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Sample records for human c5a anaphylatoxin

  1. Structural and functional characterization of human and murine C5a anaphylatoxins

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    Schatz-Jakobsen, Janus Asbjørn; Yatime, Laure, E-mail: lay@mb.au.dk; Larsen, Casper [Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus (Denmark); Petersen, Steen Vang [Aarhus University, Bartholin Building, Wilhelm Meyers Allé 4, DK-8000 Aarhus (Denmark); Klos, Andreas [Medical School Hannover, Hannover (Germany); Andersen, Gregers Rom, E-mail: lay@mb.au.dk [Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus (Denmark)

    2014-06-01

    The structure of the human C5aR antagonist, C5a-A8, reveals a three-helix bundle conformation similar to that observed for human C5a-desArg, whereas murine C5a and C5a-desArg both form the canonical four-helix bundle. These conformational differences are discussed in light of the differential C5aR activation properties observed for the human and murine complement anaphylatoxins across species. Complement is an ancient part of the innate immune system that plays a pivotal role in protection against invading pathogens and helps to clear apoptotic and necrotic cells. Upon complement activation, a cascade of proteolytic events generates the complement effectors, including the anaphylatoxins C3a and C5a. Signalling through their cognate G-protein coupled receptors, C3aR and C5aR, leads to a wide range of biological events promoting inflammation at the site of complement activation. The function of anaphylatoxins is regulated by circulating carboxypeptidases that remove their C-terminal arginine residue, yielding C3a-desArg and C5a-desArg. Whereas human C3a and C3a-desArg adopt a canonical four-helix bundle fold, the conformation of human C5a-desArg has recently been described as a three-helix bundle. Here, the crystal structures of an antagonist version of human C5a, A8{sup Δ71–73}, and of murine C5a and C5a-desArg are reported. Whereas A8{sup Δ71–73} adopts a three-helix bundle conformation similar to human C5a-desArg, the two murine proteins form a four-helix bundle. A cell-based functional assay reveals that murine C5a-desArg, in contrast to its human counterpart, exerts the same level of activition as murine C5a on its cognate receptor. The role of the different C5a conformations is discussed in relation to the differential activation of C5a receptors across species.

  2. Human C5a anaphylatoxin: gene cloning and expression in Escherichia coli.

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    Bautsch, W; Emde, M; Kretzschmar, T; Köhl, J; Suckau, D; Bitter-Suermann, D

    1992-06-01

    A gene coding for the human anaphylatoxin C5a was cloned and expressed in Escherichia coli. A combination of reverse transcription of mRNA of the U937 cell line with subsequent preparative polymerase chain reaction was employed to obtain the gene. The sequence was cloned into the plasmid vector pKK 233-2 behind an ATG initiation codon under the control of a trc promotor. After purification by ion exchange chromatography and reversed phase FPLC a mixture of predominantly non-glycosylated recombinant human C5a with a beta-mercaptoethanol adduct at cysteine 27 and the N-methionyl derivative was obtained which was homogeneous on silver-stained gels, immunoreactive with C5a-specific monoclonal antibodies and functionally active in releasing myeloperoxidase from human granulocytes and ATP from guinea pig platelets. The final yield was about 0.4-0.8 mg purified recombinant C5a per liter bacterial culture.

  3. Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes anaphylatoxin C5a activity.

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    Bielecka, Ewa; Scavenius, Carsten; Kantyka, Tomasz; Jusko, Monika; Mizgalska, Danuta; Szmigielski, Borys; Potempa, Barbara; Enghild, Jan J; Prossnitz, Eric R; Blom, Anna M; Potempa, Jan

    2014-11-21

    Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis, produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura-2 AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles naturally shed by P. gingivalis, we observed generation of C5a totally citrullinated at the C-terminal Arg-74 residue (Arg74Cit). In stark contrast, only native C5a was detected after treatment with PPAD-null outer membrane vesicles. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and Toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD-expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis.

  4. Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo

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    Thomas Sunil

    2008-01-01

    Full Text Available Abstract Background The complement system is thought to be involved in the pathogenesis of numerous neurological diseases. We previously reported that pre-treatment of murine cortico-hippocampal neuronal cultures with the complement derived anaphylatoxin C5a, protects against glutamate mediated apoptosis. Our present study with C5a receptor knock out (C5aRKO mice corroborates that the deficiency of C5a renders C5aRKO mouse more susceptible to apoptotic injury in vivo. In this study we explored potential upstream mechanisms involved in C5a mediated neuroprotection in vivo and in vitro. Methods Based on evidence suggesting that reduced expression of glutamate receptor subunit 2 (GluR2 may influence apoptosis in neurons, we studied the effect of human recombinant C5a on GluR2 expression in response to glutamate neurotoxicity. Glutamate analogs were injected into C5aRKO mice or used to treat in vitro neuronal culture and GluR2 expression were assessed in respect with cell death. Results In C5aRKO mice we found that the neurons are more susceptible to excitotoxicity resulting in apoptotic injury in the absence of the C5a receptor compared to WT control mice. Our results suggest that C5a protects against apoptotic pathways in neurons in vitro and in vivo through regulation of GluR2 receptor expression. Conclusion Complement C5a neuroprotects through regulation of GluR2 receptor subunit.

  5. DMPD: Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnonparenchymal and parenchymal cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11367531 Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnon...rect and indirect actions onnonparenchymal and parenchymal cells. PubmedID 113675...31 Title Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnonparenchymal and paren

  6. Effect of anaphylatoxin C3a, C5a on the tubular epithelial-myofibroblast transdifferentiation in vitro

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    LIU Fang; QIU Hong-yu; WEI Da-peng; GOU Rong; HUANG Jun; FU Ping; CHEN Feng; FAN Wen-xing; HUANG You-qun; ZANG Li; WU Min

    2011-01-01

    Background Tubulointerstitial renal fibrosis is the common end point of progressive kidney diseases,and tubular epithelial-myofibroblast transdifferentiation (TEMT) plays a key role in the progress of tubulointerstitial renal fibrosis.Anaphylatoxin C3a and C5a are identified as novel profibrotic factors in renal disease and as potential new therapeutic targets.The aim of this study was to investigate whether C3a,C5a can regulate TEMT by transforming growth factor-β31 (TGF-β1)/connective tissue growth factor (CTGF) signaling pathway and the effects of C3a and C5a receptor antagonists (C3aRA and C5aRA) on C3a- and C5a-induced TEMT.Methods HK-2 cells were divided into C3a and C5a groups which were subdivided into four subgroups:control group,10 ng/ml TGF-β1 group,50 nmol/L C3a group,50 nmol/L C3a plus 1 μmol/L C3aRA group; control group,10 ng/ml TGF-β31 group,50 nmol/L C5a group,50 nmol/L C5a plus 2.5 μmol/L C5aRA group.TGF-β1 receptor antagonist (TGF-β1 RA) 10 μg/ml was used to investigate the mechanism of C3a- and C5a-induced TEMT.Electron microscopy was used to observe the morphological changes.Immunocytochemistry staining,real-time PCR and Western blotting were used to detect the expressions of α smooth muscle actin (α-SMA),E-cadherin,Col-I,C3a receptor (C3aR),C5aR,CTGF and TGF-β1.Results HK-2 cells cultured with C3a and C5a for 72 hours exhibited strong staining of α-SMA,lost the positive staining of E-cadherin,and showed a slightly spindle-like shape and loss of microvilli on the cell surface.The expressions of α-SMA,E-cadherin,Col-I,C3aR,C5aR,TGF-β1 and CTGF in C3a- and C5a-treated groups were higher than normal control group (P <0.05).C3aRA and C5aRA inhibited the expressions of α-SMA,Col-I,C3aR,C5aR,and up-regulated the expression of E-cadherin (P <0.05).TGF-β1 and CTGF mRNA expressions induced by C3a and C5a were partly blocked by TGF-β1 RA (P <0.05).Conclusion C3a and C5a can induce TEMT via the up-regulations of C3aR and C5aR m

  7. Complement anaphylatoxin receptors C3aR and C5aR are required in the pathogenesis of experimental autoimmune uveitis.

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    Zhang, Lingjun; Bell, Brent A; Yu, Minzhong; Chan, Chi-Chao; Peachey, Neal S; Fung, John; Zhang, Xiaoming; Caspi, Rachel R; Lin, Feng

    2016-03-01

    Recent studies have suggested that reagents inhibiting complement activation could be effective in treating T cell mediated autoimmune diseases such as autoimmune uveitis. However, the precise role of the complement anaphylatoxin receptors (C3a and C5a receptors) in the pathogenesis of autoimmune uveitis remains elusive and controversial. We induced experimental autoimmune uveitis in mice deficient or sufficient in both C3a and C5a receptors and rigorously compared their retinal phenotype using various imaging techniques, including indirect ophthalmoscopy, confocal scanning laser ophthalmoscopy, spectral domain optical coherence tomography, topical endoscopic fundus imaging, and histopathological analysis. We also assessed retinal function using electroretinography. Moreover, we performed Ag-specific T cell recall assays and T cell adoptive transfer experiments to compare pathogenic T cell activity between wild-type and knockout mice with experimental autoimmune uveitis. These experiments showed that C3a receptor/C5a receptor-deficient mice developed much less severe uveitis than did control mice using all retinal examination methods and that these mice had reduced pathogenic T cell responses. Our data demonstrate that both complement anaphylatoxin receptors are important for the development of experimental autoimmune uveitis, suggesting that targeting these receptors could be a valid approach for treating patients with autoimmune uveitis.

  8. Differences in the involvement of prostanoids from Kupffer cells in the mediation of anaphylatoxin C5a-, zymosan-, and lipopolysaccharide-dependent hepatic glucose output and flow reduction.

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    Pestel, Sabine; Schlaf, Gerald; Götze, Otto; Jungermann, Kurt; Schieferdecker, Henrike L

    2003-12-01

    Various inflammatory stimuli such as anaphylatoxin C5a, zymosan, and lipopolysaccharides (LPSs) have been reported both to enhance glucose output in the perfused rat liver and to induce prostanoid (ie, prostaglandin and thromboxane) release from Kupffer cells, the resident liver macrophages. Because prostanoids can enhance glucose output from hepatocytes, it was the aim of this study to compare the possible roles of prostanoids released after C5a, zymosan, and LPS in the mediation of hepatic glucose output. In perfused livers both C5a and zymosan immediately enhanced glucose output, reduced flow, and induced prostanoid overflow into the hepatic vein, but with different quantities and kinetics. Only the C5a-induced but not the zymosan-induced effects were abrogated by inhibitors of prostanoid signaling as the prostanoid synthesis inhibitor indomethacin and the thromboxane receptor antagonist daltroban. In contrast to C5a and zymosan, LPS had no effect on glucose output, flow rate, or prostanoid overflow. In isolated Kupffer cells, C5a and zymosan induced maximal release of prostaglandins D(2) and E(2) and of thromboxane A(2) within a period of 0 to 2 minutes and 5 to 15 minutes, respectively. In pulse-chase experiments, maximal prostanoid release was already observed after 2 minutes of continuous stimulation with C5a, but only after 10 to 15 minutes of continuous stimulation with zymosan. LPS-dependent prostanoid release was not seen before 1 hour. Thus, even though C5a, zymosan, and LPS induced prostanoid release from Kupffer cells, only C5a quickly regulated hepatic glucose metabolism in a prostanoid-dependent manner (due to the kinetics and quantities of prostanoids released).

  9. Inhibition by prostaglandin E(2) of anaphylatoxin C5a- but not zymosan-induced prostanoid release from rat Kupffer cells.

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    Pestel, Sabine; Jungermann, Kurt; Götze, Otto; Schieferdecker, Henrike L

    2002-04-01

    The proinflammatory anaphylatoxin C5a induces the release of prostanoids, ie, prostaglandins (PG) and thromboxane (TX), from the resident liver macrophages (Kupffer cells [KC]). Because KC themselves express prostanoid receptors, prostanoids--besides having paracrine functions--might regulate their own release in an autocrine loop. So far, such a possible feedback regulation has not been investigated systematically, probably because of methodological difficulties to measure newly synthesized prostanoids in the presence of added prostanoids. Here, after prelabeling of phospholipids with [(14)C]arachidonate, cellularly formed [(14)C]prostanoids were determined in the presence of added unlabelled prostanoids by thin layer chromatography. In cultured KC, recombinant rat C5a (rrC5a) rapidly increased PGD(2), PGE(2), and TXA(2) release, which was strongly reduced by PGE(2), but neither by PGD(2) nor by the TXA(2) analog U46619. The inhibitory effect of PGE(2) was mimicked by cAMP, indicating that the G(s)-coupled PGE(2) receptors type 2 or 4 were involved. Zymosan also enhanced prostanoid release from KC, but with slightly slower kinetics; this action was neither inhibited by PGE(2) nor by cAMP. Also in perfused rat livers, rrC5a enhanced prostanoid release from KC as shown by prostanoid overflow and thereby indirectly increased glucose output from hepatocytes. Again, PGE(2), but not PGD(2), inhibited rrC5a-elicited prostanoid overflow. This resulted in a complete inhibition of rrC5a-induced, prostanoid-mediated glucose output. Thus, PGE(2) can inhibit specifically the C5a-induced prostanoid release from KC via a feedback mechanism and thereby limit prostanoid-mediated hepatocellular defense reactions, eg, glucose release.

  10. The C5a anaphylatoxin receptor CD88 is expressed in presynaptic terminals of hippocampal mossy fibres

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    Taylor Stephen M

    2009-11-01

    Full Text Available Abstract Background In the periphery, C5a acts through the G-protein coupled receptor CD88 to enhance/maintain inflammatory responses. In the brain, CD88 can be expressed on astrocytes, microglia and neurons. Previous studies have shown that the hippocampal CA3 region displays CD88-immunolabelling, and CD88 mRNA is present within dentate gyrus granule cells. As granule cells send dense axonal projections (mossy fibres to CA3 pyramidal neurons, CD88 expression could be expressed on mossy fibres. However, the cellular location of CD88 within the hippocampal CA3 region is unknown. Methods The expression of CD88 within the hippocampal CA3 region was characterized using dual-immunolabelling of hippocampal sections prepared from Wistar rats. Immunolabelling for CD88, using a monoclonal antibody, was combined with immunolabelling for markers of astrocytes (GFAP, microglia (IBA1, presynaptic proteins (synaptophysin and synapsin-1 and preterminal axons (neurofilament. In addition, electron microscopy was performed on peroxidase-visualized CD88-immunolabelling to determine its cellular localisation within the CA3 region. Results Dense CD88-immunolabelling was observed within the stratum lucidum of the CA3, consistent with the presence of CD88 on mossy fibres. Labelling for CD88 rarely co-localized with astrocytes or microglia, but was highly co-localized with presynaptic proteins. Electron microscopy revealed CD88-immunolabelling was localized to large presynaptic terminals within the stratum lucidum. Conclusion These results demonstrate that CD88 is expressed on presynaptic terminals of mossy fibres within the CA3 region of the hippocampus. Although the role of CD88 on mossy fibres remains to be established, their involvement in synaptic/cellular plasticity, and in cognitive disorders such as Alzheimer's disease deserves investigation.

