane BAX inhibitor motif containing 6)] and the viral gene (wsv024). Further analysis showed that miR-12 could synchronously mediate the 5′–3′ exonucleolytic degradation of its target mRNAs, and this degradation terminated in the vicinity of the 3′ untranslated region sequence complementary to the seed sequence of miR-12. Therefore, the present study showed novel aspects of the miRNA-mediated simultaneous regulation of multiple immune pathways. PMID:28824612

  1. Virulent and Vaccine Strains of Streptococcus equi ssp. zooepidemicus Have Different Influences on Phagocytosis and Cytokine Secretion of Macrophages.

    Science.gov (United States)

    Jie, Peng; Zhe, Ma; Chengwei, Hua; Huixing, Lin; Hui, Zhang; Chengping, Lu; Hongjie, Fan

    2017-01-06

    Swine streptococcosis is a significant threat to the Chinese pig industry, and Streptococcus equi ssp. zooepidemicus (SEZ) is one of the major pathogens. SEZ ATCC35246 is a classical virulent strain, while SEZ ST171 is a Chinese attenuated vaccine strain. In this study, we employed stable isotope labeling by amino acids in cell culture and liquid chromatography-mass spectrometry (LC-MS) to determine the differential response of macrophages to infection by these two strains. Eighty-seven upregulated proteins and 135 downregulated proteins were identified. The proteomic results were verified by real-time polymerase chain reaction for 10 chosen genes and Western blotting for three proteins. All differentially abundant proteins were analyzed for their Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations. Certain downregulated proteins were associated with immunity functions, and the upregulated proteins were related to cytomembrane and cytoskeleton regulation. The phagocytosis rate and cytokine genes transcription in Raw264.7 cells during SEZ ATCC35246 and ST171 infection were detected to confirm the bioinformatics results. These results showed that different effects on macrophage phagocytosis and cytokine expression might explain the different phenotypes of SEZ ATCC35246 and ST171 infection. This research provided clues to the mechanisms of host immunity responses to SEZ ST171and SEZ ATCC35246, which could identify potential therapy and vaccine development targets.

  2. The cellular prion protein negatively regulates phagocytosis and cytokine expression in murine bone marrow-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Min Wang

    Full Text Available The cellular prion protein (PrP(C is a glycosylphosphatidylinositol (GPI-anchored glycoprotein on the cell surface. Previous studies have demonstrated contradictory roles for PrP(C in connection with the phagocytic ability of macrophages. In the present work, we investigated the function of PrP(C in phagocytosis and cytokine expression in bone marrow-derived macrophages infected with Escherichia coli. E. coli infection induced an increase in the PRNP mRNA level. Knockout of PrP(C promoted bacterial uptake; upregulated Rab5, Rab7, and Eea1 mRNA expression; and increased the recruitment of lysosomal-associated membrane protein-2 to phagosomes, suggesting enhanced microbicidal activity. Remarkably, knockout of PrP(C suppressed the proliferation of internalized bacteria and increased the expression of cytokines such as interleukin-1β. Collectively, our data reveal an important role of PrP(C as a negative regulator for phagocytosis, phagosome maturation, cytokine expression, and macrophage microbicidal activity.

  3. Efficient Subgroup C Avian Sarcoma and Leukosis Virus Receptor Activity Requires the IgV Domain of the Tvc Receptor and Proper Display on the Cell Membrane▿

    Science.gov (United States)

    Munguia, Audelia; Federspiel, Mark J.

    2008-01-01

    We recently identified and cloned the receptor for subgroup C avian sarcoma and leukosis viruses [ASLV(C)], i.e., Tvc, a protein most closely related to mammalian butyrophilins, which are members of the immunoglobulin protein family. The extracellular domain of Tvc contains two immunoglobulin-like domains, IgV and IgC, which presumably each contain a disulfide bond important for native function of the protein. In this study, we have begun to identify the functional determinants of Tvc responsible for ASLV(C) receptor activity. We found that the IgV domain of the Tvc receptor is responsible for interacting with the glycoprotein of ASLV(C). Additional experiments demonstrated that a domain was necessary as a spacer between the IgV domain and the membrane-spanning domain for efficient Tvc receptor activity, most likely to orient the IgV domain a proper distance from the cell membrane. The effects on ASLV(C) glycoprotein binding and infection efficiency were also studied by site-directed mutagenesis of the cysteine residues of Tvc as well as conserved amino acid residues of the IgV Tvc domain compared to other IgV domains. In this initial analysis of Tvc determinants important for interacting with ASLV(C) glycoproteins, at least two aromatic amino acid residues in the IgV domain of Tvc, Trp-48 and Tyr-105, were identified as critical for efficient ASLV(C) infection. Interestingly, one or more aromatic amino acid residues have been identified as critical determinants in the other ASLV(A-E) receptors for a proper interaction with ASLV glycoproteins. This suggests that the ASLV glycoproteins may share a common mechanism of receptor interaction with an aromatic residue(s) on the receptor critical for triggering conformational changes in SU that initiate the fusion process required for efficient virus infection. PMID:18768966

  4. Efficient subgroup C avian sarcoma and leukosis virus receptor activity requires the IgV domain of the Tvc receptor and proper display on the cell membrane.

    Science.gov (United States)

    Munguia, Audelia; Federspiel, Mark J

    2008-11-01

    We recently identified and cloned the receptor for subgroup C avian sarcoma and leukosis viruses [ASLV(C)], i.e., Tvc, a protein most closely related to mammalian butyrophilins, which are members of the immunoglobulin protein family. The extracellular domain of Tvc contains two immunoglobulin-like domains, IgV and IgC, which presumably each contain a disulfide bond important for native function of the protein. In this study, we have begun to identify the functional determinants of Tvc responsible for ASLV(C) receptor activity. We found that the IgV domain of the Tvc receptor is responsible for interacting with the glycoprotein of ASLV(C). Additional experiments demonstrated that a domain was necessary as a spacer between the IgV domain and the membrane-spanning domain for efficient Tvc receptor activity, most likely to orient the IgV domain a proper distance from the cell membrane. The effects on ASLV(C) glycoprotein binding and infection efficiency were also studied by site-directed mutagenesis of the cysteine residues of Tvc as well as conserved amino acid residues of the IgV Tvc domain compared to other IgV domains. In this initial analysis of Tvc determinants important for interacting with ASLV(C) glycoproteins, at least two aromatic amino acid residues in the IgV domain of Tvc, Trp-48 and Tyr-105, were identified as critical for efficient ASLV(C) infection. Interestingly, one or more aromatic amino acid residues have been identified as critical determinants in the other ASLV(A-E) receptors for a proper interaction with ASLV glycoproteins. This suggests that the ASLV glycoproteins may share a common mechanism of receptor interaction with an aromatic residue(s) on the receptor critical for triggering conformational changes in SU that initiate the fusion process required for efficient virus infection.

  5. Correlation Between Total Flavonoid Contents and Macrophage Phagocytosis Activity of Fractions From Faloak (Sterculia quadrifida R.Br. Barks Ethanolic Extract In Vitro

    Directory of Open Access Journals (Sweden)

    Rima Munawaroh

    2018-04-01

    Full Text Available On Timor island, Nusa Tenggara Timur, faloak barks (Sterculia quadrifida R.Br. has been used empirically to restore stamina. Faloak bark ethanolic extract proved to have immunomodulatory activity in vitro, which can increase macrophage phagocytosis activity. This research aimed: (i to determine the immunomodulatory active fraction of faloak bark ethanolic extract, (ii to determine the total flavonoid contents of faloak extract and fractions, and (iii to evaluate the correlation of the total flavonoid contents of those extract and fractions with their macrophage phagocytosis activity. The simplisia powder is macerated with 96% ethanol. The extract was dissolved in methanol:water (9:1v/v was then subsequently partitioned with n-hexane, ethyl acetate, and water to obtain n-hexane fraction, ethyl acetate fraction, water fraction, and insoluble fraction. Faloak extract and fractions at concentration 62,5; 125; 250; 500μg/mL were tested for their effect on the peritoneal macrophage phagocytosis of Balb/c mice in vitro by the latex beads method. Phagocytosis capacity and phagocytosis index were analyzed using one-way anova and post hoc Tukey HSD test with 95% confidence level. The results showed that ethyl acetate fraction had the highest macrophage phagocytosis capacity and the highest total flavonoid content compared to other fractions. The highest macrophage phagocytosis capacity of ethyl acetate fraction at concentration of 250 μg/mL was 51,94±4,67%, this value was significantly different from cell control (7,50±1,29%, negative controls of 0,0625% dimethylsulphoxide (6,25±0,36%, as well as positive control of 200 μg/mL echinaceae extract syrup® (9,97±0,33%. The total flavonoid content of ethyl acetate fraction determined by aluminum chloride method was 4,290±0.029 mg of quercetin equivalent/g fraction. There was a positive and strong correlation between the total flavonoid content of these extract and fractions with their macrophage

  6. The Antiphagocytic Activity of SeM of Streptococcus equi Requires Capsule.

    Science.gov (United States)

    Timoney, John F; Suther, Pranav; Velineni, Sridhar; Artiushin, Sergey C

    2014-01-01

    Resistance to phagocytosis is a crucial virulence property of Streptococcus equi (Streptococcus equi subsp. equi; Se), the cause of equine strangles. The contribution and interdependence of capsule and SeM to killing in equine blood and neutrophils were investigated in naturally occurring strains of Se. Strains CF32, SF463 were capsule and SeM positive, strains Lex90, Lex93 were capsule negative and SeM positive and strains Se19, Se1-8 were capsule positive and SeM deficient. Phagocytosis and killing of Se19, Se1-8, Lex90 and Lex93 in equine blood and by neutrophils suspended in serum were significantly (P ≤ 0.02) greater compared to CF32 and SF463. The results indicate capsule and SeM are both required for resistance to phagocytosis and killing and that the anti-phagocytic property of SeM is greatly reduced in the absence of capsule.

  7. Emergence of anti-red blood cell antibodies triggers red cell phagocytosis by activated macrophages in a rabbit model of Epstein-Barr virus-associated hemophagocytic syndrome.

    Science.gov (United States)

    Hsieh, Wen-Chuan; Chang, Yao; Hsu, Mei-Chi; Lan, Bau-Shin; Hsiao, Guan-Chung; Chuang, Huai-Chia; Su, Ih-Jen

    2007-05-01

    Hemophagocytic syndrome (HPS) is a fatal complication frequently associated with viral infections. In childhood HPS, Epstein-Barr virus (EBV) is the major causative agent, and red blood cells (RBCs) are predominantly phagocytosed by macrophages. To investigate the mechanism of RBC phagocytosis triggered by EBV infection, we adopted a rabbit model of EBV-associated HPS previously established by using Herpesvirus papio (HVP). The kinetics of virus-host interaction was studied. Using flow cytometry, we detected the emergence of antibody-coated RBCs, as well as anti-platelet antibodies, at peak virus load period at weeks 3 to 4 after HVP injection, and the titers increased thereafter. The presence of anti-RBCs preceded RBC phagocytosis in tissues and predicted the full-blown development of HPS. The anti-RBC antibodies showed cross-reactivity with Paul-Bunnell heterophile antibodies. Preabsorption of the HVP-infected serum with control RBCs removed the majority of anti-RBC activities and remarkably reduced RBC phagocytosis. The RBC phagocytosis was specifically mediated via an Fc fragment of antibodies in the presence of macrophage activation. Therefore, the emergence of anti-RBC antibodies and the presence of macrophage activation are both essential in the development of HPS. Our observations in this animal model provide a potential mechanism for hemophagocytosis in EBV infection.

  8. IrAM—An .alpha..sub.2./sub.-macroglobulin from the hard tick Ixodes ricinus: Characterization and function in phagocytosis of a potential pathogen Chryseobacterium indologenes

    Czech Academy of Sciences Publication Activity Database

    Burešová, Veronika; Hajdušek, Ondřej; Franta, Zdeněk; Sojka, Daniel; Kopáček, Petr

    2009-01-01

    Roč. 33, č. 4 (2009), s. 489-198 ISSN 0145-305X R&D Projects: GA AV ČR IAA600220603; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : α2-macroglobulin * tick * phagocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.290, year: 2009

  9. Effect of UVB irradiation of the blood on cellular volume adherence and phagocytosis in probands and patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Mix, E; Jenssen, H L; Lehmitz, R; Buddenhagen, F; Hitzschke, B; Richter, M

    1988-01-01

    UVB-induced changes of blood cell properties were investigated in 12 multiple sclerosis (MS) patients and in 10 healthy volunteers. The mean cell volume (MCV) was determined by electronic sizing, the granulocyte and lymphocyte adherence was estimated in a capillary assay, and the phagocytic activity of granulocytes was measured in a test system based on the incorporation of opsonized baker's yeast. In MS patients the MCV of red cells and lymphocytes decreased rapidly within 6 UVB treatments. In contrast, the reduction of the granulocyte volume was delayed (between the 6th and 12th UVB). In the control group the mean value of the red cell and lymphocyte MCV remained rather unaffected. There was a slight rise of the granulocyte volume after the 6th UVB. The only significant change of adherence was an increase of granulocyte adherence in MS patients. Untreated patients had a significantly enhanced phagocytic activity in comparison to the control group. 6 UVB treatments induced a singificant reduction of the phagocytic activity in MS patients. However, subsequently the percentage of phagocytizing cells increased again, whereas the particle uptake per cell continued to decrease. In the control group only minor UVB-induced changes of phagocytosis were observed. The in vitro UV irradiation caused an enhanced phagocytosis in the majority of cases in both controls and MS patients. In general, under the UVB treatment all parameters examined changed in the sense of a normalisation, in that the measured values reached a new level lying between the extreme pretreatment values accompanied by a reduced standard deviation. The effect of UVB was more pronounced in MS patients when compared with normal control. This could result from an enhanced sensitivity to the influence of UVB of pathologically altered cells in MS patients. (Abstract Truncated)

  10. Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Ootsubo, Michiko; Izawa, Ken-ichi; Kohroki, Junya; Masuho, Yasuhiko

    2016-01-01

    The Fc domain of human IgG1 binds to Fcγ receptors (FcγRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents. The cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 cells. The binding activities of TRA to FcγRIIA and FcγRIIB were greatly enhanced by modification with mild reduction and S-alkylation with ICH2CONH2 or N-(4-aminophenyl) maleimide, while the binding activities of TRA to FcγRI and FcγRIIIA were decreased by any of the four modifications. However, the interchain disulfide bond cleavage by the different modifications did not change the antibody-dependent cell-mediated phagocytosis (ADCP) of SK-BR-3 cells by activated THP-1 cells. The order of FcγR expression levels on the THP-1 cells was FcγRII > FcγRI > FcγRIII and ADCP was inhibited by blocking antibodies against FcγRI and FcγRII. These results imply that the effect of the interchain disulfide bond cleavage on FcγRs binding and ADCP is dependent on modifications of the cysteine residues and the FcγR isotypes. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  11. RNA Processing Factor 5 is required for efficient 5' cleavage at a processing site conserved in RNAs of three different mitochondrial genes in Arabidopsis thaliana.

    Science.gov (United States)

    Hauler, Aron; Jonietz, Christian; Stoll, Birgit; Stoll, Katrin; Braun, Hans-Peter; Binder, Stefan

    2013-05-01

    The 5' ends of many mitochondrial transcripts are generated post-transcriptionally. Recently, we identified three RNA PROCESSING FACTORs required for 5' end maturation of different mitochondrial mRNAs in Arabidopsis thaliana. All of these factors are pentatricopeptide repeat proteins (PPRPs), highly similar to RESTORERs OF FERTILTY (RF), that rescue male fertility in cytoplasmic male-sterile lines from different species. Therefore, we suggested a general role of these RF-like PPRPs in mitochondrial 5' processing. We now identified RNA PROCESSING FACTOR 5, a PPRP not classified as an RF-like protein, required for the efficient 5' maturation of the nad6 and atp9 mRNAs as well as 26S rRNA. The precursor molecules of these RNAs share conserved sequence elements, approximately ranging from positions -50 to +9 relative to mature 5' mRNA termini, suggesting these sequences to be at least part of the cis elements required for processing. The knockout of RPF5 has only a moderate influence on 5' processing of atp9 mRNA, whereas the generation of the mature nad6 mRNA and 26S rRNA is almost completely abolished in the mutant. The latter leads to a 50% decrease of total 26S rRNA species, resulting in an imbalance between the large rRNA and 18S rRNA. Despite these severe changes in RNA levels and in the proportion between the 26S and 18S rRNAs, mitochondrial protein levels appear to be unaltered in the mutant, whereas seed germination capacity is markedly reduced. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  12. Efficient design and simulation of an expandable hybrid (wind-photovoltaic) power system with MPPT and inverter input voltage regulation features in compliance with electric grid requirements

    Energy Technology Data Exchange (ETDEWEB)

    Skretas, Sotirios B.; Papadopoulos, Demetrios P. [Electrical Machines Laboratory, Department of Electrical and Computer Engineering, Democritos University of Thrace (DUTH), 12 V. Sofias, 67100 Xanthi (Greece)

    2009-09-15

    In this paper an efficient design along with modeling and simulation of a transformer-less small-scale centralized DC - bus Grid Connected Hybrid (Wind-PV) power system for supplying electric power to a single phase of a three phase low voltage (LV) strong distribution grid are proposed and presented. The main components of the hybrid system are: a PV generator (PVG); and an array of horizontal-axis, fixed-pitch, small-size, variable-speed wind turbines (WTs) with direct-driven permanent magnet synchronous generator (PMSG) having an embedded uncontrolled bridge rectifier. An overview of the basic theory of such systems along with their modeling and simulation via Simulink/MATLAB software package are presented. An intelligent control method is applied to the proposed configuration to simultaneously achieve three desired goals: to extract maximum power from each hybrid power system component (PVG and WTs); to guarantee DC voltage regulation/stabilization at the input of the inverter; to transfer the total produced electric power to the electric grid, while fulfilling all necessary interconnection requirements. Finally, a practical case study is conducted for the purpose of fully evaluating a possible installation in a city site of Xanthi/Greece, and the practical results of the simulations are presented. (author)

  13. Sequence characteristics required for cooperative binding and efficient in vivo titration of the replication initiator protein DnaA in E. coli

    DEFF Research Database (Denmark)

    Hansen, Flemming G.; Christensen, Bjarke Bak; Atlung, Tove

    2007-01-01

    Plasmids carrying the mioC promoter region, which contains two DnaA boxes, R5 and R6 with one misfit to the consensus TT(A)/(T)TNCACA, are as efficient in in vivo titration of the DnaA protein as plasmids carrying a replication-inactivated oriC region with its eight DnaA boxes. Three additional Dna......A boxes around the promoter proximal R5 DnaA box were identified and shown by mutational analysis to be necessary for the cooperative binding of DnaA required for titration. These four DnaA boxes are located in the same orientation and with a spacing of two or three base-pairs. The cooperative binding...... was eliminated by insertion of half a helical turn between any of the DnaA boxes. Titration strongly depends on the presence and orientation of the promoter distal R6 DnaA box located 104 bp upstream of the R5 box as well as neighbouring sequences downstream of R6. Titration depends on the integrity of a 43 bp...

  14. Juggling Efficiency

    DEFF Research Database (Denmark)

    Andersen, Rikke Sand; Vedsted, Peter

    2015-01-01

    on institutional logics, we illustrate how a logic of efficiency organise and give shape to healthcare seeking practices as they manifest in local clinical settings. Overall, patient concerns are reconfigured to fit the local clinical setting and healthcare professionals and patients are required to juggle...... efficiency in order to deal with uncertainties and meet more complex or unpredictable needs. Lastly, building on the empirical case of cancer diagnostics, we discuss the implications of the pervasiveness of the logic of efficiency in the clinical setting and argue that provision of medical care in today......'s primary care settings requires careful balancing of increasing demands of efficiency, greater complexity of biomedical knowledge and consideration for individual patient needs....

  15. HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis

    Science.gov (United States)

    2018-01-01

    ABSTRACT Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments. IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the

  16. CO2 reduction in the Danish transportation sector. Working paper 5: Technological improvement of energy efficiency. Average requirements to energy efficiency of the new vehicles. Subsidies to research and development

    International Nuclear Information System (INIS)

    1997-03-01

    The road traffic is expected to be responsible for 9/10 of the total CO 2 emission from transportation sector in 2005. Especially private cars contribute more than half of the total CO 2 emission. Cars are not produced in Denmark, so energy efficiency of the new models depends entirely on the foreign manufacturers. Measurements of energy efficiency on test facilities show usually slightly better efficiency than on-the-road results. Efficiency estimates are based on test results. Within 10-15 years the whole car park will show essential efficiency improvement due to exchanging to newer models. Shadow price of CO 2 emission reduction is defined. (EG) Prepared for Trafikministeriet. 27 refs

  17. An interspecies comparison of the phagocytosis and dissolution of 241AmO2 particles by rat, dog and monkey alveolar macrophages in vitro

    International Nuclear Information System (INIS)

    Taya, A.; Carmack, D.B.; Muggenburg, B.A.; Mewhinney, J.A.

    1992-01-01

    Experiments were conducted to study the phagocytosis and dissolution of 241 AmO 2 particles by rat, dog and monkey alveolar macrophages (PAM) in vitro. The phagocytosis and dissolution of 241 AmO 2 particles were followed up to 20 and 72 h, respectively. Dog and monkey PAM took up 241 AmO 2 particles at similar rates, whereas rat PAM phagocytosed only 60% of the amount phagocytosed by dog and monkey PAM at 20h. The PAM of the three species dissolved 241 AmO 2 particles at similar rates; 8-10% was dissolved by 72h. The results of the 241 AmO 2 uptake in vitro may reflect in vivo situations, where the differences in uptake seen in vitro would probably diminish at later times after exposure. The dissolution results imply that the dissolution of 241 AmO 2 particles by alveolar macrophages of the three species might be species-independent. (author)

  18. The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis.

    Science.gov (United States)

    Jayaprakash, K; Demirel, I; Khalaf, H; Bengtsson, T

    2015-10-01

    Neutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps (NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram-negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild-type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild-type strain ATCC33277, whereas the other wild-type strain W50 was less effective. Quantitative real-time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P. gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P. gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Ocean Acidification Affects the Cytoskeleton, Lysozymes, and Nitric Oxide of Hemocytes: A Possible Explanation for the Hampered Phagocytosis in Blood Clams, Tegillarca granosa.

    Science.gov (United States)

    Su, Wenhao; Rong, Jiahuan; Zha, Shanjie; Yan, Maocang; Fang, Jun; Liu, Guangxu

    2018-01-01

    An enormous amount of anthropogenic carbon dioxide (CO 2 ) has been dissolved into the ocean, leading to a lower pH and changes in the chemical properties of seawater, which has been termed ocean acidification (OA). The impacts of p CO 2 -driven acidification on immunity have been revealed recently in various marine organisms. However, the mechanism causing the reduction in phagocytosis still remains unclear. Therefore, the impacts of p CO 2 -driven OA at present and near-future levels (pH values of 8.1, 7.8, and 7.4) on the rate of phagocytosis, the abundance of cytoskeleton components, the levels of nitric oxide (NO), and the concentration and activity of lysozymes (LZM) of hemocytes were investigated in a commercial bivalve species, the blood clam ( Tegillarca granosa ). In addition, the effects of OA on the expression of genes regulating actin skeleton and nitric oxide synthesis 2 ( NOS2 ) were also analyzed. The results obtained showed that the phagocytic rate, cytoskeleton component abundance, concentration and activity of LZM of hemocytes were all significantly reduced after a 2-week exposure to the future OA scenario of a pH of 7.4. On the contrary, a remarkable increase in the concentration of NO compared to that of the control was detected in clams exposed to OA. Furthermore, the expression of genes regulating the actin cytoskeleton and NOS were significantly up-regulated after OA exposure. Though the mechanism causing phagocytosis seemed to be complicated based on the results obtained in the present study and those reported previously, our results suggested that OA may reduce the phagocytosis of hemocytes by (1) decreasing the abundance of cytoskeleton components and therefore hampering the cytoskeleton-mediated process of engulfment, (2) reducing the concentration and activity of LZM and therefore constraining the degradation of the engulfed pathogen through an oxygen-independent pathway, and (3) inducing the production of NO, which may negatively

  20. In vivo and in vitro phagocytosis of Leishmania (Leishmania) amazonensis promastigotes by B-1 cells.

    Science.gov (United States)

    Geraldo, M M; Costa, C R; Barbosa, F M C; Vivanco, B C; Gonzaga, W F K M; Novaes E Brito, R R; Popi, A F; Lopes, J D; Xander, P

    2016-06-01

    Leishmaniasis is caused by Leishmania parasites that infect several cell types. The promastigote stage of Leishmania is internalized by phagocytic cells and transformed into the obligate intracellular amastigote form. B-1 cells are a subpopulation of B cells that are able to differentiate in vitro and in vivo into mononuclear phagocyte-like cells with phagocytic properties. B-1 cells use several receptors for phagocytosis, such as the mannose receptor and third complement receptor. Leishmania binds to the same receptors on macrophages. In this study, we demonstrated that phagocytes derived from B-1 cells (B-1 CDP) were able to internalize promastigotes of L. (L.) amazonensis in vitro. The internalized promastigotes differentiated into amastigotes. Our results showed that the phagocytic index was higher in B-1 CDP compared to peritoneal macrophages and bone marrow-derived macrophages. The in vivo phagocytic ability of B-1 cells was also demonstrated. Parasites were detected inside purified B-1 cells after intraperitoneal infection with L. (L.) amazonensis promastigotes. Intraperitoneal stimulation with the parasites led to an increase in both IL-10 and TNF-α. These results highlight the importance of studying B-1 CDP cells as phagocytic cells that can participate and contribute to immunity to parasites. © 2016 John Wiley & Sons Ltd.

  1. Sialoglycoproteins in morphological distinct stages of Mucor polymorphosporus and their influence on phagocytosis by human blood phagocytes.

    Science.gov (United States)

    Almeida, Catia Amancio; de Campos-Takaki, Galba Maria; Portela, Maristela Barbosa; Travassos, Luiz R; Alviano, Celuta Sales; Alviano, Daniela Sales

    2013-10-01

    The possible role of sialic acids in host cells-fungi interaction and their association with glycoproteins were evaluated using a clinical isolate of the dimorphic fungus Mucor polymorphosporus. Lectin-binding assays with spores and yeast cells denoted the presence of surface sialoglycoconjugates containing 2,3- and 2,6-linked sialylglycosyl groups. Western blotting with peroxidase-labeled Limulus polyphemus agglutinin revealed the occurrence of different sialoglycoprotein types in both cell lysates and cell wall protein extracts of mycelia, spores, and yeasts of M. polymorphosporus. Sialic acids contributed to the surface negative charge of spores and yeast forms as evaluated by adherence to a cationic substrate. Sialidase-treated spores were less resistant to phagocytosis by human neutrophils and monocytes from healthy individuals than control (untreated) fungal suspensions. The results suggest that sialic acids are terminal units of various glycoproteins of M. polymorphosporus, contributing to negative charge of yeasts and spore cells and protecting infectious propagules from destruction by host cells.

  2. Effect of a 2.45-GHz radiofrequency electromagnetic field on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells.

    Science.gov (United States)

    Koyama, Shin; Narita, Eijiro; Suzuki, Yoshihisa; Taki, Masao; Shinohara, Naoki; Miyakoshi, Junji

    2015-01-01

    The potential public health risks of radiofrequency (RF) fields have been discussed at length, especially with the use of mobile phones spreading extensively throughout the world. In order to investigate the properties of RF fields, we examined the effect of 2.45-GHz RF fields at the specific absorption rate (SAR) of 2 and 10 W/kg for 4 and 24 h on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells. Neutrophil chemotaxis was not affected by RF-field exposure, and subsequent phagocytosis was not affected either compared with that under sham exposure conditions. These studies demonstrated an initial immune response in the human body exposed to 2.45-GHz RF fields at the SAR of 2 W/kg, which is the maximum value recommended by the International Commission for Non-Ionizing Radiation Protection (ICNIRP) guidelines. The results of our experiments for RF-field exposure at an SAR under 10 W/kg showed very little or no effects on either chemotaxis or phagocytosis in neutrophil-like human HL-60 cells. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  3. Antibody-mediated platelet phagocytosis by human macrophages is inhibited by siRNA specific for sequences in the SH2 tyrosine kinase, Syk.

    Science.gov (United States)

    Lu, Ying; Wang, Weiming; Mao, Huiming; Hu, Hai; Wu, Yanling; Chen, Bing-Guan; Liu, Zhongmin

    2011-01-01

    Immune thrombocytopenia depends upon Fc receptor-mediated phagocytosis that involves signaling through the SH2 tyrosine kinase, Syk. We designed small interfering (siRNA) sequences complementary to Syk coding regions to decrease the expression of Syk in the human macrophage cell line, THP-1. To evaluate the functional effect of siRNA on phagocytosis, we developed a new in vitro assay for antibody-mediated platelet ingestion by THP-1 cells. Incubation of THP-1 cells at 37°C with fluorescence-labeled platelets and anti-platelet antibody promoted ingestion of platelets that could be quantitated by flow cytometry. Transfection of THP-1 cells with Syk-specific siRNA resulted in a reduction in the amount of FcγRII-associated Syk protein. Coincident with decreased Syk expression, we observed inhibition of antibody-mediated platelet ingestion. These results confirm a key role for Syk in antibody-mediated phagocytosis and suggest Syk-specific siRNA as a possible therapeutic candidate for immune thrombocytopenia. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Treatment of municipal wastewater in full-scale on-site sand filter reduces BOD efficiently but does not reach requirements for nitrogen and phosphorus removal.

    Science.gov (United States)

    Laaksonen, Petteri; Sinkkonen, Aki; Zaitsev, Gennadi; Mäkinen, Esa; Grönroos, Timo; Romantschuk, Martin

    2017-04-01

    A traditional sand filter for treatment of household wastewater was constructed in the fall of 2012 at Biolinja 12, Turku, Finland. Construction work was led and monitored by an authorized wastewater treatment consultant. The filter was placed on a field bordered by open ditches from all sides in order to collect excess rain and snowmelt waters. The filter was constructed and insulated from the environment so that all outflowing water was accounted for. Untreated, mainly municipal, wastewater from Varissuo suburb was pumped from a sewer separately via three septic tanks (volume = 1 m 3 each) into the filters. Normally, wastewater was distributed to ground filters automatically according to pre-programmed schedule. Initially, the daily flow was 1200 L day -1 to reflect the average organic load of a household of five persons (load: ca 237 g day -1 BOD; 73 g day -1 total N; and 10.4 g day -1 total P). Later in the test, the flow rate was decreased first to 900 and then to 600 L day -1 to better reflect the average volume produced by five persons. Volumes of inlet wastewater as well as treated water were monitored by magnetic flow meters. Samples were withdrawn from the inlet water, from the water entering the filters after the third septic tank, and from the outflowing water. After an initial adaption time, the reductions in BOD and chemical oxygen demand were constantly between 92 and 98%, showing that the biological degradation process in the filters functioned optimally and clearly comply with the national and EU standards. The reduction in total nitrogen and total phosphorus, however, reached required levels only during the first months of testing, apparently when buildup of microbial biomass was still ongoing. After this initial period of 3 months showing satisfactory reduction levels, the reduction of total nitrogen varied between 5 and 25% and total phosphorus mostly between 50 and 65%. Nitrification was efficient in the filter, but as indicated

  5. Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

    Science.gov (United States)

    2010-01-01

    Background Platelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmission from platelets to T-cells. Here, we studied the molecular mechanisms behind CLEC-2-mediated HIV-1 transmission. Results Binding studies with soluble proteins indicated that CLEC-2, in contrast to DC-SIGN, does not recognize the viral envelope protein, but a cellular factor expressed on kidney-derived 293T cells. Subsequent analyses revealed that the cellular mucin-like membranous glycoprotein podoplanin, a CLEC-2 ligand, was expressed on 293T cells and incorporated into virions released from these cells. Knock-down of podoplanin in 293T cells by shRNA showed that virion incorporation of podoplanin was required for efficient CLEC-2-dependent HIV-1 interactions with cell lines and platelets. Flow cytometry revealed no evidence for podoplanin expression on viable T-cells and peripheral blood mononuclear cells (PBMC). Podoplanin was also not detected on HIV-1 infected T-cells. However, apoptotic bystander cells in HIV-1 infected cultures reacted with anti-podoplanin antibodies, and similar results were obtained upon induction of apoptosis in a cell line and in PBMCs suggesting an unexpected link between apoptosis and podoplanin expression. Despite the absence of detectable podoplanin expression, HIV-1 produced in PBMC was transmitted to T-cells in a CLEC-2-dependent manner, indicating that T-cells might express an as yet unidentified CLEC-2 ligand. Conclusions Virion incorporation of podoplanin mediates CLEC-2 interactions of HIV-1 derived from 293T cells, while incorporation of a different cellular factor seems to be responsible for CLEC-2-dependent capture of PBMC-derived viruses. Furthermore, evidence was obtained that podoplanin expression is

  6. Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

    Directory of Open Access Journals (Sweden)

    Münch Jan

    2010-05-01

    Full Text Available Abstract Background Platelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmission from platelets to T-cells. Here, we studied the molecular mechanisms behind CLEC-2-mediated HIV-1 transmission. Results Binding studies with soluble proteins indicated that CLEC-2, in contrast to DC-SIGN, does not recognize the viral envelope protein, but a cellular factor expressed on kidney-derived 293T cells. Subsequent analyses revealed that the cellular mucin-like membranous glycoprotein podoplanin, a CLEC-2 ligand, was expressed on 293T cells and incorporated into virions released from these cells. Knock-down of podoplanin in 293T cells by shRNA showed that virion incorporation of podoplanin was required for efficient CLEC-2-dependent HIV-1 interactions with cell lines and platelets. Flow cytometry revealed no evidence for podoplanin expression on viable T-cells and peripheral blood mononuclear cells (PBMC. Podoplanin was also not detected on HIV-1 infected T-cells. However, apoptotic bystander cells in HIV-1 infected cultures reacted with anti-podoplanin antibodies, and similar results were obtained upon induction of apoptosis in a cell line and in PBMCs suggesting an unexpected link between apoptosis and podoplanin expression. Despite the absence of detectable podoplanin expression, HIV-1 produced in PBMC was transmitted to T-cells in a CLEC-2-dependent manner, indicating that T-cells might express an as yet unidentified CLEC-2 ligand. Conclusions Virion incorporation of podoplanin mediates CLEC-2 interactions of HIV-1 derived from 293T cells, while incorporation of a different cellular factor seems to be responsible for CLEC-2-dependent capture of PBMC-derived viruses. Furthermore, evidence was obtained that

  7. ABO Blood Groups Influence Macrophage-mediated Phagocytosis of Plasmodium falciparum-infected Erythrocytes

    Science.gov (United States)

    Branch, Donald R.; Hult, Annika K.; Olsson, Martin L.; Liles, W. Conrad; Cserti-Gazdewich, Christine M.; Kain, Kevin C.