  11. Micrurus snake venoms activate human complement system and generate anaphylatoxins

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    Tanaka Gabriela D

    2012-01-01

    Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

  12. Interleukin-1β and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes

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    Patte Christine

    2006-04-01

    Full Text Available Abstract C3a and C5a anaphylatoxins are proinflammatory polypeptides released during complement activation. They exert their biological activities through interaction with two G protein-coupled receptors named C3aR and C5aR, respectively. In the brain, these receptors are expressed on glial cells, and some recent data have suggested that anaphylatoxins could mediate neuroprotection. In this study, we used RT-PCR and ribonuclease protection assays (RPA to investigate the role of anaphylatoxins on neurotrophin expression by the human glioblastoma cell line T98G and by rat astrocytes. Our data show that for both cell types, anaphylatoxins upregulate expression of NGF mRNA. This response depended on a G protein-coupled pathway since pre-treatment of cells with pertussis toxin (PTX completely blocked NGF mRNA increases. This effect was anaphylatoxin-specific since pre-incubation with anti-C3a or anti-C5aR antibodies abolished the effects of C3a and C5a, respectively. The regulation of NGF mRNA by anaphylatoxins was not accompanied by translation into protein expression, but there was a significant synergic effect of anaphylatoxins/IL-1b costimulation. Our demonstration of involvement of anaphylatoxins in the NGF release process by astrocytes suggests that C3a and C5a could modulate neuronal survival in the CNS.

  13. Innate immune induction and influenza protection elicited by a response-selective agonist of human C5a.

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    Sam D Sanderson

    Full Text Available The anaphylatoxin C5a is an especially potent mediator of both local and systemic inflammation. However, C5a also plays an essential role in mucosal host defense against bacterial, viral, and fungal infection. We have developed a response-selective agonist of human C5a, termed EP67, which retains the immunoenhancing activity of C5a at the expense of its inflammatory, anaphylagenic properties. EP67 insufflation results in the rapid induction of pulmonary cytokines and chemokines. This is followed by an influx of innate immune effector cells, including neutrophils, NK cells, and dendritic cells. EP67 exhibits both prophylactic and therapeutic protection when tested in a murine model of influenza A infection. Mice treated with EP67 within a twenty-four hour window of non-lethal infection were significantly protected from influenza-induced weight loss. Furthermore, EP67 delivered twenty-four hours after lethal infection completely blocked influenza-induced mortality (0% vs. 100% survival. Since protection based on innate immune induction is not restricted to any specific pathogen, EP67 may well prove equally efficacious against a wide variety of possible viral, bacterial, and fungal pathogens. Such a strategy could be used to stop the worldwide spread of emergent respiratory diseases, including but not limited to novel strains of influenza.

  14. Radioimmunoassay for anaphylatoxins: a sensitive method for determining complement activation products in biological fluids

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    Wagner, J.L.; Hugli, T.E.

    1984-01-01

    Activation of the blood complement system generates bioactive fragments called anaphylatoxins. The three anaphylatoxins C3a, C4a, and C5a are released during classical pathway activation while only C3a and C5a are released when the alternative pathway of complement is activated. Radioimmunoassays were designed to individually detect and quantitate the activation fragments C3a, C4a, and C5a in biological fluids without interference from the precursor molecules C3, C4, and C5. Kinetics of complement activation in fresh human serum exposed to the activators zymosan, heat-aggregated immunoglobulin, or cobra venom factor were monitored using the radioimmunoassay technique. For the first time, activation of components C3, C4, and C5 was followed simultaneously in a single serum sample. Analysis of the patterns and extent of anaphylatoxin formation during activation in serum may be used to screen for deficiencies or defects in the complement cascade. Levels of the anaphylatoxins in freshly drawn serum were much higher than levels detected in EDTA-plasma. Detection of low-level complement activation in patient's blood, urine, or synovial fluid, using anaphylatoxin formation as an indicator, may prove useful in signaling numerous forms of inflammatory reactions. The demonstration of anaphylatoxins in clinical samples is being recognized as a valuable diagnostic tool in monitoring the onset of immune disease.

  15. An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection.

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    Hung, Chiung-Yu; Hurtgen, Brady J; Bellecourt, Michael; Sanderson, Sam D; Morgan, Edward L; Cole, Garry T

    2012-06-29

    Coccidioides is a fungal pathogen and causative agent of a human respiratory disease against which no clinical vaccine exists. In this study we evaluated a novel vaccine adjuvant referred to as EP67, which is a peptide agonist of the biologically active C-terminal region of human complement component C5a. The EP67 peptide was conjugated to live spores of an attenuated vaccine strain (ΔT) of Coccidioides posadasii. The non-conjugated ΔT vaccine provided partial protection to BALB/c mice against coccidioidomycosis. In this report we compared the protective efficacy of the ΔT-EP67 conjugate to the ΔT vaccine in BALB/c mice. Animals immunized subcutaneously with the ΔT-EP67 vaccine showed significant increase in survival and decrease in fungal burden over 75 days postchallenge. Increased pulmonary infiltration of dendritic cells and macrophages was observed on day 7 postchallenge but marked decrease in neutrophil numbers had occurred by 11 days. The reduced influx of neutrophils may have contributed to the observed reduction of inflammatory pathology. Mice immunized with the ΔT-EP67 vaccine also revealed enhanced expression of MHC II molecules on the surface of antigen presenting cells, and in vitro recall assays of immune splenocytes showed elevated Th1- and Th17-type cytokine production. The latter correlated with a marked increase in lung infiltration of IFN-γ- and IL-17-producing CD4(+) T cells. Elevated expression of T-bet and RORc transcription factors in ΔT-EP67-vaccinated mice indicated the promotion of Th1 and Th17 cell differentiation. Higher titers of Coccidioides antigen-specific IgG1 and IgG2a were detected in mice immunized with the EP67-conjugated versus the non-conjugated vaccine. These combined results suggest that the EP67 adjuvant enhances protective efficacy of the live vaccine by augmentation of T-cell immunity, especially through Th1- and Th17-mediated responses to Coccidioides infection.

  16. C5a alters blood-brain barrier integrity in a human in vitro model of systemic lupus erythematosus.

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    Mahajan, Supriya D; Parikh, Neil U; Woodruff, Trent M; Jarvis, James N; Lopez, Molly; Hennon, Teresa; Cunningham, Patrick; Quigg, Richard J; Schwartz, Stanley A; Alexander, Jessy J

    2015-09-01

    The blood-brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5-50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases. © 2015 John Wiley & Sons Ltd.

  17. Loxoprofen sodium induces the production of complement C5a in human serum.

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    Kumagai, Tomoaki; Yamaguchi, Nozomi; Hirai, Hiroyuki; Kojima, Shigeyuki; Kodani, Yoshiko; Hashiguchi, Akihiko; Haida, Michiko; Nakamura, Masataka

    2016-04-01

    Basophil activation test (BAT) is an in vitro allergy test that is useful to identify allergens that cause IgE-dependent allergies. The test has been used to detect not only food allergies and allergies caused by environmental factors but also to detect drug hypersensitivity, which has been known to include IgE-independent reactions. In our preliminary studies in which BAT was applied to detect hypersensitivity of loxoprofen, a non-steroidal anti-inflammatory drug (NSAID), conventional BAT with incubation for 30min did not show basophil activation by means of increased CD203c expression. In this study, we extended the incubation time to 24h on the basis of the hypothesis that loxoprofen indirectly activates basophils. Basophils from healthy control donors as well as allergic patients showed up-regulation of CD203c after incubation with loxoprofen for 24h. Activation was induced using loxoprofen-treated serum. Proteomic and pharmacologic analyses revealed that serum incubation with loxoprofen generated an active complement component C5a, which induced CD203c expression via binding to the C5a receptor on basophils. Because C3a production was also detected after incubation for 24h, loxoprofen is likely to stimulate the complement classical pathway. Our findings suggest that the complement activation is involved in drug hypersensitivity and the suppression of this activation may contribute to the elimination of false positive of BAT for drug allergies.

  18. Anaphylatoxins - Their role in bacterial infection and inflammation

    NARCIS (Netherlands)

    Haas, Pieter-Jan; van Strijp, Jos

    2007-01-01

    Activation of the complement system plays a crucial role in the pathogenesis of infection and inflammation. Especially the complement activation products C3a and C5a, known as the anaphylatoxins, are potent proinflammatory mediators. In addition to their evident role in innate immunity, it is clear

  19. Expression of the familial Mediterranean fever gene and activity of the C5a inhibitor in human primary fibroblast cultures.

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    Matzner, Y; Abedat, S; Shapiro, E; Eisenberg, S; Bar-Gil-Shitrit, A; Stepensky, P; Calco, S; Azar, Y; Urieli-Shoval, S

    2000-07-15

    Familial Mediterranean fever (FMF) is an inherited disease whose manifestations are acute but reversible attacks of sterile inflammation affecting synovial and serosal spaces. The FMF gene (MEFV) was recently cloned, and it codes for a protein (pyrin/marenostrin) homologous to known nuclear factors. We previously reported the deficient activity of a C5a/interleukin (IL)-8 inhibitor, a physiologic regulator of inflammatory processes, in FMF serosal and synovial fluids. We now describe the concomitant expression of MEFV and C5a/IL-8-inhibitor activity in primary cultures of human fibroblasts. Fibroblasts grown from synovial and peritoneal tissues displayed C5a/IL-8-inhibitor activity that could be further induced with phorbol myristate acetate (PMA) and IL-1 beta. Very low levels of chemotactic inhibitor were evident in skin fibroblast cultures or in peritoneal and skin fibroblasts obtained from FMF patients. MEFV was expressed in peritoneal and skin fibroblasts at a lower level than in neutrophils and could be further induced by PMA and IL-1 beta. In the FMF cultures, the MEFV transcript carried the M694V mutation, consistent with the genetic defect found in patients with this disease. MEFV was also expressed in other cell lines that do not produce C5a/IL-8 inhibitor. These findings suggest that human primary fibroblast cultures express MEFV and produce C5a/IL-8-inhibitor activity. The interrelationship between pyrin, the MEFV product, and the C5a/IL-8 inhibitor requires further investigation. (Blood. 2000;96:727-731)

  20. Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection

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    Sarah A. Horst

    2015-10-01

    Full Text Available The complement anaphylatoxin C5a contributes to host defense against Staphylococcus aureus. In this study, we investigated the functional role of the two known C5a receptors, C5aR1 and C5aR2, in the host response to S. aureus. We found that C5aR1−/− mice exhibited greater susceptibility to S. aureus bloodstream infection than wild type and C5aR2−/− mice, as demonstrated by the significantly higher bacterial loads in the kidneys and heart at 24 h of infection, and by the higher levels of inflammatory IL-6 in serum. Histological and immunohistochemistry investigation of infected kidneys at 24 h after bacterial inoculation revealed a discrete infiltration of neutrophils in wild type mice but already well-developed abscesses consisting of bacterial clusters surrounded by a large number of neutrophils in both C5aR1−/− and C5aR2−/− mice. Furthermore, blood neutrophils from C5aR1−/− mice were less efficient than those from wild type or C5aR2−/− mice at killing S. aureus. The requirement of C5aR1 for efficient killing of S. aureus was also demonstrated in human blood after disrupting C5a-C5aR1 signaling using specific inhibitors. These results demonstrated a role for C5aR1 in S. aureus clearance as well as a role for both C5aR1 and C5aR2 in the orchestration of the inflammatory response during infection.

  1. Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration

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    Klein Michael L

    2011-07-01

    Full Text Available Abstract Background Age related macular degeneration (AMD is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH, the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD. Methods Human peripheral blood mononuclear cells (PBMCs were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500. Results We show that C5a promotes interleukin (IL-22 and IL-17 expression by human CD4+ T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4+ cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls. Conclusions Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.

  2. Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief

    Science.gov (United States)

    Moriconi, Alessio; Cunha, Thiago M.; Souza, Guilherme R.; Lopes, Alexandre H.; Cunha, Fernando Q.; Carneiro, Victor L.; Pinto, Larissa G.; Brandolini, Laura; Aramini, Andrea; Bizzarri, Cinzia; Bianchini, Gianluca; Beccari, Andrea R.; Fanton, Marco; Bruno, Agostino; Costantino, Gabriele; Bertini, Riccardo; Galliera, Emanuela; Locati, Massimo; Ferreira, Sérgio H.; Teixeira, Mauro M.; Allegretti, Marcello

    2014-01-01

    Chronic pain resulting from inflammatory and neuropathic disorders causes considerable economic and social burden. Pharmacological therapies currently available for certain types of pain are only partially effective and may cause severe adverse side effects. The C5a anaphylatoxin acting on its cognate G protein-coupled receptor (GPCR), C5aR, is a potent pronociceptive mediator in several models of inflammatory and neuropathic pain. Although there has long been interest in the identification of C5aR inhibitors, their development has been complicated, as for many peptidomimetic drugs, mostly by poor drug-like properties. Herein, we report the de novo design of a potent and selective C5aR noncompetitive allosteric inhibitor, DF2593A, guided by the hypothesis that an allosteric site, the “minor pocket,” previously characterized in CXC chemokine receptors-1 and -2, is functionally conserved in the GPCR class. In vitro, DF2593A potently inhibited C5a-induced migration of human and rodent neutrophils. In vivo, oral administration of DF2593A effectively reduced mechanical hyperalgesia in several models of acute and chronic inflammatory and neuropathic pain, without any apparent side effects. Mechanical hyperalgesia after spared nerve injury was also reduced in C5aR−/− mice compared with WT mice. Furthermore, treatment of C5aR−/− mice with DF2593A did not produce any further antinociceptive effect compared with C5aR−/− mice treated with vehicle. The successful medicinal chemistry strategy confirms that a conserved minor pocket is amenable for the rational design of selective inhibitors and the pharmacological results support that the allosteric blockade of the C5aR represents a highly promising therapeutic approach to control chronic inflammatory and neuropathic pain. PMID:25385614

  3. Cloning, expression, cellular distribution, and role in chemotaxis of a C5a receptor in rainbow trout: the first identification of a C5a receptor in a nonmammalian species

    Science.gov (United States)

    Boshra, Hani; Li, Jun; Peters, Rodney; Hansen, John; Matlapudi, Anjan; Sunyer, J. Oriol

    2004-01-01

    C3a, C4a, and C5a anaphylatoxins generated during complement activation play a key role in inflammation. C5a is the most potent of the three anaphylatoxins in eliciting biological responses. The effects of C5a are mediated by its binding to C5a receptor (C5aR, CD88). To date, C5aR has only been identified and cloned in mammalian species, and its evolutionary history remains ill-defined. To gain insights into the evolution, conserved structural domains, and functions of C5aR, we have cloned and characterized a C5aR in rainbow trout, a teleost fish. The isolated cDNA encoded a 350-aa protein that showed the highest sequence similarity to C5aR from other species. Genomic analysis revealed the presence of one continuous exon encoding the entire open reading frame. Northern blot analysis showed significant expression of the trout C5a receptor (TC5aR) message in PBLs and kidney. Flow cytometric analysis showed that two Abs generated against two different areas of the extracellular N-terminal region of TC5aR positively stained the same leukocyte populations from PBLs. B lymphocytes and granulocytes comprised the majority of cells recognized by the anti-TC5aR. More importantly, these Abs inhibited chemotaxis of PBLs toward a chemoattractant fraction purified from complement-activated trout serum. Our data suggest that the split between C5aR and C3aR from a common ancestral molecule occurred before the emergence of teleost fish. Moreover, we demonstrate that the overall structure of C5aR as well as its role in chemotaxis have remained conserved for >300 million years.