    2012-01-01

    Erythrocyte polymorphisms associated with a survival advantage to Plasmodium falciparum infection have undergone positive selection. There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection. Based on the hypothesis that enhanced innate clearance of infected polymorphic erythrocytes is associated with protection from severe malaria, we investigated whether P. falciparum-infected O erythrocytes are more efficiently cleared by macrophages than infected A and B erythrocytes. We show that human macrophages in vitro and mouse monocytes in vivo phagocytose P. falciparum-infected O erythrocytes more avidly than infected A and B erythrocytes and that uptake is associated with increased hemichrome deposition and high molecular weight band 3 aggregates in infected O erythrocytes. Using infected A1, A2, and O erythrocytes, we demonstrate an inverse association of phagocytic capacity with the amount of A antigen on the surface of infected erythrocytes. Finally, we report that enzymatic conversion of B erythrocytes to type as O before infection significantly enhances their uptake by macrophages to observed level comparable to that with infected O wild-type erythrocytes. These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria. PMID:23071435

  8. Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family.

    Directory of Open Access Journals (Sweden)

    Douglas R Boettner

    2008-01-01

    Full Text Available Entamoeba histolytica is the cause of amebic colitis and liver abscess. This parasite induces apoptosis in host cells and utilizes exposed ligands such as phosphatidylserine to ingest the apoptotic corpses and invade deeper into host tissue. The purpose of this work was to identify amebic proteins involved in the recognition and ingestion of dead cells. A member of the transmembrane kinase family, phagosome-associated TMK96 (PATMK, was identified in a proteomic screen for early phagosomal proteins. Anti-peptide affinity-purified antibody produced against PATMK demonstrated that it was a type I integral membrane protein that was expressed on the trophozoite surface, and that co-localized with human erythrocytes at the site of contact. The role of PATMK in erythrophagocytosis in vitro was demonstrated by: (i incubation of ameba with anti-PATMK antibodies; (ii PATMK mRNA knock-down using a novel shRNA expression system; and (iii expression of a carboxy-truncation of PATMK (PATMK(delta932. Expression of the carboxy-truncation of PATMK(delta932 also caused a specific reduction in the ability of E. histolytica to establish infection in the intestinal model of amebiasis, however these amebae retained the ability to cause hepatic abscesses when directly injected in the liver. In conclusion, PATMK was identified as a member of the TMK family that participates in erythrophagocytosis and is uniquely required for intestinal infection.

  9. Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family.

    Science.gov (United States)

    Boettner, Douglas R; Huston, Christopher D; Linford, Alicia S; Buss, Sarah N; Houpt, Eric; Sherman, Nicholas E; Petri, William A

    2008-01-01

    Entamoeba histolytica is the cause of amebic colitis and liver abscess. This parasite induces apoptosis in host cells and utilizes exposed ligands such as phosphatidylserine to ingest the apoptotic corpses and invade deeper into host tissue. The purpose of this work was to identify amebic proteins involved in the recognition and ingestion of dead cells. A member of the transmembrane kinase family, phagosome-associated TMK96 (PATMK), was identified in a proteomic screen for early phagosomal proteins. Anti-peptide affinity-purified antibody produced against PATMK demonstrated that it was a type I integral membrane protein that was expressed on the trophozoite surface, and that co-localized with human erythrocytes at the site of contact. The role of PATMK in erythrophagocytosis in vitro was demonstrated by: (i) incubation of ameba with anti-PATMK antibodies; (ii) PATMK mRNA knock-down using a novel shRNA expression system; and (iii) expression of a carboxy-truncation of PATMK (PATMK(delta932)). Expression of the carboxy-truncation of PATMK(delta932) also caused a specific reduction in the ability of E. histolytica to establish infection in the intestinal model of amebiasis, however these amebae retained the ability to cause hepatic abscesses when directly injected in the liver. In conclusion, PATMK was identified as a member of the TMK family that participates in erythrophagocytosis and is uniquely required for intestinal infection.

  10. Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

    Science.gov (United States)

    Owen, R L; Allen, C L; Stevens, D P

    1981-08-01

    No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods into the epithelium, trapping invading G. muris and enclosing them in phagolysosomes. In normal mice, which clear G. muris in 4 to 6 weeks, macrophages containing digested G. muris were surrounded by rosettes of lymphoblasts in the epithelium. In nude mice deficient in lymphocytes, there was apparent hyperplasia of macrophages, which filled the follicle domes, resulting in more frequent entrapment of G. muris but no contact between macrophages and lymphoblasts in the epithelium. In nude mice, which require 6 months to control G. muris infection, lymphoblast contact with macrophages containing distinctive microtubular remnants of G. muris was only identified in the follicle dome. This close physical association of lymphoblasts and macrophages containing G. muris remnants suggests that this macrophage activity represents intraepithelial antigen processing as well as a defense against the effects of the uncontrolled entrance of microorganisms and other antigenic particles into Peyer's patch lymphoid follicles.

  11. Phagocytosis and immune response studies of Macrophage-Nanodiamond Interactions in vitro and in vivo.

    Science.gov (United States)

    Huang, K-J; Lee, C-Y; Lin, Y-C; Lin, C-Y; Perevedentseva, E; Hung, S-F; Cheng, C-L

    2017-10-01

    The applications of nanodiamond as drug delivery and bio-imaging can require the relinquishing ND-drug conjugate via blood flow, where interaction with immune cells may occur. In this work, we investigated the ND penetration in macrophage and the immune response using the tissue-resident murine macrophages (RAW 264.7). Confocal fluorescence imaging, immunofluorescence analysis of nuclear translocation of interferon regulatory factor IRF-3 and transcriptional factor NF-κΒ, analysis of pro-inflammatory cytokines production IL-1β, IL-6 IL-10 with a reverse transcription-polymerase chain reaction technique were applied. The TNF-α factor production has been studied both in vitro at ND interaction with the macrophage and in vivo after ND injection in the mice blood system using immunoassay. The macrophage antibacterial function was estimated through E. coli bacterial colony formation. ND didn't stimulate the immune response and functionality of the macrophage was not altered. Using MTT test, ND was found negligibly cytotoxic to macrophages. Thus, ND can serve as a biocompatible platform for bio-medical applications. Left: Graphic representation of Nanodiamond internalization in macrophage. Right: (a) Fluorescence images of lysosomes, (b) nanodiamond and (c) merged image of nanodiamond internalization in macrophage. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Stochastic cellular automata model of neurosphere growth: Roles of proliferative potential, contact inhibition, cell death, and phagocytosis.

    Science.gov (United States)

    Sipahi, Rifat; Zupanc, Günther K H

    2018-05-14

    Neural stem and progenitor cells isolated from the central nervous system form, under specific culture conditions, clonal cell clusters known as neurospheres. The neurosphere assay has proven to be a powerful in vitro system to study the behavior of such cells and the development of their progeny. However, the theory of neurosphere growth has remained poorly understood. To overcome this limitation, we have, in the present paper, developed a cellular automata model, with which we examined the effects of proliferative potential, contact inhibition, cell death, and clearance of dead cells on growth rate, final size, and composition of neurospheres. Simulations based on this model indicated that the proliferative potential of the founder cell and its progenitors has a major influence on neurosphere size. On the other hand, contact inhibition of proliferation limits the final size, and reduces the growth rate, of neurospheres. The effect of this inhibition is particularly dramatic when a stem cell becomes encapsulated by differentiated or other non-proliferating cells, thereby suppressing any further mitotic division - despite the existing proliferative potential of the stem cell. Conversely, clearance of dead cells through phagocytosis is predicted to accelerate growth by reducing contact inhibition. A surprising prediction derived from our model is that cell death, while resulting in a decrease in growth rate and final size of neurospheres, increases the degree of differentiation of neurosphere cells. It is likely that the cellular automata model developed as part of the present investigation is applicable to the study of tissue growth in a wide range of systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Homology Requirements for Efficient, Footprintless Gene Editing at the CFTR Locus in Human iPSCs with Helper-dependent Adenoviral Vectors

    Directory of Open Access Journals (Sweden)

    Donna J Palmer

    2016-01-01

    Full Text Available Helper-dependent adenoviral vectors mediate high efficiency gene editing in induced pluripotent stem cells without needing a designer nuclease thereby avoiding off-target cleavage. Because of their large cloning capacity of 37 kb, helper-dependent adenoviral vectors with long homology arms are used for gene editing. However, this makes vector construction and recombinant analysis difficult. Conversely, insufficient homology may compromise targeting efficiency. Thus, we investigated the effect of homology length on helper-dependent adenoviral vector targeting efficiency at the cystic fibrosis transmembrane conductance regulator locus in induced pluripotent stem cells and found a positive correlation. With 23.8 and 21.4 kb of homology, the frequencies of targeted recombinants were 50–64.6% after positive selection for vector integration, and 97.4–100% after negative selection against random integrations. With 14.8 kb, the frequencies were 26.9–57.1% after positive selection and 87.5–100% after negative selection. With 9.6 kb, the frequencies were 21.4 and 75% after positive and negative selection, respectively. With only 5.6 kb, the frequencies were 5.6–16.7% after positive selection and 50% after negative selection, but these were more than high enough for efficient identification and isolation of targeted clones. Furthermore, we demonstrate helper-dependent adenoviral vector-mediated footprintless correction of cystic fibrosis transmembrane conductance regulator mutations through piggyBac excision of the selectable marker. However, low frequencies (≤ 1 × 10−3 necessitated negative selection for piggyBac-excision product isolation.

  14. Participation of 14-3-3ε and 14-3-3ζ proteins in the phagocytosis, component of cellular immune response, in Aedes mosquito cell lines.

    Science.gov (United States)

    Trujillo-Ocampo, Abel; Cázares-Raga, Febe Elena; Del Angel, Rosa María; Medina-Ramírez, Fernando; Santos-Argumedo, Leopoldo; Rodríguez, Mario H; Hernández-Hernández, Fidel de la Cruz

    2017-08-01

    Better knowledge of the innate immune system of insects will improve our understanding of mosquitoes as potential vectors of diverse pathogens. The ubiquitously expressed 14-3-3 protein family is evolutionarily conserved from yeast to mammals, and at least two isoforms of 14-3-3, the ε and ζ, have been identified in insects. These proteins have been shown to participate in both humoral and cellular immune responses in Drosophila. As mosquitoes of the genus Aedes are the primary vectors for arboviruses, causing several diseases such as dengue fever, yellow fever, Zika and chikungunya fevers, cell lines derived from these mosquitoes, Aag-2 from Aedes aegypti and C6/36 HT from Aedes albopictus, are currently used to study the insect immune system. Here, we investigated the role of 14-3-3 proteins (ε and ζ isoform) in phagocytosis, the main cellular immune responses executed by the insects, using Aedes spp. cell lines. We evaluated the mRNA and protein expression of 14-3-3ε and 14-3-3ζ in C6/36 HT and Aag-2 cells, and demonstrated that both proteins were localised in the cytoplasm. Further, in C6/36 HT cells treated with a 14-3-3 specific inhibitor we observed a notable modification of cell morphology with filopodia-like structure caused through cytoskeleton reorganisation (co-localization of 14-3-3 proteins with F-actin), more importantly the decrease in Salmonella typhimurium, Staphylococcus aureus and E. coli phagocytosis and reduction in phagolysosome formation. Additionally, silencing of 14-3-3ε and 14-3-3ζ expression by mean of specific DsiRNA confirmed the decreased phagocytosis and phagolysosome formation of pHrodo labelled E. coli and S. aureus bacteria by Aag-2 cells. The 14-3-3ε and 14-3-3ζ proteins modulate cytoskeletal remodelling, and are essential for phagocytosis of Gram-positive and Gram-negative bacteria in Aedes spp. cell lines.

  15. Thioester-containing proteins of the tick Ixodes ricinus: Gene expression, response to microbial challenge and their role in phagocytosis of the yeast Candida albicans

    Czech Academy of Sciences Publication Activity Database

    Urbanová, Veronika; Šíma, Radek; Šauman, Ivo; Hajdušek, Ondřej; Kopáček, Petr

    2015-01-01

    Roč. 48, č. 1 (2015), s. 55-64 ISSN 0145-305X R&D Projects: GA ČR GAP506/10/2136; GA ČR GA13-11043S; GA ČR GP13-27630P; GA ČR GP13-12816P; GA MŠk(CZ) EE2.3.30.0032 EU Projects: European Commission(XE) 316304 - MODBIOLIN Institutional support: RVO:60077344 Keywords : Candida albicans * Complement * Innate immunity * Phagocytosis * Thioester-containing proteins * Tick Ixodes ricinus Subject RIV: EC - Immunology Impact factor: 3.620, year: 2015

  16. Antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC) of breast cancer cells mediated by bispecific antibody, MDX-210.

    Science.gov (United States)

    Watanabe, M; Wallace, P K; Keler, T; Deo, Y M; Akewanlop, C; Hayes, D F

    1999-02-01

    MDX-210 is a bispecific antibody (BsAb) with specificity for both the proto-oncogene product of HER-2/neu (c-erbB-2) and FcgammaRI (CD64). HER-2/neu is overexpressed in malignant tissue of approximately 30% of patients with breast cancer, and FcgammaRI is expressed on human monocytes, macrophages, and IFN-gamma activated granulocytes. We investigated phagocytosis and cytolysis of cultured human breast cancer cells by human monocyte-derived macrophages (MDM) mediated by BsAb MDX-210, its partially humanized derivative (MDX-H210), and its parent MoAb 520C9 (anti-HER-2/neu) under various conditions. Purified monocytes were cultured with GM-CSF, M-CSF, or no cytokine for five or six days. Antibody dependent cellular phagocytosis (ADCP) and cytolysis (ADCC) assays were performed with the MDM and HER-2/neu positive target cells (SK-BR-3). ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and phycoerythrin-conjugated (red) monoclonal antibodies (MoAb) against human CD14 and CD11b. ADCC was measured with a non-radioactive LDH detection kit. Both BsAb MDX-210 (via FcgammaRI) and MoAb 520C9 (mouse IgG1, via FcgammaRII) mediated similar levels of ADCP and ADCC. ADCP mediated by BsAb MDX-H210 was identical to that mediated by BsAb MDX-210. Confocal microscopy demonstrated that dual-labeled cells represented true phagocytosis. Both ADCP and ADCC were higher when MDM were pre-incubated with GM-CSF than when incubated with M-CSF. BsAb MDX-210 is as active in vitro as the parent MoAb 520C9 in inducing both phagocytosis and cytolysis of MDM. MDX-210 and its partially humanized derivative, MDX-H210, mediated similar levels of ADCP. GM-CSF appears to superior to M-CSF in inducing MDM-mediated ADCC and ADCP. These studies support the ongoing clinical investigations of BsAb MDX-210 and its partially humanized derivative.

  17. Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis.

    Science.gov (United States)

    Xu, Qingfu; Surendran, Naveen; Verhoeven, David; Klapa, Jessica; Ochs, Martina; Pichichero, Michael E

    2015-02-18

    Due to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model. C57BL/6J infant mice were intramuscularly vaccinated at age 1-3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3-4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48h after challenge. PPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6-24h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden. Trivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation

  18. Anthocyanins from black rice (Oryza sativa) promote immune responses in leukemia through enhancing phagocytosis of macrophages in vivo.

    Science.gov (United States)

    Fan, Ming-Jen; Yeh, Ping-Hsuan; Lin, Jing-Pin; Huang, An-Cheng; Lien, Jin-Cherng; Lin, Hui-Yi; Chung, Jing-Gung

    2017-07-01

    Rice is a staple food in numerous countries around the world. Anthocyanins found in black rice have been reported to reduce the risk of certain diseases, but the effects of crude extract of anthocyanins from Asia University-selected purple glutinous indica rice (AUPGA) on immune responses have not yet been demonstrated. The current study aimed to investigate whether AUPGA treatment could affect immune responses in murine leukemia cells in vivo . Murine acute myelomonocytic leukemia WEHI-3 cells were intraperitoneally injected into normal BALB/c mice to generate leukemia mice. A total of 50 mice were randomly divided into five groups (n=10 in each group) and were fed a diet supplemented with AUPGA at 0, 20, 50 or 100 mg/kg for three weeks. All mice were weighed and the blood, liver and spleen were collected for further experiments. The results indicated that AUPGA did not significantly affect animal body weight, but significantly increased spleen weight (P<0.05) and decreased liver weight (P<0.05) when compared with the control group. AUPGA significantly increased the T cell (CD3) population at treatments of 20 and 100 mg/kg (P<0.05). However, it only significantly increased the B cell (CD19) population at a treatment of 20 mg/kg (P<0.05). Furthermore, AUPGA at 50 and 100 mg/kg significantly increased the monocyte (CD11b) population and the level of macrophages (Mac-3; P<0.05 for both). AUPGA at 50 and 100 mg/kg significantly promoted macrophage phagocytosis in peripheral blood mononuclear cells (P<0.05), and all doses of AUPGA treatment significantly promoted macrophage phagocytotic activity in the peritoneum (P<0.05). AUPGA treatment significantly decreased natural killer cell activity from splenocytes (P<0.05). Finally, AUPGA treatment at 20 mg/kg treatment significantly promoted T cell proliferation (P<0.05), and treatment at 50 and 100 mg/kg significantly decreased B cell proliferation compared with the control group (P<0.05).

  19. Phagocytosis: history's lessons.

    Science.gov (United States)

    Garg, Manish; Chandawarkar, Rajiv Y

    2013-01-01

    The assimilation of lessons from the past is an essential component of education for scientists of tomorrow. These lessons are not easy to find. History books on science are few and usually highly dramatized and biographies of scientists tend to exaggerate the pomp of scientific discovery. Both underplay the hard and laborious work that is integral to any scientific pursuit. Here we illustrate one such example. A century ago, the Nobel Prize in Medicine was awarded to two scientists: Ilya Metchnikoff, a Russian zoologist, for the discovery ofphagocytosis-a cell-mediated ingestion ofmicrobes; and Paul Ehrlich, a distinguished physician-scientist, for discovering a highly antigen-specific serum-derived antibody-based immune defense. These two diametrically opposing views of the host-pathogen interaction set the stage for a strife that led to seminal advancements in immunology. Mirrored in this journey are important lessons for scientists today--ubiquitously as applicable to modern scientific life as they were a century ago. This commentaryhighlights these lessons--a fitting centenary to a well-deserved recognition.

  20. Surface motility in Pseudomonas sp DSS73 is required for efficient biological containment of the root-pathogenic microfungi Rhizoctonia solani and Pythium ultimum

    DEFF Research Database (Denmark)

    Andersen, Jens Bo; Koch, Birgit; Nielsen, T.H.

    2003-01-01

    Pseudomonas sp. DSS73 was isolated from the rhizoplane of sugar beet seedlings. This strain exhibits antagonism towards the root-pathogenic microfungi Pythium ultimum and Rhizoctonia solani. Production of the cyclic lipopeptide amphisin in combination with expression of flagella enables the growing......-pathogenic microfungi is shown to arise from amphisin-dependent surface translocation and growth by which the bacterium can lay siege to the fungi. The synergistic effects of surface motility and synthesis of a battery of antifungal compounds efficiently contain and terminate growth of the microfungi....

  1. Autographa californica multiple nucleopolyhedrovirus ac66 is required for the efficient egress of nucleocapsids from the nucleus, general synthesis of preoccluded virions and occlusion body formation

    International Nuclear Information System (INIS)

    Ke Jianhao; Wang Jinwen; Deng Riqiang; Wang Xunzhang

    2008-01-01

    Although orf66 (ac66) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is conserved in all sequenced lepidopteran baculovirus genomes, its function is not known. This paper describes generation of an ac66 knockout AcMNPV bacmid mutant and analyses of the influence of ac66 deletion on the virus replication in Sf-9 cells so as to determine the role of ac66 in the viral life cycle. Results indicated that budded virus (BV) yields were reduced over 99% in ac66-null mutant infected cells in comparison to that in wild-type virus infected cells. Optical microscopy revealed that occlusion body synthesis was significantly reduced in the ac66 knockout bacmid-transfected cells. In addition, ac66 deletion interrupted preoccluded virion synthesis. The mutant phenotype was rescued by an ac66 repair bacmid. On the other hand, real-time PCR analysis indicated that ac66 deletion did not affect the levels of viral DNA replication. Electron microscopy revealed that ac66 is not essential for nucleocapsid assembly, but for the efficient transport of nucleocapsids from the nucleus to the cytoplasm. These results suggested that ac66 plays an important role for the efficient exit of nucleocapsids from the nucleus to the cytoplasm for BV synthesis as well as for preoccluded virion and occlusion synthesis

  2. Efficient transcription of the glycolytic gene ADH1 and three translational component genes requires the GCR1 product, which can act through TUF/GRF/RAP binding sites.

    OpenAIRE

    Santangelo, G M; Tornow, J

    1990-01-01

    Glycolytic gene expression in Saccharomyces cerevisiae is thought to be activated by the GCR and TUF proteins. We tested the hypothesis that GCR function is mediated by TUF/GRF/RAP binding sites (UASRPG elements). We found that UASRPG-dependent activation of a heterologous gene and transcription of ADH1, TEF1, TEF2, and RP59 were sensitive to GCR1 disruption. GCR is not required for TUF/GRF/RAP expression or in vitro DNA-binding activity.

  3. Adhesion to sand and ability to mineralise low pesticide concentrations are required for efficient bioaugmentation of flow-through sand filters

    DEFF Research Database (Denmark)

    Samuelsen, Elin Djurhuus; Badawi, Nora; Nybroe, Ole

    2017-01-01

    (Sphingomonas sp. PM2, Sphingomonas sp. ERG5, Burkholderia sp. TFD34, Cupriavidus sp. TFD38) were characterised with regard to their motility, cell surface hydrophobicity, biofilm formation, adhesion behaviour and ability to mineralise MCPA. Strains PM2 and ERG5 were non-motile and hydrophobic, whilst strains...... TFD34 and TFD38 were motile and less hydrophobic. All the strains except ERG5 showed low biofilm formation on polystyrene, although it was significantly higher on glass. PM2 was the most efficient MCPA degrader as it displayed no lag phase and reached >50 % mineralisation at all concentrations (0.......0016-25 mg L(-1)). PM2 adhered significantly better to sand than the other strains. No link was found between motility, biofilm formation and the ability to adhere to sand. PM2 completely removed MCPA for 14 days when inoculated in sand columns with a constant inlet of 1 mg L(-1) MCPA. These results...

  4. No programming required. Mobile PCs can help physicians work more efficiently, especially when the application is designed to fit the practice.

    Science.gov (United States)

    Campbell, J

    2000-09-01

    The Jacobson Medical Group San Antonio Jacobson Medical Group (JMG) needed a way to effectively and efficiently coordinate referral information between their hospitalist physicians and specialists. JMG decided to replace paper-based binders with something more convenient and easily updated. The organization chose to implement a mobile solution that would provide its physicians with convenient access to a database of information via a hand-held computer. The hand-held solution provides physicians with full demographic profiles of primary care givers for each area where the group operates. The database includes multiple profiles based on different healthcare plans, along with details about preferred and authorized specialists. JMG adopted a user-friendly solution that the hospitalists and specialists would embrace and actually use.

  5. Over-expression of the mycobacterial trehalose-phosphate phosphatase OtsB2 results in a defect in macrophage phagocytosis associated with increased mycobacterial-macrophage adhesion

    Directory of Open Access Journals (Sweden)

    Hao Li

    2016-11-01

    Full Text Available Trehalose-6-phosphate phosphatase (OtsB2 is involved in the OtsAB trehalose synthesis pathway to produce free trehalose and is strictly essential for mycobacterial growth. We wished to determine the effects of OtsB2 expression on mycobacterial phenotypes such as growth, phagocytosis and survival in macrophages. Mycobacterium bovis-BCG (BCG over-expressing OtsB2 were able to better survive in stationary phase. Over-expression of OtsB2 led to a decrease in phagocytosis but not survival in THP-1 macrophage-like cells, and this was not due to a decrease in general macrophage phagocytic activity. Surprisingly, when we investigated macrophage-mycobacterial interactions by flow cytometry and atomic force microscopy, we discovered that BCG over-expressing OtsB2 have stronger binding to THP-1 cells than wild-type BCG. These results suggest that altering OtsB2 expression has implications for mycobacterial host-pathogen interactions. Macrophage-mycobacteria phagocytic interactions are complex and merit further study.

  6. Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Wahida H Ali

    Full Text Available Cell migration and phagocytosis ensue from extracellular-initiated signaling cascades that orchestrate dynamic reorganization of the actin cytoskeleton. The reorganization is mediated by effector proteins recruited to the site of activity by locally-generated lipid second messengers. Phosphatidic acid (PA, a membrane phospholipid generated by multiple enzyme families including Phospholipase D (PLD, has been proposed to function in this role. Here, we show that macrophages prepared from mice lacking either of the classical PLD isoforms PLD1 or PLD2, or wild-type macrophages whose PLD activity has been pharmacologically inhibited, display isoform-specific actin cytoskeleton abnormalities that likely underlie decreases observed in phagocytic capacity. Unexpectedly, PA continued to be detected on the phagosome in the absence of either isoform and even when all PLD activity was eliminated. However, a disorganized phagocytic cup was observed as visualized by imaging PA, F-actin, Rac1, an organizer of the F-actin network, and DOCK2, a Rac1 activator, suggesting that PLD-mediated PA production during phagocytosis is specifically critical for the integrity of the process. The abnormal F-actin reorganization additionally impacted neutrophil migration and extravasation from the vasculature into interstitial tissues. Although both PLD1 and PLD2 were important in these processes, we also observed isoform-specific functions. PLD1-driven processes in particular were observed to be critical in transmigration of macrophages exiting the vasculature during immune responses such as those seen in acute pancreatitis or irritant-induced skin vascularization.

  7. Immunomodulatory effect of exo-polysaccharides from submerged cultured Cordyceps sinensis: enhancement of cytokine synthesis, CD11b expression, and phagocytosis.

    Science.gov (United States)

    Kuo, Mei-Chun; Chang, Chien-Yu; Cheng, Tso-Lin; Wu, Ming-Jiuan

    2007-06-01

    Cordyceps sinensis is widely used as a traditional medicine for treatment of a wide variety of diseases or to maintain health. The immunomodulatory activity of polysaccharides prepared from submerged cultured C. sinensis BCRC36421 was investigated in human peripheral blood. Results demonstrated that Fr. A (exo-polysaccharides, 0.025 approximately 0.1 mg/ml) induced the production of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10 dose-dependently. Fr. A, as low as 0.025 mg/ml, could significantly augment surface expression of CD11b in monocytes and polymorphonuclear neutrophils. Functional assay revealed that Fr. A (0.05 mg/ml) also elevated phagocytosis in monocytes and PMN. On the other hand, Fr. B (intracellular polysaccharides) only moderately induced TNF-alpha release, CD11b expression, and phagocytosis at the same concentrations. Our results indicate that the immunomodulatory components of submerged cultured C. sinensis mainly reside in the culture filtrate.

  8. PLD$ is involved in phagocytosis of microglia: expression and localization changes of PLD4 are correlated with activation state of microglia.

    Directory of Open Access Journals (Sweden)

    Yoshinori Otani

    Full Text Available Phospholipase D4 (PLD4 is a recently identified protein that is mainly expressed in the ionized calcium binding adapter molecule 1 (Iba1-positive microglia in the early postnatal mouse cerebellar white matter. Unlike PLD1 and PLD2, PLD4 exhibits no enzymatic activity for conversion of phosphatidylcholine into choline and phosphatidic acid, and its function is completely unknown. In the present study, we examined the distribution of PLD4 in mouse cerebellar white matter during development and under pathological conditions. Immunohistochemical analysis revealed that PLD4 expression was associated with microglial activation under such two different circumstances. A primary cultured microglia and microglial cell line (MG6 showed that PLD4 was mainly present in the nucleus, except the nucleolus, and expression of PLD4 was upregulated by lipopolysaccharide (LPS stimulation. In the analysis of phagocytosis of LPS-stimulated microglia, PLD4 was co-localized with phagosomes that contained BioParticles. Inhibition of PLD4 expression using PLD4 specific small interfering RNA (siRNA in MG6 cells significantly reduced the ratio of phagocytotic cell numbers. These results suggest that the increased PLD4 in the activation process is involved in phagocytosis of activated microglia in the developmental stages and pathological conditions of white matter.

  9. Tamm-Horsfall Glycoprotein Enhances PMN Phagocytosis by Binding to Cell Surface-Expressed Lactoferrin and Cathepsin G That Activates MAP Kinase Pathway

    Directory of Open Access Journals (Sweden)

    Chia-Li Yu

    2011-03-01

    Full Text Available The molecular basis of polymorphonuclear neutrophil (PMN phagocytosis-enhancing activity (PEA by human purified urinary Tamm-Horsfall glyco- protein (THP has not been elucidated. In this study, we found human THP bound to lactoferrin (LF and cathepsin G (CG expressed on the surface of PMN, identified by a proteomic study with MALDI-TOF- LC/LC/mass spectrometric analysis. Pre-incubation of 10% SDS-PAGE electrophoresed PMN lysates with monoclonal anti-LF or anti-CG antibody reduced the binding with THP. To elucidate the signaling pathway of THP on PMN activation, we found THP enhanced ERK1/2 phosphorylation, reduced p38 MAP kinase phosphorylation, but had no effect on DNA binding of the five NF-kB family members in PMN. To further clarify whether the carbohydrate-side chains or protein-core structure in THP molecule is responsible for THP-PEA, THP was cleaved by different degrading enzymes with carbohydrate specificity (neuraminidase and β-galactosidase, protein specificity (V8 protease and proteinase K or glycoconjugate specificity (carboxylpeptidase Y and O-sialoglycoprotein endopeptidase. We clearly demonstrated that the intact protein-core structure in THP molecule was more important for THP-PEA than carbohydrate-side chains. Putting these results together, we conclude that THP adheres to surface-expressed LF and CG on PMN and transduces signaling via the MAP kinase pathway to enhance PMN phagocytosis.

  10. Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNA

    OpenAIRE

    Levy, Anat; Eyal, Miri; Hershkovits, Gitit; Salmon-Divon, Mali; Klutstein, Michael; Katcoff, Don Jay

    2008-01-01

    Nucleosome core particles in eukaryotes are linked by a stretch of DNA that is usually associated with a linker histone. Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA. In vivo deletions of Hho1p sequences showed that the second globular domain is sufficient for that repression, whereas the presence of the N terminus is required for its derepression. In contrast, a run-on assay confirmed by...

  11. Efficient transcription of the glycolytic gene ADH1 and three translational component genes requires the GCR1 product, which can act through TUF/GRF/RAP binding sites.

    Science.gov (United States)

    Santangelo, G M; Tornow, J

    1990-01-01

    Glycolytic gene expression in Saccharomyces cerevisiae is thought to be activated by the GCR and TUF proteins. We tested the hypothesis that GCR function is mediated by TUF/GRF/RAP binding sites (UASRPG elements). We found that UASRPG-dependent activation of a heterologous gene and transcription of ADH1, TEF1, TEF2, and RP59 were sensitive to GCR1 disruption. GCR is not required for TUF/GRF/RAP expression or in vitro DNA-binding activity. Images PMID:2405258

  12. The Translesion Polymerase Pol η Is Required for Efficient Epstein-Barr Virus Infectivity and Is Regulated by the Viral Deubiquitinating Enzyme BPLF1.

    Science.gov (United States)

    Dyson, Ossie F; Pagano, Joseph S; Whitehurst, Christopher B

    2017-10-01

    Epstein-Barr virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. We previously showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis (TLS) pathway, a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument, indicating that BPLF1 may function both early and late during infection. The BPLF1 protein expresses deubiquitinating activity that is strictly conserved across the Herpesviridae ; mutation of the active site cysteine results in a loss of enzymatic activity. Infection with an EBV BPLF1 knockout virus results in decreased EBV infectivity. Polymerase eta (Pol η), a specialized DNA repair polymerase, functions in TLS and allows for DNA replication complexes to bypass lesions in DNA. Here we report that BPLF1 interacts with Pol η and that Pol η protein levels are increased in the presence of functional BPLF1. BPLF1 promotes a nuclear relocalization of Pol η molecules which are focus-like in appearance, consistent with the localization observed when Pol η is recruited to sites of DNA damage. Knockdown of Pol η resulted in decreased production of infectious virus, and further, Pol η was found to bind to EBV DNA, suggesting that it may allow for bypass of damaged viral DNA during its replication. The results suggest a mechanism by which EBV recruits cellular repair factors, such as Pol η, to sites of viral DNA damage via BPLF1, thereby allowing for efficient viral DNA replication. IMPORTANCE Epstein-Barr virus is the causative agent of infectious mononucleosis and infects approximately 90% of the world's population. It causes lymphomas in individuals with acquired and innate immune disorders and is strongly associated with Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphomas, nasopharyngeal carcinoma (NPC), and

  13. Interaction of the Mouse Polyomavirus Capsid Proteins with Importins Is Required for Efficient Import of Viral DNA into the Cell Nucleus.

    Science.gov (United States)

    Soldatova, Irina; Prilepskaja, Terezie; Abrahamyan, Levon; Forstová, Jitka; Huérfano, Sandra

    2018-03-31

    The mechanism used by mouse polyomavirus (MPyV) overcomes the crowded cytosol to reach the nucleus has not been fully elucidated. Here, we investigated the involvement of importin α/β1 mediated transport in the delivery of MPyV genomes into the nucleus. Interactions of the virus with importin β1 were studied by co-immunoprecipitation and proximity ligation assay. For infectivity and nucleus delivery assays, the virus and its capsid proteins mutated in the nuclear localization signals (NLSs) were prepared and produced. We found that at early times post infection, virions bound importin β1 in a time dependent manner with a peak of interactions at 6 h post infection. Mutation analysis revealed that only when the NLSs of both VP1 and VP2/3 were disrupted, virus did not bind efficiently to importin β1 and its infectivity remarkably decreased (by 80%). Nuclear targeting of capsid proteins was improved when VP1 and VP2 were co-expressed. VP1 and VP2 were effectively delivered into the nucleus, even when one of the NLS, either VP1 or VP2, was disrupted. Altogether, our results showed that MPyV virions can use VP1 and/or VP2/VP3 NLSs in concert or individually to bind importins to deliver their genomes into the cell nucleus.