  4. Differential interaction of the staphylococcal toxins panton-valentine leukocidin and γ-hemolysin CB with human C5a receptors

    NARCIS (Netherlands)

    Spaan, András N.; Schiepers, Ariën; De Haas, Carla J C; Van Hooijdonk, Davy D J J; Badiou, Cédric; Contamin, Hugues; Vandenesch, François; Lina, Gérard; Gerard, Norma P.; Gerard, Craig; Van Kessel, Kok P M; Henry, Thomas; Van Strijp, Jos A G

    2015-01-01

    Staphylococcus aureus is well adapted to the human host. Evasion of the host phagocyte response is critical for successful infection. The staphylococcal bicomponent pore-forming toxins Panton-Valentine leukocidin LukSF-PV (PVL) and γ-hemolysin CB (HlgCB) target human phagocytes through interaction w

  5. Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis.

    NARCIS (Netherlands)

    Sprong, T.; Brandtzaeg, P.; Fung, M.; Pharo, A.M.; Hoiby, E.A.; Michaelsen, T.E.; Aase, A.; Meer, J.W.M. van der; Deuren, M. van; Mollnes, T.E.

    2003-01-01

    The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the effe

  6. Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis.

    NARCIS (Netherlands)

    Sprong, T.; Brandtzaeg, P.; Fung, M.; Pharo, A.M.; Hoiby, E.A.; Michaelsen, T.E.; Aase, A.; Meer, J.W.M. van der; Deuren, M. van; Mollnes, T.E.

    2003-01-01

    The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the

  7. Enhancement of In Vivo and In Vitro Immune Functions by a Conformationally-Biased, Response-Selective Agonist of Human C5a: Implications for a Novel Adjuvant in Vaccine Design

    Science.gov (United States)

    Morgan, Edward L.; Morgan, Brandon N.; Stein, Elisabeth A.; Vitrs, Elizabeth L.; Thoman, Marilyn L.; Sanderson, Sam D.; Phillips, Joy A.

    2009-01-01

    A conformationally-biased, agonist of human C5a65–74 (EP67) was assessed for its adjuvant activities in vitro and in vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). Serum from mice immunized with EP67-ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like antibody (A)b class switch. Spleen cell cultures from wild type mice but not CD88−/− mice showed an enhanced OVA-specific proliferative response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant PMID:19836478

  8. HSV neutralization by the microbicidal candidate C5A

    NARCIS (Netherlands)

    de Witte, L.; Bobardt, M.D.; Chatterji, U.; van Loenen, F.B.; Verjans, G.M.G.M.; Geijtenbeek, T.B.H.; Gallay, P.A.

    2011-01-01

    Genital herpes is a major risk factor in acquiring human immunodeficiency virus type-1 (HIV-1) infection and is caused by both Herpes Simplex virus type 1 (HSV-1) and HSV-2. The amphipathic peptide C5A, derived from the non-structural hepatitis C virus (HCV) protein 5A, was shown to prevent HIV-1 in

  9. Protective effects of C5a blockade in sepsis

    DEFF Research Database (Denmark)

    Czermak, B J; Sarma, V; Pierson, C L

    1999-01-01

    Sepsis in humans is a difficult condition to treat and is often associated with a high mortality rate. In this study, we induced sepsis in rats using cecal ligation and puncture (CLP). In rats depleted of the complement factor C3, CLP led to very short survival times (about 4 days). Of the rats......). These data indicate that sepsis causes an excessive production of C5a, which compromises the bactericidal function of neutrophils. Thus, C5a may be a useful target for the treatment of sepsis....

  10. THE NATURE OF ANAPHYLATOXIN : STUDIES ON IMMUNITY. II.

    Science.gov (United States)

    Bronfenbrenner, J

    1915-05-01

    1. The union of fresh serum of pregnant or immunized animals with the corresponding boiled protein (substratum) is accompanied by the formation of poisonous substances. 2. The poison originates from the serum as a result of its autodigestion, and not from the substratum. 3. The process of autodigestion may be determined by the specific or non-specific removal of the antitrypsin of the serum. 4. The poisons originating from the serum are toxic only for homologous animals. 5. The autodigestion of the serum, if allowed to proceed far enough, may go beyond the toxic stage. 6. The biological properties of these poisons indicate their close similarity to the anaphylatoxin, and suggest that the anaphylatoxin of Friedberger is a product of the autodigestion of serum, and not of the protein outside of the serum.

  11. Deletion of the complement C5a receptor alleviates the severity of acute pneumococcal otitis media following influenza A virus infection in mice.

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    Hua Hua Tong

    Full Text Available There is considerable evidence that influenza A virus (IAV promotes adherence, colonization, and superinfection by S. pneumoniae (Spn and contributes to the pathogenesis of otitis media (OM. The complement system is a critical innate immune defense against both pathogens. To assess the role of the complement system in the host defense and the pathogenesis of acute pneumococcal OM following IAV infection, we employed a well-established transtympanically-induced mouse model of acute pneumococcal OM. We found that antecedent IAV infection enhanced the severity of acute pneumococcal OM. Mice deficient in complement C1qa (C1qa-/- or factor B (Bf -/- exhibited delayed viral and bacterial clearance from the middle ear and developed significant mucosal damage in the eustachian tube and middle ear. This indicates that both the classical and alternative complement pathways are critical for the oto-immune defense against acute pneumococcal OM following influenza infection. We also found that Spn increased complement activation following IAV infection. This was characterized by sustained increased levels of anaphylatoxins C3a and C5a in serum and middle ear lavage samples. In contrast, mice deficient in the complement C5a receptor (C5aR demonstrated enhanced bacterial clearance and reduced severity of OM. Our data support the concept that C5a-C5aR interactions play a significant role in the pathogenesis of acute pneumococcal OM following IAV infection. It is possible that targeting the C5a-C5aR axis might prove useful in attenuating acute pneumococcal OM in patients with influenza infection.

  12. C5a receptor (CD88) inhibition improves hypothermia-induced neuroprotection in an in vitro ischemic model.

    Science.gov (United States)

    Thundyil, John; Pavlovski, Dale; Hsieh, Yu-Hsuan; Gelderblom, Mathias; Magnus, Tim; Fairlie, David P; Arumugam, Thiruma V

    2012-03-01

    The concept of 'salvageble penumbra' has prompted both scientists and physicians to explore various neuroprotective approaches that could be beneficial during stroke therapy. Unfortunately, most of them have proved ineffective in targeting multiple cellular death cascades incited within the ischemic penumbra. Hypothermia has been shown to be capable of addressing this problem to some extent. Although many studies have shown that hypothermia targets several cellular processes, its effects on innate immune receptor-mediated apoptotic death still remain unclear. Moreover, whether inhibiting the signaling of innate immune receptors like complement anaphylatoxin C5a receptor (CD88) plays a role in this hypothermic neuroprotection still need to be deciphered. Using various types of ischemic insults in different neuronal cells, we confirm that hypothermia does indeed attenuate apoptotic neuronal cell death in vitro and this effect can be further enhanced by pharmacologically blocking or knocking out CD88. Thus, our study raises a promising therapeutic possibility of adding CD88 antagonists along with hypothermia to improve stroke outcomes.

  13. C5a enhances dysregulated inflammatory and angiogenic responses to malaria in vitro: potential implications for placental malaria.

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    Andrea Conroy

    Full Text Available BACKGROUND: Placental malaria (PM is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI enhanced C5a receptor expression (CD88 on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10, chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM. CONCLUSIONS AND SIGNIFICANCE: These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function.

  14. C5a receptor signaling prevents folate deficiency-induced neural tube defects in mice.

    Science.gov (United States)

    Denny, Kerina J; Coulthard, Liam G; Jeanes, Angela; Lisgo, Steven; Simmons, David G; Callaway, Leonie K; Wlodarczyk, Bogdan; Finnell, Richard H; Woodruff, Trent M; Taylor, Stephen M

    2013-04-01

    The complement system is involved in a range of diverse developmental processes, including cell survival, growth, differentiation, and regeneration. However, little is known about the role of complement in embryogenesis. In this study, we demonstrate a novel role for the canonical complement 5a receptor (C5aR) in the development of the mammalian neural tube under conditions of maternal dietary folic acid deficiency. Specifically, we found C5aR and C5 to be expressed throughout the period of neurulation in wild-type mice and localized the expression to the cephalic regions of the developing neural tube. C5aR was also found to be expressed in the neuroepithelium of early human embryos. Ablation of the C5ar1 gene or the administration of a specific C5aR peptide antagonist to folic acid-deficient pregnant mice resulted in a high prevalence of severe anterior neural tube defect-associated congenital malformations. These findings provide a new and compelling insight into the role of the complement system during mammalian embryonic development.

  15. The C5a/C5aR1 axis controls the development of experimental allergic asthma independent of LysM-expressing pulmonary immune cells.

    Science.gov (United States)

    Wiese, Anna V; Ender, Fanny; Quell, Katharina M; Antoniou, Konstantina; Vollbrandt, Tillman; König, Peter; Köhl, Jörg; Laumonnier, Yves

    2017-01-01

    C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1). Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs) and monocyte-derived DCs (moDCs) during the allergic effector phase using a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we determined the role of C5aR1 signaling in neutrophils, moDCs and macrophages for the pulmonary recruitment of such cells and the importance of C5aR1-mediated activation of LysM-expressing cells for the development of allergic asthma. We used LysM-C5aR1 KO mice with a specific deletion of C5aR1 in LysMCre-expressing cells and confirmed the specific deletion of C5aR1 in neutrophils, macrophages and moDCs in the airways and/or the lung tissue. We found that alveolar macrophage numbers were significantly increased in LysM-C5aR1 KO mice. Induction of ovalbumin (OVA)-driven experimental allergic asthma in GFP-C5aR1fl/fl and LysM-C5aR1 KO mice resulted in strong but similar airway resistance, mucus production and Th2/Th17 cytokine production. In contrast, the number of airway but not of pulmonary neutrophils was lower in LysM-C5aR1 KO as compared with GFP-C5aR1fl/fl mice. The recruitment of macrophages, cDCs, moDCs, T cells and type 2 innate lymphoid cells was not altered in LysM-C5aR1 KO mice. Our findings demonstrate that C5aR1 is critical for steady state control of alveolar macrophage numbers and the transition of neutrophils from the lung into the airways in OVA-driven allergic asthma. However, C5aR1 activation of LysM-expressing cells plays a surprisingly minor role in the recruitment and activation of such cells and the development of the allergic phenotype in OVA-driven experimental allergic asthma.

  16. Complement factor C5a and C5a receptor contribute to morphine tolerance and withdrawal-induced hyperalgesia in rats.

    Science.gov (United States)

    Li, Yan-Hua; Jin, Hua; Xu, Jing-Shu; Guo, Guang-Qiong; Chen, DA-Lin; Bo, Yun

    2012-10-01

    Morphine is a potent opioid analgesic. However, the repeated use of morphine causes tolerance and hyperalgesia. Neuroinflammation has been reported to be involved in morphine tolerance and withdrawal-induced hyperalgesia. The complement system is a crucial effector mechanism of immune responses. The present study investigated the roles of complement factor C5a and C5a receptor (C5aR) in the development of morphine tolerance and withdrawal-induced hyperalgesia. In the present study, the levels of C5a and C5aR were increased in the L5 lumbar spinal cords of morphine-tolerant rats. The administration of C5a promoted the development of hyperalgesia and the expression of spinal antinociceptive tolerance to intrathecal morphine in both mechanical and thermal test. However, these phenomena caused by morphine were significantly attenuated by the C5aR antagonist PMX53. These results suggest that complement activation within the spinal cord is involved in morphine tolerance and withdrawal-induced hyperalgesia. C5a and C5aR may serve as novel targets for the control of morphine tolerance and withdrawal-induced hyperalgesia.

  17. Real-Time Imaging of Interactions of Neutrophils with Cryptococcus neoformans Demonstrates a Crucial Role of Complement C5a-C5aR Signaling.

    Science.gov (United States)

    Sun, Donglei; Zhang, Mingshun; Liu, Gongguan; Wu, Hui; Zhu, Xiaoping; Zhou, Hong; Shi, Meiqing

    2015-10-26

    Neutrophils have been shown to efficiently kill Cryptococcus neoformans, a causative agent of meningoencephalitis. Here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with C. neoformans and the underlying mechanisms in real time. Neutrophils were directly seen to chase C. neoformans cells and then rapidly internalize them. Complement C5a-C5aR signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of the organisms. The addition of recombinant complement C5a enhanced neutrophil movement but did not induce chemotaxis, suggesting that the C5a gradient is crucial. Incubation with C. neoformans resulted in enhanced activation of Erk and p38 mitogen-activated protein (MAP) kinases (MAPKs) in neutrophils. Inhibition of the p38 MAPK pathway, but not the Erk pathway, significantly impaired neutrophil migration and its subsequent killing of C. neoformans. Deficiency of CD11b or blocking of CD11b did not affect the migration of neutrophils toward C. neoformans but almost completely abolished phagocytosis and killing of the organisms by neutrophils. C5a-C5aR signaling induced enhanced surface expression of CD11b. Interestingly, the original surface expression of CD11b was essential and sufficient for neutrophils to attach to C. neoformans but was unable to mediate phagocytosis. In contrast, the enhanced surface expression of CD11b induced by C5a-C5aR signaling was essential for neutrophil phagocytosis and subsequent killing of yeast cells. Collectively, this is the first report of the dynamic interactions of neutrophils with C. neoformans, demonstrating a crucial role of C5a-C5aR signaling in neutrophil killing of C. neoformans in real time.