  14. N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability

    Directory of Open Access Journals (Sweden)

    Chiung-Fang Chang

    2016-06-01

    Full Text Available R-spondin 1 (Rspo1 plays an essential role in stem cell biology by potentiating Wnt signaling activity. Despite the fact that Rspo1 holds therapeutic potential for a number of diseases, its biogenesis is not fully elucidated. All Rspo proteins feature two amino-terminal furin-like repeats, which are responsible for Wnt signal potentiation, and a thrombospondin type 1 (TSR1 domain that can provide affinity towards heparan sulfate proteoglycans. Using chemical inhibitors, deglycosylase and site-directed mutagenesis, we found that human Rspo1 and Rspo3 are both N-glycosylated at N137, a site near the C-terminus of the furin repeat 2 domain, and Rspo2 is N-glycosylated at N160, a position near the N-terminus of TSR1 domain. Elimination of N-glycosylation at these sites affects their accumulation in media but have no effect on the ability towards heparin. Introduction of the N-glycosylation site to Rspo2 mutant at the position homologous to N137 in Rspo1 restored full glycosylation and rescued the accumulation defect of nonglycosylated Rspo2 mutant in media. Similar effect can be observed in the N137 Rspo1 or Rspo3 mutant engineered with Rspo2 N-glycosylation site. The results highlight the importance of N-glycosylation at these two positions in efficient folding and secretion of Rspo family. Finally, we further showed that human Rspo1 is subjected to endoplasmic reticulum (ER quality control in N-glycan-dependent manner. While N-glycan of Rspo1 plays a role in its intracellular stability, it had little effect on secreted Rspo1. Our findings provide evidence for the critical role of N-glycosylation in the biogenesis of Rspo1.

  15. A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae.

    Science.gov (United States)

    Allan, Christopher M; Hill, Shauna; Morvaridi, Susan; Saiki, Ryoichi; Johnson, Jarrett S; Liau, Wei-Siang; Hirano, Kathleen; Kawashima, Tadashi; Ji, Ziming; Loo, Joseph A; Shepherd, Jennifer N; Clarke, Catherine F

    2013-04-01

    Coenzyme Qn (ubiquinone or Qn) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail of n isoprene units. Saccharomyces cerevisiae coq1-coq9 mutants have defects in Q biosynthesis, lack Q6, are respiratory defective, and sensitive to stress imposed by polyunsaturated fatty acids. The hallmark phenotype of the Q-less yeast coq mutants is that respiration in isolated mitochondria can be rescued by the addition of Q2, a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q6. Structure determination of the Caulobacter crescentus Coq10 homolog (CC1736) revealed a steroidogenic acute regulatory protein-related lipid transfer (START) domain, a hydrophobic tunnel known to bind specific lipids in other START domain family members. Here we show that purified CC1736 binds Q2, Q3, Q10, or demethoxy-Q3 in an equimolar ratio, but fails to bind 3-farnesyl-4-hydroxybenzoic acid, a farnesylated analog of an early Q-intermediate. Over-expression of C. crescentus CC1736 or COQ8 restores respiratory electron transport and antioxidant function of Q6 in the yeast coq10 null mutant. Studies with stable isotope ring precursors of Q reveal that early Q-biosynthetic intermediates accumulate in the coq10 mutant and de novo Q-biosynthesis is less efficient than in the wild-type yeast or rescued coq10 mutant. The results suggest that the Coq10 polypeptide:Q (protein:ligand) complex may serve essential functions in facilitating de novo Q biosynthesis and in delivering newly synthesized Q to one or more complexes of the respiratory electron transport chain. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Lubricants trying to meet the diverging requirements of environmental compatibility and efficient performance; Schmierstoffe im Spannungsfeld zwischen Umweltvertraeglichkeit und technischem Leistungsanspruch

    Energy Technology Data Exchange (ETDEWEB)

    Hornscheidt, G.A. [Carl Bechem GmbH, Hagen (Germany)

    1998-10-01

    The article addresses the political goal, to substitute lubricants on a mineral oil basis by biologically degradable oils, primarily from renewable sources as e.g. rapeseed or sunflower oils, but animal oils as well. These products can be further processed by oleochemical treatment to synthetic esters which meet the high performance requirements of technical applications. The Federal Government supports research and development activities and thus has given attractive incentives for a reorientation towards biological oils. This will not heal the hole in the ozone layer, nor will it halt destruction of the rainforests, but nevertheless enhances the chances for active environmental protection through application of new, less hazardous substances. (orig./CB) [Deutsch] Wie es im Vortrag dargestellt wird, ist es ein erklaertes Ziel der Bundesregierung, problematische mineraloelbasische Schmierstoffe durch den Einsatz biologisch schnell abbaubarer Grundfluessigkeiten, vorrangig nachwachsender Rohstoffe wie Raps- und Sonnenblumenoele, aber auch tierischer Oele, zu ersetzen. Fuer technisch anspruchsvolle Anwendungen koennen diese Produkte von der Oleochemie zu synthetischen Estern weiterverarbeitet werden. Durch die Foerderung von Forschungs- und Entwicklungsmassnahmen fuer Bio-Schmieroele setzt die Bundesregierung hier deutliche Akzente. Kein Schmierstoff dieser Welt kann die Umwelt verbessern. Weder laesst sich mit Bio-Oel das Ozonloch `stopfen`, noch das Problem der sterbenden Regenwaelder loesen. Dennoch kann mit den neuen innovativen Schmierstoffen aktiv Umweltschutz betrieben werden. (orig.)

  17. Slow Off-rates and Strong Product Binding Are Required for Processivity and Efficient Degradation of Recalcitrant Chitin by Family 18 Chitinases.

    Science.gov (United States)

    Kurašin, Mihhail; Kuusk, Silja; Kuusk, Piret; Sørlie, Morten; Väljamäe, Priit

    2015-11-27

    Processive glycoside hydrolases are the key components of enzymatic machineries that decompose recalcitrant polysaccharides, such as chitin and cellulose. The intrinsic processivity (P(Intr)) of cellulases has been shown to be governed by the rate constant of dissociation from polymer chain (koff). However, the reported koff values of cellulases are strongly dependent on the method used for their measurement. Here, we developed a new method for determining koff, based on measuring the exchange rate of the enzyme between a non-labeled and a (14)C-labeled polymeric substrate. The method was applied to the study of the processive chitinase ChiA from Serratia marcescens. In parallel, ChiA variants with weaker binding of the N-acetylglucosamine unit either in substrate-binding site -3 (ChiA-W167A) or the product-binding site +1 (ChiA-W275A) were studied. Both ChiA variants showed increased off-rates and lower apparent processivity on α-chitin. The rate of the production of insoluble reducing groups on the reduced α-chitin was an order of magnitude higher than koff, suggesting that the enzyme can initiate several processive runs without leaving the substrate. On crystalline chitin, the general activity of the wild type enzyme was higher, and the difference was magnifying with hydrolysis time. On amorphous chitin, the variants clearly outperformed the wild type. A model is proposed whereby strong interactions with polymer in the substrate-binding sites (low off-rates) and strong binding of the product in the product-binding sites (high pushing potential) are required for the removal of obstacles, like disintegration of chitin microfibrils. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. RasGRP1, but not RasGRP3, is required for efficient thymic β-selection and ERK activation downstream of CXCR4.

    Directory of Open Access Journals (Sweden)

    Dominic P Golec

    Full Text Available T cell development is a highly dynamic process that is driven by interactions between developing thymocytes and the thymic microenvironment. Upon entering the thymus, the earliest thymic progenitors, called CD4(-CD8(- 'double negative' (DN thymocytes, pass through a checkpoint termed "β-selection" before maturing into CD4(+CD8(+ 'double positive' (DP thymocytes. β-selection is an important developmental checkpoint during thymopoiesis where developing DN thymocytes that successfully express the pre-T cell receptor (TCR undergo extensive proliferation and differentiation towards the DP stage. Signals transduced through the pre-TCR, chemokine receptor CXCR4 and Notch are thought to drive β-selection. Additionally, it has long been known that ERK is activated during β-selection; however the pathways regulating ERK activation remain unknown. Here, we performed a detailed analysis of the β-selection events in mice lacking RasGRP1, RasGRP3 and RasGRP1 and 3. We report that RasGRP1 KO and RasGRP1/3 DKO deficient thymi show a partial developmental block at the early DN3 stage of development. Furthermore, DN3 thymocytes from RasGRP1 and RasGRP1/3 double knock-out thymi show significantly reduced proliferation, despite expression of the TCRβ chain. As a result of impaired β-selection, the pool of TCRβ(+ DN4 is significantly diminished, resulting in inefficient DN to DP development. Also, we report that RasGRP1 is required for ERK activation downstream of CXCR4 signaling, which we hypothesize represents a potential mechanism of RasGRP1 regulation of β-selection. Our results demonstrate that RasGRP1 is an important regulator of proliferation and differentiation at the β-selection checkpoint and functions downstream of CXCR4 to activate the Ras/MAPK pathway.

  19. C-type lectin B (SpCTL-B) regulates the expression of antimicrobial peptides and promotes phagocytosis in mud crab Scylla paramamosain.

    Science.gov (United States)

    Wei, Xiaoyuan; Wang, Limin; Sun, Wanwei; Zhang, Ming; Ma, Hongyu; Zhang, Yueling; Zhang, Xinxu; Li, Shengkang

    2018-07-01

    RNA transcriptional level and protein translational level in mud crab. Meantime, the phagocytosis rate and the expression of three phagocytosis related genes were declined after RNAi of SpCTL-B in hemocytes in mud crab. Collectively, our results suggest that SpCTL-B might play its roles as a pattern recognition receptor (PRR) in immune response towards pathogens infection through influencing the expression of AMPs and the phagocytosis of hemocytes in mud crab S. paramamosain. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence

    DEFF Research Database (Denmark)

    Gustafsson, Caj Ulrik Mattias; Lannergård, Jonas; Nilsson, Olof Rickard

    2013-01-01

    Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against...... represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited...... to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed...

  1. Factor H Binds to the Hypervariable Region of Many Streptococcus pyogenes M Proteins but Does Not Promote Phagocytosis Resistance or Acute Virulence

    Science.gov (United States)

    Kristensen, Bodil M.; Olsen, John E.; Harris, Claire L.; Ufret-Vincenty, Rafael L.; Stålhammar-Carlemalm, Margaretha; Lindahl, Gunnar

    2013-01-01

    Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems. PMID:23637608

  2. Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence.

    Directory of Open Access Journals (Sweden)

    Mattias C U Gustafsson

    Full Text Available Many pathogens express a surface protein that binds the human complement regulator factor H (FH, as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems.

  3. Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.

    Directory of Open Access Journals (Sweden)

    Yasuhisa Ano

    Full Text Available Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer's disease and to identify the responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD, intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ and hippocampal inflammation (TNF-α and MIP-1α production, and enhancing hippocampal neurotrophic factors (BDNF and GDNF. A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer's disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia.

  4. Glycogen synthase kinase-3 (GSK3) regulates TNF production and haemocyte phagocytosis in the immune response of Chinese mitten crab Eriocheir sinensis.

    Science.gov (United States)

    Li, Xiaowei; Jia, Zhihao; Wang, Weilin; Wang, Lingling; Liu, Zhaoqun; Yang, Bin; Jia, Yunke; Song, Xiaorui; Yi, Qilin; Qiu, Limei; Song, Linsheng

    2017-08-01

    Glycogen synthase kinase-3 (GSK3) is a serine/threonine protein kinase firstly identified as a regulator of glycogen synthesis. Recently, it has been proved to be a key regulator of the immune reaction. In the present study, a GSK3 homolog gene (designated as EsGSK3) was cloned from Chinese mitten crab, Eriocheir sinensis. The open reading frame (ORF) was 1824 bp, which encoded a predicted polypeptide of 607 amino acids. There was a conserved Serine/Threonine Kinase domain and a DNA binding domain found in EsGSK3. Phylogenetic analysis showed that EsGSK3 was firstly clustered with GSK3-β from oriental river prawn Macrobrachium nipponense in the invertebrate branch, while GSK3s from vertebrates formed the other distinct branch. EsGSK3 mRNA transcripts could be detected in all tested tissues of the crab including haepatopancreas, eyestalk, muscle, gonad, haemocytes and haematopoietic tissue with the highest expression level in haepatopancreas. And EsGSK3 protein was mostly detected in the cytoplasm of haemocyte by immunofluorescence analysis. The expression levels of EsGSK3 mRNA increased significantly at 6 h after Aeromonas hydrophila challenge (p level at 48 h (p > 0.05). The mRNA expression of lipopolysaccharide-induced tumor necrosis factor (TNF)-α factor (EsLITAF) was also induced by A. hydrophila challenge. However, the mRNA expression of EsLITAF and TNF-α production was significantly suppressed after EsGSK3 was blocked in vivo with specific inhibitor lithium, while the phagocytosis of crab haemocytes was significantly promoted. These results collectively demonstrated that EsGSK3 could regulate the innate immune responses of E. sinensis by promoting TNF-α production and inhibiting haemocyte phagocytosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.

    Science.gov (United States)

    Ano, Yasuhisa; Ozawa, Makiko; Kutsukake, Toshiko; Sugiyama, Shinya; Uchida, Kazuyuki; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer's disease and to identify the responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer's disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia.

  6. Preventive Effects of a Fermented Dairy Product against Alzheimer’s Disease and Identification of a Novel Oleamide with Enhanced Microglial Phagocytosis and Anti-Inflammatory Activity

    Science.gov (United States)

    Ano, Yasuhisa; Ozawa, Makiko; Kutsukake, Toshiko; Sugiyama, Shinya; Uchida, Kazuyuki; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer’s disease and to identify the responsible component. Here, in a mouse model of Alzheimer’s disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer’s disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia. PMID:25760987

  7. Tackling obesity requires efficient government policies

    Directory of Open Access Journals (Sweden)

    Cecchini Michele

    2012-04-01

    Full Text Available Abstract Changes in food supply and eating habits, combined with a dramatic fall in physical activity, have made obesity a global epidemic. Across OECD countries, one in two adults is currently overweight and one in six is obese. Children have not been spared, with up to one in three currently overweight. Obese people are more likely to develop diseases such as diabetes, cardiovascular disease, and cancer, and have a shorter life expectancy than people of normal weight. A prevention strategy combining health promotion campaigns, government regulation, counseling of individuals at risk in primary care, and paying special attention to the most vulnerable, would enhance population health at an affordable cost, with likely beneficial effects on health inequalities. Failure to implement such a strategy would impose heavy burdens on future generations. The new IJHPR paper by Ginsberg and Rosenberg illustrates how particular countries can assess alternative strategies for tackling obesity in a rigorous fashion. This is a commentary on http://www.ijhpr.org/content/1/1/17/

  8. Energy efficiency

    International Nuclear Information System (INIS)

    Marvillet, Ch.; Tochon, P.; Mercier, P.

    2004-01-01

    World energy demand is constantly rising. This is a legitimate trend, insofar as access to energy enables enhanced quality of life and sanitation levels for populations. On the other hand, such increased consumption generates effects that may be catastrophic for the future of the planet (climate change, environmental imbalance), should this growth conform to the patterns followed, up to recent times, by most industrialized countries. Reduction of greenhouse gas emissions, development of new energy sources and energy efficiency are seen as the major challenges to be taken up for the world of tomorrow. In France, the National Energy Debate indeed emphasized, in 2003, the requirement to control both demand for, and offer of, energy, through a strategic orientation law for energy. The French position corresponds to a slightly singular situation - and a privileged one, compared to other countries - owing to massive use of nuclear power for electricity generation. This option allows France to be responsible for a mere 2% of worldwide greenhouse gas emissions. Real advances can nonetheless still be achieved as regards improved energy efficiency, particularly in the transportation and residential-tertiary sectors, following the lead, in this respect, shown by industry. These two sectors indeed account for over half of the country CO 2 emissions (26% and 25% respectively). With respect to transportation, the work carried out by CEA on the hydrogen pathway, energy converters, and electricity storage has been covered by the preceding chapters. As regards housing, a topic addressed by one of the papers in this chapter, investigations at CEA concern integration of the various devices enabling value-added use of renewable energies. At the same time, the organization is carrying through its activity in the extensive area of heat exchangers, allowing industry to benefit from improved understanding in the modeling of flows. An activity evidenced by advances in energy efficiency for

  9. Efficient incremental relaying

    KAUST Repository

    Fareed, Muhammad Mehboob; Alouini, Mohamed-Slim

    2013-01-01

    We propose a novel relaying scheme which improves the spectral efficiency of cooperative diversity systems by utilizing limited feedback from destination. Our scheme capitalizes on the fact that relaying is only required when direct transmission

  10. Analysis of proposed eco-design requirements for boilers and water heaters. Paper within the framwork of the ''Material Efficiency and Resource Conservation'' (MaRess) Project - Task 14

    Energy Technology Data Exchange (ETDEWEB)

    Barthel, Klaus; Franke, Moritz [Wuppertal Institute for Climate, Environment and Energy, Wuppertal (Germany)

    2009-12-15

    In 2005, the European Union released the EuP Directive focusing on ecodesign requirements for energy-using products (2005/32/EC: EU Parliament and Council of the EU 2005). This directive, also called Ecodesign Directive, is a framework directive establishing a structure in which so-called implementing measures define specific requirements for placing products on the market and/or putting them into service within the internal European market. These requirements can be environmental performance standards (e.g. minimum energy efficiency or emission standards) and labelling or information requirements. Some existing European directives are already declared as being implementing measures of the Ecodesign Directive. Additionally, new implementing measures have been and will further be developed. Product-specific preparatory studies on behalf of the European Commission provide the basis for this. The preparatory studies for boilers (Lot 1) and water heaters (Lot 2) have been conducted from February 2006 to October 2007 by Van Holsteijn en Kemna (VHK). Based on the preparatory studies, the EU Commission has released several working documents (WD) on possible ecodesign requirements for boilers and water heaters at the beginning of 2008. Following these documents, boilers and water heaters comprise gas-fired, oil-fired and electric central heating (CH) (combi-) boilers / dedicated water heaters in combination with capturing solar thermal energy or ambient heat1. The requirements contain basically energy labelling measures, minimum efficiency performance standards and limits on NOx emissions. An ''Ecoboiler Model'' resp. an ''Eco Hot Water Model'' has been elaborated within the preparatory studies. These models are a crucial part of the requirements and allow for calculation of the efficiencies of boilers and water heaters. Since the models have a high degree of complexity, the Federal Environment Agency (UBA) has asked Wuppertal

  11. Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview

    Directory of Open Access Journals (Sweden)

    Katsnelson BA

    2015-04-01

    Full Text Available Boris A Katsnelson,1 Larisa I Privalova,1 Marina P Sutunkova,1 Vladimir B Gurvich,1 Nadezhda V Loginova,1 Ilzira A Minigalieva,1 Ekaterina P Kireyeva,1 Vladimir Y Shur,2 Ekaterina V Shishkina,2 Ya B Beikin,3 Oleg H Makeyev,4 Irene E Valamina4 1The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia; 2The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg, Russia; 3The City Clinical Diagnostics Centre, Ekaterinburg, Russia; 4The Ural State Medical University, Ekaterinburg, Russia Abstract: The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 µm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other. Our data testify to the high activity of the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that safe levels of exposure to airborne NPs are possible in principle. However, there are no reliable foundations for establishing different permissible exposure levels for particles of different size within the nanometric range. For workroom air, such permissible exposure levels of metallic NP can be proposed at this stage, even if tentatively, based on a sufficiently

  12. Energy efficiency

    International Nuclear Information System (INIS)

    2010-01-01

    After a speech of the CEA's (Commissariat a l'Energie Atomique) general administrator about energy efficiency as a first rank challenge for the planet and for France, this publications proposes several contributions: a discussion of the efficiency of nuclear energy, an economic analysis of R and D's value in the field of fourth generation fast reactors, discussions about biofuels and the relationship between energy efficiency and economic competitiveness, and a discussion about solar photovoltaic efficiency

  13. Role of the PufX protein in photosynthetic growth of Rhodobacter sphaeroides. 2. PufX is required for efficient ubiquinone/ubiquinol exchange between the reaction center QB site and the cytochrome bc1 complex.

    Science.gov (United States)

    Barz, W P; Verméglio, A; Francia, F; Venturoli, G; Melandri, B A; Oesterhelt, D

    1995-11-21

    The PufX membrane protein is essential for photosynthetic growth of Rhodobacter sphaeroides because it is required for multiple-turnover electron transfer under anaerobic conditions [see accompanying article; Barz, W. P., Francia, F., Venturoli, G., Melandri, B. A., Verméglio, A., & Oesterhelt, D. (1995) Biochemistry 34, 15235-15247]. In order to understand the molecular role of PufX, light-induced absorption spectroscopy was performed using a pufX- mutant, a pufX+ strain, and two suppressor mutants. We show that the reaction center (RC) requires PufX for its functionality under different redox conditions than the cytochrome bc1 complex: When the kinetics of flash-induced reduction of cytochrome b561 were monitored in chromatophores, we observed a requirement of PufX for turnover of the cytochrome bc1 complex only at high redox potential (Eh > 140 mV), suggesting a function of PufX in lateral ubiquinol transfer from the RC. In contrast, PufX is required for multiple turnover of the RC only under reducing conditions: When the Q pool was partially oxidized in vivo using oxygen or electron acceptors like dimethyl sulfoxide or trimethylamine N-oxide, the deletion of PufX had no effect on light-driven electron flow through the RC. Flash train experiments under anaerobic in vivo conditions revealed that RC photochemistry does not depend on PufX for the first two flash excitations. Following the third and subsequent flashes, however, efficient charge separation requires PufX, indicating an important role of PufX for fast Q/QH2 exchange at the QB site of the RC. We show that the Q/QH2 exchange rate is reduced approximately 500-fold by the deletion of PufX when the Q pool is nearly completely reduced, demonstrating an essential role of PufX for the access of ubiquinone to the QB site. The fast ubiquinone/ubiquinol exchange is partially restored by suppressor mutations altering the macromolecular antenna structure. These results suggest an indirect role of PufX in

  14. Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Yuan-Chang Chang

    2011-01-01

    Full Text Available Emodin is one of major compounds in rhubarb (Rheum palmatum L., a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3 and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca2+ and reduced the level of ΔΨm by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

  15. Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A.

    Directory of Open Access Journals (Sweden)

    Christopher B Guest

    Full Text Available Type 2 diabetes (T2D is associated with accelerated atherosclerosis, which accounts for approximately 75% of all diabetes-related deaths. Here we investigate the link between diabetes and macrophage cholesteryl ester accumulation. When diabetic (db/db mice are given cholesteryl ester intraperitoneally (IP, peritoneal macrophages (PerMPhis recovered from these animals showed a 58% increase in intracellular cholesteryl ester accumulation over PerMPhis from heterozygote control (db/+ mice. Notably, PerMPhi fluid-phase endocytosis and large particle phagocytosis was equivalent in db/+and db/db mice. However, IP administration of CD36 and SR-A blocking antibodies led to 37% and 25% reductions in cholesteryl ester accumulation in PerMPhi. Finally, in order to determine if these scavenger receptors (SRs were part of the mechanism responsible for the increased accumulation of cholesteryl esters observed in the diabetic mouse macrophages, receptor expression was quantified by flow cytometry. Importantly, db/db PerMPhis showed a 43% increase in CD36 expression and an 80% increase in SR-A expression. Taken together, these data indicate that direct cholesteryl ester accumulation in mouse macrophages is mediated by CD36 and SR-A, and the magnitude of accumulation is increased in db/db macrophages due to increased scavenger receptor expression.

  16. Complement Receptor 3-Mediated Inhibition of Inflammasome Priming by Ras GTPase-Activating Protein During Francisella tularensis Phagocytosis by Human Mononuclear Phagocytes

    Directory of Open Access Journals (Sweden)

    Ky V. Hoang

    2018-03-01

    Full Text Available Francisella tularensis is a remarkably infectious facultative intracellular bacterium of macrophages that causes tularemia. Early evasion of host immune responses contributes to the success of F. tularensis as a pathogen. F. tularensis entry into human monocytes and macrophages is mediated by the major phagocytic receptor, complement receptor 3 (CR3, CD11b/CD18. We recently determined that despite a significant increase in macrophage uptake following C3 opsonization of the virulent Type A F. tularensis spp. tularensis Schu S4, this phagocytic pathway results in limited pro-inflammatory cytokine production. Notably, MAP kinase/ERK activation is suppressed immediately during C3-opsonized Schu S4-CR3 phagocytosis. A mathematical model of CR3-TLR2 crosstalk predicted early involvement of Ras GTPase-activating protein (RasGAP in immune suppression by CR3. Here, we link CR3-mediated uptake of opsonized Schu S4 by human monocytes and macrophages with inhibition of early signal 1 inflammasome activation, evidenced by limited caspase-1 cleavage and IL-18 release. This inhibition is due to increased RasGAP activity, leading to a reduction in the Ras-ERK signaling cascade upstream of the early inflammasome activation event. Thus, our data uncover a novel signaling pathway mediated by CR3 following engagement of opsonized virulent F. tularensis to limit inflammasome activation in human phagocytic cells, thereby contributing to evasion of the host innate immune system.

  17. The AgI/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes.

    Directory of Open Access Journals (Sweden)

    Linda Franklin

    Full Text Available Streptococcus pyogenes (GAS is a human pathogen that causes pharyngitis and invasive diseases such as toxic shock syndrome and sepsis. The upper respiratory tract is the primary reservoir from which GAS can infect new hosts and cause disease. The factors involved in colonisation are incompletely known however. Previous evidence in oral streptococci has shown that the AgI/II family proteins are involved. We hypothesized that the AspA member of this family might be involved in GAS colonization. We describe a novel mouse model of GAS colonization of the nasopharynx and lower respiratory tract to elucidate these interactions. We used two clinical M serotypes expressing AspA, and their aspA gene deletant isogenic mutants in experiments using adherence assays to respiratory epithelium, macrophage phagocytosis and neutrophil killing assays and in vivo models of respiratory tract colonisation and infection. We demonstrated the requirement for AspA in colonization of the respiratory tract. AspA mutants were cleared from the respiratory tract and were deficient in adherence to epithelial cells, and susceptible to phagocytosis. Expression of AspA in the surrogate host Lactococcus lactis protected bacteria from phagocytosis. Our results suggest that AspA has an essential role in respiratory infection, and may function as a novel anti-phagocytic factor.

  18. Efficient incremental relaying

    KAUST Repository

    Fareed, Muhammad Mehboob

    2013-07-01

    We propose a novel relaying scheme which improves the spectral efficiency of cooperative diversity systems by utilizing limited feedback from destination. Our scheme capitalizes on the fact that relaying is only required when direct transmission suffers deep fading. We calculate the packet error rate for the proposed efficient incremental relaying scheme with both amplify and forward and decode and forward relaying. Numerical results are also presented to verify their analytical counterparts. © 2013 IEEE.

  19. Relevance of splenic tissue preservation to bacteria phagocytosis; Importancia da preservacao de tecido esplenico para a fagocitose bacteriana

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Ruy Garcia [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Faculdade de Ciencias Medicas. Dept. de Cirurgia Geral]. E-mail: rmarques@uerj.br; Petroianu, Andy [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Dept. de Cirurgia; Oliveira, Marcia Betania Nunes de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab.de Radiofarmacia; Bernardo Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria

    2002-07-01

    Objective: Being the major lymphoid organ of human body, spleen performs critical immunological functions such as bacteria depuration from bloodstream and precocious antibody production against various antigenic particles. Spleen, liver and lung accounts for more than 95% of phagocytic activity in humans. Methods: We used intravenous inoculation of Escherichia coli AB 1157 in Wistar rats in order to evaluate this function. Young and adult rats of both sexes were submitted to total splenectomy and compared to animals not submitted to any surgical procedure. Sixteen weeks later, rats of both groups were challenged with a suspension of E. coli labeled with Tc-{sup 99}m, and, after twenty minutes, they were killed. Liver, lung, spleen and a blood clot sample were removed for radioactivity determination. The statistical study was performed with Student.s t test. Results: There were no significant differences in the radioactivity uptake obtained from young and adult splenectomized rats. However, these rats were associated with higher levels of blood counts than animals of the control group (p<0.0001) due to a larger bacteria remnant in the bloodstream. Conclusion: This finding suggests that some failure in mononuclear phagocytic system occurs in spleen absence adaptation, ratifying the necessity of development of alternative surgical techniques to total splenectomy in patients requiring spleen removal. (author)

  20. FcγRII-binding Centyrins mediate agonism and antibody-dependent cellular phagocytosis when fused to an anti-OX40 antibody.

    Science.gov (United States)

    Zhang, Di; Whitaker, Brian; Derebe, Mehabaw G; Chiu, Mark L

    2018-04-01

    Immunostimulatory antibodies against the tumor necrosis factor receptors (TNFR) are emerging as promising cancer immunotherapies. The agonism activity of such antibodies depends on crosslinking to Fc gamma RIIB receptor (FcγRIIB) to enable the antibody multimerization that drives TNFR activation. Previously, Fc engineering was used to enhance the binding of such antibodies to Fcγ receptors. Here, we report the identification of Centyrins as alternative scaffold proteins with binding affinities to homologous FcγRIIB and FcγRIIA, but not to other types of Fcγ receptors. One Centyrin, S29, was engineered at distinct positions of an anti-OX40 SF2 antibody to generate bispecific and tetravalent molecules named as mAbtyrins. Regardless of the position of S29 on the SF2 antibody, SF2-S29 mAbtyrins could bind FcγRIIB and FcγRIIA specifically while maintaining binding to OX40 receptors. In a NFκB reporter assay, attachment of S29 Centyrin molecules at the C-termini, but not the N-termini, resulted in SF2 antibodies with increased agonism owing to FcγRIIB crosslinking. The mAbtyrins also showed agonism in T-cell activation assays with immobilized FcγRIIB and FcγRIIA, but this activity was confined to mAbtyrins with S29 specifically at the C-termini of antibody heavy chains. Furthermore, regardless of the position of the molecule, S29 Centyrin could equip an otherwise Fc-silent antibody with antibody-dependent cellular phagocytosis activity without affecting the antibody's intrinsic antibody-dependent cell-meditated cytotoxicity and complement-dependent cytotoxicity. In summary, the appropriate adoption FcγRII-binding Centyrins as functional modules represents a novel strategy to engineer therapeutic antibodies with improved functionalities.

  1. Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis.

    Science.gov (United States)

    Ashraf, S Q; Umana, P; Mössner, E; Ntouroupi, T; Brünker, P; Schmidt, C; Wilding, J L; Mortensen, N J; Bodmer, W F

    2009-11-17

    The effect of glycoengineering a membrane specific anti-carcinoembryonic antigen (CEA) (this paper uses the original term CEA for the formally designated CEACAM5) antibody (PR1A3) on its ability to enhance killing of colorectal cancer (CRC) cell lines by human immune effector cells was assessed. In vivo efficacy of the antibody was also tested. The antibody was modified using EBNA cells cotransfected with beta-1,4-N-acetylglucosaminyltransferase III and the humanised hPR1A3 antibody genes. The resulting alteration of the Fc segment glycosylation pattern enhances the antibody's binding affinity to the FcgammaRIIIa receptor on human immune effector cells but does not alter the antibody's binding capacity. Antibody-dependent cellular cytotoxicity (ADCC) is inhibited in the presence of anti-FcgammaRIII blocking antibodies. This glycovariant of hPR1A3 enhances ADCC 10-fold relative to the parent unmodified antibody using either unfractionated peripheral blood mononuclear or natural killer (NK) cells and CEA-positive CRC cells as targets. NK cells are far more potent in eliciting ADCC than either freshly isolated monocytes or granulocytes. Flow cytometry and automated fluorescent microscopy have been used to show that both versions of hPR1A3 can induce antibody-dependent cellular phagocytosis (ADCP) by monocyte-derived macrophages. However, the glycovariant antibody did not mediate enhanced ADCP. This may be explained by the relatively low expression of FcgammaRIIIa on cultured macrophages. In vivo studies show the efficacy of glycoengineered humanised IgG1 PR1A3 in significantly improving survival in a CRC metastatic murine model. The greatly enhanced in vitro ADCC activity of the glycoengineered version of hPR1A3 is likely to be clinically beneficial.

  2. Treatment of serum with supernatants from cultures of Candida albicans reduces its serum-dependent phagocytosis Tratamento de soro com sobrenadante de cultura de Candida albicans reduz a fagocitose soro-dependente

    Directory of Open Access Journals (Sweden)

    Aderbal Antonio dos Santos

    2002-01-01

    Full Text Available Candida albicans is a potent activator of the complement system, and heat labile opsonins produced by activation of C3 (C3b and iC3b enhance phagocytosis of C. albicans mediated by complement receptors. In this study we treated mouse serum with supernatants from cultures of a protease producer strain of C. albicans and evaluated the ability of this serum to enhance phagocytosis of C. albicans. Cell-free supernatants from cultures of C. albicans were concentrated 5 fold and added to mouse serum for 30 min at 37ºC, before using this serum for opsonization of glutaraldehyde-fixed yeast cells. We observed that normal mouse serum increased about 3 fold the phagocytosis of C. albicans by mice peritoneal macrophages, whereas supernatant-treated serum did not increase phagocytosis. This effect of supernatants on serum was prevented by addition of pepstatin (5 µg/ ml; an inhibitor of C. albicans acid proteases to the medium. Serum treated with supernatants from cultures of a protease-deficient mutant of C. albicans also increased about 3 fold phagocytosis of the yeast. These results suggest that a protease produced by C. albicans causes proteolysis of serum opsonins, thereby reducing the phagocytosis of the yeast.Candida albicans é um potente ativador do sistema complemento, e opsoninas lábeis ao calor produzidas por ativação de C3 (C3b e iC3b aumentam a fagocitose de C. albicans mediada por receptores de complemento. Neste estudo, tratamos o soro de camundongo com sobrenadante de culturas de uma cepa de C. albicans produtora de proteases e avaliamos a capacidade deste soro reduzir a fagocitose de C. albicans. Sobrenadantes livres de células obtidos de cultura de C. albicans foram concentrados 5 vezes e adicionados ao soro de camundongo por 30 minutos a 37ºC, antes deste soro ser usado para opsonização de C. albicans na forma de levedura e fixadas em glutaraldeido. Nós observamos que soro normal aumentou 3 vezes a fagocitose de C. albicans por

  3. Batch efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Schwickerath, Ulrich; Silva, Ricardo; Uria, Christian, E-mail: Ulrich.Schwickerath@cern.c, E-mail: Ricardo.Silva@cern.c [CERN IT, 1211 Geneve 23 (Switzerland)

    2010-04-01

    A frequent source of concern for resource providers is the efficient use of computing resources in their centers. This has a direct impact on requests for new resources. There are two different but strongly correlated aspects to be considered: while users are mostly interested in a good turn-around time for their jobs, resource providers are mostly interested in a high and efficient usage of their available resources. Both things, the box usage and the efficiency of individual user jobs, need to be closely monitored so that the sources of the inefficiencies can be identified. At CERN, the Lemon monitoring system is used for both purposes. Examples of such sources are poorly written user code, inefficient access to mass storage systems, and dedication of resources to specific user groups. As a first step for improvements CERN has launched a project to develop a scheduler add-on that allows careful overloading of worker nodes that run idle jobs.