  18. Increased local concentration of complement C5a contributes to incisional pain in mice

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    Clark David J

    2011-07-01

    Full Text Available Abstract Background In our previous study, we demonstrated that local injection of complement C5a and C3a produce mechanical and heat hyperalgesia, and that C5a and C3a activate and sensitize cutaneous nociceptors in normal skin, suggesting a contribution of complement fragments to acute pain. Other studies also have shown that the complement system can be activated by surgical incision, and the systemic blockade of C5a receptor (C5aR reduces incision-induced pain and inflammation. In this study, we further examined the possible contribution of wound area C5a to incisional pain. Methods Using of a hind paw incisional model, the effects of a selective C5aR antagonist, PMX53, on nociceptive behaviors were measured after incision in vivo. mRNA levels of C5 and C5aR in skin, dorsal root ganglia (DRG and spinal cord, and C5a protein levels in the skin were quantified after incision. The responses of nociceptors to C5a were also evaluated using the in vitro skin-nerve preparation. Results Local administration of PMX53 suppressed heat hyperalgesia and mechanical allodynia induced by C5a injection or after hind paw incision in vivo. mRNA levels of C5 and C5aR in the skin, but not DRG and spinal cord, were dramatically increased after incision. C5a protein in the skin was also increased after incision. In vitro C5a did not increase the prevalence of fibers with ongoing activity in afferents from incised versus control, unincised skin. C5a sensitized C-fiber afferent responses to heat; however, this was less evident in afferents adjacent to the incision. PMX53 blocked sensitization of C-fiber afferents to heat by C5a but did not by itself influence ongoing activity or heat sensitivity in afferents innervating control or incised skin. The magnitude of mechanical responses was also not affected by C5a in any nociceptive fibers innervating incised or unincised skin. Conclusions This study demonstrates that high locally generated C5a levels are present in

  19. Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner.

    Science.gov (United States)

    Jain, Umang; Cao, Qi; Thomas, Nikhil A; Woodruff, Trent M; Schwaeble, Wilhelm J; Stover, Cordula M; Stadnyk, Andrew W

    2015-04-01

    Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium-induced colitis. Following infection, properdin knockout (P(KO)) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell-derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to P(KO) mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of P(KO) mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury.

  20. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

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    Chloë R McDonald

    2015-09-01

    Full Text Available The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.

  1. C5a receptor deficiency alters energy utilization and fat storage.

    Directory of Open Access Journals (Sweden)

    Christian Roy

    Full Text Available OBJECTIVE: To investigate the impact of whole body C5a receptor (C5aR deficiency on energy metabolism and fat storage. DESIGN: Male wildtype (WT and C5aR knockout (C5aRKO mice were fed a low fat (CHOW or a high fat high sucrose diet-induced obesity (DIO diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR. RESULTS: At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (-7% CHOW, -12% DIO as well as smaller gonadal (-38% CHOW, -36% DIO and inguinal (-29% CHOW, -30% DIO fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW and liver (CHOW and DIO and PPARγ was increased in muscle and liver. CONCLUSION: These observations point towards a role (either direct or indirect for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

  2. Reduced expression of C5a receptors on neutrophils from cord blood

    DEFF Research Database (Denmark)

    Nybo, Mads; Sørensen, O; Leslie, R;

    1998-01-01

    MLP was tested by measuring migration and exocytosis of myeloperoxidase and lactoferrin. RESULTS: C5a mean fluorescence on neutrophils from neonates was significantly lower (22.4 (SD 3.5)) than in adult controls (31.5 (3.1)). Neutrophils from neonates migrated poorly towards both C5a and fMLP compared with those...... from adult controls. Exocytosis of myeloperoxidase, but not lactoferrin from neonatal neutrophils stimulated with C5a, was significantly lower than in adult controls. fMLP stimulation, on the other hand, resulted in significantly higher exocytosis in neonates. CONCLUSION: The lower expression of C5a...... receptors on neutrophils from neonates could be related to reduced C5a mediated exocytosis of myeloperoxidase....

  3. The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen.

    Science.gov (United States)

    Kawamoto, Seiji; Yalcindag, Ali; Laouini, Dhafer; Brodeur, Scott; Bryce, Paul; Lu, Bao; Humbles, Alison A; Oettgen, Hans; Gerard, Craig; Geha, Raif S

    2004-08-01

    Mechanical injury to the skin results in activation of the complement component C3 and release of the anaphylatoxin C3a. C3a binds to a seven-transmembrane G protein-coupled receptor, C3aR. We used C3aR(-/-) mice to examine the role of C3a in a mouse model of allergic inflammation induced by epicutaneous sensitization with OVA. C3aR(-/-) mice exhibited an exaggerated Th2 response to epicutaneous but not to intraperitoneal sensitization with OVA, as evidenced by significantly elevated levels of serum OVA-specific IgG1 and significantly increased secretion of the Th2 cytokines IL-4, IL-5, and IL-10 by antigen-stimulated splenocytes. Presentation of OVA peptide by C3aR(-/-) APCs caused significantly more IL-4 and IL-5 secretion by T cells from OVA-T cell receptor (OVA-TCR) transgenic mice compared with presentation by WT APCs. C3a inhibited the ability of splenocytes, but not of highly purified T cells, to secrete Th2 cytokines in response to TCR ligation. This inhibition was mediated by IL-12 secreted by APCs in response to C3a. These results suggest that C3a-C3aR interactions inhibit the ability of APCs to drive Th2 cell differentiation in response to epicutaneously introduced antigen and may have important implications for allergic skin diseases.

  4. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

    Science.gov (United States)

    Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

    2016-04-01

    Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1-3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents.

  5. A Novel Role for the Receptor of the Complement Cleavage Fragment C5a, C5aR1, in CCR5-Mediated Entry of HIV into Macrophages.

    Science.gov (United States)

    Moreno-Fernandez, Maria E; Aliberti, Julio; Groeneweg, Sander; Köhl, Jörg; Chougnet, Claire A

    2016-04-01

    The complement system is an ancient pattern recognition system that becomes activated during all stages of HIV infection. Previous studies have shown that C5a can enhance the infection of monocyte-derived macrophages and T cells indirectly through the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and the attraction of dendritic cells. C5a exerts its multiple biologic functions mainly through activation of C5a receptor 1 (C5aR1). Here, we assessed the role of C5aR1 as an enhancer of CCR5-mediated HIV infection. We determined CCR5 and C5aR1 heterodimer formation in myeloid cells and the impact of C5aR1 blockade on HIV entry and genomic integration. C5aR1/CCR5 heterodimer formation was identified by immunoprecipitation and western blotting. THP-1 cells and monocyte-derived macrophages (MDM) were infected by R5 laboratory strains or HIV pseudotyped for the vesicular stomatitis virus (VSV) envelope. Levels of integrated HIV were measured by quantitative PCR after targeting of C5aR1 by a C5aR antagonist, neutralizing C5aR1 monoclonal antibody (mAb) or hC5a. C5aR1 was also silenced by specific siRNA prior to viral entry. We found that C5aR1 forms heterodimers with the HIV coreceptor CCR5 in myeloid cells. Targeting C5aR1 significantly decreased integration by R5 viruses but not by VSV-pseudotyped viruses, suggesting that C5aR1 is critical for viral entry. The level of inhibition achieved with C5aR1-blocking reagents was comparable to that of CCR5 antagonists. Mechanistically, C5aR1 targeting decreased CCR5 expression. MDM from CCR5Δ32 homozygous subjects expressed levels of C5aR1 similar to CCR5 WT individuals, suggesting that mere C5aR1 expression is not sufficient for HIV infection. HIV appeared to preferentially enter THP-1 cells expressing high levels of both C5aR1 and CCR5. Targeted reduction of C5aR1 expression in such cells reduced HIV infection by ~50%. Our data thus suggest that C5aR1 acts as an enhancer of CCR5-mediated HIV entry into

  6. C5a Regulates IL-1β Production and Leukocyte Recruitment in a Murine Model of Monosodium Urate Crystal-Induced Peritonitis

    Science.gov (United States)

    Khameneh, Hanif J.; Ho, Adrian W. S.; Laudisi, Federica; Derks, Heidi; Kandasamy, Matheswaran; Sivasankar, Baalasubramanian; Teng, Gim Gee; Mortellaro, Alessandra

    2017-01-01

    Gouty arthritis results from the generation of monosodium urate (MSU) crystals within joints. These MSU crystals elicit acute inflammation characterized by massive infiltration of neutrophils and monocytes that are mobilized by the pro-inflammatory cytokine IL-1β. MSU crystals also activate the complement system, which regulates the inflammatory response; however, it is unclear whether or how MSU-mediated complement activation is linked to IL-1β release in vivo, and the various roles that might be played by individual components of the complement cascade. Here we show that exposure to MSU crystals in vivo triggers the complement cascade, leading to the generation of the biologically active complement proteins C3a and C5a. C5a, but not C3a, potentiated IL-1β and IL-1α release from LPS–primed MSU-exposed peritoneal macrophages and human monocytic cells in vitro; while in vivo MSU–induced C5a mediated murine neutrophil recruitment as well as IL-1β production at the site of inflammation. These effects were significantly ameliorated by treatment of mice with a C5a receptor antagonist. Mechanistic studies revealed that C5a most likely increased NLRP3 inflammasome activation via production of reactive oxygen species (ROS), and not through increased transcription of inflammasome components. Therefore we conclude that C5a generated upon MSU-induced complement activation increases neutrophil recruitment in vivo by promoting IL-1 production via the generation of ROS, which activate the NLRP3 inflammasome. Identification of the C5a receptor as a key determinant of IL-1-mediated recruitment of inflammatory cells provides a novel potential target for therapeutic intervention to mitigate gouty arthritis. PMID:28167912

  7. A pro-inflammatory role of C5L2 in C5a-primed neutrophils for ANCA-induced activation.

    Directory of Open Access Journals (Sweden)

    Jian Hao

    Full Text Available BACKGROUND: The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV. In particular, C5a and its receptor on neutrophils, CD88, play a central role. The functional role of the second receptor of C5a, C5L2, remains unclear. In the current study, we investigated the role of C5L2 in C5a-primed neutrophils for ANCA-induced activation. METHODS: The effect of blocking C5L2 by anti-human C5L2 blocking antibody were tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA, as well as on membrane-bound proteinase 3 (mPR3 and concentration of myeloperoxidase (MPO in supernatant of C5a-primed neutrophils. An antagonist for CD88 was also employed. RESULTS: Blocking C5L2 resulted in a significantly decreased MPO concentration in the supernatant of C5a-primed neutrophils. mPR3 expression increased from 209.0±43.0 in untreated cells to 444.3±60.8 after C5a treatment (P<0.001, and decreased to 375.8±65.44, 342.2±54.3 and 313.7±43.6 by pre-incubating blocking C5L2 antibody at 2.5 µg/ml, 5 µg/ml or 10 µg/ml (compared with C5a-priming group, P<0.001, P<0.001, and P<0.001, respectively. In C5a-primed neutrophils, subsequently activating with MPO-ANCA-positive IgG, the MFI value was 425.8±160.6, which decreased to 292.8±141.2, 289.7±130.0 and 280.3±136.4 upon pre-incubation with mouse anti-human C5L2 blocking antibody at 2.5 µg/ml, 5 µg/ml or 10 µg/ml (compared with C5a-primed neutrophils, for MPO-ANCA-positive IgG-induced activation, P<0.05, P<0.05, and P<0.05, respectively. Blocking C5L2 also resulted in significantly decreased C5a-primed neutrophils for PR3-ANCA-positive IgG-induced activation. Moreover, the lactoferrin concentration in the supernant significantly decreased in pre-incubation with anti-human C5L2 blocking antibody, compared with C5a-primed neutrophils induced by PR3- or MPO-ANCA-positive IgG. CONCLUSIONS: C5L2 may be implicated in

  8. Structural complexes of the agonist, inverse agonist and antagonist bound C5a receptor: insights into pharmacology and signaling.

    Science.gov (United States)

    Rana, Soumendra; Sahoo, Amita Rani; Majhi, Bharat Kumar

    2016-04-26

    The C5a receptor (C5aR) is a pharmacologically important G-protein coupled receptor (GPCR) that interacts with (h)C5a, by recruiting both the "orthosteric" sites (site1 at the N-terminus and site2 at the ECS, extra cellular surface) on C5aR in a two site-binding model. However, the complex pharmacological landscape and the distinguishing chemistry operating either at the "orthosteric" site1 or at the functionally important "orthosteric" site2 of C5aR are still not clear, which greatly limits the understanding of C5aR pharmacology. One of the major bottlenecks is the lack of an experimental structure or a refined model structure of C5aR with appropriately defined active sites. The study attempts to understand the pharmacology at the "orthosteric" site2 of C5aR rationally by generating a highly refined full-blown model structure of C5aR through advanced molecular modeling techniques, and further subjecting it to automated docking and molecular dynamics (MD) studies in the POPC bilayer. The first series of structural complexes of C5aR respectively bound to a linear native peptide agonist ((h)C5a-CT), a small molecule inverse agonist (NDT) and a cyclic peptide antagonist (PMX53) are reported, apparently establishing the unique pharmacological landscape of the "orthosteric" site2, which also illustrates an energetically distinct but coherent competitive chemistry ("cation-π" vs. "π-π" interactions) involved in distinguishing the established ligands known for targeting the "orthosteric" site2 of C5aR. Over a total of 1 μs molecular dynamics (MD) simulation in the POPC bilayer, it is evidenced that while the agonist prefers a "cation-π" interaction, the inverse agonist prefers a "cogwheel/L-shaped" interaction in contrast to the "edge-to-face/T-shaped" type π-π interactions demonstrated by the antagonist by engaging the F275(7.28) of the C5aR. In the absence of a NMR or crystallographically guided model structure of C5aR, the computational model complexes not only

  9. CYP4F18-Deficient Neutrophils Exhibit Increased Chemotaxis to Complement Component C5a

    Directory of Open Access Journals (Sweden)

    Rachel Vaivoda

    2015-01-01

    Full Text Available CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4. CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild-type and Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response to LTB4, but the response to complement component C5a increased 1.9–2.25-fold in knockout cells compared to wild-type (P < 0.01. This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes in expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences in activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent chemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue myeloperoxidase between wild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to use LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges of CYP knockout studies.