  4. Fuzzy efficiency without convexity

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Balezentis, Tomas

    2014-01-01

    approach builds directly upon the definition of Farrell's indexes of technical efficiency used in crisp FDH. Therefore we do not require the use of fuzzy programming techniques but only utilize ranking probabilities of intervals as well as a related definition of dominance between pairs of intervals. We...

  5. Stages of in vitro phagocytosis of Plasmodium falciparum-infected erythrocytes by human monocytes Estágios da fagocitose in vitro por monócitos humanos de eritrócitos infectados por Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Maria Imaculada Muniz-Junqueira

    2009-04-01

    Full Text Available Monocytes/macrophages play a critical role in the defense mechanisms against malaria parasites, and are the main cells responsible for the elimination of malaria parasites from the blood circulation. We carried out a microscope-aided evaluation of the stages of in vitro phagocytosis of Plasmodium falciparum-infected erythrocytes, by human monocytes. These cells were obtained from healthy adult individuals by means of centrifugation through a cushion of Percoll density medium and were incubated with erythrocytes infected with Plasmodium falciparum that had previously been incubated with a pool of anti-plasmodial immune serum. We described the stages of phagocytosis, starting from adherence of infected erythrocytes to the phagocyte membrane and ending with their destruction within the phagolisosomes of the monocytes. We observed that the different erythrocytic forms of the parasite were ingested by monocytes, and that the process of phagocytosis may be completed in around 30 minutes. Furthermore, we showed that phagocytosis may occur continuously, such that different phases of the process were observed in the same phagocyte.Monócitos/macrófagos desempenham uma função crítica nos mecanismos de defesa antiplasmódio e constituem as principais células responsáveis pela eliminação das formas eritrocitárias do plasmódio da circulação sangüínea. Realizamos uma avaliação microscópica dos estágios da fagocitose in vitro de eritrócitos infectados por Plasmodium falciparum por monócitos humanos. Essas células foram obtidas de indivíduos adultos sadios por centrifugação em Percoll e incubadas com eritrócitos infectados por Plasmodium falciparum previamente incubados com um pool de soro imune contra plasmódio. Descrevemos os estágios da fagocitose, desde a aderência dos eritrócitos infectados até sua destruição nos fagolisossomas dos monócitos. Observou-se que eritrócitos infectados por todos os diferentes est

  6. Bovine S protein (vitronectin increases phagocytosis of Streptococcus dysgalactiae Aumento na fagocitose de Streptococcus dysgalactiae pela ação da proteína S bovina (vitronectina

    Directory of Open Access Journals (Sweden)

    Laerte Francisco Filippsen

    1999-01-01

    Full Text Available The effects of bovine S protein (vitronectin on phagocytosis of Streptococcus dysgalactiae strains isolated from cattle with mastitis were investigated. Phagocytized streptococci were determined by a fluorometric microassay using glass adherent polymorphonuclear neutrophils (PMN. Preincubation of S. dysgalactiae with bovine S protein significantly increased their phagocytosis by PMN. Bovine S protein had no effect on phagocytic killing of non-S protein binding S. pyogenes cultures. Enzymatic digestion of the bovine S protein binding sites on S. dysgalactiae with pronase resulted in a significative reduction of the effects of S protein on phagocytosis. It could thus be concluded that in addition to its role as a promoter of cellular adhesion and complement inhibitor, bovine S protein may also influence the phagocytosis of S. dysgalactiae during inflammatory processes.Foram investigados os efeitos da proteína S bovina (vitronectina na fagocitose de amostras de Streptococcus dysgalactiae isoladas de bovinos com mastite. A determinação do número de estreptococos fagocitados foi realizada pelo método fluorométrico utilizando neutrófilos polimorfonucleares (NPM aderidos em lâminas de vidro. A pré-incubação do S. dysgalactiae com a proteína S bovina aumentou significativamente a sua fagocitose por NPM. A proteína S bovina não causou efeito na fagocitose de culturas de S. pyogenes, já que não apresentam sítios de ligação para esta proteína. A digestão enzimática com pronase dos sítios de ligação S. dysgalactiae para a proteína S bovina resultou numa significativa redução do efeito da proteína S na fagocitose. Pode-se concluir que além do papel como promotor da adesão celular e inibidor do complemento, a proteína S bovina pode também influir na fagocitose do S. dysgalactiae durante os processos inflamatórios.

  7. Phagocytosis of haemozoin (malarial pigment enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE

    Directory of Open Access Journals (Sweden)

    Giribaldi Giuliana

    2008-08-01

    Full Text Available Abstract Background It has been shown previously that human monocytes fed with haemozoin (HZ or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9 enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects. Methods Native HZ freshly isolated from Plasmodium falciparum (Palo Alto strain, Mycoplasma-free, delipidized HZ, beta-haematin (lipid-free synthetic HZ, trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting. Results Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants and protein/mRNA expression (in cell lysates of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R-hydroxy-6,8,11,13-eicosatetraenoic acid a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator

  8. Non-immune binding of human IgG to M-related proteins confers resistance to phagocytosis of group A streptococci in blood.

    Directory of Open Access Journals (Sweden)

    Harry S Courtney

    Full Text Available The non-immune binding of immunoglobulins by bacteria is thought to contribute to the pathogenesis of infections. M-related proteins (Mrp are group A streptococcal (GAS receptors for immunoglobulins, but it is not known if this binding has any impact on virulence. To further investigate the binding of immunoglobulins to Mrp, we engineered mutants of an M type 4 strain of GAS by inactivating the genes for mrp, emm, enn, sof, and sfbX and tested these mutants in IgG-binding assays. Inactivation of mrp dramatically decreased the binding of human IgG, whereas inactivation of emm, enn, sof, and sfbx had only minor effects, indicating that Mrp is a major IgG-binding protein. Binding of human immunoglobulins to a purified, recombinant form of Mrp indicated that it selectively binds to the Fc domain of human IgG, but not IgA or IgM and that it preferentially bound subclasses IgG₁>IgG₄>IgG₂>IgG₃. Recombinant proteins encompassing different regions of Mrp were engineered and used to map its IgG-binding domain to its A-repeat region and a recombinant protein with 3 A-repeats was a better inhibitor of IgG binding than one with a single A-repeat. A GAS mutant expressing Mrp with an in-frame deletion of DNA encoding the A-repeats had a dramatically reduced ability to bind human IgG and to grow in human blood. Mrp exhibited host specificity in binding IgG; human IgG was the best inhibitor of the binding of IgG followed by pig, horse, monkey, and rabbit IgG. IgG from goat, mouse, rat, cow, donkey, chicken, and guinea pig were poor inhibitors of binding. These findings indicate that Mrp preferentially binds human IgG and that this binding contributes to the ability of GAS to resist phagocytosis and may be a factor in the restriction of GAS infections to the human host.

  9. Trichoderma asperelloides Spores Downregulate dectin1/2 and TLR2 Receptors of Mice Macrophages and Decrease Candida parapsilosis Phagocytosis Independent of the M1/M2 Polarization

    Directory of Open Access Journals (Sweden)

    Andréa G. dos Santos

    2017-09-01

    Full Text Available The intensive use of pesticides to control pests in agriculture has promoted several issues relating to environment. As chemical pesticides remain controversial, biocontrol agents originating from fungi could be an alternative. Among them, we highlight biocontrol agents derived from the fungi genus Trichoderma, which have been documented in limiting the growth of other phytopathogenic fungus in the roots and leaves of several plant species. An important member of this genus is Trichoderma asperelloides, whose biocontrol agents have been used to promote plant growth while also treating soil diseases caused by microorganisms in both greenhouses and outdoor crops. To evaluate the safety of fungal biological agents for human health, tests to detect potentially adverse effects, such as allergenicity, toxicity, infectivity and pathogenicity, are crucial. In addition, identifying possible immunomodulating properties of fungal biocontrol agents merits further investigation. Thus, the aim of this study was to evaluate the effects of T. asperelloides spores in the internalization of Candida parapsilosis yeast by mice phagocytes, in order to elucidate the cellular and molecular mechanism of this interaction, as a model to understand possible in vivo effects of this fungus. For this, mice were exposed to a fungal spore suspension through-intraperitoneal injection, euthanized and cells from the peripheral blood and peritoneal cavity were collected for functional, quantitative and phenotypic analysis, throughout analysis of membrane receptors gene expression, phagocytosis ability and cells immunophenotyping M1 (CCR7 and CD86 and M2 (CCR2 and CD206. Our analyses showed that phagocytes exposed to fungal spores had reduced phagocytic capacity, as well as a decrease in the quantity of neutrophils and monocytes in the peripheral blood and peritoneal cavity. Moreover, macrophages exposed to T. asperelloides spores did not display the phenotypic profile M1/M2, and

  10. Phagocytosis and Epithelial Cell Invasion by Crohn’s Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine

    Directory of Open Access Journals (Sweden)

    Federica Migliore

    2018-05-01

    Full Text Available Adherent-invasive Escherichia coli (AIEC strains are overrepresented in the dysbiotic microbiota of Crohn’s disease (CD patients, and contribute to the onset of the chronic inflammation typical of the disease. However, the effects of anti-inflammatory drugs used for CD treatment on AIEC virulence have not yet been investigated. In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells. Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages. Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells. To this aim, we grew LF82 in the presence of glucose, which leads to inhibition of cAMP synthesis. Growth in glucose-supplemented medium resulted in a reduction in AIEC adhesion to epithelial cells and uptake by macrophages. Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli. In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells. To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides. 6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC. Our results provide strong evidence

  11. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients.

    Science.gov (United States)

    Petricevic, Branka; Laengle, Johannes; Singer, Josef; Sachet, Monika; Fazekas, Judit; Steger, Guenther; Bartsch, Rupert; Jensen-Jarolim, Erika; Bergmann, Michael

    2013-12-12

    Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena. We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS). ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells. The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to

  12. Consequences of the quota requirement for energy efficiency. Can a Swedish quota obligation systems give less energy usage?; Konsekvenser av kvotplikt foer energieffektivisering. Kan ett svenskt kvotpliktssystem ge mindre energianvaendning?

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerkroth, Sara; Bladh, Mats; Holmberg, Rurik; Lock, Anna; Naderi, Ronak; Widerstroem, Glenn

    2012-11-01

    The Agency has on behalf of the government investigated what the consequences would be of the introduction of a compulsory quota system in Sweden. Under the proposed new EU directive on energy efficiency, all Member States should introduce a compulsory quota system, where energy companies actively initiate measures for energy efficiency among end users. In Sweden, a quota obligation system of this kind would mean energy efficiency of about 3 TWh per year, which can be difficult to achieve. The Swedish Energy Agency suggests that if a compulsory quota system is introduced, the quota obligation should be placed on the network companies. If not, there is a risk of complications in the Swedish and Nordic electricity market. The Energy Markets Inspectorate consider that the quota obligation can not be on the network companies because of their function as regulated monopoly. The Swedish Energy Agency suggests that efficiency measures can be implemented in all sectors, including transport.

  13. National energy efficiency programme

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper focusses on energy conservation and specifically on energy efficiency which includes efficiency in the production, delivery and utilisation of energy as part of the total energy system of the economy. A National Energy Efficiency Programme is being launched in the Eighth Plan that will take into account both macro level and policy and planning considerations as well as micro level responses for different category of users in the industry, agriculture, transport and domestic sectors. The need for such a National Energy Efficiency Programme after making an assessment of existing energy conservation activities in the country is discussed. The broad framework and contents of the National Energy Efficiency Programme have been outlined and the Eighth Plan targets for energy conservation and their break-up have been given. These targets, as per the Eighth Plan document are 5000 MW in electricity installed capacity and 6 million tonnes of petroleum products by the terminal year of the Eighth Plan. The issues that need to be examined for each sector for achieving the above targets for energy conservation in the Eighth Plan are discussed briefly. They are: (a) policy and planning, (b) implementation arrangements which include the institutional setup and selective legislation, (c) technological requirements, and (d) resource requirements which include human resources and financial resources. (author)

  14. From energy efficiency towards resource efficiency within the Ecodesign Directive

    DEFF Research Database (Denmark)

    Bundgaard, Anja Marie; Mosgaard, Mette; Remmen, Arne

    2017-01-01

    on the most significant environmental impact has often resulted in a focus on energy efficiency in the use phase. Therefore, the Ecodesign Directive should continue to target resource efficiency aspects but also consider environ- mental aspects with a large improvement potential in addition to the most...... significant environmental impact. For the introduction of resource efficiency requirements into the Ecodesign Directive, these requirements have to be included in the preparatory study. It is therefore recommended to broaden the scope of the Methodology for the Ecodesign of Energy-related products and the Eco......The article examines the integration of resource efficiency into the European Ecodesign Directive. The purpose is to analyse the processes and stakeholder interactions, which formed the basis for integrating resource efficiency requirements into the implementing measure for vacuum cleaners...

  15. Financing Energy Efficient Homes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    Existing buildings require over 40% of the world's total final energy consumption, and account for 24% of world CO2 emissions (IEA, 2006). Much of this consumption could be avoided through improved efficiency of building energy systems (IEA, 2006) using current, commercially-viable technology. In most cases, these technologies make economic sense on a life-cycle cost analysis (IEA, 2006b). Moreover, to the extent that they reduce dependence on risk-prone fossil energy sources, energy efficient technologies also address concerns of energy security.

  16. Financing Energy Efficient Homes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    Existing buildings require over 40% of the world's total final energy consumption, and account for 24% of world CO2 emissions (IEA, 2006). Much of this consumption could be avoided through improved efficiency of building energy systems (IEA, 2006) using current, commercially-viable technology. In most cases, these technologies make economic sense on a life-cycle cost analysis (IEA, 2006b). Moreover, to the extent that they reduce dependence on risk-prone fossil energy sources, energy efficient technologies also address concerns of energy security.

  17. Environmental Requirements Management

    Energy Technology Data Exchange (ETDEWEB)

    Cusack, Laura J.; Bramson, Jeffrey E.; Archuleta, Jose A.; Frey, Jeffrey A.

    2015-01-08

    CH2M HILL Plateau Remediation Company (CH2M HILL) is the U.S. Department of Energy (DOE) prime contractor responsible for the environmental cleanup of the Hanford Site Central Plateau. As part of this responsibility, the CH2M HILL is faced with the task of complying with thousands of environmental requirements which originate from over 200 federal, state, and local laws and regulations, DOE Orders, waste management and effluent discharge permits, Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) response and Resource Conservation and Recovery Act (RCRA) corrective action documents, and official regulatory agency correspondence. The challenge is to manage this vast number of requirements to ensure they are appropriately and effectively integrated into CH2M HILL operations. Ensuring compliance with a large number of environmental requirements relies on an organization’s ability to identify, evaluate, communicate, and verify those requirements. To ensure that compliance is maintained, all changes need to be tracked. The CH2M HILL identified that the existing system used to manage environmental requirements was difficult to maintain and that improvements should be made to increase functionality. CH2M HILL established an environmental requirements management procedure and tools to assure that all environmental requirements are effectively and efficiently managed. Having a complete and accurate set of environmental requirements applicable to CH2M HILL operations will promote a more efficient approach to: • Communicating requirements • Planning work • Maintaining work controls • Maintaining compliance

  18. Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells.

    Science.gov (United States)

    Tóth, Beáta; Garabuczi, Eva; Sarang, Zsolt; Vereb, György; Vámosi, György; Aeschlimann, Daniel; Blaskó, Bernadett; Bécsi, Bálint; Erdõdi, Ferenc; Lacy-Hulbert, Adam; Zhang, Ailiang; Falasca, Laura; Birge, Raymond B; Balajthy, Zoltán; Melino, Gerry; Fésüs, László; Szondy, Zsuzsa

    2009-02-15

    Transglutaminase 2 (TG2), a protein cross-linking enzyme with many additional biological functions, acts as coreceptor for integrin beta(3). We have previously shown that TG2(-/-) mice develop an age-dependent autoimmunity due to defective in vivo clearance of apoptotic cells. Here we report that TG2 on the cell surface and in guanine nucleotide-bound form promotes phagocytosis. Besides being a binding partner for integrin beta(3), a receptor known to mediate the uptake of apoptotic cells via activating Rac1, we also show that TG2 binds MFG-E8 (milk fat globulin EGF factor 8), a protein known to bridge integrin beta(3) to apoptotic cells. Finally, we report that in wild-type macrophages one or two engulfing portals are formed during phagocytosis of apoptotic cells that are characterized by accumulation of integrin beta(3) and Rac1. In the absence of TG2, integrin beta(3) cannot properly recognize the apoptotic cells, is not accumulated in the phagocytic cup, and its signaling is impaired. As a result, the formation of the engulfing portals, as well as the portals formed, is much less efficient. We propose that TG2 has a novel function to stabilize efficient phagocytic portals.

  19. Energy efficiency policies and measures

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This document makes a review of the energy efficiency and demand side management (DSM) policies and measures in European Union countries and Norway in 1999: institutional changes, measures and programmes, budget, taxation, existence of a national DSM programme, national budgets for DSM programmes, electricity pricing: energy/environment tax, national efficiency standards and regulation for new electrical appliances, implementation of Commission directives, efficiency requirements, labelling, fiscal and economic incentives. (J.S.)

  20. Offsetting efficiency

    International Nuclear Information System (INIS)

    Katz, M.

    1995-01-01

    Whichever way the local distribution company (LDC) tries to convert residential customers to gas or expand their use of it, the process itself has become essential for the natural gas industry. The amount of gas used by each residential customer has been decreasing for 25 years -- since the energy crisis of the early 1970s. It's a direct result of better-insulated homes and more-efficient gas appliances, and that trend is continuing. So, LDCs have a choice of either finding new users and uses for gas, or recognizing that their throughput per customer is going to continue declining. The paper discusses strategies that several gas utilities are using to increase the number of gas appliances in the customer's homes. These and other strategies keep the gas industry optimistic about the future of the residential market: A.G.A. has projected that by 2010 demand will expand, from 1994's 5.1 quadrillion Btu (quads) to 5.7 quads, even with continued improvements in appliance efficiency. That estimate, however, will depend on the industry-s utilities and whether they keep converting, proselytizing, persuading and influencing customers to use more natural gas

  1. Efficient Learning Design

    DEFF Research Database (Denmark)

    Godsk, Mikkel

    This paper presents the current approach to implementing educational technology with learning design at the Faculty of Science and Technology, Aarhus University, by introducing the concept of ‘efficient learning design’. The underlying hypothesis is that implementing learning design is more than...... engaging educators in the design process and developing teaching and learning, it is a shift in educational practice that potentially requires a stakeholder analysis and ultimately a business model for the deployment. What is most important is to balance the institutional, educator, and student...... perspectives and to consider all these in conjunction in order to obtain a sustainable, efficient learning design. The approach to deploying learning design in terms of the concept of efficient learning design, the catalyst for educational development, i.e. the learning design model and how it is being used...

  2. Measuring efficiency in logistics

    Directory of Open Access Journals (Sweden)

    Milan Milovan Andrejić

    2013-06-01

    Full Text Available Dynamic market and environmental changes greatly affect operating of logistics systems. Logistics systems have to realize their activities and processes in an efficient way. The main objective of this paper is to analyze different aspects of efficiency measurement in logistics and to propose appropriate models of measurement. Measuring efficiency in logistics is a complex process that requires consideration of all subsystems, processes and activities as well as the impact of various financial, operational, environmental, quality and other factors. The proposed models have a basis in the Data Envelopment Analysis method. They could help managers in decision making and corrective actions processes. The tests and results of the model show the importance of input and output variables selection.

  3. The effect of various antibiotics on the labelling efficiency of human white blood cells with 111In-oxine

    International Nuclear Information System (INIS)

    Sinzinger, Helmut; Granegger, Susanne

    1988-01-01

    Earlier clinical studies revealed that in patients suffering from chronic osteomyelitis undergoing antibiotic therapy the white blood cell scanning missed the right diagnosis in 40% of cases, whereas all the acute untreated cases were imaged correctly. Thus, it was suspected that an impaired labelling efficiency and white blood cell function might have been causative. Retrospective analysis of labelling efficiency exhibited no difference between patients on antibiotics and those not on antibiotics. Prospective cellular viability testing in 81 patients, 71 of whom were on various antibiotics, using latex particles (phagocytosis) and the Trypan blue exclusion test, did not reveal any different function behaviour either. Examining the labelling efficiency (after 111 In-oxine and 111 In-oxine-sulphate labelling), recovery, half-life and viability of white blood cells of 107 patients undergoing therapy with various antibiotics as compared to controls, it becomes evident that the antibiotic therapy is not causative of the clinical difference observed. (author)

  4. Software requirements

    CERN Document Server

    Wiegers, Karl E

    2003-01-01

    Without formal, verifiable software requirements-and an effective system for managing them-the programs that developers think they've agreed to build often will not be the same products their customers are expecting. In SOFTWARE REQUIREMENTS, Second Edition, requirements engineering authority Karl Wiegers amplifies the best practices presented in his original award-winning text?now a mainstay for anyone participating in the software development process. In this book, you'll discover effective techniques for managing the requirements engineering process all the way through the development cy

  5. Energy efficiency in pumps

    Energy Technology Data Exchange (ETDEWEB)

    Kaya, Durmus; Yagmur, E. Alptekin [TUBITAK-MRC, P.O. Box 21, 41470 Gebze, Kocaeli (Turkey); Yigit, K. Suleyman; Eren, A. Salih; Celik, Cenk [Engineering Faculty, Kocaeli University, Kocaeli (Turkey); Kilic, Fatma Canka [Department of Air Conditioning and Refrigeration, Kocaeli University, Kullar, Kocaeli (Turkey)

    2008-06-15

    In this paper, ''energy efficiency'' studies, done in a big industrial facility's pumps, are reported. For this purpose; the flow rate, pressure and temperature have been measured for each pump in different operating conditions and at maximum load. In addition, the electrical power drawn by the electric motor has been measured. The efficiencies of the existing pumps and electric motor have been calculated by using the measured data. Potential energy saving opportunities have been studied by taking into account the results of the calculations for each pump and electric motor. As a conclusion, improvements should be made each system. The required investment costs for these improvements have been determined, and simple payback periods have been calculated. The main energy saving opportunities result from: replacements of the existing low efficiency pumps, maintenance of the pumps whose efficiencies start to decline at certain range, replacements of high power electric motors with electric motors that have suitable power, usage of high efficiency electric motors and elimination of cavitation problems. (author)

  6. Energy efficiency in pumps

    International Nuclear Information System (INIS)

    Kaya, Durmus; Yagmur, E. Alptekin; Yigit, K. Suleyman; Kilic, Fatma Canka; Eren, A. Salih; Celik, Cenk

    2008-01-01

    In this paper, 'energy efficiency' studies, done in a big industrial facility's pumps, are reported. For this purpose; the flow rate, pressure and temperature have been measured for each pump in different operating conditions and at maximum load. In addition, the electrical power drawn by the electric motor has been measured. The efficiencies of the existing pumps and electric motor have been calculated by using the measured data. Potential energy saving opportunities have been studied by taking into account the results of the calculations for each pump and electric motor. As a conclusion, improvements should be made each system. The required investment costs for these improvements have been determined, and simple payback periods have been calculated. The main energy saving opportunities result from: replacements of the existing low efficiency pumps, maintenance of the pumps whose efficiencies start to decline at certain range, replacements of high power electric motors with electric motors that have suitable power, usage of high efficiency electric motors and elimination of cavitation problems

  7. Efficient STFT

    International Nuclear Information System (INIS)

    Aamir, K.M.; Maud, M.A.

    2004-01-01

    Small perturbations in signals (or any time series), at some particular instant, affect the whole frequency spectrum due to the global function e/sup j omega t/ in Fourier Transform formulation. However, the Fourier spectrum does not convey the time instant at which the perturbation occurred. Consequently the information on the particular time instance of occurrence of that perturbation is lost when spectrum is observed. Apparently Fourier analysis seems to be inadequate in such situations. This inadequacy is overcome by the use of Short Time Fourier Transform (STFT), which keeps track of time as well as frequency information. In STFT analysis, a fixed length window, say of length N, is moved sample by sample as the data arrives. The Discrete Fourier Transform (DFT) of this fixed window of length N is calculated using Fast Fourier Transform (FFT) algorithm. If the total number of points is M > N, the computational complexity of this scheme works out to be at least ((M-N) N log/sub 2/N). On the other hand, STFT is shown to be of computational complexity 6NM and 8NM in the literature. In this paper, two algorithms are presented which compute the same STFT more efficiently. The computational complexity of the proposed algorithms works out to be MN of one algorithm and even lesser in the other algorithm. This reduction in complexity becomes significant for large data sets. This algorithm also remains valid if a stationary part of signal is skipped. (author)

  8. Phagocytosis and production of reactive oxygen species by peripheral blood phagocytes in patients with different stages of alcohol-induced liver disease: effect of acute exposure to low ethanol concentrations

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Paulus, S. B.

    2003-01-01

    BACKGROUND: In rodents, the development of alcoholic liver disease (ALD) after chronic alcohol feeding was shown to depend on the activity of enzymes that are necessary for production of reactive oxygen species (ROS) in phagocytes. The aim of this study was to determine the formation of ROS...... by resting and challenged phagocytes of patients with different stages of ALD in the presence of ethanol concentrations commonly found in the blood of alcohol abusers. PATIENTS AND METHODS: The release of ROS and the phagocytosis of bacteria by neutrophils and monocytes obtained from 60 patients, who were...... produced significantly more ROS than those of healthy controls. Basal values of ROS production from neutrophils correlated closely to markers of the severity of ALD. ROS formation was depressed dose-dependently by ethanol in the healthy controls but not in alcohol abusers. CONCLUSIONS: Changes in the ROS...

  9. National Action Plan for Energy Efficiency Report

    Energy Technology Data Exchange (ETDEWEB)

    National Action Plan for Energy Efficiency

    2006-07-01

    Summarizes recommendations, key barriers, and methods for energy efficiency in utility ratemaking as well as revenue requirements, resource planning processes, rate design, and program best practices.

  10. Energy efficiency; Energieffektivisering

    Energy Technology Data Exchange (ETDEWEB)

    2009-06-15

    The Low Energy Panel will halve the consumption in buildings. The Panel has proposed a halving of consumption in the construction within 2040 and 20 percent reduction in the consumption in the industry within 2020. The Panel consider it as possible to gradually reduce consumption in buildings from the current level of 80 TWh with 10 TWh in 2020, 25 TWh in 2030 and 40 TWh in 2040. According the committee one such halving can be reached by significant efforts relating to energy efficiency, by greater rehabilitations, energy efficiency in consisting building stock and stricter requirements for new construction. For the industry field the Panel recommend a political goal to be set at least 20 percent reduction in specific energy consumption in the industry and primary industry beyond general technological development by the end of 2020. This is equivalent to approximately 17 TWh based on current level of activity. The Panel believes that a 5 percent reduction should be achieved by the end of 2012 by carrying out simple measures. The Low Energy Panel has since March 2009 considered possibilities to strengthen the authorities' work with energy efficiency in Norway. The wide complex panel adds up proposals for a comprehensive approach for increased energy efficiency in particular in the building- and industry field. The Panel has looked into the potential for energy efficiency, barriers for energy efficiency, assessment of strengths and weaknesses in the existing policy instruments and members of the Panel's recommendations. In addition the report contains a review of theoretical principles for effects of instruments together with an extensive background. One of the committee members have chosen to take special notes on the main recommendations in the report. (AG)

  11. An Assessment of the IMEF Depot-Level Corrosion Prevention and Control Program and the Viability of Making it More Efficient and/or Outsourcing the Requirements through Private Sector Initiatives

    Science.gov (United States)

    2002-12-01

    as follows, with A being the simplest and C being the most inclusive: • Category A: Surface preparation, paint and undercoating; no bodywork . (This... bodywork due to the corrosion replacement or repair of corroded components such as door, battery boxes, or fenders with time of work not to exceed...8 hours. • Category C: Includes everything listed in category B in addition to some component disassembly required to treat corrosion. Bodywork

  12. Contribution to the Task 4.3.1 investigate how training should be planned to ensure efficient utilization of OSS. Task 4.3.2 evaluate how the introduction of OSS influences requirements to the basic education of the operator

    International Nuclear Information System (INIS)

    Balducelli, C.

    1995-01-01

    The introduction of computerized supports to improve efficiency in the activity of an intelligent agent (the operator in NPP case) increases the agent training demand. In fact also the informatic support can be viewed as an ''artificial agent'', more or less ''active'' depending on its internal degree of autonomy: the human agent needs to be trained to ''coordinate'' his behaviour with the behaviour of the artificial agent. The basic idea of this work is that a more safe, complete and integrated OSS could be a system (an artificial agent) that gives support to the human agent not only during the plant real operations, but also during the different phases of operator education and training for normal and emergency situations management. 7 refs, 2 figs

  13. Higher Efficiency HVAC Motors

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, Charles Joseph [QM Power, Inc., Kansas City, MO (United States)

    2018-02-13

    The objective of this project was to design and build a cost competitive, more efficient heating, ventilation, and air conditioning (HVAC) motor than what is currently available on the market. Though different potential motor architectures among QMP’s primary technology platforms were investigated and evaluated, including through the building of numerous prototypes, the project ultimately focused on scaling up QM Power, Inc.’s (QMP) Q-Sync permanent magnet synchronous motors from available sub-fractional horsepower (HP) sizes for commercial refrigeration fan applications to larger fractional horsepower sizes appropriate for HVAC applications, and to add multi-speed functionality. The more specific goal became the research, design, development, and testing of a prototype 1/2 HP Q-Sync motor that has at least two operating speeds and 87% peak efficiency compared to incumbent electronically commutated motors (EC or ECM, also known as brushless direct current (DC) motors), the heretofore highest efficiency HVACR fan motor solution, at approximately 82% peak efficiency. The resulting motor prototype built achieved these goals, hitting 90% efficiency and .95 power factor at full load and speed, and 80% efficiency and .7 power factor at half speed. Q-Sync, developed in part through a DOE SBIR grant (Award # DE-SC0006311), is a novel, patented motor technology that improves on electronically commutated permanent magnet motors through an advanced electronic circuit technology. It allows a motor to “sync” with the alternating current (AC) power flow. It does so by eliminating the constant, wasteful power conversions from AC to DC and back to AC through the synthetic creation of a new AC wave on the primary circuit board (PCB) by a process called pulse width modulation (PWM; aka electronic commutation) that is incessantly required to sustain motor operation in an EC permanent magnet motor. The Q-Sync circuit improves the power factor of the motor by removing all

  14. EFFECT OF DRY COW THERAPY DRUGS ON PHAGOCYTOSIS RATES EFEITO DE MEDICAMENTOS INDICADOS PARA O TRATAMENTO DE MASTITE BOVINA NO PERÍODO SECO SOBRE OS ÍNDICES DE FAGOCITOSE

    Directory of Open Access Journals (Sweden)

    Alice Maria Melville Paiva Della Libera

    2009-07-01

    Full Text Available The dry period is considered to be a phase when cows are very vulnerable to mastitis and phagocytosis mechanisms are specially important at this moment. The objective of the present trial was to evaluate the influence of dry cow therapy drugs available in the market on the phagocytic function of leukocytes obtained from cow milk. In order to do that, paired milk samples negative in bacteriological examination were submitted to in vitro phagocytosis test, after they were exposed to solutions of the following drugs: anhydrous cephalonium (M1, Gentamicin (M2, Benzylpenicillin procaine associated with Nafcillin and Dihydrostreptomycin (M3 and Cloxacillin benzathine (M4. Mean phagocytosis rates of control samples and of cells submitted to treatments M1 and M3 were, respectively, (58.88% ± 12.04, (64.87% ± 15.36 and (65.14% ± 17.96 there were no differences among these samples, as well as in the comparison with the control group. Mean phagocytosis rate obtained in cells submitted to treatment M4 (46.90% ± 22.08 was lower than that of the control group, and than that of cells submitted to treatments M1 and M3. On the other hand, mean phagocytosis rate of cells submitted to treatment M2 (0.68% ± 1.63 was lower than that observed in the control group, and than that of all other treatments. These results show that the use of drugs available for dry cow therapy may no be totally innocuous for the host.

    KEY WORDS: Dry period, mastitis, phagocytosis, treatment.
    O período seco é considerado uma fase da lactação muito vulnerável à mastite, e os mecanismos de fagocitose são especialmente importantes nessa etapa. Para avaliar a influência de medicamentos indicados para o tratamento de mastite no período seco sobre a função fagocítica de leucócitos obtidos do leite de vacas, foram utilizadas amostras pareadas de leite de vacas, negativas ao exame bacteriológico. Submeteram-se essas células à prova de fagocitose in vitro, ap

  15. Role of PufX protein in photosynthetic growth of Rhodobacter sphaeroides. 1. PufX is required for efficient light-driven electron transfer and photophosphorylation under anaerobic conditions.

    Science.gov (United States)

    Barz, W P; Francia, F; Venturoli, G; Melandri, B A; Verméglio, A; Oesterhelt, D

    1995-11-21

    The pufX gene is essential for photoheterotrophic growth of the purple bacterium Rhodobacter sphaeroides. In order to analyze the molecular function of the PufX membrane protein, we constructed a chromosomal pufX deletion mutant and phenotypically compared it to a pufX+ control strain and to two suppressor mutants which are able to grow photosynthetically in the absence of pufX. Using this genetic background, we confirmed that PufX is required for photoheterotrophic growth under anaerobic conditions, although all components of the photosynthetic apparatus were present in similar amounts in all strains investigated. We show that the deletion of PufX is not lethal for illuminated pufX- cells, suggesting that PufX is required for photosynthetic cell division. Since chromatophores isolated from the pufX- mutant were found to be unsealed vesicles, the role of PufX in photosynthetic energy transduction was studied in vivo. We show that PufX is essential for light-induced ATP synthesis (photophosphorylation) in anaerobically incubated cells. Measurements of absorption changes induced by a single turnover flash demonstrated that PufX is not required for electron flow through the reaction center and the cytochrome bc1 complex under anaerobic conditions. During prolonged illumination, however, PufX is essential for the generation of a sufficiently large membrane potential to allow photosynthetic growth. These in vivo results demonstrate that under anaerobic conditions PufX plays an essential role in facilitating effective interaction of the components of the photosynthetic apparatus.

  16. High-efficiency high-energy Ka source for the critically-required maximum illumination of x-ray optics on Z using Z-petawatt-driven laser-breakout-afterburner accelerated ultrarelativistic electrons LDRD .

    Energy Technology Data Exchange (ETDEWEB)

    Sefkow, Adam B.; Bennett, Guy R.

    2010-09-01

    Under the auspices of the Science of Extreme Environments LDRD program, a <2 year theoretical- and computational-physics study was performed (LDRD Project 130805) by Guy R Bennett (formally in Center-01600) and Adam B. Sefkow (Center-01600): To investigate novel target designs by which a short-pulse, PW-class beam could create a brighter K{alpha} x-ray source than by simple, direct-laser-irradiation of a flat foil; Direct-Foil-Irradiation (DFI). The computational studies - which are still ongoing at this writing - were performed primarily on the RedStorm supercomputer at Sandia National Laboratories Albuquerque site. The motivation for a higher efficiency K{alpha} emitter was very clear: as the backlighter flux for any x-ray imaging technique on the Z accelerator increases, the signal-to-noise and signal-to-background ratios improve. This ultimately allows the imaging system to reach its full quantitative potential as a diagnostic. Depending on the particular application/experiment this would imply, for example, that the system would have reached its full design spatial resolution and thus the capability to see features that might otherwise be indiscernible with a traditional DFI-like x-ray source. This LDRD began FY09 and ended FY10.

  17. Technological requirements for the efficiency and security in the industry of natural gas in Colombia; Requerimientos tecnologicos para la eficiencia y seguridad en la industria del gas natural en Colombia

    Energy Technology Data Exchange (ETDEWEB)

    Arrieta Andres, Amell; Gil B, Edison

    1996-11-01

    In Colombia cities will be gasified to more than 1000 m. of altitude. The theoretical analyses and experimental evidences show that to these conditions the systems work with decrease of power and excessive emissions of carbon Monoxide (CO) The supply of natural gas will come from a diversity of locations with different chemical compositions. The experience points out that teams that use gas of different composition behave in a different way, being able to locate its operation under undesirable conditions when another substitutes a gas. The studies of interchange of gases in an installed park of teams or to install they allow defining the margin of security in the use of gases of different compositions. The purpose of this report is to show the importance that for the efficient and sure use of the natural gas in Colombia have the studies of the incidence of the altitude and the hygrometry in the good operation from the atmospheric systems to gas and the interchange of the Colombian gases.

  18. Closure requirements

    International Nuclear Information System (INIS)

    Hutchinson, I.P.G.; Ellison, R.D.

    1992-01-01

    Closure of a waste management unit can be either permanent or temporary. Permanent closure may be due to: economic factors which make it uneconomical to mine the remaining minerals; depletion of mineral resources; physical site constraints that preclude further mining and beneficiation; environmental, regulatory or other requirements that make it uneconomical to continue to develop the resources. Temporary closure can occur for a period of several months to several years, and may be caused by factors such as: periods of high rainfall or snowfall which prevent mining and waste disposal; economic circumstances which temporarily make it uneconomical to mine the target mineral; labor problems requiring a cessation of operations for a period of time; construction activities that are required to upgrade project components such as the process facilities and waste management units; and mine or process plant failures that require extensive repairs. Permanent closure of a mine waste management unit involves the provision of durable surface containment features to protect the waters of the State in the long-term. Temporary closure may involve activities that range from ongoing maintenance of the existing facilities to the installation of several permanent closure features in order to reduce ongoing maintenance. This paper deals with the permanent closure features

  19. 1994 report on Task 4.3.1 investigate how training should be planned to ensure efficient utilisation or OSS. Task 4.3.2 evaluate how the introduction of OSS influences requirements to the basic education of the operator

    International Nuclear Information System (INIS)

    1995-01-01

    According to the experience coming from countries where new concepts of nuclear power plants control rooms equipped with integrated system of OSSs have recently been largely tested in experimental centres equipped with powerful real-time plant simulators (e.g. NORWAY - Halden project; Japan) a training in use of the OSS is important, so that the operator can use it in the right situation and in right manner. Experiments, in which mostly experienced active control room operators from operating NPPs took part showed as well, that both the requirements for additional basic education of operators and the planning of training is influenced by a number of different factors like complexity of system structure and interface, system function, capabilities of training centres, operators background, experience and age and others. 6 refs

  20. Energy Efficient Hydraulic Hybrid Drives

    OpenAIRE

    Rydberg, Karl-Erik

    2009-01-01

    Energy efficiency of propulsion systems for cars, trucks and construction machineries has become one of the most important topics in today’s mobile system design, mainly because of increased fuel costs and new regulations about engine emissions, which is needed to save the environment. To meet the increased requirements on higher efficiency and better functionality, components and systems have been developed over the years. For the last ten years the development of hybrid systems can be divid...

  1. Two separable functional domains of simian virus 40 large T antigen: carboxyl-terminal region of simian virus 40 large T antigen is required for efficient capsid protein synthesis.

    Science.gov (United States)

    Tornow, J; Polvino-Bodnar, M; Santangelo, G; Cole, C N

    1985-01-01

    The carboxyl-terminal portion of simian virus 40 large T antigen is essential for productive infection of CV-1 and CV-1p green monkey kidney cells. Mutant dlA2459, lacking 14 base pairs at 0.193 map units, was positive for viral DNA replication, but unable to form plaques in CV-1p cells (J. Tornow and C.N. Cole, J. Virol. 47:487-494, 1983). In this report, the defect of dlA2459 is further defined. Simian virus 40 late mRNAs were transcribed, polyadenylated, spliced, and transported in dlA2459-infected cells, but the level of capsid proteins produced in infected CV-1 green monkey kidney cells was extremely low. dlA2459 large T antigen lacks those residues known to be required for adenovirus helper function, and the block to productive infection by dlA2459 occurs at the same stage of infection as the block to productive adenovirus infection of CV-1 cells. These results suggest that the adenovirus helper function is required for productive infection by simian virus 40. Mutant dlA2459 was able to grow on the Vero and BSC-1 lines of African green monkey kidney cells. Additional mutants affecting the carboxyl-terminal portion of large T were prepared. Mutant inv2408 contains an inversion of the DNA between the BamHI and BclI sites (0.144 to 0.189 map units). This inversion causes transposition of the carboxyl-terminal 26 amino acids of large T antigen and the carboxyl-terminal 18 amino acids of VP1. This mutant was viable, even though the essential information absent from dlA2459 large T antigen has been transferred to the carboxyl terminus of VP1 of inv2408. The VP1 polypeptide carrying this carboxyl-terminal portion of large T could overcome the defect of dlA2459. This indicates that the carboxyl terminus of large T antigen is a separate and separable functional domain. Images PMID:2982029

  2. Efficient Fingercode Classification

    Science.gov (United States)

    Sun, Hong-Wei; Law, Kwok-Yan; Gollmann, Dieter; Chung, Siu-Leung; Li, Jian-Bin; Sun, Jia-Guang

    In this paper, we present an efficient fingerprint classification algorithm which is an essential component in many critical security application systems e. g. systems in the e-government and e-finance domains. Fingerprint identification is one of the most important security requirements in homeland security systems such as personnel screening and anti-money laundering. The problem of fingerprint identification involves searching (matching) the fingerprint of a person against each of the fingerprints of all registered persons. To enhance performance and reliability, a common approach is to reduce the search space by firstly classifying the fingerprints and then performing the search in the respective class. Jain et al. proposed a fingerprint classification algorithm based on a two-stage classifier, which uses a K-nearest neighbor classifier in its first stage. The fingerprint classification algorithm is based on the fingercode representation which is an encoding of fingerprints that has been demonstrated to be an effective fingerprint biometric scheme because of its ability to capture both local and global details in a fingerprint image. We enhance this approach by improving the efficiency of the K-nearest neighbor classifier for fingercode-based fingerprint classification. Our research firstly investigates the various fast search algorithms in vector quantization (VQ) and the potential application in fingerprint classification, and then proposes two efficient algorithms based on the pyramid-based search algorithms in VQ. Experimental results on DB1 of FVC 2004 demonstrate that our algorithms can outperform the full search algorithm and the original pyramid-based search algorithms in terms of computational efficiency without sacrificing accuracy.

  3. Immunoglobulin Fc receptors in clinical strains of Staphylococcus aureus do not confer resistance to Phagocytosis in an in vitro assay Los receptores Fc para inmunoglobulinas en cepas clínicas de Staphylococcus aureus no confieren resistencia a la fagocitosis in vitro

    Directory of Open Access Journals (Sweden)

    Benito VEGA

    1999-05-01

    Full Text Available Staphylococcus aureus binds Immunoglobulin G (IgG on its external surface due to the presence of specific receptors for the Fc domain of this immunoglobulin. This mechanism represents a kind of camouflage against phagocytic cells. In order to confirm that possibility an in vitro evaluation of the phagocytic activity of leukocytes polymorpho-nuclear (PMN against strains of Staphylococcus aureus was done, comparing 18 strains isolated from clinical samples and 16 from healthy individuals. The presence of Fc receptors was evaluated by haemagglutination (HA with erythrocytes group A after incubation of the strains with IgG anti blood group A. Phagocytosis of S. aureus was carried out by mixing live bacteria with a suspension of human PMN and incubating at 37 °C for 1 h; survivors were counted as colony forming units by plating. The strains from clinical specimens showed higher HA than those from healthy individuals (p = 0.01; but the former were killed more efficiently than the latter (80-90% and 40%, respectively. It is may be possible that S. aureus showed different behavior in vivo, where could express other virulence factors to prevent the action of phagocytes.Staphylococcus aureus liga inmunoglobulinas G (IgG a su superficie externa debido a la presencia de receptores para el dominio Fc de esas inmunoglobulinas. Este mecanismo representa una clase de camuflage contra células fagocíticas. Para confirmar tal posibilidad se realizó una evaluación in vitro de la actividad fagocítica de leucocitos polimorfonucleares (PMN contra cepas de Staphylococcus aureus, comparando 18 cepas aisladas de casos clínicos y 16 de individuos sanos. La presencia de receptores fue evaluada por hemaglutinación (HA con eritrocitos grupo A luego que las cepas fueron incubadas con IgG anti grupo sanguíneo A. La fagocitosis de S. aureus fue realizada mezclando células vivas con una suspensión de PMN e incubada a 37 °C por una hora; las bacterias sobrevivientes

  4. Energy efficient data centers

    Energy Technology Data Exchange (ETDEWEB)

    Tschudi, William; Xu, Tengfang; Sartor, Dale; Koomey, Jon; Nordman, Bruce; Sezgen, Osman

    2004-03-30

    Data Center facilities, prevalent in many industries and institutions are essential to California's economy. Energy intensive data centers are crucial to California's industries, and many other institutions (such as universities) in the state, and they play an important role in the constantly evolving communications industry. To better understand the impact of the energy requirements and energy efficiency improvement potential in these facilities, the California Energy Commission's PIER Industrial Program initiated this project with two primary focus areas: First, to characterize current data center electricity use; and secondly, to develop a research ''roadmap'' defining and prioritizing possible future public interest research and deployment efforts that would improve energy efficiency. Although there are many opinions concerning the energy intensity of data centers and the aggregate effect on California's electrical power systems, there is very little publicly available information. Through this project, actual energy consumption at its end use was measured in a number of data centers. This benchmark data was documented in case study reports, along with site-specific energy efficiency recommendations. Additionally, other data center energy benchmarks were obtained through synergistic projects, prior PG&E studies, and industry contacts. In total, energy benchmarks for sixteen data centers were obtained. For this project, a broad definition of ''data center'' was adopted which included internet hosting, corporate, institutional, governmental, educational and other miscellaneous data centers. Typically these facilities require specialized infrastructure to provide high quality power and cooling for IT equipment. All of these data center types were considered in the development of an estimate of the total power consumption in California. Finally, a research ''roadmap'' was developed

  5. CONTROLLING AND BUSINESS EFFICIENCY

    Directory of Open Access Journals (Sweden)

    Tina Vuko

    2013-02-01

    Full Text Available Managing business successfully in dynamic environment requires effective controlling system. Controlling is the process of defining objectives, planning and management control so that every decision maker can act in accordance with agreed objectives. Controlling function as a separate department contributes business efficiency trough ensuring transparency of business result and business processes. Controlling takes place when manager and controller cooperate. The aim of this paper is to investigate the effectiveness of controlling function (i.e. controlling department in Croatian companies and to address the specific features of the function that contribute significantly to overall business performance. The research is conducted on the sample of companies listed on the Regulated market of the Zagreb Stock Exchange. Survey is used as a method to collect the data regarding the controlling function, while financial data necessary for the research are extracted from the published financial statements. Results of the research indicate that controlling department has positive effects on the business performance.

  6. The labor competition like a requirement of efficiency.

    Directory of Open Access Journals (Sweden)

    Dolores Virgen de la Cruz Lozada

    2010-10-01

    Full Text Available Through this study the analysis of a pertinent situation in the organization will be undertaken, by means of the application of a new structure from February of the current year, where the functions of each charge are not defined yet in each of the cases. It also serves as a training way for each directive in the confrontation of the suitability evaluation, in the respectfulness regarding the objective of their job, and in the accomplishment of the mission; what constitutes the main objective of this work, and also assessing the consequences that will originate the lack of knowledge of the labor competitions and its relation with the abilities of every individual who occuppies the job in question. In this work it is used as a method the observation, related with the analysis - synthesis, action - participation and observation - participant and also techniques such as: interview and surveys. The results are in the inexperience of those involved in their functions: labor competition, which gives the difficulty to face the DNA (determination of the learning necessities of the human resources and as a consequence the Training Plan doesn't solve all the workers expectations.

  7. Energy efficiency in future wireless networks: cognitive radio standardization requirements

    CSIR Research Space (South Africa)

    Masonta, M

    2012-09-01

    Full Text Available Energy consumption of mobile and wireless networks and devices is significant, indirectly increasing greenhouse gas emissions and energy costs for operators. Cognitive radio (CR) solutions can save energy for such networks and devices; moreover...

  8. Energy sustainability: consumption, efficiency, and ...

    Science.gov (United States)

    One of the critical challenges in achieving sustainability is finding a way to meet the energy consumption needs of a growing population in the face of increasing economic prosperity and finite resources. According to ecological footprint computations, the global resource consumption began exceeding planetary supply in 1977 and by 2030, global energy demand, population, and gross domestic product are projected to greatly increase over 1977 levels. With the aim of finding sustainable energy solutions, we present a simple yet rigorous procedure for assessing and counterbalancing the relationship between energy demand, environmental impact, population, GDP, and energy efficiency. Our analyses indicated that infeasible increases in energy efficiency (over 100 %) would be required by 2030 to return to 1977 environmental impact levels and annual reductions (2 and 3 %) in energy demand resulted in physical, yet impractical requirements; hence, a combination of policy and technology approaches is needed to tackle this critical challenge. This work emphasizes the difficulty in moving toward energy sustainability and helps to frame possible solutions useful for policy and management. Based on projected energy consumption, environmental impact, human population, gross domestic product (GDP), and energy efficiency, for this study, we explore the increase in energy-use efficiency and the decrease in energy use intensity required to achieve sustainable environmental impact le

  9. Contracting for Efficiency. A Best Practices Guide for Energy-Efficient Product Procurement

    Energy Technology Data Exchange (ETDEWEB)

    Bunch, Saralyn [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States); Payne, Christopher [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-04-01

    The requirement to buy energy- and water-efficient products applies to federal purchases made through any procurement pathway (e.g., purchase cards, e-retailers, and solicitations) and to a wide variety of federal projects. The Federal Energy Management Program’s (FEMP's) Buy Energy-Efficient Products buyer overview fact sheet and Contracting for Efficiency best practices guide for product procurement are designed to support federal buyers in the purchase of energy- and water-efficient products.

  10. Contracting for Efficiency: A Best Practices Guide for Energy Efficient Product Procurement

    Energy Technology Data Exchange (ETDEWEB)

    Bunch, Saralyn [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States); Payne, Christopher [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-11-01

    The requirement to buy energy- and water-efficient products applies to federal purchases made through any procurement pathway (e.g., purchase cards, e-retailers, and solicitations) and to a wide variety of federal projects. The Federal Energy Management Program’s (FEMP's) Buy Energy-Efficient Products buyer overview fact sheet and Contracting for Efficiency best practices guide for product procurement are designed to support federal buyers in the purchase of energy- and water-efficient products.

  11. Robust and Efficient Parametric Face Alignment

    NARCIS (Netherlands)

    Tzimiropoulos, Georgios; Zafeiriou, Stefanos; Pantic, Maja

    2011-01-01

    We propose a correlation-based approach to parametric object alignment particularly suitable for face analysis applications which require efficiency and robustness against occlusions and illumination changes. Our algorithm registers two images by iteratively maximizing their correlation coefficient

  12. Automotive fuel efficiency

    International Nuclear Information System (INIS)

    Abelson, P.H.

    1992-01-01

    For at least the remainder of this century, the United States faces a growing dependence on imported oil. Costs are substantial, and they will mount. In June 1992, net imports provided nearly 50% of supplies, and their cost was $4.3 billion. Cost of net imports of motor vehicles and parts amounted to $3.0 billion. The two items combined totaled more than the negative trade balance of $6.6 billion. The light-duty highway fleet alone accounted for 38.2% of U.S. oil consumption in 1988. Correspondingly, the fleet was a substantial emitter of air pollutants - NO x , CO, and nonmethane hydrocarbons. In addition, it was a major source of CO 2 . The twin problems of oil imports and pollution would be ameliorated if the fuel economy if cars and trucks could be improved and their emissions were also reduced. In principle, the mileage of US automobiles could be substantially improved. But on purchasing a car, U.S. buyers rank fuel efficiency eight when making their choice. They are attracted to options that lower mileage. Consumers also tend to prefer large cars over small ones for reasons of safety. Increasingly, buyers are purchasing light trucks and vans that have inferior fuel efficiency. As a result of the above trends, the average mileage of the US automotive fleet has been diminishing. As long as fuel is available at comparatively low prices and there is no federal requirement for better mileage, improvement is unlikely. Moreover, even if improvements were mandated, change would be slow

  13. Efficiency of contactors

    International Nuclear Information System (INIS)

    Orth, D.A.; Graham, F.R.; Holt, D.L.

    1986-01-01

    The Savannah River Plant has two separations plants that began Purex operations in 1954 and 1955 with pump-mix mixer-settlers as contactors to process nuclear fuels. The only changes to the extraction equipment were replacement of most of the mixer-settlers in one plant with larger units in 1959, and the further replacement of the large 1A bank with a bank of rapid-contact centrifugal contactors in 1966. Improved performance of the old units has become highly desirable, and an experimental program is underway. Good contact between the phases, and adequate settling without entrainment of the opposite phase are required for high efficiency operation of the mixer-settlers. Factors that determine efficiency are mixer design, drop size generated, and phase coalescence properties. The original development work and accumulated plant data confirm that the tip speed of a given impeller design determines the throughput capacity and extraction performance. An experimental unit with three full-scale stages has been constructed and is being utilized to test different impeller designs; reduced pumping and better mixing with lower speeds appear to be the key factors for improvement. Decontamination performance of the rapid-contact centrifugal contactors is limited by the number of scrub contacts and the time of contact because of slowly equilibrating fission product species. Where solvent degradation is not a factor, the longer scrub contact of mixer-settlers gives better decontamination than the centrifugals. This kinetic effect can be overcome with long scrub contacts that follow the initial short extraction and short scrub contacts in the centrifugal contactors. A hybrid experimental unit with both rapid contact sections and longer contact scrub sections is under development to establish the degree of improvement that might be attained

  14. Reconsidering energy efficiency

    International Nuclear Information System (INIS)

    Goldoni, Giovanni

    2007-01-01

    Energy and environmental policies are reconsidering energy efficiency. In a perfect market, rational and well informed consumers reach economic efficiency which, at the given prices of energy and capital, corresponds to physical efficiency. In the real world, market failures and cognitive frictions distort the consumers from perfectly rational and informed choices. Green incentive schemes aim at balancing market failures and directing consumers toward more efficient goods and services. The problem is to fine tune the incentive schemes [it

  15. Knowing requires data

    Science.gov (United States)

    Naranjo, Ramon C.

    2017-01-01

    Groundwater-flow models are often calibrated using a limited number of observations relative to the unknown inputs required for the model. This is especially true for models that simulate groundwater surface-water interactions. In this case, subsurface temperature sensors can be an efficient means for collecting long-term data that capture the transient nature of physical processes such as seepage losses. Continuous and spatially dense network of diverse observation data can be used to improve knowledge of important physical drivers, conceptualize and calibrate variably saturated groundwater flow models. An example is presented for which the results of such analysis were used to help guide irrigation districts and water management decisions on costly upgrades to conveyance systems to improve water usage, farm productivity and restoration efforts to improve downstream water quality and ecosystems.

  16. Energy efficiency; Efficacite energetique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-06-15

    This road-map proposes by the Group Total aims to inform the public on the energy efficiency. It presents the energy efficiency and intensity around the world with a particular focus on Europe, the energy efficiency in industry and Total commitment. (A.L.B.)

  17. The plant efficiency of fusion power stations

    International Nuclear Information System (INIS)

    Darvas, J.; Foerster, S.

    1976-01-01

    Due to the circulating energy, lower efficiencies are to be expected with fusion power plants than with nuclear fission power plants. According to the systems analysis, the mirror machine is not very promising as a power plant. The plant efficiency of the laser fusion strongly depends on the laser efficiency about which one can only make speculative statements at present. The Tokamak requires a relatively low circulating energy and is certainly able to compete regarding efficiency as long as the consumption time can be kept large (> 100 sec) and the dead time between the power pulses small ( [de

  18. Energy efficiency and renewables policies: Promoting efficiency or facilitating monopsony?

    International Nuclear Information System (INIS)

    Brennan, Timothy J.

    2011-01-01

    The cliche in the electricity sector, the 'cheapest power plant is the one we don't build,' neglects the benefits of the energy that plant would generate. That economy-wide perspective need not apply in considering benefits to only consumers if not building that plant was the exercise of monopsony power. A regulator maximizing consumer welfare may need to avoid rationing demand at monopsony prices. Subsidizing energy efficiency to reduce electricity demand at the margin can solve that problem, if energy efficiency and electricity use are substitutes. Renewable energy subsidies, percentage use standards, or feed in tariffs may also serve monopsony as well with sufficient inelasticity in fossil fuel electricity supply. We may not observe these effects if the regulator can set price as well as quantity, lacks buyer-side market power, or is legally precluded from denying generators a reasonable return on capital. Nevertheless, the possibility of monopsony remains significant in light of the debate as to whether antitrust enforcement should maximize consumer welfare or total welfare. - Research Highlights: → Subsidizing energy efficiency can promote monopsony, if efficiency and use are substitutes. → Renewable energy subsidies, portfolio standards, or feed-in tariffs may also promote monopsony. → Effects require buyer-side market power and ability to deny generators a reasonable return. → Monopsony is significant in light of whether antitrust should maximize consumer or total welfare.

  19. Lightweight and Energy Efficient Heat Pump, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Future Spacecraft from the JPL will require increasingly sophisticated thermal control technology. A need exists for efficient, lightweight Vapor Compression Cycle...

  20. Efficient boiler operations sourcebook

    Energy Technology Data Exchange (ETDEWEB)

    Payne, F.W. (comp.)

    1985-01-01

    This book emphasizes the practical aspects of industrial and commercial boiler operations. It starts with a comprehensive review of general combustion and boiler fundamentals and then deals with specific efficiency improvement methods, and the cost savings which result. The book has the following chapter headings: boiler combustion fundamentals; boiler efficiency goals; major factors controlling boiler efficiency; boiler efficiency calculations; heat loss; graphical solutions; preparation for boiler testing; boiler test procedures; efficiency-related boiler maintenance procedures; boiler tune-up; boiler operational modifications; effect of water side and gas side scale deposits; load management; auxillary equipment to increase boiler efficiency; air preheaters and economizers; other types of auxillary equipment; combustion control systems and instrumentation; boiler O/sub 2/ trim controls; should you purchase a new boiler.; financial evaluation procedures; case studies. The last chapter includes a case study of a boiler burning pulverized coal and a case study of stoker-fired coal.

  1. Mechanism of hyperinsulinemia after reticuloendothelial system phagocytosis.

    Science.gov (United States)

    Filkins, J P; Yelich, M R

    1982-02-01

    Endocytic loading of the reticuloendothelial system (RES) results in acute hyperinsulinemia and functional hyperinsulinism. Colloidal carbon blockade of the RES in rats resulted in elevations of both portal vein and systemic serum immunoreactive insulin and increases in the hepatic portal vein insulin glucose ratios. Two mechanisms for the hyperinsulinemia were evaluated: 1) decreased removal of insulin by the postendocytic liver and 2) increased secretion of insulin by the isolated perfused pancreas. Colloidal carbon blockade did not alter removal of 125I-insulin as evaluated in the isolated perfused rat liver. Pancreases from postendocytic donor rats when perfused according to the technique of Grodsky manifested enhanced insulin secretion. Macrophage culture-conditioned media enhanced glucose-mediated insulin secretion both as assayed in vivo and in the isolated perfused rat pancreas. The data suggest that postendocytic activated macrophages secrete a monokine that alters insulin release and thus produces the hyperinsulinemia of RES blockade. The acronym MIRA for macrophage insulin-releasing activity is proposed for the monokine.

  2. Curvature recognition and force generation in phagocytosis

    Directory of Open Access Journals (Sweden)

    Prassler Jana

    2010-12-01

    Full Text Available Abstract Background The uptake of particles by actin-powered invagination of the plasma membrane is common to protozoa and to phagocytes involved in the immune response of higher organisms. The question addressed here is how a phagocyte may use geometric cues to optimize force generation for the uptake of a particle. We survey mechanisms that enable a phagocyte to remodel actin organization in response to particles of complex shape. Results Using particles that consist of two lobes separated by a neck, we found that Dictyostelium cells transmit signals concerning the curvature of a surface to the actin system underlying the plasma membrane. Force applied to a concave region can divide a particle in two, allowing engulfment of the portion first encountered. The phagosome membrane that is bent around the concave region is marked by a protein containing an inverse Bin-Amphiphysin-Rvs (I-BAR domain in combination with an Src homology (SH3 domain, similar to mammalian insulin receptor tyrosine kinase substrate p53. Regulatory proteins enable the phagocyte to switch activities within seconds in response to particle shape. Ras, an inducer of actin polymerization, is activated along the cup surface. Coronin, which limits the lifetime of actin structures, is reversibly recruited to the cup, reflecting a program of actin depolymerization. The various forms of myosin-I are candidate motor proteins for force generation in particle uptake, whereas myosin-II is engaged only in retracting a phagocytic cup after a switch to particle release. Thus, the constriction of a phagocytic cup differs from the contraction of a cleavage furrow in mitosis. Conclusions Phagocytes scan a particle surface for convex and concave regions. By modulating the spatiotemporal pattern of actin organization, they are capable of switching between different modes of interaction with a particle, either arresting at a concave region and applying force in an attempt to sever the particle there, or extending the cup along the particle surface to identify the very end of the object to be ingested. Our data illustrate the flexibility of regulatory mechanisms that are at the phagocyte's disposal in exploring an environment of irregular geometry.

  3. PHAGOCYTOSIS AND REMODELING OF COLLAGEN MATRICES

    OpenAIRE

    Abraham, Leah C.; Dice, J Fred.; Lee, Kyongbum; Kaplan, David L.

    2007-01-01

    The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lun...

  4. Influence of radiographic contrast media on phagocytosis

    International Nuclear Information System (INIS)

    Rasmussen, F.; Georgsen, J.; Grunnet, N.; Aalborg Sygehus

    1988-01-01

    To evaluate the influence of radiographic contrast media (CM) on human polymorphonuclear leucocytes (PML), the ability of these cells to ingest latex particles after in vitro exposure to five different radiographic contrast media was investigated. All CM inhibited the phagocytic properties of PML. The inhibition was dose dependent. The inhibitory effect was partly due to hyperosmolality but CM specific inhibition was also evident. (orig.)

  5. Enhanced Phagocytosis and Antibody Production by Tinospora ...

    African Journals Online (AJOL)

    SERVER

    2008-01-18

    Jan 18, 2008 ... antibody production through in vitro and in vivo studies. MATERIALS AND METHODS. Collection ..... components with candidicidal activity in human, rabbit and guinea pig leukocytes. Infect. Immun., 11: 1226-1234. Manjrekar ...

  6. Improving Gas Flooding Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Reid Grigg; Robert Svec; Zheng Zeng; Alexander Mikhalin; Yi Lin; Guoqiang Yin; Solomon Ampir; Rashid Kassim

    2008-03-31

    This study focuses on laboratory studies with related analytical and numerical models, as well as work with operators for field tests to enhance our understanding of and capabilities for more efficient enhanced oil recovery (EOR). Much of the work has been performed at reservoir conditions. This includes a bubble chamber and several core flood apparatus developed or modified to measure interfacial tension (IFT), critical micelle concentration (CMC), foam durability, surfactant sorption at reservoir conditions, and pressure and temperature effects on foam systems.Carbon dioxide and N{sub 2} systems have been considered, under both miscible and immiscible conditions. The injection of CO2 into brine-saturated sandstone and carbonate core results in brine saturation reduction in the range of 62 to 82% brine in the tests presented in this paper. In each test, over 90% of the reduction occurred with less than 0.5 PV of CO{sub 2} injected, with very little additional brine production after 0.5 PV of CO{sub 2} injected. Adsorption of all considered surfactant is a significant problem. Most of the effect is reversible, but the amount required for foaming is large in terms of volume and cost for all considered surfactants. Some foams increase resistance to the value beyond what is practical in the reservoir. Sandstone, limestone, and dolomite core samples were tested. Dissolution of reservoir rock and/or cement, especially carbonates, under acid conditions of CO2 injection is a potential problem in CO2 injection into geological formations. Another potential change in reservoir injectivity and productivity will be the precipitation of dissolved carbonates as the brine flows and pressure decreases. The results of this report provide methods for determining surfactant sorption and can be used to aid in the determination of surfactant requirements for reservoir use in a CO{sub 2}-foam flood for mobility control. It also provides data to be used to determine rock permeability

  7. Educated for Efficiency

    DEFF Research Database (Denmark)

    Amore, Mario Daniele; Bennedsen, Morten; Larsen, Birthe

    We study the effect of CEO education on a firm’s energy efficiency. Using a unique dataset of Danish firms, we document that firms led by more educated CEOs exhibit greater energy efficiency. We establish causality by employing exogenous CEO hospitalization episodes: the hospitalization of highly......-educated CEOs induces a drop in a firm’s energy efficiency, whereas the hospitalization of low-education CEOs does not have any significant effect. Disentangling the effect of educational length from that of the field of study, we find that the greater energy efficiency is mostly driven by the cumulated years...

  8. Hadoop Tutorial - Efficient data ingestion

    CERN Multimedia

    CERN. Geneva; Baranowski, Zbigniew

    2016-01-01

    The Hadoop ecosystem is the leading opensource platform for distributed storage and processing of "big data". The Hadoop platform is available at CERN as a central service provided by the IT department. Real-time data ingestion to Hadoop ecosystem due to the system specificity is non-trivial process and requires some efforts (which is often underestimated) in order to make it efficient (low latency, optimize data placement, footprint on the cluster). In this tutorial attendees will learn about: The important aspects of storing the data in Hadoop Distributed File System (HDFS).  Data ingestion techniques and engines that are capable of shipping data to Hadoop in an efficient way. Setting up a full data ingestion flow into a Hadoop Distributed Files System from various sources (streaming, log files, databases) using the best practices and components available around the ecosystem (including Sqoop, Kite, Flume, Kafka...

  9. Efficient flapping flight of pterosaurs

    Science.gov (United States)

    Strang, Karl Axel

    In the late eighteenth century, humans discovered the first pterosaur fossil remains and have been fascinated by their existence ever since. Pterosaurs exploited their membrane wings in a sophisticated manner for flight control and propulsion, and were likely the most efficient and effective flyers ever to inhabit our planet. The flapping gait is a complex combination of motions that sustains and propels an animal in the air. Because pterosaurs were so large with wingspans up to eleven meters, if they could have sustained flapping flight, they would have had to achieve high propulsive efficiencies. Identifying the wing motions that contribute the most to propulsive efficiency is key to understanding pterosaur flight, and therefore to shedding light on flapping flight in general and the design of efficient ornithopters. This study is based on published results for a very well-preserved specimen of Coloborhynchus robustus, for which the joints are well-known and thoroughly described in the literature. Simplifying assumptions are made to estimate the characteristics that can not be inferred directly from the fossil remains. For a given animal, maximizing efficiency is equivalent to minimizing power at a given thrust and speed. We therefore aim at finding the flapping gait, that is the joint motions, that minimize the required flapping power. The power is computed from the aerodynamic forces created during a given wing motion. We develop an unsteady three-dimensional code based on the vortex-lattice method, which correlates well with published results for unsteady motions of rectangular wings. In the aerodynamic model, the rigid pterosaur wing is defined by the position of the bones. In the aeroelastic model, we add the flexibility of the bones and of the wing membrane. The nonlinear structural behavior of the membrane is reduced to a linear modal decomposition, assuming small deflections about the reference wing geometry. The reference wing geometry is computed for

  10. Institutions, Equilibria and Efficiency

    DEFF Research Database (Denmark)

    Competition and efficiency is at the core of economic theory. This volume collects papers of leading scholars, which extend the conventional general equilibrium model in important ways. Efficiency and price regulation are studied when markets are incomplete and existence of equilibria in such set...... in OLG, learning in OLG and in games, optimal pricing of derivative securities, the impact of heterogeneity...