  10. p38MAPK, ERK and PI3K signaling pathways are involved in C5a-primed neutrophils for ANCA-mediated activation.

    Directory of Open Access Journals (Sweden)

    Jian Hao

    Full Text Available BACKGROUND: The complement system is one of the important contributing factors in the development of antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV. C5a and the neutrophil C5a receptor play a central role in antineutrophil cytoplasmic antibody (ANCA-mediated neutrophil recruitment and activation. The current study further investigated the signaling pathways of C5a-mediated priming of human neutrophils for ANCA-induced neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: The effects of the p38 mitogen-activated protein kinase (p38MAPK inhibitor (SB202190, extracellular signal-regulated kinase (ERK inhibitor (PD98059, c-Jun N-terminal kinase (JNK inhibitor (6o and phosphoinositol 3-kinase (PI3K inhibitor (LY294002 were tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA, as well as on C5a-induced increase in expression of membrane-bound PR3 (mPR3 on neutrophils. For C5a-primed neutrophils for MPO-ANCA-induced respiratory burst, the mean fluorescence intensity (MFI value was 254.8±67.1, which decreased to 203.6±60.3, 204.4±36.7, 202.4±49.9 and 188±47.9 upon pre-incubation with SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.05, respectively. For PR3-ANCA-positive IgG, the MFI value increased in C5a-primed neutrophils, which decreased upon pre-incubation with above-mentioned inhibitors. The lactoferrin concentration increased in C5a-primed neutrophils induced by MPO or PR3-ANCA-positive IgG supernatant and decreased upon pre-incubation with above-mentioned three inhibitors. mPR3 expression increased from 923.3±182.4 in untreated cells to 1278.3±299.3 after C5a treatment and decreased to 1069.9±188.9, 1100±238.2, 1092.3±231.8 and 1053.9±200.3 by SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0

  11. Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement

    DEFF Research Database (Denmark)

    Czermak, B J; Lentsch, A B; Bless, N M;

    1999-01-01

    Complement plays an important role in many acute inflammatory responses. In the current studies it was demonstrated that, in the presence of either C5a or sublytic forms of the complement-derived membrane attack complex (MAC), rat alveolar macrophages costimulated with IgG immune complexes...... increased neutrophil accumulation occurred, as did lung injury. These observations suggest that C5a and MAC function synergistically with a costimulus to enhance chemokine generation and the intensity of the lung inflammatory response....

  12. Complement component C5a permits the coexistence of pathogenic Th17 cells and type I IFN in lupus.

    Science.gov (United States)

    Pawaria, Sudesh; Ramani, Kritika; Maers, Kelly; Liu, Youhua; Kane, Lawrence P; Levesque, Marc C; Biswas, Partha S

    2014-10-01

    Systemic lupus erythematosus (SLE) is a type I IFN (IFN-I)-driven autoimmune disorder with exaggerated B and Th cell responses. Th17 cells, a recently identified Th cell subset, have been strongly implicated in the pathogenesis of SLE. Because IFN-I suppresses the generation and expansion of Th17 cells in an IL-27-dependent manner, it is unclear how pathogenic Th17 cells are generated in SLE in the presence of an environment characterized by high IFN-I levels. In this study, we showed that activation of c5aR on murine macrophages blocked IFN-I-mediated IL-27 production, thus permitting the development of Th17 cells. C5aR activation on IFN-I-responsive macrophages inhibits IRF-1-mediated transactivation of IL-27 gene expression via the PI3K/Akt pathway. Consistently, C5aR-deficient mice exhibited increased IL-27 expression and fewer Th17 cells and consequently developed reduced lupus nephritis in comparison with wild-type mice. In support of these findings in mice, we found that C5a inhibited IFN-I-induced IL-27 production from macrophages of lupus subjects. Moreover, the level of serum C5a correlated with Th17 frequency in peripheral blood. Collectively, these data indicate an essential role for C5a in the generation of pathogenic Th17 responses in SLE. Thus, therapeutic strategies to block C5aR activation may be beneficial for controlling pathogenic Th17-mediated inflammation in SLE.

  13. Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat.

    Science.gov (United States)

    Woodruff, Trent M; Strachan, Anna J; Dryburgh, Nathan; Shiels, Ian A; Reid, Robert C; Fairlie, David P; Taylor, Stephen M

    2002-09-01

    To determine if the new, orally active C5a receptor antagonist, the cyclic peptide AcF-[OPdChaWR], reduces the severity of pathology in a rat model of immune-mediated monarticular arthritis. Arthritis was induced in the right knee of previously sensitized rats by the intraarticular injection of methylated bovine serum albumin. Rats were examined for either 14 days or 28 days, or for 49 days following a second antigen challenge at 28 days. The C5a antagonist (1 or 3 mg/kg/day) and/or ibuprofen (30 mg/kg/day) were administered orally on a daily basis either before or after arthritis induction. Rats receiving AcF-[OPdChaWR] had significant reductions in right knee swelling, gait disturbance, lavaged joint cell numbers, and right knee histopathology, as well as in serum levels of tumor necrosis factor alpha (TNFalpha) and intraarticular levels of interleukin-6 and TNFalpha on day 14. In the 14- and 28-day studies, ibuprofen resulted in a similar reduction in gait abnormalities and intraarticular inflammatory cells compared with the C5a antagonist, but was less effective in reducing knee swelling over the course of the study and had no effect on knee histopathology. Combination therapy with AcF-[OPdChaWR] and ibuprofen resulted in no greater efficacy than with the C5a antagonist alone. Rats injected twice with the antigen in the 49-day study displayed the most severe histopathology and this, as well as knee swelling and gait abnormalities, was significantly reduced by repeated treatment with the C5a antagonist. An agent that inhibits the action of C5a in this model significantly reduced joint pathology, while ibuprofen was not effective. C5a antagonists could therefore have broader therapeutic benefits than nonsteroidal antiinflammatory drugs as antiarthritic agents for rheumatoid arthritis.

  14. Complement C3a and C5a modulate osteoclast formation and inflammatory response of osteoblasts in synergism with IL-1β.

    Science.gov (United States)

    Ignatius, Anita; Schoengraf, Philipp; Kreja, Ludwika; Liedert, Astrid; Recknagel, Stefan; Kandert, Sebastian; Brenner, Rolf E; Schneider, Marion; Lambris, John D; Huber-Lang, Markus

    2011-09-01

    There is a tight interaction of the bone and the immune system. However, little is known about the relevance of the complement system, an important part of innate immunity and a crucial trigger for inflammation. The aim of this study was, therefore, to investigate the presence and function of complement in bone cells including osteoblasts, mesenchymal stem cells (MSC), and osteoclasts. qRT-PCR and immunostaining revealed that the central complement receptors C3aR and C5aR, complement C3 and C5, and membrane-bound regulatory proteins CD46, CD55, and CD59 were expressed in human MSC, osteoblasts, and osteoclasts. Furthermore, osteoblasts and particularly osteoclasts were able to activate complement by cleaving C5 to its active form C5a as measured by ELISA. Both C3a and C5a alone were unable to trigger the release of inflammatory cytokines interleukin (IL)-6 and IL-8 from osteoblasts. However, co-stimulation with the pro-inflammatory cytokine IL-1β significantly induced IL-6 and IL-8 expression as well as the expression of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) indicating that complement may modulate the inflammatory response of osteoblastic cells in a pro-inflammatory environment as well as osteoblast-osteoclast interaction. While C3a and C5a did not affect osteogenic differentiation, osteoclastogenesis was significantly induced even in the absence of RANKL and macrophage-colony stimulating factor (M-CSF) suggesting that complement could directly regulate osteoclast formation. It can therefore be proposed that complement may enhance the inflammatory response of osteoblasts and increase osteoclast formation, particularly in a pro-inflammatory environment, for example, during bone healing or in inflammatory bone disorders.

  15. Characterization of Cracking and Crack Growth Properties of the C5A Aircraft Tie-Box Forging

    Science.gov (United States)

    Piascik, Robert S.; Smith, Stephen W.; Newman, John A.; Willard, Scott A.

    2003-01-01

    Detailed destructive examinations were conducted to characterize the integrity and material properties of two aluminum alloy (7075-T6) horizontal stabilizer tie box forgings removed.from US. Air Force C5A and C5B transport aircraft. The C5B tie box forging was,found to contain no evidence of cracking. Thirteen cracks were found in the CSA,forging. All but one of the cracks observed in the C5A component were located along the top cap region (one crack was located in the bottom cap region). The cracks in the C5A component initiated at fastener holes and propagated along a highly tunneled intergranular crack path. The tunneled crack growth configuration is a likelv result of surface compressive stress produced during peening of the .forging suijace. The tie box forging ,fatigue crack growth, fracture and stress corrosion cracking (SCC) properties were characterized. Reported herein are the results of laboratory air ,fatigue crack growth tests and 95% relative humidity SCC tests conducted using specimens machined from the C5A ,forging. SCC test results revealed that the C5A ,forging material was susceptible to intergranular environmental assisted cracking: the C5A forging material exhibited a SCC crack-tip stress-intensity factor threshold of less than 6 MPadn. Fracture toughness tests revealed that the C5A forging material exhibited a fracture toughness that was 25% less than the C5B forging. The C5A forging exhibited rapid laboratory air fatigue crack growth rates having a threshold crack-tip stress-intensity factor range of less than 0.8 MPa sup m. Detailed fractographic examinations revealed that the ,fatigue crack intergranular growth crack path was similar to the cracking observed in the C5A tie box forging. Because both fatigue crack propagation and SCC exhibit similar intergranular crack path behavior, the damage mechanism resulting in multi-site cracking of tie box forgings cannot be determined unless local cyclic stresses can be quantified.

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

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    Ning Ma

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

  17. In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha

    DEFF Research Database (Denmark)

    Czermak, B J; Sarma, V; Bless, N M

    1999-01-01

    Under a variety of conditions, alveolar macrophages can generate early response cytokines (TNF-alpha, IL-1), complement components, and chemotactic cytokines (chemokines). In the current studies, we determined the requirements for TNF-alpha and the complement activation product C5a in chemokine...... production in vitro and in vivo. Two rat CXC chemokines (macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (CINC)) as well as three rat CC chemokines (MIP-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1) were investigated. Chemokine generation in vitro...... was studied in rat alveolar macrophages stimulated with IgG immune complexes in the absence or presence of Abs to TNF-alpha or C5a. The rat lung injury model induced by IgG immune complex deposition was employed for in vivo studies. Abs to TNF-alpha or C5a were administered intratracheally or i...

  18. 基于STC12C5A60S2单片机的光立方设计%Design of Light Cube Based on STC12C5A60S2 MCU

    Institute of Scientific and Technical Information of China (English)

    徐志颖; 廖远; 聂玲子

    2016-01-01

    Aimed at the limitation of the traditional flat panel display, this paper puts forward a light cube based on STC12C5A60S2 MCU. It uses STC12C5A60S2 microcomputer as the core controller, adopts monochromatic fog shaped square LEDs to form the light cube, and chooses NPN transistors to form the driven circuit. So users can use the program to achieve 3D animation display. The system has excellent features of low cost of production, good dis-play effect and functional perfection.%针对传统平面显示单一的局限性,本文设计了一种基于STC12C5A60S2单片机的光立方。整个光立方以STC12C5A60S2单片机作为核心控制器,采用单色雾状方形LED组成光立方灯体,并配以NPN型三极管构成驱动电路。用户可以通过编程实现自定义3D动画显示功能,该系统具有制作成本低、显示效果好、功能完善的特点。

  19. Compromised neutrophil function and severe bovine E.coli mastitis: is C5a the missing link?

    Science.gov (United States)

    Around the periparturient period and during early lactation dairy cows have an elevated risk for clinical mastitis. The severity of Gram-negative infections during these periods has been correlated with reduced neutrophil functions. In this review we focus on the potential role of C5a in the develop...

  20. Augmentation of Antitumor T-Cell Responses by Increasing APC T-Cell C5a/C3a-C5aR/C3aR Interactions

    Science.gov (United States)

    2013-03-01

    signaling which drives Th1/ Th17 effector cell responses (14). While we described the connection of C3aR/C5aR signaling with the PI-3Kγ- AKT-mTOR...involved in controlling the anti-tumor immune response, i.e. biasing between Th1/ Th17 effector cell vs Treg commitment, but also directly involved in

  1. A Potential Link between the C5a Receptor 1 and the β1-Adrenoreceptor in the Mouse Heart.

    Directory of Open Access Journals (Sweden)

    Kuan Hua Khor

    Full Text Available Inflammation may contribute to the pathogenesis of specific cardiovascular diseases, but it is uncertain if mediators released during the inflammatory process will affect the continued efficacy of drugs used to treat clinical signs of the cardiac disease. We investigated the role of the complement 5a receptor 1 (C5aR1/CD88 in the cardiac response to inflammation or atenolol, and the effect of C5aR1 deletion in control of baseline heart rate in an anesthetized mouse model.An initial study showed that PMX53, an antagonist of C5aR1 in normal C57BL6/J (wild type, WT mice reduced heart rate (HR and appeared to have a protective effect on the heart following induced sepsis. C5aR1 knockout (CD88-/- mice had a lower HR than wild type mice, even during sham surgery. A model to assess heart rate variability (HRV in anesthetized mice was developed to assess the effects of inhibiting the β1-adrenoreceptor (β1-AR in a randomized crossover study design.HR and LF Norm were constitutively lower and SDNN and HF Norm constitutively higher in the CD88-/- compared with WT mice (P 0.05, except for the reduced LF/HF (Lower frequency/High frequency ratio (P< 0.05 at 60 min post-atenolol, suggesting increased parasympathetic tone of the heart due to the effect of atenolol administration. The HR of the WT mice were lower post atenolol compared to the CD88-/- mice (P = 0.001 but the HRV of CD88-/- mice were significantly increased (P< 0.05, compared with WT mice.Knockout of the C5aR1 attenuated the effect of β1-AR in the heart, suggesting an association between the β1-AR and C5aR1, although further investigation is required to determine if this is a direct or causal association.

  2. Roles for C-X-C chemokines and C5a in lung injury after hindlimb ischemia-reperfusion

    DEFF Research Database (Denmark)

    Bless, N M; Warner, R L; Padgaonkar, V A;

    1999-01-01

    We evaluated the roles of the C-X-C chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) as well as the complement activation product C5a in development of lung injury after hindlimb ischemia-reperfusion in rats. During reperfusion, CD11b...... and CD18, but not CD11a, were upregulated on neutrophils [bronchoalveolar lavage (BAL) and blood] and lung macrophages. BAL levels of CINC and MIP-2 were increased during the ischemic and reperfusion periods. Treatment with either anti-CINC or anti-MIP-2 IgG significantly reduced lung vascular......, 58, and 23%, respectively (P MIP-2 as well as the complement activation product C5a are required for lung neutrophil recruitment and full induction of lung injury after hindlimb ischemia-reperfusion in rats....