  11. Energy Efficiency Collaboratives

    Energy Technology Data Exchange (ETDEWEB)

    Li, Michael [US Department of Energy, Washington, DC (United States); Bryson, Joe [US Environmental Protection Agency, Washington, DC (United States)

    2015-09-01

    Collaboratives for energy efficiency have a long and successful history and are currently used, in some form, in more than half of the states. Historically, many state utility commissions have used some form of collaborative group process to resolve complex issues that emerge during a rate proceeding. Rather than debate the issues through the formality of a commission proceeding, disagreeing parties are sent to discuss issues in a less-formal setting and bring back resolutions to the commission. Energy efficiency collaboratives take this concept and apply it specifically to energy efficiency programs—often in anticipation of future issues as opposed to reacting to a present disagreement. Energy efficiency collaboratives can operate long term and can address the full suite of issues associated with designing, implementing, and improving energy efficiency programs. Collaboratives can be useful to gather stakeholder input on changing program budgets and program changes in response to performance or market shifts, as well as to provide continuity while regulators come and go, identify additional energy efficiency opportunities and innovations, assess the role of energy efficiency in new regulatory contexts, and draw on lessons learned and best practices from a diverse group. Details about specific collaboratives in the United States are in the appendix to this guide. Collectively, they demonstrate the value of collaborative stakeholder processes in producing successful energy efficiency programs.

  12. efficience technico-economique

    African Journals Online (AJOL)

    USER

    ABSTRACT. TECHNICO-ECONOMIC EFFICIENCY : CASE OF THE PRODUCERS OF ONION AND POTATO IN KNOW IN MOROCCO. In the new context ... Key words : Technico-economic efficiency, stochastic frontier, potato production, onion production, Morocco ..... sont le labour, le cover-cropage et le traçage. 82 % des ...

  13. Nitrogen use efficiency (NUE)

    NARCIS (Netherlands)

    Oenema, O.

    2015-01-01

    There is a need for communications about resource use efficiency and for measures to increase the use efficiency of nutrients in relation to food production. This holds especially for nitrogen. Nitrogen (N) is essential for life and a main nutrient element. It is needed in relatively large

  14. Logistics, Management and Efficiency

    OpenAIRE

    Mircea UDRESCU; Sandu CUTURELA

    2014-01-01

    The problem related to the efficiency of the management for organization is general being the concern off all managers. In the present essay we consider that the efficacy of the organization begins from the structural systemization of the organizational management into general management, management of logistics and management of production which demands a new managerial process, more competitive based on economic efficiency.

  15. Energy efficiency and behaviour

    DEFF Research Database (Denmark)

    Carstensen, Trine Agervig; Kunnasvirta, Annika; Kiviluoto, Katariina

    separate key aspects hinders strategic energy efficiency planning. For this reason, the PLEEC project – “Planning for Energy Efficient Cities” – funded by the EU Seventh Framework Programme uses an integrative approach to achieve the sus‐ tainable, energy– efficient, smart city. By coordinating strategies...... to conduct behavioural interventions, to be presented in Deliverable 5.5., the final report. This report will also provide valuable information for the WP6 general model for an Energy-Smart City. Altogether 38 behavioural interventions are analysed in this report. Each collected and analysed case study...... of the European Union’s 20‐20‐20 plan is to improve energy efficiency by 20% in 2020. However, holistic knowledge about energy efficiency potentials in cities is far from complete. Currently, a WP4 location in PLEEC project page 3 variety of individual strategies and approaches by different stakeholders tackling...

  16. High-efficient electron linacs

    International Nuclear Information System (INIS)

    Glavatskikh, K.V.; Zverev, B.V.; Kalyuzhnyj, V.E.; Morozov, V.L.; Nikolaev, S.V.; Plotnikov, S.N.; Sobenin, N.P.; Vovna, V.A.; Gryzlov, A.V.

    1993-01-01

    Comparison analysis of ELA on running and still waves designed for 10 MeV energy and with high efficiency is carried out. It is shown, that from the point of view of dimensions ELA with a still wave or that of a combined type is more preferable. From the point of view of impedance characteristics in any variant with application of magnetron as HF-generator it is necessary to implement special requirements to the accelerating structure if no ferrite isolation is provided in HF-channel. 3 refs., 4 figs., 1 tab

  17. Energy efficiency: a recipe for success

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-09-15

    Produced in cooperation with ADEME and Enerdata, this report presents and evaluates energy efficiency policies and trends in about 90 countries around the world. It reviews the impact of energy efficiency measures and highlights the trends and results of their implementation. Energy efficiency is ''a low hanging fruit'' on the ''energy tree'' which can help address a number of objectives at the same time and at a low or negative cost: security of supply, environmental impacts, competitiveness, balance of trade, investment requirements, social aspects and others. Despite its significant potential for energy savings, energy efficiency is still far from realising this potential. Why? There is no single answer to this question. A meaningful response requires major research and an analytical effort.

  18. Energy efficiency: a recipe for success

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-09-15

    Produced in cooperation with ADEME and Enerdata, this report presents and evaluates energy efficiency policies and trends in about 90 countries around the world. It reviews the impact of energy efficiency measures and highlights the trends and results of their implementation. Energy efficiency is ''a low hanging fruit'' on the ''energy tree'' which can help address a number of objectives at the same time and at a low or negative cost: security of supply, environmental impacts, competitiveness, balance of trade, investment requirements, social aspects and others. Despite its significant potential for energy savings, energy efficiency is still far from realising this potential. Why? There is no single answer to this question. A meaningful response requires major research and an analytical effort.

  19. Transition Towards Energy Efficient Machine Tools

    CERN Document Server

    Zein, André

    2012-01-01

    Energy efficiency represents a cost-effective and immediate strategy of a sustainable development. Due to substantial environmental and economic implications, a strong emphasis is put on the electrical energy requirements of machine tools for metalworking processes. The improvement of energy efficiency is however confronted with diverse barriers, which sustain an energy efficiency gap of unexploited potential. The deficiencies lie in the lack of information about the actual energy requirements of machine tools, a minimum energy reference to quantify improvement potential and the possible actions to improve the energy demand. Therefore, a comprehensive concept for energy performance management of machine tools is developed which guides the transition towards energy efficient machine tools. It is structured in four innovative concept modules, which are embedded into step-by-step workflow models. The capability of the performance management concept is demonstrated in an automotive manufacturing environment. The ...

  20. Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl amino-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

    Directory of Open Access Journals (Sweden)

    Rodrigo Juliano Oliveira

    2018-02-01

    Full Text Available Abstract The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl amino-4-oxobut-2-enoic acid (IR-01 and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment.

  1. Feed tank transfer requirements

    International Nuclear Information System (INIS)

    Freeman-Pollard, J.R.

    1998-01-01

    This document presents a definition of tank turnover; DOE responsibilities; TWRS DST permitting requirements; TWRS Authorization Basis (AB) requirements; TWRS AP Tank Farm operational requirements; unreviewed safety question (USQ) requirements; records and reporting requirements, and documentation which will require revision in support of transferring a DST in AP Tank Farm to a privatization contractor for use during Phase 1B

  2. Nutrients requirements in biological industrial wastewater treatment ...

    African Journals Online (AJOL)

    In both these wastewaters nutrients were not added. A simple formula is introduced to calculate nutrient requirements based on removal efficiency and observed biomass yield coefficient. Key Words: Olive mill wastewater; anaerobic treatment; aerobic treatment; sequencing batch reactor; biomass yield; nutrient requirement.

  3. Efficient Reanalysis Procedures in Structural Topology Optimization

    DEFF Research Database (Denmark)

    Amir, Oded

    This thesis examines efficient solution procedures for the structural analysis problem within topology optimization. The research is motivated by the observation that when the nested approach to structural optimization is applied, most of the computational effort is invested in repeated solutions...... on approximate reanalysis. For cases where memory limitations require the utilization of iterative equation solvers, we suggest efficient procedures based on alternative termination criteria for such solvers. These approaches are tested on two- and three-dimensional topology optimization problems including...

  4. Efficient pooling designs for library screening

    OpenAIRE

    Bruno, William J.; Knill, Emanuel; Balding, David J.; Bruce, D. C.; Doggett, N. A.; Sawhill, W. W.; Stallings, R. L.; Whittaker, Craig C.; Torney, David C.

    1994-01-01

    We describe efficient methods for screening clone libraries, based on pooling schemes which we call ``random $k$-sets designs''. In these designs, the pools in which any clone occurs are equally likely to be any possible selection of $k$ from the $v$ pools. The values of $k$ and $v$ can be chosen to optimize desirable properties. Random $k$-sets designs have substantial advantages over alternative pooling schemes: they are efficient, flexible, easy to specify, require fewer pools, and have er...

  5. Efficient quantum computing with weak measurements

    International Nuclear Information System (INIS)

    Lund, A P

    2011-01-01

    Projective measurements with high quantum efficiency are often assumed to be required for efficient circuit-based quantum computing. We argue that this is not the case and show that the fact that they are not required was actually known previously but was not deeply explored. We examine this issue by giving an example of how to perform the quantum-ordering-finding algorithm efficiently using non-local weak measurements considering that the measurements used are of bounded weakness and some fixed but arbitrary probability of success less than unity is required. We also show that it is possible to perform the same computation with only local weak measurements, but this must necessarily introduce an exponential overhead.

  6. PV inverter test setup for European efficiency, static and dynamic MPPT efficiency evaluation

    DEFF Research Database (Denmark)

    Sera, Dezso; Teodorescu, Remus; Valentini, Massimo

    2008-01-01

    This paper concerns the evaluation of performance of grid-connected PV inverters in terms of conversion efficiency, European efficiency, static and dynamic MPP efficiency. Semi-automated tests were performed in the PV laboratory of the Institute of Energy Technology at the Aalborg University...... (Denmark) on a commercial transformerless PV inverter. Thanks to the available experimental test setups, that provide the required high measuring accuracy, and the developed PV simulator, which is required for MPPT performance evaluation, PV Inverters can be pretested before being tested by accredited...

  7. Transparent Electrodes for Efficient Optoelectronics

    KAUST Repository

    Morales-Masis, Monica

    2017-03-30

    With the development of new generations of optoelectronic devices that combine high performance and novel functionalities (e.g., flexibility/bendability, adaptability, semi or full transparency), several classes of transparent electrodes have been developed in recent years. These range from optimized transparent conductive oxides (TCOs), which are historically the most commonly used transparent electrodes, to new electrodes made from nano- and 2D materials (e.g., metal nanowire networks and graphene), and to hybrid electrodes that integrate TCOs or dielectrics with nanowires, metal grids, or ultrathin metal films. Here, the most relevant transparent electrodes developed to date are introduced, their fundamental properties are described, and their materials are classified according to specific application requirements in high efficiency solar cells and flexible organic light-emitting diodes (OLEDs). This information serves as a guideline for selecting and developing appropriate transparent electrodes according to intended application requirements and functionality.

  8. Efficient Spin Injection into Semiconductor

    International Nuclear Information System (INIS)

    Nahid, M.A.I.

    2010-06-01

    Spintronic research has made tremendous progress nowadays for making future devices obtain extra advantages of low power, and faster and higher scalability compared to present electronic devices. A spintronic device is based on the transport of an electron's spin instead of charge. Efficient spin injection is one of the very important requirements for future spintronic devices. However, the effective spin injection is an exceedingly difficult task. In this paper, the importance of spin injection, basics of spin current and the essential requirements of spin injection are illustrated. The experimental technique of electrical spin injection into semiconductor is also discussed based on the experimental experience. The electrical spin injection can easily be implemented for spin injection into any semiconductor. (author)

  9. Transparent Electrodes for Efficient Optoelectronics

    KAUST Repository

    Morales-Masis, Monica; De Wolf, Stefaan; Woods-Robinson, Rachel; Ager, Joel W.; Ballif, Christophe

    2017-01-01

    With the development of new generations of optoelectronic devices that combine high performance and novel functionalities (e.g., flexibility/bendability, adaptability, semi or full transparency), several classes of transparent electrodes have been developed in recent years. These range from optimized transparent conductive oxides (TCOs), which are historically the most commonly used transparent electrodes, to new electrodes made from nano- and 2D materials (e.g., metal nanowire networks and graphene), and to hybrid electrodes that integrate TCOs or dielectrics with nanowires, metal grids, or ultrathin metal films. Here, the most relevant transparent electrodes developed to date are introduced, their fundamental properties are described, and their materials are classified according to specific application requirements in high efficiency solar cells and flexible organic light-emitting diodes (OLEDs). This information serves as a guideline for selecting and developing appropriate transparent electrodes according to intended application requirements and functionality.

  10. Energy efficiency through energy audit

    International Nuclear Information System (INIS)

    Esan, A. A.

    2000-08-01

    through a pilot demonstration energy audit project. External technical assistance from UNIDO is to provide expertise from energy efficiency programs undertaken in OECD country industries. The experience from textile industries shows that energy auditing can reduce specific energy consumption by about thirteen percent (13%) from entrepreneurial point of view, it is a profitable venture since its pay back is usually much shorter than anticipated (one year). From macro economical point of view, energy conservation reached through energy audits helps, inter alia, to postpone the necessity to construct new energy generating capacities which require extensive financial investments. Equally important benefit is the environmental protection. More efficient energy use means lower emissions of pollutants such as CO 2 , SO 2 , NO x and fly ash generated by fuel burning

  11. Energy Efficiency: Finding Leadership Opportunities

    Directory of Open Access Journals (Sweden)

    William Rosehart

    2014-01-01

    buildings, and by issuing an annual “premier’s report card,” making public the progress on province-wide efficiency efforts. For a province that continues to enjoy growth in business and population, updated guidelines around new building codes have been proven to improve energy efficiency. And there remains a significant opportunity for Alberta to improve efficiency in its commercial and industrial sectors, the largest users of energy, by providing government incentives to replace ageing equipment with more efficient technology. Alberta is also well suited for a shift toward more combined heat and power generation plants, which can repurpose generated heat that is otherwise wasted, significantly reducing energy demand and costs. And in a province awash in natural gas, incentives to encourage travel using compressed or liquefied natural gas vehicles could serve to boost energy efficiency in the transportation sector as well. Alberta is fortunate in that it has abundant energy and prosperity, making improved energy efficiency a matter of choice, rather than — as in some jurisdictions — one of urgent necessity. It is, however, a choice that Alberta has enough reasons, and resources, to make. All it requires is the will.

  12. 42 CFR 440.370 - Economy and efficiency.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Economy and efficiency. 440.370 Section 440.370...-Equivalent Coverage § 440.370 Economy and efficiency. Benchmark and benchmark-equivalent coverage and any... requirements and other economy and efficiency principles that would otherwise be applicable to the services or...

  13. Ownership and efficiency in nuclear power production

    International Nuclear Information System (INIS)

    Pollitt, M.G.

    1995-01-01

    This paper aims to contribute to the relatively small amount of academic literature on the efficiency of nuclear power production. The author draws on world-wide comparisons to illustrate the situation in the United Kingdom, where the nuclear generating capacity, conceived of and constructed as a public concern, has recently been privatised. The theory and evidence for links between ownership and productive efficiency is received. Efficiency measures used are explained as are the linear programs required to generate them. Data Envelopment Analysis (DEA) is used to analyse productive efficiency of nuclear power plants before and after privatisation. Results of the DEA are used to test the hypothesis that ownership has no effect on productive efficiency. (UK)

  14. Efficiency of emergency exercises

    International Nuclear Information System (INIS)

    Zander, N.; Sogalla, M.

    2011-01-01

    In order to cope with accidents beyond the design basis within German nuclear power plants which possibly lead to relevant radiological consequences, the utilities as well as the competent authorities exist emergency organisations. The efficiency, capacity for teamwork and preparedness of such organisations should be tested by regular, efficient exercise activities. Such activities can suitably be based on scenarios which provide challenging tasks for all units of the respective emergency organisation. Thus, the demonstration and further development of the efficiency of the respective organisational structures, including their ability to collaborate, is promoted. (orig.)

  15. Learning efficient correlated equilibria

    KAUST Repository

    Borowski, Holly P.; Marden, Jason R.; Shamma, Jeff S.

    2014-01-01

    The majority of distributed learning literature focuses on convergence to Nash equilibria. Correlated equilibria, on the other hand, can often characterize more efficient collective behavior than even the best Nash equilibrium. However, there are no existing distributed learning algorithms that converge to specific correlated equilibria. In this paper, we provide one such algorithm which guarantees that the agents' collective joint strategy will constitute an efficient correlated equilibrium with high probability. The key to attaining efficient correlated behavior through distributed learning involves incorporating a common random signal into the learning environment.

  16. Learning efficient correlated equilibria

    KAUST Repository

    Borowski, Holly P.

    2014-12-15

    The majority of distributed learning literature focuses on convergence to Nash equilibria. Correlated equilibria, on the other hand, can often characterize more efficient collective behavior than even the best Nash equilibrium. However, there are no existing distributed learning algorithms that converge to specific correlated equilibria. In this paper, we provide one such algorithm which guarantees that the agents\\' collective joint strategy will constitute an efficient correlated equilibrium with high probability. The key to attaining efficient correlated behavior through distributed learning involves incorporating a common random signal into the learning environment.

  17. Shrew trap efficiency

    DEFF Research Database (Denmark)

    Gambalemoke, Mbalitini; Mukinzi, Itoka; Amundala, Drazo

    2008-01-01

    We investigated the efficiency of four trap types (pitfall, Sherman LFA, Victor snap and Museum Special snap traps) to capture shrews. This experiment was conducted in five inter-riverine forest blocks in the region of Kisangani. The total trapping effort was 6,300, 9,240, 5,280 and 5,460 trap......, our results indicate that pitfall traps are the most efficient for capturing shrews: not only do they have a higher efficiency (yield), but the taxonomic diversity of shrews is also higher when pitfall traps are used....

  18. The Efficient Windows Collaborative

    Energy Technology Data Exchange (ETDEWEB)

    Petermann, Nils

    2006-03-31

    The Efficient Windows Collaborative (EWC) is a coalition of manufacturers, component suppliers, government agencies, research institutions, and others who partner to expand the market for energy efficient window products. Funded through a cooperative agreement with the U.S. Department of Energy, the EWC provides education, communication and outreach in order to transform the residential window market to 70% energy efficient products by 2005. Implementation of the EWC is managed by the Alliance to Save Energy, with support from the University of Minnesota and Lawrence Berkeley National Laboratory.

  19. Display Parameters and Requirements

    Science.gov (United States)

    Bahadur, Birendra

    The following sections are included: * INTRODUCTION * HUMAN FACTORS * Anthropometry * Sensory * Cognitive * Discussions * THE HUMAN VISUAL SYSTEM - CAPABILITIES AND LIMITATIONS * Cornea * Pupil and Iris * Lens * Vitreous Humor * Retina * RODS - NIGHT VISION * CONES - DAY VISION * RODS AND CONES - TWILIGHT VISION * VISUAL PIGMENTS * MACULA * BLOOD * CHOROID COAT * Visual Signal Processing * Pathways to the Brain * Spatial Vision * Temporal Vision * Colour Vision * Colour Blindness * DICHROMATISM * Protanopia * Deuteranopia * Tritanopia * ANOMALOUS TRICHROMATISM * Protanomaly * Deuteranomaly * Tritanomaly * CONE MONOCHROMATISM * ROD MONOCHROMATISM * Using Colour Effectively * COLOUR MIXTURES AND THE CHROMATICITY DIAGRAM * Colour Matching Functions and Chromaticity Co-ordinates * CIE 1931 Colour Space * CIE PRIMARIES * CIE COLOUR MATCHING FUNCTIONS AND CHROMATICITY CO-ORDINATES * METHODS FOR DETERMINING TRISTIMULUS VALUES AND COLOUR CO-ORDINATES * Spectral Power Distribution Method * Filter Method * CIE 1931 CHROMATICITY DIAGRAM * ADDITIVE COLOUR MIXTURE * CIE 1976 Chromaticity Diagram * CIE Uniform Colour Spaces and Colour Difference Formulae * CIELUV OR L*u*v* * CIELAB OR L*a*b* * CIE COLOUR DIFFERENCE FORMULAE * Colour Temperature and CIE Standard Illuminants and source * RADIOMETRIC AND PHOTOMETRIC QUANTITIES * Photopic (Vλ and Scotopic (Vλ') Luminous Efficiency Function * Photometric and Radiometric Flux * Luminous and Radiant Intensities * Incidence: Illuminance and Irradiance * Exitance or Emittance (M) * Luminance and Radiance * ERGONOMIC REQUIREMENTS OF DISPLAYS * ELECTRO-OPTICAL PARAMETERS AND REQUIREMENTS * Contrast and Contrast Ratio * Luminance and Brightness * Colour Contrast and Chromaticity * Glare * Other Aspects of Legibility * SHAPE AND SIZE OF CHARACTERS * DEFECTS AND BLEMISHES * FLICKER AND DISTORTION * ANGLE OF VIEW * Switching Speed * Threshold and Threshold Characteristic * Measurement Techniques For Electro-optical Parameters * RADIOMETRIC

  20. USSR energy efficiency and prospects

    International Nuclear Information System (INIS)

    Sinyak, Y.

    1991-06-01

    The U.S.S.R. is the largest energy producer and the second largest energy consumer in the world. Its share of global energy use reached above 17% in 1988. The soviet energy system is characterized by low efficiency and high per capita energy consumption, although there are some reasons justifying the greater U.S.S.R. energy use per unit of product output than in other industrialized countries. The present energy-savings potential is approximately equal to one-half of the domestic energy consumption. Improvements in energy efficiency at all levels of the national economy are now considered to be the primary goal of national energy policy for the next couple of decades. Being endowed with abundant natural gas resources, the U.S.S.R. will count on this energy source in the future to improve its energy efficiency, reduce expenses and cope with air pollution. After 2005-2010, stabilized primary energy consumption may be reached or there may even be a decline of total energy use. The U.S.S.R. could reduce CO 2 emissions by 20% by 2030 but with substantial negative impacts on GNP growth. Required improvements in the Soviet energy system depend on changes in energy management, including reduction of the role of centralized planning, decentralization and privatization of energy-producing facilities, energy-price reforms, reshaping of investment patterns, reduction in military expenditures, etc. (author)

  1. Energy-efficient cooking methods

    Energy Technology Data Exchange (ETDEWEB)

    De, Dilip K. [Department of Physics, University of Jos, P.M.B. 2084, Jos, Plateau State (Nigeria); Muwa Shawhatsu, N. [Department of Physics, Federal University of Technology, Yola, P.M.B. 2076, Yola, Adamawa State (Nigeria); De, N.N. [Department of Mechanical and Aerospace Engineering, The University of Texas at Arlington, Arlington, TX 76019 (United States); Ikechukwu Ajaeroh, M. [Department of Physics, University of Abuja, Abuja (Nigeria)

    2013-02-15

    Energy-efficient new cooking techniques have been developed in this research. Using a stove with 649{+-}20 W of power, the minimum heat, specific heat of transformation, and on-stove time required to completely cook 1 kg of dry beans (with water and other ingredients) and 1 kg of raw potato are found to be: 710 {+-}kJ, 613 {+-}kJ, and 1,144{+-}10 s, respectively, for beans and 287{+-}12 kJ, 200{+-}9 kJ, and 466{+-}10 s for Irish potato. Extensive researches show that these figures are, to date, the lowest amount of heat ever used to cook beans and potato and less than half the energy used in conventional cooking with a pressure cooker. The efficiency of the stove was estimated to be 52.5{+-}2 %. Discussion is made to further improve the efficiency in cooking with normal stove and solar cooker and to save food nutrients further. Our method of cooking when applied globally is expected to contribute to the clean development management (CDM) potential. The approximate values of the minimum and maximum CDM potentials are estimated to be 7.5 x 10{sup 11} and 2.2 x 10{sup 13} kg of carbon credit annually. The precise estimation CDM potential of our cooking method will be reported later.

  2. Transport Energy Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    Transport is the sector with the highest final energy consumption and, without any significant policy changes, is forecast to remain so. In 2008, the IEA published 25 energy efficiency recommendations, among which four are for the transport sector. The recommendations focus on road transport and include policies on improving tyre energy efficiency, fuel economy standards for both light-duty vehicles and heavy-duty vehicles, and eco-driving. Implementation of the recommendations has been weaker in the transport sector than others. This paper updates the progress that has been made in implementing the transport energy efficiency recommendations in IEA countries since March 2009. Many countries have in the last year moved from 'planning to implement' to 'implementation underway', but none have fully implemented all transport energy efficiency recommendations. The IEA calls therefore for full and immediate implementation of the recommendations.

  3. Improving efficiency in stereology

    DEFF Research Database (Denmark)

    Keller, Kresten Krarup; Andersen, Ina Trolle; Andersen, Johnnie Bremholm

    2013-01-01

    of the study was to investigate the time efficiency of the proportionator and the autodisector on virtual slides compared with traditional methods in a practical application, namely the estimation of osteoclast numbers in paws from mice with experimental arthritis and control mice. Tissue slides were scanned......, a proportionator sampling and a systematic, uniform random sampling were simulated. We found that the proportionator was 50% to 90% more time efficient than systematic, uniform random sampling. The time efficiency of the autodisector on virtual slides was 60% to 100% better than the disector on tissue slides. We...... conclude that both the proportionator and the autodisector on virtual slides may improve efficiency of cell counting in stereology....

  4. Energy Efficient Cryogenics

    Science.gov (United States)

    Meneghelli, Barry J.; Notardonato, William; Fesmire, James E.

    2016-01-01

    The Cryogenics Test Laboratory, NASA Kennedy Space Center, works to provide practical solutions to low-temperature problems while focusing on long-term technology targets for the energy-efficient use of cryogenics on Earth and in space.

  5. Power-Efficient Design Challenges

    Science.gov (United States)

    Pangrle, Barry

    Design teams find themselves facing decreasing power budgets while simultaneously the products that they design continue to require the integration of increasingly complex levels of functionality. The market place (driven by consumer preferences) and new regulations and guidelines on energy efficiency and environmental impact are the key drivers. This in turn has generated new approaches in all IC and electronic system design domains from the architecture to the physical layout of ICs, to design-for-test, as well as for design verification to insure that the design implementation actually meets the intended requirements and specifications. This chapter covers key aspects of these forces from a technological and market perspective that are driving designers to produce more energy-efficient products. Observations by significant industry leaders from AMD, ARM, IBM, Intel, nVidia and TSMC are cited, and the emerging techniques and technologies used to address these issues now and into the future are explored. Topic areas include: System level: Architectural analysis and transaction-level modeling. How architectural decisions can dramatically reduce the design power and the importance of modeling hardware and software together. IC (Chip) level: The impact of creating on-chip power domains for selectively turning power off and/or multi-voltage operation on: (1) chip verification, (2) multi-corner multi-mode analysis during placement and routing of logic cells and (3) changes to design-for-test, all in order to accommodate for power-gating and multi-voltage control logic, retention registers, isolation cells and level shifters needed to implement these power saving techniques. Process level: The disappearing impact of body-bias techniques on leakage control and why new approaches like High-K Metal Gate (HKMG) technology help but don't eliminate power issues. Power-efficient design is impacting the way chip designers work today, and this chapter focuses on where the most

  6. More efficient together

    DEFF Research Database (Denmark)

    Zhang, Tian

    2015-01-01

    The solar-to-biomass conversion efficiency of natural photosynthesis is between 2.9 and 4.3% for most crops (1, 2). Improving the efficiency of photosynthesis could help increase the appeal of biologically derived fuels and chemicals in comparison with traditional petrochemical processes. One app...... competition between biotechnology and the food industry and avoid the environmental perturbation caused by intensive agriculture (3)....

  7. Thermodynamically efficient solar concentrators

    Science.gov (United States)

    Winston, Roland

    2012-10-01

    Non-imaging Optics is the theory of thermodynamically efficient optics and as such depends more on thermodynamics than on optics. Hence in this paper a condition for the "best" design is proposed based on purely thermodynamic arguments, which we believe has profound consequences for design of thermal and even photovoltaic systems. This new way of looking at the problem of efficient concentration depends on probabilities, the ingredients of entropy and information theory while "optics" in the conventional sense recedes into the background.

  8. Study notes separability of oil company profitability, efficiency

    International Nuclear Information System (INIS)

    Thompson, R.G.

    1993-01-01

    In recent years, the large publicly traded oil companies have been restructuring and downsizing to improve efficiency. Newly developed decision theory forces one to question the widely held singular focus on efficiency because improving efficiency will not necessarily improve profits. This is especially likely in the oil industry, where price volatility is the norm. Because its products are so basic, its price volatility typically ripples widely throughout the economy. In light of this, efficiency and profitability in the oil industry require separate treatment. More specifically, the efficient are not necessarily the most profitable; conversely, the most profitable are not necessarily the most efficient. Such a decoupling of efficiency and profitability requires a totally new look at business strategy. In the face of highly variable prices, firms can no longer depend on the long-accepted duality norm between profits and efficiency

  9. Efficient Windows Collaborative

    Energy Technology Data Exchange (ETDEWEB)

    Nils Petermann

    2010-02-28

    The project goals covered both the residential and commercial windows markets and involved a range of audiences such as window manufacturers, builders, homeowners, design professionals, utilities, and public agencies. Essential goals included: (1) Creation of 'Master Toolkits' of information that integrate diverse tools, rating systems, and incentive programs, customized for key audiences such as window manufacturers, design professionals, and utility programs. (2) Delivery of education and outreach programs to multiple audiences through conference presentations, publication of articles for builders and other industry professionals, and targeted dissemination of efficient window curricula to professionals and students. (3) Design and implementation of mechanisms to encourage and track sales of more efficient products through the existing Window Products Database as an incentive for manufacturers to improve products and participate in programs such as NFRC and ENERGY STAR. (4) Development of utility incentive programs to promote more efficient residential and commercial windows. Partnership with regional and local entities on the development of programs and customized information to move the market toward the highest performing products. An overarching project goal was to ensure that different audiences adopt and use the developed information, design and promotion tools and thus increase the market penetration of energy efficient fenestration products. In particular, a crucial success criterion was to move gas and electric utilities to increase the promotion of energy efficient windows through demand side management programs as an important step toward increasing the market share of energy efficient windows.

  10. Feedback and efficient behavior.

    Directory of Open Access Journals (Sweden)

    Sandro Casal

    Full Text Available Feedback is an effective tool for promoting efficient behavior: it enhances individuals' awareness of choice consequences in complex settings. Our study aims to isolate the mechanisms underlying the effects of feedback on achieving efficient behavior in a controlled environment. We design a laboratory experiment in which individuals are not aware of the consequences of different alternatives and, thus, cannot easily identify the efficient ones. We introduce feedback as a mechanism to enhance the awareness of consequences and to stimulate exploration and search for efficient alternatives. We assess the efficacy of three different types of intervention: provision of social information, manipulation of the frequency, and framing of feedback. We find that feedback is most effective when it is framed in terms of losses, that it reduces efficiency when it includes information about inefficient peers' behavior, and that a lower frequency of feedback does not disrupt efficiency. By quantifying the effect of different types of feedback, our study suggests useful insights for policymakers.

  11. Muc5b is required for airway defence

    Science.gov (United States)

    Roy, Michelle G.; Livraghi-Butrico, Alessandra; Fletcher, Ashley A.; McElwee, Melissa M.; Evans, Scott E.; Boerner, Ryan M.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S.; Bowden, M. Gabriela; Sisson, Joseph H.; Woodruff, Prescott G.; Thornton, David J.; Rousseau, Karine; de La Garza, Maria M.; Moghaddam, Seyed J.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.; Davis, C. William; Terrell, Kristy A.; Grubb, Barbara R.; O'Neal, Wanda K.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Boucher, Richard C.; Dickey, Burton F.; Evans, Christopher M.

    2014-01-01

    Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b-/- mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

  12. Supernovae Discovery Efficiency

    Science.gov (United States)

    John, Colin

    2018-01-01

    Abstract:We present supernovae (SN) search efficiency measurements for recent Hubble Space Telescope (HST) surveys. Efficiency is a key component to any search, and is important parameter as a correction factor for SN rates. To achieve an accurate value for efficiency, many supernovae need to be discoverable in surveys. This cannot be achieved from real SN only, due to their scarcity, so fake SN are planted. These fake supernovae—with a goal of realism in mind—yield an understanding of efficiency based on position related to other celestial objects, and brightness. To improve realism, we built a more accurate model of supernovae using a point-spread function. The next improvement to realism is planting these objects close to galaxies and of various parameters of brightness, magnitude, local galactic brightness and redshift. Once these are planted, a very accurate SN is visible and discoverable by the searcher. It is very important to find factors that affect this discovery efficiency. Exploring the factors that effect detection yields a more accurate correction factor. Further inquires into efficiency give us a better understanding of image processing, searching techniques and survey strategies, and result in an overall higher likelihood to find these events in future surveys with Hubble, James Webb, and WFIRST telescopes. After efficiency is discovered and refined with many unique surveys, it factors into measurements of SN rates versus redshift. By comparing SN rates vs redshift against the star formation rate we can test models to determine how long star systems take from the point of inception to explosion (delay time distribution). This delay time distribution is compared to SN progenitors models to get an accurate idea of what these stars were like before their deaths.

  13. High-power, high-efficiency FELs

    International Nuclear Information System (INIS)

    Sessler, A.M.

    1989-04-01

    High power, high efficiency FELs require tapering, as the particles loose energy, so as to maintain resonance between the electromagnetic wave and the particles. They also require focusing of the particles (usually done with curved pole faces) and focusing of the electromagnetic wave (i.e. optical guiding). In addition, one must avoid transverse beam instabilities (primarily resistive wall) and longitudinal instabilities (i.e sidebands). 18 refs., 7 figs., 3 tabs

  14. Extracellular requirements for the endocytosis of carcinogenic crystalline nickel sulfide particles by facultative phagocytes

    International Nuclear Information System (INIS)

    Heck, J.D.; Costa, M.

    1982-01-01

    Various culture medium components were examined for their effect upon the phagocytosis of carcinogenic crystalline and non-carcinogenic amorphous NiS by cultured fibroblastic cells using both a visual and radioactive assay for phagocytosis. Crystalline 63 NiS was phagocytosed by cells in a simple salts/glucose maintenance medium to an extent similar to that observed in complex culture medium fortified with 10% fetal bovine serum (FBS), suggesting that serum proteins and other components in complex culture medium exert little influence upon the uptake of these heavy metal particles. Phagocytosis of crystalline NiS was shown to be highly dependent upon Ca 2+ since omission of Ca 2+ from the salts/glucose medium substantially reduced phagocytosis, while readdition of Ca 2+ stimulated uptake in a concentration-dependent manner. The uptake of the NiS particles was inhibited by trifluoperazine, a calmodulin antagonist, implicating intracellular Ca 2+ in this phagocytosis process. Since the opposite surface charge of crystalline and amorphous NiS has been related to their different phagocytic uptake by cells whose primary function is not phagocytosis (facultative phagocytes), these results show that the culture medium components do not modify the surface charge of these particles in a way that significantly influences their uptake. (Auth.)

  15. Feed tank transfer requirements

    International Nuclear Information System (INIS)

    Freeman-Pollard, J.R.