  3. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    Directory of Open Access Journals (Sweden)

    Arheden Håkan

    2010-09-01

    Full Text Available Abstract Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg, a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8 or saline (9 mg/ml, n = 8. Area at risk (AAR was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007. Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23. The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

  4. Control of the collective migration of enteric neural crest cells by the Complement anaphylatoxin C3a and N-cadherin.

    Science.gov (United States)

    Broders-Bondon, Florence; Paul-Gilloteaux, Perrine; Gazquez, Elodie; Heysch, Julie; Piel, Matthieu; Mayor, Roberto; Lambris, John D; Dufour, Sylvie

    2016-06-01

    We analyzed the cellular and molecular mechanisms governing the adhesive and migratory behavior of enteric neural crest cells (ENCCs) during their collective migration within the developing mouse gut. We aimed to decipher the role of the complement anaphylatoxin C3a during this process, because this well-known immune system attractant has been implicated in cephalic NCC co-attraction, a process controlling directional migration. We used the conditional Ht-PA-cre transgenic mouse model allowing a specific ablation of the N-cadherin gene and the expression of a fluorescent reporter in migratory ENCCs without affecting the central nervous system. We performed time-lapse videomicroscopy of ENCCs from control and N-cadherin mutant gut explants cultured on fibronectin (FN) and micropatterned FN-stripes with C3a or C3aR antagonist, and studied cell migration behavior with the use of triangulation analysis to quantify cell dispersion. We performed ex vivo gut cultures with or without C3aR antagonist to determine the effect on ENCC behavior. Confocal microscopy was used to analyze the cell-matrix adhesion properties. We provide the first demonstration of the localization of the complement anaphylatoxin C3a and its receptor on ENCCs during their migration in the embryonic gut. C3aR receptor inhibition alters ENCC adhesion and migration, perturbing directionality and increasing cell dispersion both in vitro and ex vivo. N-cadherin-null ENCCs do not respond to C3a co-attraction. These findings indicate that C3a regulates cell migration in a N-cadherin-dependent process. Our results shed light on the role of C3a in regulating collective and directional cell migration, and in ganglia network organization during enteric nervous system ontogenesis. The detection of an immune system chemokine in ENCCs during ENS development may also shed light on new mechanisms for gastrointestinal disorders.

  5. Characterization of the stoichiometry of the complex formed by Staphylococcal toxin LukSF and human C5a receptor

    NARCIS (Netherlands)

    Haapasalo-Tuomainen, Karita; Wollman, Adam; De Haas, Carla; Aerts, Piet; Van'T Veld, Esther; Strijbis, Karin; Wubbolts, Richard; Van Kessel, Kok; Leake, Mark; Van Strijp, Jos

    2016-01-01

    Staphylococcus aureus causes diseases ranging from superficial skin and soft tissue infections (SSTI) to severe invasive diseases like osteomyelitis and necrotizing pneumonia. Panton Valentine Leukocidin (PVL) is a powerful leukocidal toxin produced by multiple S. aureus isolates. It is a pro-phage

  6. 基于STC12C5A60S2单片机的智能机器人设计%Design of the Intelligent Robot Based on the STC12C5A60S2 MCU

    Institute of Scientific and Technical Information of China (English)

    梁明亮; 孙逸洁

    2012-01-01

    The paper explains the general design of an I telligent robot that the key part of the control system is based on Type STC12C5A60S2Single Chip Micyoco and the design principle and methods of the type of robot.It is the higher liability of the robot that it won the technical skill competition for higher vocational colleges all over China.The robot has contribute a lot to the excellent competition result.%介绍一种以STC12C5A60S2单片机为控制核心的智能机器人的总体设计思路,阐述了智能机器人的硬件设计原理和C51软件设计方法。该机器人参加全国职业院校技能大赛,运行稳定可靠,为获得优异的竞赛成绩起到了重要作用。

  7. Design of Intelligent Tracking Car Based on STC12C5A60S2%基于STC12C5A60S2的智能循迹小车设计

    Institute of Scientific and Technical Information of China (English)

    陈和娟

    2012-01-01

      The design adopts STC12C5A60S2 microcontrol er as the core device of simple smart car. The tracking module is composed of a plurality of photoelectric tube, by reflecting infrared changes in judgments of black have to achieve the tracking function, motor drive module selection of commonly used H bridge driver L293D with single-chip microcomputer to control the motor working. The electric circuit construction of whole system is simple, reliable performance. It can meet a variety of design requirements.%  本设计采用STC12C5A60S2单片机为简易智能小车的核心器件。循迹模块由3对红外收发管组成,通过反射红外线的变化判断黑线的有无以达到循迹的功能,电机驱动模块选用H桥驱动芯片L293D结合单片机来控制电机工作。整个系统的电路结构简单,可靠性能高,能满足设计的要求。

  8. Fosb gene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia.

    Science.gov (United States)

    Nomaru, Hiroko; Sakumi, Kunihiko; Katogi, Atsuhisa; Ohnishi, Yoshinori N; Kajitani, Kosuke; Tsuchimoto, Daisuke; Nestler, Eric J; Nakabeppu, Yusaku

    2014-08-01

    The Fosb gene encodes subunits of the activator protein-1 transcription factor complex. Two mature mRNAs, Fosb and ΔFosb, encoding full-length FOSB and ΔFOSB proteins respectively, are formed by alternative splicing of Fosb mRNA. Fosb products are expressed in several brain regions. Moreover, Fosb-null mice exhibit depressive-like behaviors and adult-onset spontaneous epilepsy, demonstrating important roles in neurological and psychiatric disorders. Study of Fosb products has focused almost exclusively on neurons; their function in glial cells remains to be explored. In this study, we found that microglia express equivalent levels of Fosb and ΔFosb mRNAs to hippocampal neurons and, using microarray analysis, we identified six microglial genes whose expression is dependent on Fosb products. Of these genes, we focused on C5ar1 and C5ar2, which encode receptors for complement C5a. In isolated Fosb-null microglia, chemotactic responsiveness toward the truncated form of C5a was significantly lower than that in wild-type cells. Fosb-null mice were significantly resistant to kainate-induced seizures compared with wild-type mice. C5ar1 mRNA levels and C5aR1 immunoreactivity were increased in wild-type hippocampus 24 hours after kainate administration; however, such induction was significantly reduced in Fosb-null hippocampus. Furthermore, microglial activation after kainate administration was significantly diminished in Fosb-null hippocampus, as shown by significant reductions in CD68 immunoreactivity, morphological change and reduced levels of Il6 and Tnf mRNAs, although no change in the number of Iba-1-positive cells was observed. These findings demonstrate that, under excitotoxicity, Fosb products contribute to a neuroinflammatory response in the hippocampus through regulation of microglial C5ar1 and C5ar2 expression.

  9. 基于STC12C5A60S2自动太阳能跟踪器的设计%Design of automatic solar tracker based on STC12C5A60S2

    Institute of Scientific and Technical Information of China (English)

    张树人; 周景雷

    2015-01-01

    在此阐述了利用光敏电阻寻找直射太阳的原理,以STC12C5A60S2为控制核心,设计了一种自动太阳能跟踪器。太阳照射情况通过太阳能电池板4边上的4个光敏电阻测得,经过放大后输送到单片机,在单片机内由软件进行分析计算,得出电池板需要偏移的方向和角度,最后通过2个伺服电机对电池板左右和上下偏移进行控制,从而提高了转化效率。%The principle to look for the direct sun by using photosensitive resistance is expounded in this article. An auto⁃matic solar tracker taking the STC12C5A60S2 as its core was designed. The sun’s irradiation status is measured by the four pho⁃tosensitive resistances embedded on four sides of the solar panel,sent to the single chip microcomputer(SCM)after amplifica⁃tion,and then analyzed and calculated in the SCM by software to get deviation direction and angle that the panel needs to be moved. At last,two servo motors are adopted to control panels’left⁃right and up⁃down migration,and improve the luminous effi⁃ciency.

  10. Validation of MIL-F-9490D. General Specification for Flight Control System for Piloted Military Aircraft. Volume III. C-5A Heavy Logistics Transport Validation

    Science.gov (United States)

    1977-04-01

    of IELT -F-9490D are not compatible with the C-5A. The elevation of the pilot affects his visibility. Although there is similarity in the provisions...requiremnts. Other considerations were to insure that the air vehicle and its subsysbems, trainers , engines, test vehicles, ground support equipment, •tc

  11. Expression of complement C5a receptor and the viability of 4T1 tumor cells following agonist–antagonist treatment

    Directory of Open Access Journals (Sweden)

    Nurneqman Nashreq Kosni

    2016-01-01

    Conclusion: This experiment shows the presence of C5a receptor on 4T1 cell line. We believe that the antagonist peptide is eligible to be used widely in cancer immunotherapy field; but in vivo studies need to be carried out first in the future, as it will determine how these drugs affect the tumor cell growth.

  12. Treatment with anti-C5aR mAb leads to early-onset clinical and mechanistic effects in the murine delayed-type hypersensitivity arthritis model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Nansen, Anneline; Usher, Pernille A.

    2015-01-01

    Blockade of the complement cascade at the C5a/C5a receptor (C5aR)-axis is believed to be an attractive treatment avenue in rheumatoid arthritis (RA). However, the effects of such interventions during the early phases of arthritis remain to be clarified. In this study we use the murine delayed-typ...

  13. Levels of complement components C3a and C5a in renal injury among trichloroethylene-sensitized BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    查晚生

    2014-01-01

    Objective To determine the levels of complement components C3a and C5a in the kidneys of trichloroethylene(TCE)-sensitized BALB/c mice,and to investigate the role of complement components in TCE-induced renal injury among BALB/c mice.Methods Sixty-two female BALB/c mice were randomly divided into blank control group,vehicle control group,and TCE sensitization

  14. 基于STC12C5A08AD单片机的自动电阻测试仪的设计

    Institute of Scientific and Technical Information of China (English)

    龚成莹; 何辉; 兰聪花; 陶冶

    2012-01-01

    阐述利用电阻分压原理实现自动电阻测量的设计思想和系统实现.通过场效应管电阻测量电路采样的电压,经高速A/D转换器MAX187和微控制器STC12C5A08AD处理后在12864液晶上实时显示被测阻值.系统具有4档量程,可实现“自动与手动测量转换、电阻的筛选、自动测量和显示电位器阻值随旋转角度变化曲线”等功能,用户界面友好,操作简单.%This paper describes the basic idea and implementation about achieving resistor-divider principle of automatic resistance measurement Voltage is sampled by the FET resistance measurement circuit and processed by high-speed A/D converter MAX 187 and microcontroller STC12C5A08AD and measured resistance is displayed on the LCD 12864.System has 4 ranges, can achieve "automatic and manual measurement conversion, resistance selection, automatic measurement and display the curve of changed potentiometer" and etc. User-friendly interface, simple operation.

  15. Neutrophil Recruitment to the Lung in both C5a and CXCL1-Induced Alveolitis is Impaired in Vitamin D Binding Protein Deficient Mice

    Science.gov (United States)

    Trujillo, Glenda; Habiel, David M.; Ge, Lingyin; Ramadass, Mahalakshmi; Cooke, Nancy E.; Kew, Richard R.

    2013-01-01

    Knowledge of how neutrophils respond to chemotactic signals in a complex inflammatory environment is not completely understood. Moreover, even less is known about factors in physiological fluids that regulate the activity of chemoattractants. The vitamin D binding protein (DBP) has been shown to significantly enhance chemotaxis to complement activation peptide C5a using purified proteins in vitro, and by ex vivo depletion of DBP in physiological fluids, but this function has not been determined in vivo. DBP null (-/-) mice were used to investigate how a systemic absence of this plasma protein affects leukocyte recruitment in alveolitis models of lung inflammation. DBP-/- mice had significantly reduced (~50%) neutrophil recruitment to the lungs compared to their wild-type DBP+/+ counterparts in three different alveolitis models, two acute and one chronic. The histology of DBP-/- mouse lungs also showed significantly less injury than wild-type animals. The chemotactic cofactor function of DBP appears to be selective for neutrophil recruitment, but in contrast to previous in vitro results, in vivo DBP can enhance the activity of other chemoattractants including CXCL1. The reduced neutrophil response in DBP-/- mice could be rescued to wild-type levels by administering exogenous DBP. Finally, in inflammatory fluids DBP binds to G-actin released from damaged cells and this complex may be the active chemotactic cofactor. Results show for the first time that DBP is a significant chemotactic cofactor in vivo and not specific for C5a, suggesting that this ubiquitous plasma protein may have a more significant role in neutrophil recruitment than previously recognized. PMID:23752613

  16. Neutrophil recruitment to the lung in both C5a- and CXCL1-induced alveolitis is impaired in vitamin D-binding protein-deficient mice.

    Science.gov (United States)

    Trujillo, Glenda; Habiel, David M; Ge, Lingyin; Ramadass, Mahalakshmi; Cooke, Nancy E; Kew, Richard R

    2013-07-15

    Knowledge of how neutrophils respond to chemotactic signals in a complex inflammatory environment is not completely understood. Moreover, even less is known about factors in physiological fluids that regulate the activity of chemoattractants. The vitamin D-binding protein (DBP) has been shown to significantly enhance chemotaxis to complement activation peptide C5a using purified proteins in vitro, and by ex vivo depletion of DBP in physiological fluids, but this function has not been determined in vivo. DBP null ((-/-)) mice were used to investigate how a systemic absence of this plasma protein affects leukocyte recruitment in alveolitis models of lung inflammation. DBP(-/-) mice had significantly reduced (~50%) neutrophil recruitment to the lungs compared with their wild-type DBP(+/+) counterparts in three different alveolitis models, two acute and one chronic. The histology of DBP(-/-) mouse lungs also showed significantly less injury than wild-type animals. The chemotactic cofactor function of DBP appears to be selective for neutrophil recruitment, but, in contrast to previous in vitro results, in vivo DBP can enhance the activity of other chemoattractants, including CXCL1. The reduced neutrophil response in DBP(-/-) mice could be rescued to wild-type levels by administering exogenous DBP. Finally, in inflammatory fluids, DBP binds to G-actin released from damaged cells, and this complex may be the active chemotactic cofactor. To our knowledge, results show for the first time that DBP is a significant chemotactic cofactor in vivo and not specific for C5a, suggesting that this ubiquitous plasma protein may have a more significant role in neutrophil recruitment than previously recognized.