    1998-01-01

    This document presents a definition of tank turnover. Also, DOE and PC responsibilities; TWRS DST permitting requirements; TWRS Authorization Basis (AB) requirements; TWRS AP Tank Farm operational requirements; unreviewed safety question (USQ) requirements are presented for two cases (i.e., tank modifications occurring before tank turnover and tank modification occurring after tank turnover). Finally, records and reporting requirements, and documentation which will require revision in support of transferring a DST in AP Tank Farm to a privatization contractor are presented

  16. Feed tank transfer requirements

    Energy Technology Data Exchange (ETDEWEB)

    Freeman-Pollard, J.R.

    1998-09-16

    This document presents a definition of tank turnover. Also, DOE and PC responsibilities; TWRS DST permitting requirements; TWRS Authorization Basis (AB) requirements; TWRS AP Tank Farm operational requirements; unreviewed safety question (USQ) requirements are presented for two cases (i.e., tank modifications occurring before tank turnover and tank modification occurring after tank turnover). Finally, records and reporting requirements, and documentation which will require revision in support of transferring a DST in AP Tank Farm to a privatization contractor are presented.

  17. THEORETICAL FOUNDATIONS EFFICIENT MASS VALUATION

    Directory of Open Access Journals (Sweden)

    Koshel A.

    2016-08-01

    composition of results and consideration of cost, given different definitions of efficiency and offered various ways to measure. The question of social, environmental and other efficiency are considered generally as elements that complement economic efficiency. For land evaluation work efficiency are the following types: economic (increase in tax collection and tax payments; ecological (removal of the negative impact on the earth, the environment; social (improvement of living conditions of the population in a particular area; information (identifying objects not previously recorded, increasing the number of taxpayers. Achieving economic or social effect due to the need for ongoing and one-time costs. The ongoing related costs included in cost of production. In order to improve the efficiency of monetary value of land mass based methods, in our view, to apply emergency measures to correct the situation in the monetary evaluation assessments, namely: - need to develop clear and understandable regulations for the implementation of mass land valuation, passage of expertise, information and other aspects of the implementation of inventory and evaluation work; - should develop new or significantly alter already existing methods so that they meet the requirements of international law, international standards of evaluation, and allow the user to understand the simple manufacturing process works; - appraiser who performs the mass appraisal should be fully independent and protected by law from public authorities.

  18. Productivity and energy efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Lovins, H. [Rocky Mountain Inst., Snowmass, CO (United States)

    1995-12-31

    Energy efficient building and office design offers the possibility of significantly increased worker productivity. By improving lighting, heating and cooling, workers can be made more comfortable and productive. An increase of 1 percent in productivity can provide savings to a company that exceed its entire energy bill. Efficient design practices are cost effective just from their energy savings. The resulting productivity gains make them indispensable. This paper documents eight cases in which efficient lighting, heating, and cooling have measurably increased worker productivity, decreased absenteeism, and/or improved the quality of work performed. They also show that efficient lighting can measurably increase work quality by removing errors and manufacturing defects. The case studies presented include retrofit of existing buildings and the design of new facilities, and cover a variety of commercial and industrial settings. Each case study identifies the design changes that were most responsible for increased productivity. As the eight case studies illustrate, energy efficient design may be one of the least expensive ways for a business to improve the productivity of its workers and the quality of its product. (author). 15 refs.

  19. Span efficiency in hawkmoths.

    Science.gov (United States)

    Henningsson, Per; Bomphrey, Richard J

    2013-07-06

    Flight in animals is the result of aerodynamic forces generated as flight muscles drive the wings through air. Aerial performance is therefore limited by the efficiency with which momentum is imparted to the air, a property that can be measured using modern techniques. We measured the induced flow fields around six hawkmoth species flying tethered in a wind tunnel to assess span efficiency, ei, and from these measurements, determined the morphological and kinematic characters that predict efficient flight. The species were selected to represent a range in wingspan from 40 to 110 mm (2.75 times) and in mass from 0.2 to 1.5 g (7.5 times) but they were similar in their overall shape and their ecology. From high spatio-temporal resolution quantitative wake images, we extracted time-resolved downwash distributions behind the hawkmoths, calculating instantaneous values of ei throughout the wingbeat cycle as well as multi-wingbeat averages. Span efficiency correlated positively with normalized lift and negatively with advance ratio. Average span efficiencies for the moths ranged from 0.31 to 0.60 showing that the standard generic value of 0.83 used in previous studies of animal flight is not a suitable approximation of aerodynamic performance in insects.

  20. Energy efficient design

    International Nuclear Information System (INIS)

    1991-01-01

    Solar Applications and Energy Efficiency in Building Design and Town Planning (RER/87/006) is a United Nations Development Programme (UNDP) project of the Governments of Albania, Bulgaria, Cyprus, The Czech and Slovak Federal Republic, France, Hungary, Malta, Poland, Turkey, United Kingdom and Yugoslavia. The project began in 1988 and comes to a conclusion at the end of 1991. It is to enhance the professional skills of practicing architects, engineers and town planners in European countries to design energy efficient buildings which reduce energy consumption and make greater use of passive solar heating and natural cooling techniques. The United Nations Economic Commission for Europe (ECE) is the Executing Agency of the project which is implemented under the auspices of the Committee on Energy, General Energy Programme of Work for 1990-1994, sub-programme 5 Energy Conservation and Efficiency (ECE/ENERGY/15). The project has five main outputs or results: an international network of institutions for low energy building design; a state-of-the-art survey of energy use in the built environment of European IPF countries; a simple computer program for energy efficient building design; a design guide and computer program operators' manual; and a series of international training courses in participating European IPF countries. Energy Efficient Design is the fourth output of the project. It comprises the design guide for practicing architects and engineers, for use mainly in mid-career training courses, and the operators' manual for the project's computer program

  1. Energy Efficiency Center - Overview

    International Nuclear Information System (INIS)

    Obryk, E.

    2000-01-01

    Full text: The Energy Efficiency Center (EEC) activities have been concentrated on Energy Efficiency Network (SEGE), education and training of energy auditors. EEC has started studies related to renewable fuels (bio fuel, wastes) and other topics related to environment protection. EEC has continued close collaboration with Institute for Energy Technology, Kjeller, Norway. It has been organized and conducted Seminar and Workshop on ''How to Reduce Energy and Water Cost in Higher Education Buildings'' for general and technical managers of the higher education institutions. This Seminar was proceeded by the working meeting on energy efficiency strategy in higher education at the Ministry of National Education. EEC has worked out proposal for activities of Cracow Regional Agency for Energy Efficiency and Environment and has made offer to provide services for this Agency in the field of training, education and consulting. The vast knowledge and experiences in the field of energy audits have been used by the members of EEC in lecturing at energy auditors courses authorized by the National Energy Efficiency Agency (KAPE). Altogether 20 lectures have been delivered. (author)

  2. Transition towards energy efficient machine tools

    Energy Technology Data Exchange (ETDEWEB)

    Zein, Andre [Technische Univ. Braunschweig (Germany). Inst. fuer Werkzeugmaschinen und Fertigungstechnik

    2012-07-01

    Provides unique data about industrial trends affecting the energy demand of machine tools. Presents a comprehensive methodology to assess the energy efficiency of machining processes. Contains an integrated management concept to implement energy performance measures into existing industrial systems. Includes an industrial case study with two exemplary applications. Energy efficiency represents a cost-effective and immediate strategy of a sustainable development. Due to substantial environmental and economic implications, a strong emphasis is put on the electrical energy requirements of machine tools for metalworking processes. The improvement of energy efficiency is however confronted with diverse barriers, which sustain an energy efficiency gap of unexploited potential. The deficiencies lie in the lack of information about the actual energy requirements of machine tools, a minimum energy reference to quantify improvement potential and the possible actions to improve the energy demand. Therefore, a comprehensive concept for energy performance management of machine tools is developed which guides the transition towards energy efficient machine tools. It is structured in four innovative concept modules, which are embedded into step-by-step workflow models. The capability of the performance management concept is demonstrated in an automotive manufacturing environment. The target audience primarily comprises researchers and practitioners challenged to enhance energy efficiency in manufacturing. The book may also be beneficial for graduate students who want to specialize in this field.

  3. Efficient convolutional sparse coding

    Science.gov (United States)

    Wohlberg, Brendt

    2017-06-20

    Computationally efficient algorithms may be applied for fast dictionary learning solving the convolutional sparse coding problem in the Fourier domain. More specifically, efficient convolutional sparse coding may be derived within an alternating direction method of multipliers (ADMM) framework that utilizes fast Fourier transforms (FFT) to solve the main linear system in the frequency domain. Such algorithms may enable a significant reduction in computational cost over conventional approaches by implementing a linear solver for the most critical and computationally expensive component of the conventional iterative algorithm. The theoretical computational cost of the algorithm may be reduced from O(M.sup.3N) to O(MN log N), where N is the dimensionality of the data and M is the number of elements in the dictionary. This significant improvement in efficiency may greatly increase the range of problems that can practically be addressed via convolutional sparse representations.

  4. Efficiency of scanning automatons

    International Nuclear Information System (INIS)

    Shkundenkov, V.N.

    1977-01-01

    Investigated are the methods for improving the efficiency of the picture processing system based on an automatic scanner. Discussed are two types of such a system. In the first case the system contains both automatic and semi-automatic scanners. In the second case the system includes only the automatic scanners with the man-to-computer dialog facilities. For analyzing the role of the automatic scanner and the role of the operator in the processing system use is made of the processing system balance equation. It is proved that the picture processing system should be designed in two steps. The first step should, by all means, insure high efficiency in processing but the high capacity is not obligatory. The second step is aimed at higher capacity along with high efficiency. So, such a two-step designing makes it possible to solve the problem of higher capacity and lesser cost of picture processing

  5. Efficiency in Microfinance Cooperatives

    Directory of Open Access Journals (Sweden)

    HARTARSKA, Valentina

    2012-12-01

    Full Text Available In recognition of cooperatives’ contribution to the socio-economic well-being of their participants, the United Nations has declared 2012 as the International Year of Cooperatives. Microfinance cooperatives make a large part of the microfinance industry. We study efficiency of microfinance cooperatives and provide estimates of the optimal size of such organizations. We employ the classical efficiency analysis consisting of estimating a system of equations and identify the optimal size of microfinance cooperatives in terms of their number of clients (outreach efficiency, as well as dollar value of lending and deposits (sustainability. We find that microfinance cooperatives have increasing returns to scale which means that the vast majority can lower cost if they become larger. We calculate that the optimal size is around $100 million in lending and half of that in deposits. We find less robust estimates in terms of reaching many clients with a range from 40,000 to 180,000 borrowers.

  6. Bandwidth efficient coding

    CERN Document Server

    Anderson, John B

    2017-01-01

    Bandwidth Efficient Coding addresses the major challenge in communication engineering today: how to communicate more bits of information in the same radio spectrum. Energy and bandwidth are needed to transmit bits, and bandwidth affects capacity the most. Methods have been developed that are ten times as energy efficient at a given bandwidth consumption as simple methods. These employ signals with very complex patterns and are called "coding" solutions. The book begins with classical theory before introducing new techniques that combine older methods of error correction coding and radio transmission in order to create narrowband methods that are as efficient in both spectrum and energy as nature allows. Other topics covered include modulation techniques such as CPM, coded QAM and pulse design.

  7. Roots, plant production and nutrient use efficiency

    NARCIS (Netherlands)

    Willigen, de P.; Noordwijk, van M.

    1987-01-01

    The role of roots in obtaining high crop production levels as well as a high nutrient use efficiency is discussed. Mathematical models of diffusion and massflow of solutes towards roots are developed for a constant daily uptake requirement. Analytical solutions are given for simple and more

  8. Efficient Methods of Estimating Switchgrass Biomass Supplies

    Science.gov (United States)

    Switchgrass (Panicum virgatum L.) is being developed as a biofuel feedstock for the United States. Efficient and accurate methods to estimate switchgrass biomass feedstock supply within a production area will be required by biorefineries. Our main objective was to determine the effectiveness of in...

  9. Energy efficiency indicators. Case study, Liguria

    International Nuclear Information System (INIS)

    Ciarallo, M. A.

    2001-01-01

    The report examines the trend in the Liguria Region's energy requirements over the period 1988-1996. The trend was analysed using the regional energy balances and energy efficiency indicators, both in aggregate form and on a single sector basis. The residential sector, in particular, was singled out for an in-depth analysis using publishing and processed data [it

  10. Sustaining with efficiency the renewable energy sources

    International Nuclear Information System (INIS)

    Bano, L.; Lorenzoni, A.

    2008-01-01

    European energy policy requires actions, in favour of a more widespread diffusion of renewable energy sources. Is essential to have an efficient financial support to reduce costs. Are presented an estimated of electric power from renewable energy sources and some criticism. Is proposed a modification of green certificates market based on bilateral tradable agreements [it

  11. The Energy Efficient Enterprise

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Bashir

    2010-09-15

    Since rising energy costs have become a crucial factor for the economy of production processes, the optimization of energy efficiency is of essential importance for industrial enterprises. Enterprises establish energy saving programs, specific to their needs. The most important elements of these energy efficiency programs are energy savings, energy controlling, energy optimization, and energy management. This article highlights the industrial enterprise approach to establish sustainable energy management programs based on the above elements. Globally, if organizations follow this approach, they can significantly reduce the overall energy consumption and cost.

  12. Dimensions of energy efficiency

    International Nuclear Information System (INIS)

    Ramani, K.V.

    1992-01-01

    In this address the author describes three dimensions of energy efficiency in order of increasing costs: conservation, resource and technology substitution, and changes in economic structure. He emphasizes the importance of economic rather than environmental rationales for energy efficiency improvements in developing countries. These countries do not place high priority on the problems of global climate change. Opportunities for new technologies may exist in resource transfer, new fuels and, possibly, small reactors. More research on economic and social impacts of technologies with greater sensitivity to user preferences is needed

  13. Efficient use of energy

    CERN Document Server

    Dryden, IGC

    2013-01-01

    The Efficient Use of Energy, Second Edition is a compendium of papers discussing the efficiency with which energy is used in industry. The collection covers relevant topics in energy handling and describes the more important features of plant and equipment. The book is organized into six parts. Part I presents the various methods of heat production. The second part discusses the use of heat in industry and includes topics in furnace design, industrial heating, boiler plants, and water treatment. Part III deals with the production of mechanical and electrical energy. It tackles the principles o

  14. Efficient computation of hashes

    International Nuclear Information System (INIS)

    Lopes, Raul H C; Franqueira, Virginia N L; Hobson, Peter R

    2014-01-01

    The sequential computation of hashes at the core of many distributed storage systems and found, for example, in grid services can hinder efficiency in service quality and even pose security challenges that can only be addressed by the use of parallel hash tree modes. The main contributions of this paper are, first, the identification of several efficiency and security challenges posed by the use of sequential hash computation based on the Merkle-Damgard engine. In addition, alternatives for the parallel computation of hash trees are discussed, and a prototype for a new parallel implementation of the Keccak function, the SHA-3 winner, is introduced.

  15. Requirements on high resolution detectors

    Energy Technology Data Exchange (ETDEWEB)

    Koch, A. [European Synchrotron Radiation Facility, Grenoble (France)

    1997-02-01

    For a number of microtomography applications X-ray detectors with a spatial resolution of 1 {mu}m are required. This high spatial resolution will influence and degrade other parameters of secondary importance like detective quantum efficiency (DQE), dynamic range, linearity and frame rate. This note summarizes the most important arguments, for and against those detector systems which could be considered. This article discusses the mutual dependencies between the various figures which characterize a detector, and tries to give some ideas on how to proceed in order to improve present technology.

  16. Testing requirements for SCWR radiolysis

    International Nuclear Information System (INIS)

    Guzonas, D.; Stuart, C.; Jay-Gerin, J.-P.; Meesungnoen, J.

    2010-01-01

    The Generation IV supercritical water-cooled reactor (SCWR) designs under consideration would operate at ∼430-625 o C and 25 MPa, i.e., well beyond the thermodynamic critical point of water. Supercritical (light/heavy) water (SCW)-cooled reactors would enable thermodynamic cycle efficiencies as high as ∼44% (versus ∼33% for existing water reactors), thus generating lower-cost electricity. The purpose of this report is to survey the literature on SCW radiolysis, describe the recent modeling performed at the Universite de Sherbrooke, and to broadly outline the testing required to develop a benchmarked SCW radiolysis model. (author)

  17. Regional level approach for increasing energy efficiency

    International Nuclear Information System (INIS)

    Viholainen, Juha; Luoranen, Mika; Väisänen, Sanni; Niskanen, Antti; Horttanainen, Mika; Soukka, Risto

    2016-01-01

    Highlights: • Comprehensive snapshot of regional energy system for decision makers. • Connecting regional sustainability targets and energy planning. • Involving local players in energy planning. - Abstract: Actions for increasing the renewable share in the energy supply and improving both production and end-use energy efficiency are often built into the regional level sustainability targets. Because of this, many local stakeholders such as local governments, energy producers and distributors, industry, and public and private sector operators require information on the current state and development aspects of the regional energy efficiency. The drawback is that an overall view on the focal energy system operators, their energy interests, and future energy service needs in the region is often not available for the stakeholders. To support the local energy planning and management of the regional energy services, an approach for increasing the regional energy efficiency is being introduced. The presented approach can be seen as a solid framework for gathering the required data for energy efficiency analysis and also evaluating the energy system development, planned improvement actions, and the required energy services at the region. This study defines the theoretical structure of the energy efficiency approach and the required steps for revealing such energy system improvement actions that support the regional energy plan. To demonstrate the use of the approach, a case study of a Finnish small-town of Lohja is presented. In the case example, possible actions linked to the regional energy targets were evaluated with energy efficiency analysis. The results of the case example are system specific, but the conducted study can be seen as a justified example of generating easily attainable and transparent information on the impacts of different improvement actions on the regional energy system.

  18. Exigências de energia para mantença e eficiência de utilização da energia metabolizável para mantença e ganho de peso de caprinos Moxotó Energy requirements for maintenance and net efficiency of metabolizable energy utilization for maintenance and weight gain of Moxotó kids

    Directory of Open Access Journals (Sweden)

    Kaliandra Souza Alves

    2008-08-01

    Full Text Available Objetivou-se avaliar as exigências líquidas de energia para mantença e as eficiências de utilização da energia metabolizável (EUEM para mantença (km e ganho de peso (kf. Utilizaram-se 26 animais da raça Moxotó, machos não-castrados com peso vivo (PV médio inicial de 15 kg e 7 a 8 meses de idade, alimentados com dieta contendo 2,6 Mcal de energia metabolizável. No início do experimento, seis animais foram abatidos e serviram como referência para estimativa da composição corporal e do peso de corpo vazio (PCVZ iniciais. Posteriormente, os animais foram distribuídos inteiramente ao acaso em grupos homogêneos de quatro animais, um para cada nível de consumo: alimentação à vontade (AV e alimentação restrita (85, 70 e 55% do consumido pelo grupo que recebeu alimentação à vontade. No momento em que o PV dos animais que recebiam alimentação à vontade se aproximava de 25 kg, o grupo era abatido. As exigências líquidas de energia para mantença foram estimadas pelas relações logarítmica ou exponencial da produção de calor (PC e o consumo de energia metabolizável (CEM. As km e kf foram calculadas como a relação entre a energia líquida da dieta para ganho ou mantença e a concentração de energia metabolizável das dietas. Posteriormente, estimaram-se as exigências de EM e NDT. A exigência de energia líquida para mantença, de 55,11 kcal/kgPCVZ0,75, foi próxima ao predito pelas normas norte-americanas para essa espécie. Esse valor é considerado baixo se comparado aos reportados na literatura brasileira pesquisada. A km estimada foi de 0,57 e as kf para as concentrações de 2,99; 2,95; 2,56 e 2,5 Mcal/kg de MS foram de 0,22; 0,19; 0,28 e 0,36, respectivamente.Twenty-six Moxotó non-castrated male kids (averaging 15 kg of initial live weight (LW and 6-8 months old fed a diet with 2.6 Mcal of metabolizable energy were used to predict the net energy requirements for maintenance and net efficiency of

  19. Energy efficient technologies for the mining industry

    Energy Technology Data Exchange (ETDEWEB)

    Klein, B.; Bamber, A.; Weatherwax, T.; Dozdiak, J.; Nadolski, S.; Roufail, R.; Parry, J.; Roufail, R.; Tong, L.; Hall, R. [British Columbia Univ., Vancouver, BC (Canada). Centre for Environmental Research in Minerals, Metals and Materials, Norman B. Keevil Inst. of Mining Engineering

    2010-07-01

    Mining in British Columbia is the second largest industrial electricity consumer. This presentation highlighted methods to help the mining industry reduce their energy requirements by limiting waste and improving efficiency. The measures are aimed at optimizing energy-use and efficiency in mining and processing and identifying opportunities and methods of improving this efficiency. Energy conservation in comminution and beneficiation is a primary focus of research activities at the University of British Columbia (UBC). The objective is to reduce energy usage in metal mines by 20 per cent overall. Open pit copper, gold and molybdenum mines are being targeted. Projects underway at UBC were outlined, with particular reference to energy usage, recovery and alternative energy sources; preconcentration; reducing energy usage from comminution in sorting, high pressure grinding rolls and high speed stirred mills; Hydromet; other energy efficient technologies such as control and flotation; and carbon dioxide sequestration. Studies were conducted at various mining facilities, including mines in Sudbury, Ontario. tabs., figs.

  20. An efficient quantum algorithm for spectral estimation

    Science.gov (United States)

    Steffens, Adrian; Rebentrost, Patrick; Marvian, Iman; Eisert, Jens; Lloyd, Seth

    2017-03-01

    We develop an efficient quantum implementation of an important signal processing algorithm for line spectral estimation: the matrix pencil method, which determines the frequencies and damping factors of signals consisting of finite sums of exponentially damped sinusoids. Our algorithm provides a quantum speedup in a natural regime where the sampling rate is much higher than the number of sinusoid components. Along the way, we develop techniques that are expected to be useful for other quantum algorithms as well—consecutive phase estimations to efficiently make products of asymmetric low rank matrices classically accessible and an alternative method to efficiently exponentiate non-Hermitian matrices. Our algorithm features an efficient quantum-classical division of labor: the time-critical steps are implemented in quantum superposition, while an interjacent step, requiring much fewer parameters, can operate classically. We show that frequencies and damping factors can be obtained in time logarithmic in the number of sampling points, exponentially faster than known classical algorithms.

  1. Corporate efficiency in Europe

    Czech Academy of Sciences Publication Activity Database

    Hanousek, Jan; Kočenda, E.; Shamshur, Anastasiya

    2015-01-01

    Roč. 32, June (2015), s. 24-40 ISSN 0929-1199 R&D Projects: GA ČR(CZ) GA15-15927S Institutional support: PRVOUK-P23 Keywords : efficiency * ownership structure * firms Subject RIV: AH - Economics Impact factor: 1.286, year: 2015

  2. Robust efficient video fingerprinting

    Science.gov (United States)

    Puri, Manika; Lubin, Jeffrey

    2009-02-01

    We have developed a video fingerprinting system with robustness and efficiency as the primary and secondary design criteria. In extensive testing, the system has shown robustness to cropping, letter-boxing, sub-titling, blur, drastic compression, frame rate changes, size changes and color changes, as well as to the geometric distortions often associated with camcorder capture in cinema settings. Efficiency is afforded by a novel two-stage detection process in which a fast matching process first computes a number of likely candidates, which are then passed to a second slower process that computes the overall best match with minimal false alarm probability. One key component of the algorithm is a maximally stable volume computation - a three-dimensional generalization of maximally stable extremal regions - that provides a content-centric coordinate system for subsequent hash function computation, independent of any affine transformation or extensive cropping. Other key features include an efficient bin-based polling strategy for initial candidate selection, and a final SIFT feature-based computation for final verification. We describe the algorithm and its performance, and then discuss additional modifications that can provide further improvement to efficiency and accuracy.

  3. Efficient Immutable Collections

    NARCIS (Netherlands)

    Steindorfer, M.J.

    2017-01-01

    This thesis proposes novel and efficient data structures, suitable for immutable collection libraries, that carefully balance memory footprint and runtime performance of operations, and are aware of constraints and platform co-design challenges on the Java Virtual Machine (JVM). Collection data

  4. Efficient XPath Evaluation

    NARCIS (Netherlands)

    Wang, B.; Feng, L.; Shen, Y.

    Inspired by the best querying performance of ViST among the rest of the approaches in the literature, and meanwhile to overcome its shortcomings, in this paper, we present another efficient and novel geometric sequence mechanism, which transforms XML documents and XPath queries into the

  5. ERP=Efficiency

    Science.gov (United States)

    Violino, Bob

    2008-01-01

    This article discusses the enterprise resource planning (ERP) system. Deploying an ERP system is one of the most extensive--and expensive--IT projects a college or university can undertake. The potential benefits of ERP are significant: a more smoothly running operation with efficiencies in virtually every area of administration, from automated…

  6. Microeconomics : Equilibrium and Efficiency

    NARCIS (Netherlands)

    Ten Raa, T.

    2013-01-01

    Microeconomics: Equilibrium and Efficiency teaches how to apply microeconomic theory in an innovative, intuitive and concise way. Using real-world, empirical examples, this book not only covers the building blocks of the subject, but helps gain a broad understanding of microeconomic theory and

  7. Institutions, Equilibria and Efficiency

    DEFF Research Database (Denmark)

    Competition and efficiency is at the core of economic theory. This volume collects papers of leading scholars, which extend the conventional general equilibrium model in important ways. Efficiency and price regulation are studied when markets are incomplete and existence of equilibria in such set......Competition and efficiency is at the core of economic theory. This volume collects papers of leading scholars, which extend the conventional general equilibrium model in important ways. Efficiency and price regulation are studied when markets are incomplete and existence of equilibria...... in such settings is proven under very general preference assumptions. The model is extended to include geographical location choice, a commodity space incorporating manufacturing imprecision and preferences for club-membership, schools and firms. Inefficiencies arising from household externalities or group...... membership are evaluated. Core equivalence is shown for bargaining economies. The theory of risk aversion is extended and the relation between risk taking and wealth is experimentally investigated. Other topics include: determinacy in OLG with cash-in-advance constraints, income distribution and democracy...

  8. Web anonymization efficiency study

    Science.gov (United States)

    Sochor, Tomas

    2017-11-01

    The analysis of TOR, JonDo and CyberGhost efficiency (measured the as latency increase and transmission speed decrease) is presented in the paper. Results showed that all tools have relatively favorable latency increase (no more than 60% RTT increase). The transmission speed increase was much more significant (more than 60%), and even more for JonDo (above 90%).

  9. Energy efficiency in Finland

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    In Finland a significant portion of energy originates from renewable sources and cogeneration, that is, combined production of electricity and heat. Combined heat and electricity production is typical in the Finnish industry and in the district heating sector. One third of all electricity and 15 % of district heating is produced by cogeneration. District heating schemes provide about 45 % of heat in buildings. Overall efficiency in industry exceeds 80 % and is even higher in the district heating sector. In 1996 25 % of Finland`s primary energy was produced from renewable energy sources which is a far higher proportion than the European Union average of 6 %. Finland is one of the leading users of bioenergy. Biomass including peat, provides approximately 50 % of fuel consumed by industry and is utilised in significant amounts in combined heat and electricity plants. For example, in the pulp and paper industry, by burning black liquor and bark during the production of chemical pulp, significant amounts of energy are generated and used in paper mills. Conservation and efficient use of energy are central to the Finnish Government`s Energy Strategy. The energy conservation programme aims to increase energy efficiency by 10-20 % by the year 2010. Energy saving technology plays a key role in making the production and use of energy more efficient. In 1996 of FIM 335 million (ECU 57 million) spent on funding research, FIM 120 million (ECU 20 million) was spent on research into energy conservation

  10. Cataloging Efficiency and Effectiveness.

    Science.gov (United States)

    McCain, Cheryl; Shorten, Jay

    2002-01-01

    Reports on a survey of academic libraries that was conducted to supplement findings of cost studies by providing measures of efficiency and effectiveness for cataloging departments based on reported productivity, number of staff, task distribution, and quality measures including backlogs, authority control, and database maintenance. Identifies…

  11. Jet Inlet Efficiency

    Science.gov (United States)

    2013-08-08

    AFRL-RW-EG-TR-2014-044 Jet Inlet Efficiency Nigel Plumb Taylor Sykes-Green Keith Williams John Wohleber Munitions Aerodynamics Sciences...CONTRACT NUMBER N/A 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER N/A 6. AUTHOR(S) Nigel Plumb Taylor Sykes-Green Keith Williams John

  12. An efficiency correction model

    NARCIS (Netherlands)

    Francke, M.K.; de Vos, A.F.

    2009-01-01

    We analyze a dataset containing costs and outputs of 67 American local exchange carriers in a period of 11 years. This data has been used to judge the efficiency of BT and KPN using static stochastic frontier models. We show that these models are dynamically misspecified. As an alternative we

  13. From Policy to Compliance: Federal Energy Efficient Product Procurement

    Energy Technology Data Exchange (ETDEWEB)

    DeMates, Laurèn [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Scodel, Anna [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-09-06

    Federal buyers are required to purchase energy-efficient products in an effort to minimize energy use in the federal sector, save the federal government money, and spur market development of efficient products. The Federal Energy Management Program (FEMP)’s Energy Efficient Product Procurement (EEPP) Program helps federal agencies comply with the requirement to purchase energy-efficient products by providing technical assistance and guidance and setting efficiency requirements for certain product categories. Past studies have estimated the savings potential of purchasing energy-efficient products at over $500 million per year in energy costs across federal agencies.1 Despite the strong policy support for EEPP and resources available, energy-efficient product purchasing operates within complex decision-making processes and operational structures; implementation challenges exist that may hinder agencies’ ability to comply with purchasing requirements. The shift to purchasing green products, including energy-efficient products, relies on “buy in” from a variety of potential actors throughout different purchasing pathways. Challenges may be especially high for EEPP relative to other sustainable acquisition programs given that efficient products frequently have a higher first cost than non-efficient ones, which may be perceived as a conflict with fiscal responsibility, or more simply problematic for agency personnel trying to stretch limited budgets. Federal buyers may also face challenges in determining whether a given product is subject to EEPP requirements. Previous analysis on agency compliance with EEPP, conducted by the Alliance to Save Energy (ASE), shows that federal agencies are getting better at purchasing energy-efficient products. ASE conducted two reviews of relevant solicitations for product and service contracts listed on Federal Business Opportunities (FBO), the centralized website where federal agencies are required to post procurements greater

  14. Encouraging energy efficiency: Policies and programs

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Successfully overcoming the barriers to higher energy efficiency requires development of policies designed for specific users and locations. Reform of energy pricing, which entails removing subsidies and beginning internalization of externalities, is critical to give technology producers and users proper signals for investment and management decisions. But while a rise in energy prices increases the amount of energy-efficiency improvement that is cost-effective, it does not remove other barriers that deter investment. Minimum efficiency standards or agreements can raise the market floor, and are important because they affect the entire market in the near-term. But they may not raise the celining very much, and do little to push the efficiency frontier. To accomplish these goals, incentives and other market-development strategies are needed. Utility programs in particular can play a key role in pushing energy efficiency beyond the level where users are likely to invest on their own. Policies, programs, and pricing should complement one another. Pricing reform alone will not overcome the many entrenched barriers to higher energy efficiency, but trying to accelerate energy efficiency improvement without addressing energy pricing problems will lead to limited success. Whether tagerting new equipment or management of existing systems, policies must reflect a thorough understanding of the particular system and an awareness of the motivations of the actors. 25 refs

  15. National energy efficiency study. The Czech Republic

    International Nuclear Information System (INIS)

    Maly, M.; Jakubes, J.; Spitz, J.; Van Wees, M.T.; Uyterlinde, M.A.; Martens, J.W.; Van Oostvoorn, F.; Henelova, V.; Vazac, V.; Zalesak, M.; Marousek, J.; Szomolanyiova, J.; Havlickova, M.; Zeman, J.; Ten Donkelaar, M.; Travnicek, S.; Stejskal, F.; Pribyl, E.; Blokker, L.; Bizek, V.; Velthuijsen, J.W.

    1999-08-01

    Energy efficiency and renewable energy production contribute to the three major goals of the national energy policy of the Czech Republic: overall competitiveness, security of supply; and environmental protection. Therefore, the Czech Government aims to promote these two sustainable options. The National Energy Efficiency Study has developed specific policies for the promotion of end use energy efficiency and renewables. These are described in two Action Plans, and in this report which serves as a background document. It contains detailed information on options and measures, potentials, barriers and policy instruments for energy efficiency and renewables. The main part is a detailed outline for a new energy efficiency and renewable policy, including a listing of actions for implementation. Also, it includes recommendations for financing schemes to overcome the investment constraints in the Czech Republic. Finally, a list of concrete projects is presented to support project identification. In addition, two separate Action Plans have been published: (1) The Energy Efficiency Action Plan focuses on promotion of energy efficiency in end-use (separate document, ECN-C-99-065); and (2) The Renewable Energy Action Plan (separate document, ECN-C-99-064) deals with policy on promotion of renewable energy production. These two policy documents should provide policy makers in the Czech Government with essential information on potentials, targets, the required budget, and recommended policy instruments. The core of the Action Plans is the list of concrete policy actions, ready for implementation

  16. Highly efficient high temperature electrolysis

    DEFF Research Database (Denmark)

    Hauch, Anne; Ebbesen, Sune; Jensen, Søren Højgaard

    2008-01-01

    High temperature electrolysis of water and steam may provide an efficient, cost effective and environmentally friendly production of H-2 Using electricity produced from sustainable, non-fossil energy sources. To achieve cost competitive electrolysis cells that are both high performing i.e. minimum...... internal resistance of the cell, and long-term stable, it is critical to develop electrode materials that are optimal for steam electrolysis. In this article electrolysis cells for electrolysis of water or steam at temperatures above 200 degrees C for production of H-2 are reviewed. High temperature...... electrolysis is favourable from a thermodynamic point of view, because a part of the required energy can be supplied as thermal heat, and the activation barrier is lowered increasing the H-2 production rate. Only two types of cells operating at high temperature (above 200 degrees C) have been described...

  17. Efficient measurement of radon daughters

    International Nuclear Information System (INIS)

    Rolle, R.