  17. Treatment with anti-C5aR mAb leads to early-onset clinical and mechanistic effects in the murine delayed-type hypersensitivity arthritis model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Nansen, Anneline; Usher, Pernille A.;

    2015-01-01

    Blockade of the complement cascade at the C5a/C5a receptor (C5aR)-axis is believed to be an attractive treatment avenue in rheumatoid arthritis (RA). However, the effects of such interventions during the early phases of arthritis remain to be clarified. In this study we use the murine delayed...... lymph node is also reduced following a single dose of anti-C5aR, suggesting that modulation of the C5a/C5aR axis results in effects on the T cell compartment in inflammatory arthritis. In summary, these data demonstrate that blockade of C5aR leads to rapid and significant effects on arthritic disease......-type hypersensitivity arthritis (DTHA) model to study the very early effects of a blocking, non-depleting anti-C5aR mAb on joint inflammation with treatment synchronised with disease onset, an approach not previously described. The DTHA model is a single-paw inflammatory arthritis model characterised by synchronised...

  18. 基于STC12 C5 A60 S2的双向DC-DC变换器的系统设计

    Institute of Scientific and Technical Information of China (English)

    汤正

    2016-01-01

    本文以2015年全国大学生电子设计竞赛为背景,系统设计了一种基于STC12C5A60S2单片机微处理器,使用集成电路芯片TPS5430和UC3842作为主控制芯片的双向DC-DC变换器.本设计由可控硅构成静态开关,当电池放电时,DC-DC变换器以Boost工作模式运行;当电池充电时,DC-DC变换器以Buck工作模式运行.此外使用TLC2543和TLV5618两款芯片通过AD采样和DA输出的电流检测技术实现了对直流充电电流测量,并由STC单片机控制液晶显示屏进行显示,成功设计出了一个高性能双向DC-DC变换电路,实现对18650型锂电池的充放电功能.本设计具有低成本高性能、结构简单、控制方便、直观显示等优点.

  19. 基于STC12C5A60S2单片机的模拟路灯控制系统设计%Design of simulation street lamp control system based on STC12C5A60S2 single chip

    Institute of Scientific and Technical Information of China (English)

    张旭彬; 丁戈; 王航宇

    2013-01-01

    文中详细描述了路灯模拟控制系统的设计方法.系统包括单片机控制、显示、红外感应、恒流驱动、路灯单元控制、故障检测与报警等6个模块.单片机控制模块以STC12C5A60S2为核心,完成各感应器件的信号采集任务,控制LED灯的工作模式,LCD显示各种数据.采用PWM波数字调节恒流源输出功率,达到控制LED路灯的照度;故障检测与报警模块可以实时检测各路灯单元的工作状态.实验证明该系统电路运行可靠.%This article describes in detail the design method of analog control system of street lamp.The system consists of microcomputer control,display,the six module of infrared induction,constant current drive,street lamp unit control,fault detection and alarm etc..MCU control module with STC12C5A60S2 as the core,to complete the signal acquisition task in each sensor,control LED lamp operating mode,LCD display data.Using the PWM wave digital control constant current source output power,achieve the illumination control LED lamp; fault detection and alarm module can work in real-time detection of each lamp unit state.The experiment proves that the system circuit is reliable in operation.

  20. Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

    Directory of Open Access Journals (Sweden)

    Reza Rezvani

    2014-01-01

    Full Text Available Objective. Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation. We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2 would be associated with pre- or postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predict metabolic profiles after weight loss surgery. Materials and Methods. Fasting plasma (hormone, lipid, and enzyme analysis and liver biopsies (RT-PCR gene expression were obtained from 91 women during surgery. Results. Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women (P<0.01 and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (all P<0.05. While plasma ASP was lower in pre- versus postmenopausal women (P<0.01, the hepatic C5L2/C5aR mRNA ratio was increased (P<0.001 and correlated positively with estrone (P<0.01 and estradiol (P<0.001 and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (all P<0.05. Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT, P<0.05, AST and GGT, P<0.001 2-way-ANOVA. Conclusion. C5L2-C5aR association with other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.

  1. 基于STC12C5A60S2单片机的室内环境检测系统设计%Design of Indoor Environment Detecting System Based on STC12C5A60S2 Microcontroller

    Institute of Scientific and Technical Information of China (English)

    兰高羽; 边树海

    2012-01-01

    介绍了基于STC12C5A60S2单片机的室内环境检测系统设计方法。为了对室内不同环境(包括客厅、卧室、厨房和卫生间)的不同参数进行实时检测,整个系统以客厅为核心,将实时检测到的卧室、厨房、卫生间等处的环境参数值传送给客厅系统,实现了对室内不同环境、不同参数的实时检测和显示。当室内环境中的CO浓度、NH,浓度、H2S浓度、煤气浓度或甲醛浓度超标时,系统会自动报警,同时根据实时检测到的温、湿度和光照度值来决定电器(如空调、加湿器、灯具)的开关状态,以达到节能的效果。该系统简单,可靠性强,成本低,可扩展性好。%A design method of indoor environment detecting system based on STC12C5A60S2 microcontroller was introduced. In order to detect different parameters in the real time in different indoor environment, including the sitting room, bedroom, kitchen and toilet, the whole system centers on sitting room system, transmits the environment parameters detected from bedroom, kitchen and toilet respectively to the sitting room system, realizes the detection and display of different parameters in different indoor environment. When the concentration of CO, NH3 , H2S, coal gas and formaldehyde in the indoor environment is higher than respective criterion, the system will alarm automatically based on the temperature, humidity, intensity of illumination detecting, the system decides to open or close household appliances in order to get the result of energy saving. The system is simple, it has strong reliability, low cost and good expansibility, and it can be used in the intelligent community.

  2. Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production

    DEFF Research Database (Denmark)

    Moghimi, S.M.; Hamad, I.; Andresen, Thomas Lars;

    2006-01-01

    Methoxy(polyethylene glycol), mPEG, -grafted liposomes are known to exhibit prolonged circulation time in the blood, but their infusion into a substantial percentage of human subjects triggers immediate non-IgE-mediated hypersensitivity reactions. These reactions are strongly believed to arise from...

  3. Design of music player based on MCU STC12C5A60S2%一种基于51单片机的音乐播放器的设计

    Institute of Scientific and Technical Information of China (English)

    何谐; 唐大权; 张淑廷; 陈雪

    2014-01-01

    The hardware design method of the music player based on MCU STC12C5A60S2 is introduced in this paper. The program design of the music player based on principle of FAT32 file system is studied. In the music player, MCU STC12C5A60S2 is taken as a main controller,SD card as a memory medium of music files and VS1003 chip as a decoder unit. When the player is running,MCU STC12C5A60S2 reads the music file from the SD card and continuously transfers data flow to VS1003 for decoding. In the meantime,the OLED liquid crystal display shows the message of the music in real time. The tested results from experiments show the music player can play the music files in multiple formats fluently if the player is connected with ear phone.%主要介绍一种基于51单片机的音乐播放器的硬件设计方法,并研究在FAT32文件系统下音乐播放器的程序设计。该音乐播放器采用STC12C5A60S2单片机为主控制器,SD卡作为音乐文件的存储介质,VS1003芯片作为解码器。STC12C5A60S2单片机从 SD卡中读取音乐文件,并不断将数据流传送至VS1003解码,最后连接耳机播放,同时STC12C5A60S2连接OLED液晶显示屏实时显示音乐播放信息。实验表明,该音乐播放器连接耳机能流畅播放多种格式的音乐文件。

  4. Arginine-rich cationic proteins of human eosinophil granules

    Energy Technology Data Exchange (ETDEWEB)

    Olsson, I.; Venge, P.; Spitznagel, J.K.; Lehrer, R.I.

    1977-01-01

    Several arginine-rich cationic proteins previously isolated from granules of leukemic myeloid cells have been found to reside primarily in human eosinophil leukocytes. The major component has a molecular weight of 21,000 and it contains approximately 2.6 moles of zinc per mole of protein. Velocity centrifugation of cytoplasm from leukocytes of patients with marked eosinophilia showed that this group of proteins is packaged in the crystalloid-containing large eosinophil granules. Approximately 30% of the protein content of eosinophil granules belonged to this group of cationic proteins. Bactericidal or esterolytic activities of the cationic proteins were not detected, nor did they inhibit guinea pig anaphylatoxin or histamine-induced contraction. The basic protein previously demonstrated in guinea pig eosinophils may be analogous to the group of basic proteins of human eosinophils but great differences are found for molecular weight and amino acid composition.

  5. Designof temperature acquisition system based on STC12CSA16S2%基于STC12C5A16S2的温度采集系统的设计

    Institute of Scientific and Technical Information of China (English)

    王鑫; 崔忠林; 刘建

    2012-01-01

    Based on the semiconductor physical and electrical properties of semiconductor devices, a low temperature self-start heater thermostat is designed for making sure the low temperature self-start and using as few components as possible to form a complete closed-loop control system. In this paper, using the temperature characteristic of PT100 metal platinum resistance with three wire connection and STC12C5A165S2 to acquire temperature signal, and 485 line of industry is used as communication of the temperature transfer in order to improving the reliability of information transmission. Through the thermal simulation experiment, the feasibility of the low-temperature self-start temperature acquisition system is verified.%以半导体器件的物理特性和电学特性为依据,设计了一种低温自启动恒温加热器,保证系统内部温度处于芯片正常工作范围内,并以尽可能少的元件构成完整的闭环控制系统。剃用PT100型金属铂电阻温度特性,使用三线制接法,采用STC12C5A16S2型单片机芯片对温度信号进行采集。使用工业上常用的RS485总线作为温度传输的通讯方式,以提高信息传输的可靠性。通过在高低温环境下实验,验证了该温度采集系统的可行性。

  6. 基于STC12C5A60S2单片机的视频遥控小车设计%The Design of Wireless Video Remote Control Car Based on STC12 Series MCU

    Institute of Scientific and Technical Information of China (English)

    宋扬; 朱江

    2014-01-01

    该文对视频遥控小车进行了深入的研究,设计出了一套基于STC12C5A60S2单片机的视频遥控小车系统。为了能够远程控制小车的运行状态,采用无线视频发射与接收模块将小车在现场采集到的视频信号显示在PC机上,以便控制室的人能够观察到小车现场的实时情况,利用无线数据传输模块完成主控体对小车的控制及小车运行状态的反馈,最终实现了小车的远程实时控制。%In this paper, wireless video remote control car is studied deeply, and designs a system of wireless video remote control car based on STC12C5A60S2 MCU. In order to control operation state of car wirelessly, by using the wireless video transmission and reception module, the video signal is displayed on PC in time to make person who is in control room observe the scene of the car, the use of wireless date transmission module completes the control of controller for car and a feedback of car for control-ler.

  7. Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs

    DEFF Research Database (Denmark)

    Cheng, Shih-Chin; Sprong, Tom; Joosten, Leo A B

    2012-01-01

    In experimental studies, the role of complement in antifungal host defense has been attributed to its opsonizing capability. In this study, we report that in humans an activated complement system mainly augments Candida albicans-induced host proinflammatory cytokine production via C5a-C5a......R signaling, while phagocytosis and intracellular killing of Candida are not influenced. By blocking the C5a-C5aR signaling pathway, either with anti-C5a antagonist antibodies or with the C5aR antagonist W-54001, C. albicans-induced IL-6 and IL-1β levels were significantly reduced. Recombinant C5a augmented...... in augmenting host proinflammatory cytokine production upon contact with C. albicans, and define the role of the complement system in anti-Candida host defense in humans....

  8. Role of C5 Activation Products in Sepsis

    Directory of Open Access Journals (Sweden)

    Peter A. Ward

    2010-01-01

    Full Text Available Complement activation products are known to be generated in the setting of both experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the membrane attack complex [MAC] C5b-9 are generated during sepsis following infusion of endotoxin, or after cecal ligation and puncture (CLP, which produces polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner that creates the “cytokine storm”, and is associated with development of multiorgan failure (MOF. A number of other complications arising from the interaction of C5a with its receptors include apoptosis of lymphoid cells, loss of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes, cardiomyopathy, disseminated intravascular coagulation, and complications associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a receptors greatly reduces the adverse events in the setting of sepsis, markedly attenuates MOF, and greatly improves survival. Regarding the possible role of C5b-9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception.

  9. Staphylococcal SSL5 inhibits leukocyte activation by chemokines and anaphylatoxins

    NARCIS (Netherlands)

    Bestebroer, Jovanka; van Kessel, Kok P. M.; Azouagh, Hafida; Walenkamp, Annemiek M.; Boer, Ingrid G. J.; Romijn, Roland A.; van Strijp, Jos A. G.; de Haas, Carla J. C.

    2009-01-01

    Staphylococcus aureus secretes several virulence factors modulating immune responses. Staphylococcal superantigen-like (SSL) proteins are a family of 14 exotoxins with homology to superantigens, but with generally unknown function. Recently, we showed that SSL5 binds to P-selectin glycoprotein ligan

  10. Complement activated granulocytes can cause autologous tissue destruction in man

    Directory of Open Access Journals (Sweden)

    E. Löhde

    1992-01-01

    Full Text Available Activation of polymorphonuclear granulocytes (PMNs by C5a is thought to be important in the pathogenesis of multiple organ failure during sepsis and after trauma. In our experiment exposure of human PMNs to autologous zymosan activated plasma (ZAP leads to a rapid increase in chemiluminescence. Heating the ZAP at 56°C for 30 min did not alter the changes, while untreated plasma induced only baseline activity. The respiratory burst could be completely abolished by decomplementation and preincubation with rabbit antihuman C5a antibodies. Observation of human omentum using electron microscopy showed intravascular aggregation of PMNs, with capillary thrombosis and diapedesis of the cells through endothelial junctions 90 s after exposure to ZAP. PMNs caused disruption of connections between the mesothelial cells. After 4 min the mesothelium was completely destroyed, and connective tissue and fat cells exposed. Native plasma and minimum essential medium did not induce any morphological changes. These data support the concept that C5a activated PMNs can cause endothelial and mesothelial damage in man. Even though a causal relationship between anaphylatoxins and organ failure cannot be proved by these experiments C5a seems to be an important mediator in the pathogenesis of changes induced by severe sepsis and trauma in man.