    1992-01-01

    In environmental control there is an increasing need for efficient measurement of radon and thoron daughters in air. Measuring instruments should be rugged and portable for field use, while also permitting unattended operation for several days. Simple operating procedures should permit evaluation of rapidly changing concentrations over extended periods. These requirements demand careful balance in the design of hardware and measuring procedures. The design principles for a continuous flow-through spectrometer, that has been developed for precision sequential measurement of radon and thoron daughters, are described. Because of the high precision of measurement, this type of instrument should find application in environments from technologically enhanced natural radiation to the very lowest natural background situations. (author)

  18. Energy Efficiency in Manufacturing Systems

    CERN Document Server

    Thiede, Sebastian

    2012-01-01

    Energy consumption is of great interest to manufacturing companies. Beyond considering individual processes and machines, the perspective on process chains and factories as a whole holds major potentials for energy efficiency improvements. To exploit these potentials, dynamic interactions of different processes as well as auxiliary equipment (e.g. compressed air generation) need to be taken into account. In addition, planning and controlling manufacturing systems require  balancing technical, economic and environmental objectives. Therefore, an innovative and comprehensive methodology – with a generic energy flow-oriented manufacturing simulation environment as a core element – is developed and embedded into a step-by-step application cycle. The concept is applied in its entirety to a wide range of case studies such as aluminium die casting, weaving mills, and printed circuit board assembly in order to demonstrate the broad applicability and the benefits that can be achieved.

  19. Assessing Requirements Quality through Requirements Coverage

    Science.gov (United States)

    Rajan, Ajitha; Heimdahl, Mats; Woodham, Kurt

    2008-01-01

    In model-based development, the development effort is centered around a formal description of the proposed software system the model. This model is derived from some high-level requirements describing the expected behavior of the software. For validation and verification purposes, this model can then be subjected to various types of analysis, for example, completeness and consistency analysis [6], model checking [3], theorem proving [1], and test-case generation [4, 7]. This development paradigm is making rapid inroads in certain industries, e.g., automotive, avionics, space applications, and medical technology. This shift towards model-based development naturally leads to changes in the verification and validation (V&V) process. The model validation problem determining that the model accurately captures the customer's high-level requirements has received little attention and the sufficiency of the validation activities has been largely determined through ad-hoc methods. Since the model serves as the central artifact, its correctness with respect to the users needs is absolutely crucial. In our investigation, we attempt to answer the following two questions with respect to validation (1) Are the requirements sufficiently defined for the system? and (2) How well does the model implement the behaviors specified by the requirements? The second question can be addressed using formal verification. Nevertheless, the size and complexity of many industrial systems make formal verification infeasible even if we have a formal model and formalized requirements. Thus, presently, there is no objective way of answering these two questions. To this end, we propose an approach based on testing that, when given a set of formal requirements, explores the relationship between requirements-based structural test-adequacy coverage and model-based structural test-adequacy coverage. The proposed technique uses requirements coverage metrics defined in [9] on formal high-level software

  20. 5G technologies boosting efficient mobile learning

    Directory of Open Access Journals (Sweden)

    Leligou Helen C.

    2017-01-01

    Full Text Available The needs for education, learning and training proliferate primarily due to the facts that economy becomes more and more knowledge based (mandating continuous lifelong learning and people migrate among countries, which introduces the need for learning other languages, for training on different skills and learning about the new cultural and societal framework. Given that in parallel, time schedules continuously become tighter, learning through mobile devices continuously gains in popularity as it allows for learning anytime, anywhere. To increase the learning efficiency, personalisation (in terms of selecting the learning content, type and presentation and adaptation of the learning experience in real time based on the experienced affect state are key instruments. All these user requirements challenge the current network architectures and technologies. In this paper, we investigate the requirements implied by efficient mobile learning scenarios and we explore how 5G technologies currently under design/testing/validation and standardisation meet these requirements.

  1. Energy Efficiency Project Development

    Energy Technology Data Exchange (ETDEWEB)

    IUEP

    2004-03-01

    The International Utility Efficiency Partnerships, Inc. (IUEP) has been a leader among the industry groups that have supported voluntary initiatives to promote international energy efficiency projects and address global climate change. The IUEP maintains its leadership by both supporting international greenhouse gas (GHG) reduction projects under the auspices of the U.S. Department of Energy (DOE) and by partnering with U.S. and international organizations to develop and implement strategies and specific energy efficiency projects. The goals of the IUEP program are to (1) provide a way for U.S. industry to maintain a leadership role in international energy efficiency infrastructure projects; (2) identify international energy project development opportunities to continue its leadership in supporting voluntary market-based mechanisms to reduce GHG emissions; and (3) demonstrate private sector commitment to voluntary approaches to global climate issues. The IUEP is dedicated to identifying, promoting, managing, and assisting in the registration of international energy efficiency projects that result in demonstrated voluntary reductions of GHG emissions. This Final Technical Report summarizes the IUEP's work in identifying, promoting, managing, and assisting in development of these projects and IUEP's effort in creating international cooperative partnerships to support project development activities that develop and deploy technologies that (1) increase efficiency in the production, delivery and use of energy; (2) increase the use of cleaner, low-carbon fuels in processing products; and (3) capture/sequester carbon gases from energy systems. Through international cooperative efforts, the IUEP intends to strengthen partnerships for energy technology innovation and demonstration projects capable of providing cleaner energy in a cost-effective manner. As detailed in this report, the IUEP met program objectives and goals during the reporting period January 1

  2. Energy Efficient Task Light

    DEFF Research Database (Denmark)

    Logadottir, Asta; Ardkapan, Siamak Rahimi; Johnsen, Kjeld

    2014-01-01

    The objectives of this work is to develop a task light for office lighting that fulfils the minimum requirements of the European standard EN12464 - 1 : Light and lighting – Lighting of work places, Part 1: Indoor workplaces and the Danish standard DS 700 : Lys og belysning I arbejdsrum , or more...... specifically the requirements that apply to the work area and the immediate surrounding area. By providing a task light that fulfils the requirements for task lighting and the immediate surrounding area, the general lighting only needs to provide the illuminance levels required for background lighting...... and thereby a reduction in installed power for general lighting of about 40 % compared to the way illuminance levels are designed in an office environment in Denmark today. This lighting strategy is useful when the placement of the task area is not defined in the space before the lighting is design ed...

  3. USE Efficiency: an innovative educational programme for energy efficiency in buildings

    Science.gov (United States)

    Papadopoulos, Theofilos A.; Christoforidis, Georgios C.; Papagiannis, Grigoris K.

    2017-10-01

    Power engineers are expected to play a pivotal role in transforming buildings into smart and energy-efficient structures, which is necessary since buildings are responsible for a considerable amount of the total energy consumption. To fulfil this role, a holistic approach in education is required, tackling subjects traditionally related to other engineering disciplines. In this context, USE Efficiency is an inter-institutional and interdisciplinary educational programme implemented in nine European Universities targeting energy efficiency in buildings. The educational programme effectively links professors, students, engineers and industry experts, creating a unique learning environment. The scope of the paper is to present the methodology and the general framework followed in the USE Efficiency programme. The proposed methodology can be adopted for the design and implementation of educational programmes on energy efficiency and sustainable development in higher education. End-of-course survey results showed positive feedback from the participating students, indicating the success of the programme.

  4. Efficiency and Logistics

    CERN Document Server

    Hompel, Michael; Klumpp, Matthias

    2013-01-01

    The „EffizienzCluster LogistikRuhr“ was a winner in the Leading Edge Science Cluster competition run by the German federal Ministry of Education and Research. The mission and aim of the „EffizienzCluster LogistikRuhr“ is to facilitate tomorrow’s individuality – in the sense of individual goods supply, mobility, and production – using 75 percent of today’s resources. Efficiency – both in economical and ecological terms – is enabled by state-of-the-art and innovative logistical solutions including transportation, production and intralogistics. These proceedings “Efficiency and Logistics” give first answers from 27 research projects as an insight into the current state of research of Europe’s leading research and development cluster in logistics and as a contribution to the discussion on how logistics as a science can help to cope with foreseeable resource shortage and sustainability as global challenges.

  5. Danish Energy Efficiency Policy

    DEFF Research Database (Denmark)

    Togeby, Mikael; Larsen, Anders; Dyhr-Mikkelsen, Kirsten

    2009-01-01

    Ten groups of policy instruments for promoting energy efficiency are actively used in Denmark. Among these are the EU instruments such as the CO2 emissions trading scheme and labelling of appliances, labelling of all buildings, combined with national instruments such as high taxes especially...... of the entire Danish energy efficiency policy portfolio must be carried out before end 2008 and put forward for discussion among governing parties no later than February 2009. A consortium comprising Ea Energy Analyses, Niras, the Department of Society and Globalisation (Roskilde University) and 4-Fact...... on households and the public sector, obligations for energy companies (electricity, natural gas, district heating, and oil) to deliver documented savings, strict building codes, special instructions for the public sector, and an Electricity Saving Trust. A political agreement from 2005 states that an evaluation...

  6. Energy efficiency system development

    Science.gov (United States)

    Leman, A. M.; Rahman, K. A.; Chong, Haw Jie; Salleh, Mohd Najib Mohd; Yusof, M. Z. M.

    2017-09-01

    By subjecting to the massive usage of electrical energy in Malaysia, energy efficiency is now one of the key areas of focus in climate change mitigation. This paper focuses on the development of an energy efficiency system of household electrical appliances for residential areas. Distribution of Questionnaires and pay a visit to few selected residential areas are conducted during the fulfilment of the project as well as some advice on how to save energy are shared with the participants. Based on the collected data, the system developed by the UTHM Energy Team is then evaluated from the aspect of the consumers' behaviour in using electrical appliances and the potential reduction targeted by the team. By the end of the project, 60% of the participants had successfully reduced the electrical power consumption set by the UTHM Energy Team. The reasons for whether the success and the failure is further analysed in this project.

  7. Negotiating Efficient PPP Contracts

    DEFF Research Database (Denmark)

    Tvarnø, Christina D.

    . An opportunity the member states should consider using when procuring a PPP. This paper looks at the negotiation and contracting of a PPP in an economic theoretical and EU public procurement perspective and discusses how to establish an efficient PPP contract under a strong public law doctrine. Governments......This paper concerns Public Private Partnership (PPP) contracts in concern to the coming new 2014/24IEU public procurement directive. The new EU public procurement directive gives the public authority the opportunity to negotiate PPPs much more when they are implemented in national law...... procurement law. Furthermore, the paper seeks to establish a connection between public law, private law and the efficient PPP contract by drawing upon economic theory and empirical contract data from UK, US and Danish partnering contracts from the construction industry and the aim of contracting joint utility...

  8. Carbon Efficient Building Solutions

    Directory of Open Access Journals (Sweden)

    Pellervo Matilainen

    2010-03-01

    Full Text Available Traditionally, the Finnish legislation have focused on energy use and especially on energy used for heating space in buildings. However, in many cases this does not lead to the optimal concept in respect to minimizing green house gases. This paper studies how CO2 emission levels are affected by different measures to reduce energy use in buildings. This paper presents two real apartment buildings with different options of energy efficiency and power sources. The calculations clearly show that in the future electricity and domestic hot water use will have high importance in respect to energy efficiency, and therefore also CO2 equivalent (eq emissions. The importance increases when the energy efficiency of the building increases. There are big differences between average Finnish production and individual power plants; CO2 eq emissions might nearly double depending on the energy source and the power plant type. Both a building with an efficient district heating as a power source, and a building with ground heat in addition to nuclear power electricity as a complimentary electricity source performed very similarly to each other in respect to CO2 eq emissions. However, it is dangerous to conclude that it is not important which energy source is chosen. If hypothetically, the use of district heating would dramatically drop, the primary energy factor and CO2 eq emissions from electricity would rise, which in turn would lead to the increase of the ground heat systems emissions. A problem in the yearly calculations is that the fact that it is very important, sometimes even crucial, when energy is needed, is always excluded.

  9. Stirling Engine Cycle Efficiency

    OpenAIRE

    Naddaf, Nasrollah

    2012-01-01

    ABSTRACT This study strives to provide a clear explanation of the Stirling engine and its efficiency using new automation technology and the Lab View software. This heat engine was invented by Stirling, a Scottish in 1918. The engine’s working principles are based on the laws of thermodynamics and ability of volume expansion of ideal gases at different temperatures. Basically there are three types of Stirling engines: the gamma, beta and alpha models. The commissioner of the thesis ...

  10. Comminution efficiency attracts attention

    International Nuclear Information System (INIS)

    Daniel, M.J.; Lewis-Gray, E.

    2011-01-01

    The mining sector, both at a technical and board level is pursuing opportunities to achieve cost savings and reduce energy usage in their operations. Research and debate on step change efficiency benefits is particularly evident in the field of comminution (crushing and grinding) circuit design and operation. Published literature that quantifies mining related energy consumption in South Africa and Australia has been reviewed by the authors.

  11. HIGH EFFICIENCY TURBINE

    OpenAIRE

    VARMA, VIJAYA KRUSHNA

    2012-01-01

    Varma designed ultra modern and high efficiency turbines which can use gas, steam or fuels as feed to produce electricity or mechanical work for wide range of usages and applications in industries or at work sites. Varma turbine engines can be used in all types of vehicles. These turbines can also be used in aircraft, ships, battle tanks, dredgers, mining equipment, earth moving machines etc, Salient features of Varma Turbines. 1. Varma turbines are simple in design, easy to manufac...

  12. Efficient Non Linear Loudspeakers

    DEFF Research Database (Denmark)

    Petersen, Bo R.; Agerkvist, Finn T.

    2006-01-01

    Loudspeakers have traditionally been designed to be as linear as possible. However, as techniques for compensating non linearities are emerging, it becomes possible to use other design criteria. This paper present and examines a new idea for improving the efficiency of loudspeakers at high levels...... by changing the voice coil layout. This deliberate non-linear design has the benefit that a smaller amplifier can be used, which has the benefit of reducing system cost as well as reducing power consumption....

  13. Efficient HVAC. New products

    International Nuclear Information System (INIS)

    2016-01-01

    Jung is responding to the challenge of energy efficiency, ease of operation and economic profitability in all of its solutions for the tertiary sector, whether for newly constructed buildings or refurbishments, for full management of the electrical system or the partial control of lighting, HVAC, mood settings, access control, etc., for the bedrooms or specific areas of the building. In the specific case of hotels, Jung offers each a custom-made solution in line with its possibilities and objectives. (Author)

  14. High efficiency, variable geometry, centrifugal cryogenic pump

    International Nuclear Information System (INIS)

    Forsha, M.D.; Nichols, K.E.; Beale, C.A.

    1994-01-01

    A centrifugal cryogenic pump has been developed which has a basic design that is rugged and reliable with variable speed and variable geometry features that achieve high pump efficiency over a wide range of head-flow conditions. The pump uses a sealless design and rolling element bearings to achieve high reliability and the ruggedness to withstand liquid-vapor slugging. The pump can meet a wide range of variable head, off-design flow requirements and maintain design point efficiency by adjusting the pump speed. The pump also has features that allow the impeller and diffuser blade heights to be adjusted. The adjustable height blades were intended to enhance the pump efficiency when it is operating at constant head, off-design flow rates. For small pumps, the adjustable height blades are not recommended. For larger pumps, they could provide off-design efficiency improvements. This pump was developed for supercritical helium service, but the design is well suited to any cryogenic application where high efficiency is required over a wide range of head-flow conditions

  15. Postmarket Requirements and Commitments

    Data.gov (United States)

    U.S. Department of Health & Human Services — Provides information to the public on postmarket requirements and commitments. The phrase postmarket requirements and commitments refers to studies and clinical...

  16. Requirements for existing buildings

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    This report collects energy performance requirements for existing buildings in European member states by June 2012.......This report collects energy performance requirements for existing buildings in European member states by June 2012....

  17. Replacing reserve requirements

    OpenAIRE

    Edward J. Stevens

    1993-01-01

    An examination of the fading significance of the Federal Reserve System's reserve requirements and the recent flowering of required clearing balances, a rapidly growing feature of Reserve Bank operations.

  18. Economics of appliance efficiency

    International Nuclear Information System (INIS)

    Tiedemann, K.H.

    2009-01-01

    Several significant developments occurred in 2001 that affect the impact of market transformation programs. This paper presented and applied an econometric approach to the identification and estimation of market models for refrigerators, clothes washers, dishwashers and room air conditioners. The purpose of the paper was to understand the impact of energy conservation policy developments on sales of energy efficient appliances. The paper discussed the approach with particular reference to building a database of sales and drivers of sales using publicly available information; estimation of the determinants of sales using econometric models; and estimation of the individual impacts of prices, gross domestic product (GDP) and energy conservation policies on sales using regression results. Market and policy developments were also presented, such as change a light, save the world promotion; the California energy crisis; and the Pacific Northwest drought induced hydro power shortage. It was concluded that an increase in GDP increased the sales of both more efficient and less efficient refrigerators, clothes washers, dishwashers, and room air conditioners. An increase in electricity price increased sales of Energy Star refrigerators, clothes washers, dishwashers, and room air conditioners. 4 refs., 8 tabs.

  19. How energy efficiency fails in the building industry

    International Nuclear Information System (INIS)

    Ryghaug, Marianne; Sorensen, Knut H.

    2009-01-01

    This paper examines how energy efficiency fails in the building industry based on many years of research into the integration of energy efficiency in the construction of buildings and sustainable architecture in Norway. It argues that energy-efficient construction has been seriously restrained by three interrelated problems: (1) deficiencies in public policy to stimulate energy efficiency, (2) limited governmental efforts to regulate the building industry, and (3) a conservative building industry. The paper concludes that innovation and implementation of new, energy-efficient technologies in the building industry requires new policies, better regulations and reformed practices in the industry itself

  20. PIT Coating Requirements Analysis

    International Nuclear Information System (INIS)

    MINTEER, D.J.

    2000-01-01

    This study identifies the applicable requirements for procurement and installation of a coating intended for tank farm valve and pump pit interior surfaces. These requirements are intended to be incorporated into project specification documents and design media. This study also evaluates previously recommended coatings and identifies requirement-compliant coating products

  1. PIT Coating Requirements Analysis

    Energy Technology Data Exchange (ETDEWEB)

    MINTEER, D.J.

    2000-10-20

    This study identifies the applicable requirements for procurement and installation of a coating intended for tank farm valve and pump pit interior surfaces. These requirements are intended to be incorporated into project specification documents and design media. This study also evaluates previously recommended coatings and identifies requirement-compliant coating products.

  2. Future Home Network Requirements

    DEFF Research Database (Denmark)

    Charbonnier, Benoit; Wessing, Henrik; Lannoo, Bart

    This paper presents the requirements for future Home Area Networks (HAN). Firstly, we discuss the applications and services as well as their requirements. Then, usage scenarios are devised to establish a first specification for the HAN. The main requirements are an increased bandwidth (towards 1...

  3. User Requirements for Wireless

    DEFF Research Database (Denmark)

    in the elicitation process. Cases and user requirement elements discussed in the book include: User requirements elicitation processes for children, construction workers, and farmers User requirements for personalized services of a broadcast company Variations in user involvement Practical elements of user...

  4. Energy efficiency fallacies revisited

    International Nuclear Information System (INIS)

    Brookes, Leonard

    2000-01-01

    A number of governments including that of the UK subscribe to the belief that a national program devoted to raising energy efficiency throughout the economy provides a costless - indeed profitable - route to meeting international environmental obligations. This is a seductive policy. It constitutes the proverbial free lunch - not only avoiding politically unpopular measures like outlawing, taxing or rationing offending fuels or expanding non-carboniferous sources of energy like nuclear power but doing so with economic benefit. The author of this contribution came to doubt the validity of this solution when it was offered as a way of mitigating the effect of the OPEC price hikes of the 1970s, maintaining that economically justified improvement in energy efficiency led to higher levels of energy consumption at the economy-wide level than in the absence of any efficiency response. More fundamentally, he argues that there is no case for preferentially singling out energy, from among all the resources available to us, for efficiency maximisation. The least damaging policy is to determine targets, enact the restrictive measures needed to curb consumption, and then leave it to consumers - intermediate and final - to reallocate all the resources available to them to best effect subject to the new enacted constraints and any others they might be experiencing. There is no reason to suppose that it is right for all the economic adjustment following a new resource constraint to take the form of improvements in the productivity of that resource alone. As many others have argued, any action to impose resource constraint entails an inevitable economic cost in the shape of a reduction in production and consumption possibilities: there would be no free lunch. In the last few years debate about the validity of these contentions has blossomed, especially under the influence of writers on the western side of the Atlantic. In this contribution the author outlines the original arguments

  5. Driving Extreme Efficiency to Market

    Science.gov (United States)

    Garbesi, Karina

    2014-03-01

    The rapid development of extremely energy efficient appliances and equipment is essential to curtail catastrophic climate disruption. This will require the on-going development of products that apply all best-practices and that take advantage of the synergies of hybridization and building integration. Beyond that, it requires the development of new disruptive technologies and concepts. To facilitate these goals, in 2011 the Lawrence Berkeley National Laboratory and the U.S. Department of Energy launched the Max Tech and Beyond Design Competition for Ultra-Low-Energy-Use Appliances and Equipment. Now in its third year, the competition supports faculty-lead student design teams at U.S. universities to develop and test new technology prototypes. This talk describes what the competition and the Max Tech Program are doing to drive such rapid technology progress and to facilitate the entry to the market of successful Max Tech prototypes. The talk also initiates a discussion of physicists' unique role in driving that technology progress faster and farther. Emerging Technologies, Building Technologies Office, U.S. Department of Energy.

  6. High-efficiency photovoltaic cells

    Science.gov (United States)

    Yang, H.T.; Zehr, S.W.

    1982-06-21

    High efficiency solar converters comprised of a two cell, non-lattice matched, monolithic stacked semiconductor configuration using optimum pairs of cells having bandgaps in the range 1.6 to 1.7 eV and 0.95 to 1.1 eV, and a method of fabrication thereof, are disclosed. The high band gap subcells are fabricated using metal organic chemical vapor deposition (MOCVD), liquid phase epitaxy (LPE) or molecular beam epitaxy (MBE) to produce the required AlGaAs layers of optimized composition, thickness and doping to produce high performance, heteroface homojunction devices. The low bandgap subcells are similarly fabricated from AlGa(As)Sb compositions by LPE, MBE or MOCVD. These subcells are then coupled to form a monolithic structure by an appropriate bonding technique which also forms the required transparent intercell ohmic contact (IOC) between the two subcells. Improved ohmic contacts to the high bandgap semiconductor structure can be formed by vacuum evaporating to suitable metal or semiconductor materials which react during laser annealing to form a low bandgap semiconductor which provides a low contact resistance structure.

  7. Measuring cardiac efficiency using PET/MRI

    Energy Technology Data Exchange (ETDEWEB)

    Gullberg, Grand [Lawrence Berkeley National Laboratory (United States); Aparici, Carina Mari; Brooks, Gabriel [University of California San Francisco (United States); Liu, Jing; Guccione, Julius; Saloner, David; Seo, Adam Youngho; Ordovas, Karen Gomes [Lawrence Berkeley National Laboratory (United States)

    2015-05-18

    Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost $160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

  8. Measuring cardiac efficiency using PET/MRI

    International Nuclear Information System (INIS)

    Gullberg, Grand; Aparici, Carina Mari; Brooks, Gabriel; Liu, Jing; Guccione, Julius; Saloner, David; Seo, Adam Youngho; Ordovas, Karen Gomes

    2015-01-01

    Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost $160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

  9. Measures for energy efficiency improvement of buildings

    Directory of Open Access Journals (Sweden)

    Vukadinović Ana V.

    2015-01-01

    Full Text Available The increase in energy consumption in buildings causes the need to propose energy efficiency improvement measures. Urban planning in accordance with micro location conditions can lead to energy consumption reduction in buildings through the passive solar design. While satisfying the thermal comfort to the user space purpose, energy efficiency can be achieved by optimizing the architectural and construction parameters such as shape of the building, envelope structure and the percentage of glazing. The improvement of the proposed measures, including the use of renewable energy sources, can meet requirements of Directive 2010/31 / EU of 'nearly zero energy buildings'.

  10. Efficient methods of piping cleaning

    Directory of Open Access Journals (Sweden)

    Orlov Vladimir Aleksandrovich

    2014-01-01

    Full Text Available The article contains the analysis of the efficient methods of piping cleaning of water supply and sanitation systems. Special attention is paid to the ice cleaning method, in course of which biological foil and various mineral and organic deposits are removed due to the ice crust buildup on the inner surface of water supply and drainage pipes. These impurities are responsible for the deterioration of the organoleptic properties of the transported drinking water or narrowing cross-section of drainage pipes. The co-authors emphasize that the use of ice compared to other methods of pipe cleaning has a number of advantages due to the relative simplicity and cheapness of the process, economical efficiency and lack of environmental risk. The equipment for performing ice cleaning is presented, its technological options, terms of cleansing operations, as well as the volumes of disposed pollution per unit length of the water supply and drainage pipelines. It is noted that ice cleaning requires careful planning in the process of cooking ice and in the process of its supply in the pipe. There are specific requirements to its quality. In particular, when you clean drinking water system the ice applied should be hygienically clean and meet sanitary requirements.In pilot projects, in particular, quantitative and qualitative analysis of sediments adsorbed by ice is conducted, as well as temperature and the duration of the process. The degree of pollution of the pipeline was estimated by the volume of the remote sediment on 1 km of pipeline. Cleaning pipelines using ice can be considered one of the methods of trenchless technologies, being a significant alternative to traditional methods of cleaning the pipes. The method can be applied in urban pipeline systems of drinking water supply for the diameters of 100—600 mm, and also to diversion collectors. In the world today 450 km of pipelines are subject to ice cleaning method.Ice cleaning method is simple

  11. TRANSPORTATION SYSTEM REQUIREMENTS DOCUMENT

    International Nuclear Information System (INIS)

    2004-01-01

    This document establishes the Transportation system requirements for the U.S. Department of Energy's (DOE's) Civilian Radioactive Waste Management System (CRWMS). These requirements are derived from the Civilian Radioactive Waste Management System Requirements Document (CRD). The Transportation System Requirements Document (TSRD) was developed in accordance with LP-3.1Q-OCRWM, Preparation, Review, and Approval of Office of National Transportation Level-2 Baseline Requirements. As illustrated in Figure 1, the TSRD forms a part of the DOE Office of Civilian Radioactive Waste Management (OCRWM) Technical Baseline

  12. Transportation System Requirements Document

    International Nuclear Information System (INIS)

    1993-09-01

    This Transportation System Requirements Document (Trans-SRD) describes the functions to be performed by and the technical requirements for the Transportation System to transport spent nuclear fuel (SNF) and high-level radioactive waste (HLW) from Purchaser and Producer sites to a Civilian Radioactive Waste Management System (CRWMS) site, and between CRWMS sites. The purpose of this document is to define the system-level requirements for Transportation consistent with the CRWMS Requirement Document (CRD). These requirements include design and operations requirements to the extent they impact on the development of the physical segments of Transportation. The document also presents an overall description of Transportation, its functions, its segments, and the requirements allocated to the segments and the system-level interfaces with Transportation. The interface identification and description are published in the CRWMS Interface Specification

  13. Thermodynamic equipartition for increased second law efficiency

    International Nuclear Information System (INIS)

    Thiel, Gregory P.; McGovern, Ronan K.; Zubair, Syed M.; Lienhard V, John H.

    2014-01-01

    Highlights: • Efficiency gains from equipartition to minimize entropy generation are quantified. • The equipartition factor (Ξ) quantifies the variance of thermodynamic affinities. • Systems with low (Ξ) and low efficiency gain most when redesigned for equipartition. • For lumped capacitance systems long normalized charging times correlate with low (Ξ). - Abstract: In this work, a clear distinction is drawn between irreversibility associated with a finite mean driving force in a transport process and irreversibility associated with variance in the spatial and/or temporal distribution of this driving force. The portion of irreversibility associated with driving force variance is quantified via a newly defined dimensionless quantity, the equipartition factor. This equipartition factor, related to the variance in dimensionless driving force throughout the system, is employed to formulate an expression for second law efficiency. Consequently, the equipartition factor may be employed to identify the improvement in efficiency achievable via system redesign for a reduction in driving force variance, while holding fixed the system output for fixed system dimensions in time and space. It is shown that systems with low second law efficiency and low equipartition factor will have the greatest benefit from a redesign to obtain equipartition. The utility of the equipartition factor in identifying situations where efficiency can be increased without requiring a spatial or temporal increase in system size is illustrated through its application to several simple systems

  14. Efficiency model of Russian banks

    OpenAIRE

    Pavlyuk, Dmitry

    2006-01-01

    The article deals with problems related to the stochastic frontier model of bank efficiency measurement. The model is used to study the efficiency of the banking sector of The Russian Federation. It is based on the stochastic approach both to the efficiency frontier location and to individual bank efficiency values. The model allows estimating bank efficiency values, finding relations with different macro- and microeconomic factors and testing some economic hypotheses.

  15. High-efficiency CARM

    Energy Technology Data Exchange (ETDEWEB)

    Bratman, V.L.; Kol`chugin, B.D.; Samsonov, S.V.; Volkov, A.B. [Institute of Applied Physics, Nizhny Novgorod (Russian Federation)

    1995-12-31

    The Cyclotron Autoresonance Maser (CARM) is a well-known variety of FEMs. Unlike the ubitron in which electrons move in a periodical undulator field, in the CARM the particles move along helical trajectories in a uniform magnetic field. Since it is much simpler to generate strong homogeneous magnetic fields than periodical ones for a relatively low electron energy ({Brit_pounds}{le}1-3 MeV) the period of particles` trajectories in the CARM can be sufficiently smaller than in the undulator in which, moreover, the field decreases rapidly in the transverse direction. In spite of this evident advantage, the number of papers on CARM is an order less than on ubitron, which is apparently caused by the low (not more than 10 %) CARM efficiency in experiments. At the same time, ubitrons operating in two rather complicated regimes-trapping and adiabatic deceleration of particles and combined undulator and reversed guiding fields - yielded efficiencies of 34 % and 27 %, respectively. The aim of this work is to demonstrate that high efficiency can be reached even for a simplest version of the CARM. In order to reduce sensitivity to an axial velocity spread of particles, a short interaction length where electrons underwent only 4-5 cyclotron oscillations was used in this work. Like experiments, a narrow anode outlet of a field-emission electron gun cut out the {open_quotes}most rectilinear{close_quotes} near-axis part of the electron beam. Additionally, magnetic field of a small correcting coil compensated spurious electron oscillations pumped by the anode aperture. A kicker in the form of a sloping to the axis frame with current provided a control value of rotary velocity at a small additional velocity spread. A simple cavity consisting of a cylindrical waveguide section restricted by a cut-off waveguide on the cathode side and by a Bragg reflector on the collector side was used as the CARM-oscillator microwave system.

  16. Late Washing efficiency

    International Nuclear Information System (INIS)

    Morrissey, M.F.

    1992-01-01

    Interim Waste Technology has demonstrated the Late Washing concept on the Experimental Laboratory Filter (ELF) at TNX. In two tests, washing reduced the [NO 2 - ] from 0.08 M to approximately 0.01 M on slurries with 2 year equivalent radiation exposures and 9.5 wt. % solids. For both washes, the [NO 2 - ] decreased at rates near theoretical for a constant volume stirred vessel, indicating approximately l00% washing efficiency. Permeate flux was greater than 0.05 gpm/ft 2 for both washes at a transmembrane pressure of 50 psi and flow velocity of 9 ft/sec

  17. Merging {DBMs} Efficiently

    DEFF Research Database (Denmark)

    David, Alexandre

    2005-01-01

    In this paper we present different algorithms to reduce the number of DBMs in federations by merging them. Federations are unions of DBMs and are used to represent non-convex zones. Inclusion checking between DBMs is a limited technique to reduce the size of federations and how to choose some DBMs...... to merge them into a larger one is a combi-natorial problem. We present a number of simple but efficient techniques to avoid searching the combinations while still being able to merge any number of DBMs...

  18. High efficiency positron moderation

    International Nuclear Information System (INIS)

    Taqqu, D.

    1990-01-01

    A new positron moderation scheme is proposed. It makes use of electric and magnetic fields to confine the β + emitted by a radioactive source forcing them to slow down within a thin foil. A specific arrangement is described where an intermediary slowed-down beam of energy below 10 keV is produced. By directing it towards a standard moderator optimal conversion into slow positrons is achieved. This scheme is best applied to short lived β + emitters for which a 25% moderation efficiency can be reached. Within the state of the art technology a slow positron source intensity exceeding 2 x 10 10 e + /sec is achievable. (orig.)

  19. Efficiency improvements in transport

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, J. [Technical Univ. of Denmark. DTU Mechanical Engineering, Kgs. Lyngby (Denmark); Christensen, Linda; Jensen, Thomas C. [Technical Univ. of Denmark. DTU Transport, Kgs. Lyngby (Denmark)

    2012-11-15

    Transport of people, personal belongings and goods in private cars is fundamental to our modern welfare society and economic growth, and has grown steadily over many decades. Motor fuels have been based almost entirely on crude oil for the last century. During the last couple of decades engines built for traditional fuels have become more advanced and efficient; this has reduced fuel consumption by around 40% and emissions by more than 90%. Only in the same time span have we begun to look at alternatives to fossil fuels. Biofuels such as biodiesel, bioethanol, biomethanol and biogas can replace petrol and diesel, and in recent years algae have shown a new potential for diesel fuel. Natural gas is also becoming an interesting fuel due to its large resources worldwide. GTL, CTL and BTL are liquid fuels produced from solid or gaseous sources. GTL and CTL are expensive to produce and not very CO{sub 2}-friendly, but they are easily introduced and need little investment in infrastructure and vehicles. DME is an excellent fuel for diesel engines. Methanol and DME produced from biomass are among the most CO{sub 2}-reducing fuels and at the same time the most energy-efficient renewable fuels. Fuel cell vehicles (FCVs) are currently fuelled by hydrogen, but other fuels are also possible. There are, however, several barriers to the implementation of fuel cell vehicles. In particular, a hydrogen infrastructure needs to be developed. Electric vehicles (EVs) have the advantage that energy conversion is centralised at the power plant where it can be done at optimum efficiency and emissions. EVs have to be charged at home, and also away from home when travelling longer distances. With an acceptable fast charging infrastructure at least 85% of the one-car families in Denmark could be potential EV customers. Range improvements resulting from better batteries are expected to create a large increase in the number of EVs in Denmark between 2020 and 2030. The hybrid electric vehicle

  20. Energy Efficient Digital Networks

    Energy Technology Data Exchange (ETDEWEB)

    Lanzisera, Steven [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Brown, Richard [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2013-01-01

    Digital networks are the foundation of the information services, and play an expanding and indispensable role in our lives, via the Internet, email, mobile phones, etc. However, these networks consume energy, both through the direct energy use of the network interfaces and equipment that comprise the network, and in the effect they have on the operating patterns of devices connected to the network. The purpose of this research was to investigate a variety of technology and policy issues related to the energy use caused by digital networks, and to further develop several energy-efficiency technologies targeted at networks.