  11. Roles for NHERF1 and NHERF2 on the regulation of C3a receptor signaling in human mast cells.

    Directory of Open Access Journals (Sweden)

    Hariharan Subramanian

    Full Text Available BACKGROUND: The anaphylatoxin C3a binds to the G protein coupled receptor (GPCR, C3aR and activates divergent signaling pathways to induce degranulation and cytokine production in human mast cells. Adapter proteins such as the Na(+/H(+ exchange regulatory factor (NHERF1 and NHERF2 have been implicated in regulating functions of certain GPCRs by binding to the class I PDZ (PSD-95/Dlg/Zo1 motifs present on their cytoplasmic tails. Although C3aR possesses a class I PDZ motif, the possibility that it interacts with NHERF proteins to modulate signaling in human mast cells has not been determined. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcription PCR and Western blotting, we found that NHERF1 and NHERF2 are expressed in human mast cell lines (HMC-1, LAD2 and CD34(+-derived primary human mast cells. Surprisingly, however, C3aR did not associate with these adapter proteins. To assess the roles of NHERFs on signaling downstream of C3aR, we used lentiviral shRNA to stably knockdown the expression of these proteins in human mast cells. Silencing the expression of NHERF1 and NHERF2 had no effect on C3aR desensitization, agonist-induced receptor internalization, ERK/Akt phosphorylation or chemotaxis. However, loss of NHERF1 and NHERF2 resulted in significant inhibition of C3a-induced mast cell degranulation, NF-κB activation and chemokine production. CONCLUSION/SIGNIFICANCE: This study demonstrates that although C3aR possesses a class I PDZ motif, it does not associate with NHERF1 and NHERF2. Surprisingly, these proteins provide stimulatory signals for C3a-induced degranulation, NF-κB activation and chemokine generation in human mast cells. These findings reveal a new level of complexity for the functional regulation of C3aR by NHERFs in human mast cells.

  12. Isolation and sequence analysis of a cDNA clone encoding the fifth complement component

    DEFF Research Database (Denmark)

    Lundwall, Åke B; Wetsel, Rick A; Kristensen, Torsten

    1985-01-01

    obtained further predicted an arginine-rich sequence (RPRR) immediately upstream of the N-terminal threonine of C5a, indicating that the promolecule form of C5 is synthesized with a beta alpha-chain orientation as previously shown for pro-C3 and pro-C4. The C5 cDNA clone was sheared randomly by sonication......We have used available protein sequence data for the anaphylatoxin (C5a) portion of the fifth component of human complement (residues 19-25) to synthesize a mixed-sequence oligonucleotide probe. The labeled oligonucleotide was then used to screen a human liver cDNA library, and a single candidate cDNA...... clone of 1.85 kilobase pairs was isolated. Hybridization of the mixed-sequence probe to the complementary strand of the plasmid insert and sequence analysis by the dideoxy method predicted the expected protein sequence of C5a (positions 1-12), amino-terminal to the anticipated priming site. The sequence...

  13. Complement mediated renal inflammation induced by donor brain death : role of renal C5a-C5aR interaction

    NARCIS (Netherlands)

    van Werkhoven, M. B.; Damman, J.; van Dijk, M. C. R. F.; Daha, M. R.; de Jong, I. J.; Leliveld, A.; Krikke, C.; Leuvenink, H. G.; van Goor, H.; van Son, W. J.; Olinga, P.; Hillebrands, J. -L.; Seelen, M. A. J.

    2013-01-01

    Kidneys retrieved from brain-dead donors have impaired allograft function after transplantation compared to kidneys from living donors. Donor brain death (BD) triggers inflammatory responses, including both systemic and local complement activation. The mechanism by which systemic activated complemen

  14. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses.

    Directory of Open Access Journals (Sweden)

    Guido Moll

    Full Text Available Infusion of human third-party mesenchymal stromal cells (MSCs appears to be a promising therapy for acute graft-versus-host disease (aGvHD. To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46 and DAF (CD55, but were protected from complement lysis via expression of protectin (CD59. Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.

  15. Prokaryotic expression and immunogenicity analysis of C5a peptidase (ScpB) of Streptococcus agalactiae isolated from tilapia%罗非鱼无乳链球菌C5a肽酶(ScpB)的原核表达及其免疫原性

    Institute of Scientific and Technical Information of China (English)

    李庆勇; 可小丽; 卢迈新; 朱华平; 高风英; 刘志刚

    2014-01-01

    Streptococcus agalactiae is a major bacterial pathogen that has caused severe economic losses in many spe-cies of freshwater, marine and estuarine fish worldwide. ScpB is a highly conserved surface protein among all group B streptococcus (GBS) strains and is an attractive surface-exposed antigen for inclusion among vaccine components against GBS. In this study, the scpB gene was amplified from the genomic DNA of an S. agalactiae strain isolated from diseased tilapia farmed in Guangdong province, China. The scpB gene contains a 2 799 bp open reading frame (ORF), encoding 932 amino acids. The molecular mass of the deduced protein was 103 kD. Blast analysis showed that it shares high similarity with scpB sequences of human GBSs registered in GenBank. Prokaryotic expression vector pET32a (+) was used to construct a recombinant expression vector pET32a (+)-scpB, which was transformed into Escherichia coli BL21 (DE3). Colonies containing the recombinant expression vector pET32a (+)-scpB were selected and then induced to express using 0.5 mmol/L IPTG for 8 h at 37℃. The expressed recombinant protein was purified by nickel chelate affinity chromatography and ultrafiltration tube enrichment. SDS-PAGE analysis and western blotting showed a spe-cific protein band of about 121 kD. The recombinant strain could produce large amounts of ScpB protein, mainly in the form of an inclusion body. To analyze the immunogenicity of the recombinant protein, the purified fusion protein and Freund’s adjuvant were mixed according to a certain proportions to produce vaccines. Three immune dosages, 1μg/g(F1), 3μg/g(F3) and 5μg/g(F5) were used. Four weeks after immunization, tilapia were challenged by artificial infection with the GBS ZP-N strain, which was previously isolated and confirmed to be a tilapia pathogen by our labo-ratory. The recorded relative percent survivals (RPS) of the vaccinated groups ranged from 69.99%to 89%, of which group F5 has the highest RPS. The lysozyme

  16. UDP-glucosyltransferase71c5, a major glucosyltransferase, mediates abscisic acid homeostasis in Arabidopsis.

    Science.gov (United States)

    Liu, Zhen; Yan, Jin-Ping; Li, De-Kuan; Luo, Qin; Yan, Qiujie; Liu, Zhi-Bin; Ye, Li-Ming; Wang, Jian-Mei; Li, Xu-Feng; Yang, Yi

    2015-04-01

    Abscisic acid (ABA) plays a key role in plant growth and development. The effect of ABA in plants mainly depends on its concentration, which is determined by a balance between biosynthesis and catabolism of ABA. In this study, we characterize a unique UDP-glucosyltransferase (UGT), UGT71C5, which plays an important role in ABA homeostasis by glucosylating ABA to abscisic acid -: glucose ester (GE) in Arabidopsis (Arabidopsis thaliana). Biochemical analyses show that UGT71C5 glucosylates ABA in vitro and in vivo. Mutation of UGT71C5 and down-expression of UGT71C5 in Arabidopsis cause delay in seed germination and enhanced drought tolerance. In contrast, overexpression of UGT71C5 accelerates seed germination and reduces drought tolerance. Determination of the content of ABA and ABA-GE in Arabidopsis revealed that mutation in UGT71C5 and down-expression of UGT71C5 resulted in increased level of ABA and reduced level of ABA-GE, whereas overexpression of UGT71C5 resulted in reduced level of ABA and increased level of ABA-GE. Furthermore, altered levels of ABA in plants lead to changes in transcript abundance of ABA-responsive genes, correlating with the concentration of ABA regulated by UGT71C5 in Arabidopsis. Our work shows that UGT71C5 plays a major role in ABA glucosylation for ABA homeostasis.

  17. Synthesis and interactions of sulfated C5a-receptor and CHIPS mimics

    NARCIS (Netherlands)

    Bunschoten, A.|info:eu-repo/dai/nl/304836958

    2010-01-01

    Post-translational modifications are modifications of peptides or proteins after they have been synthesized in the ribosomes. These post-translational modifications (PTM’s) are intended to augment functional diversity of the 20 natural L-amino acids of which proteins are constructed. PTM’s have impo

  18. Complement activation in the context of stem cells and tissue repair

    Institute of Scientific and Technical Information of China (English)

    Ingrid; U; Schraufstatter; Sophia; K; Khaldoyanidi; Richard; G; DiScipio

    2015-01-01

    The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.

  19. Molecules Great and Small: The Complement System.

    Science.gov (United States)

    Mathern, Douglas R; Heeger, Peter S

    2015-09-04

    The complement cascade, traditionally considered an effector arm of innate immunity required for host defense against pathogens, is now recognized as a crucial pathogenic mediator of various kidney diseases. Complement components produced by the liver and circulating in the plasma undergo activation through the classical and/or mannose-binding lectin pathways to mediate anti-HLA antibody-initiated kidney transplant rejection and autoantibody-initiated GN, the latter including membranous glomerulopathy, antiglomerular basement membrane disease, and lupus nephritis. Inherited and/or acquired abnormalities of complement regulators, which requisitely limit restraint on alternative pathway complement activation, contribute to the pathogenesis of the C3 nephropathies and atypical hemolytic uremic syndrome. Increasing evidence links complement produced by endothelial cells and/or tubular cells to the pathogenesis of kidney ischemia-reperfusion injury and progressive kidney fibrosis. Data emerging since the mid-2000s additionally show that immune cells, including T cells and antigen-presenting cells, produce alternative pathway complement components during cognate interactions. The subsequent local complement activation yields production of the anaphylatoxins C3a and C5a, which bind to their respective receptors (C3aR and C5aR) on both partners to augment effector T-cell proliferation and survival, while simultaneously inhibiting regulatory T-cell induction and function. This immune cell-derived complement enhances pathogenic alloreactive T-cell immunity that results in transplant rejection and likely contributes to the pathogenesis of other T cell-mediated kidney diseases. C5a/C5aR ligations on neutrophils have additionally been shown to contribute to vascular inflammation in models of ANCA-mediated renal vasculitis. New translational immunology efforts along with the development of pharmacologic agents that block human complement components and receptors now permit

  20. In-vitro activation of complement system by lactic acidosis in newborn and adults

    Directory of Open Access Journals (Sweden)

    Friederike Hecke

    2001-01-01

    Full Text Available Introduction: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis.

  1. Targeted complement inhibition and microvasculature in transplants: a therapeutic perspective.

    Science.gov (United States)

    Khan, M A; Hsu, J L; Assiri, A M; Broering, D C

    2016-02-01

    Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during allograft acceptance. The complement cascade releases the powerful proinflammatory mediators C3a and C5a anaphylatoxins, C3b, C5b opsonins and terminal membrane attack complex into tissues, which are deleterious if unchecked. Blocking complement mediators has been considered to be a promising approach in the modern drug discovery plan, and a significant number of therapeutic alternatives have been developed to dampen complement activation and protect host cells. Numerous immune cells, especially macrophages, develop both anaphylatoxin and opsonin receptors on their cell surface and their binding affects the macrophage phenotype and their angiogenic properties. This review discusses the mechanism that complement contributes to angiogenic injury, and the development of future therapeutic targets by antagonizing activated complement mediators to preserve microvasculature in rejecting the transplanted organ.

  2. Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway.

    Science.gov (United States)

    Güven, Esin; Duus, Karen; Laursen, Inga; Højrup, Peter; Houen, Gunnar

    2013-01-01

    Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes complement components and activates the complement system. We show that complement activation by Al(OH)3 involves the three major pathways by monitoring complement components in Al(OH)3-treated serum and in Al(OH)3-containing precipitates. Al(OH)3 activation of complement results in deposition of C3 cleavage products and membrane attack complex (MAC) and in generation of the anaphylatoxins C3a and C5a. Complement activation was time dependent and inhibited by chelation with EDTA but not EGTA+Mg(2+). We thus confirm that Al(OH)3 activates the complement system and show that the alternative pathway is of major importance.

  3. Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway.

    Directory of Open Access Journals (Sweden)

    Esin Güven

    Full Text Available Al(OH3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH3 treatment of serum depletes complement components and activates the complement system. We show that complement activation by Al(OH3 involves the three major pathways by monitoring complement components in Al(OH3-treated serum and in Al(OH3-containing precipitates. Al(OH3 activation of complement results in deposition of C3 cleavage products and membrane attack complex (MAC and in generation of the anaphylatoxins C3a and C5a. Complement activation was time dependent and inhibited by chelation with EDTA but not EGTA+Mg(2+. We thus confirm that Al(OH3 activates the complement system and show that the alternative pathway is of major importance.

  4. Aluminum Hydroxide Adjuvant Differentially Activates the Three Complement Pathways with Major Involvement of the Alternative Pathway

    Science.gov (United States)

    Güven, Esin; Duus, Karen; Laursen, Inga; Højrup, Peter; Houen, Gunnar

    2013-01-01

    Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes complement components and activates the complement system. We show that complement activation by Al(OH)3 involves the three major pathways by monitoring complement components in Al(OH)3-treated serum and in Al(OH)3-containing precipitates. Al(OH)3 activation of complement results in deposition of C3 cleavage products and membrane attack complex (MAC) and in generation of the anaphylatoxins C3a and C5a. Complement activation was time dependent and inhibited by chelation with EDTA but not EGTA+Mg2+. We thus confirm that Al(OH)3 activates the complement system and show that the alternative pathway is of major importance. PMID:24040248

  5. Different activation signals induce distinct mast cell degranulation strategies

    Science.gov (United States)

    Sibilano, Riccardo; Marichal, Thomas; Reber, Laurent L.; Cenac, Nicolas; McNeil, Benjamin D.; Dong, Xinzhong; Hernandez, Joseph D.; Sagi-Eisenberg, Ronit; Hammel, Ilan; Roers, Axel; Valitutti, Salvatore; Tsai, Mindy

    2016-01-01

    Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-β during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P–dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation. PMID:27643442

  6. Human See, Human Do.

    Science.gov (United States)

    Tomasello, Michael

    1997-01-01

    A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

  7. Acidosis activates complement system in vitro

    Directory of Open Access Journals (Sweden)

    Michael Emeis

    1998-01-01

    Full Text Available We investigated the in vitro effect of different form s of acidosis (pH 7.0 on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 μ mol/ml blood or lactic acid (5.5 μ mol/ml to heparin blood (N=12 caused significant activation of C3a and C5a compared to control (both p=0.002. Respiratory acidosis activated C3a (p=0.007 and C5a (p=0.003 compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5.

  8. Acidosis activates complement system in vitro.

    Science.gov (United States)

    Emeis, M; Sonntag, J; Willam, C; Strauss, E; Walka, M M; Obladen, M

    1998-01-01

    We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5. PMID:9927235

  9. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  10. In-vitro activation of complement system by lactic acidosis in newborn and adults.

    Science.gov (United States)

    Hecke, F; Hoehn, T; Strauss, E; Obladen, M; Sonntag, J

    2001-01-01

    INTRODUCTION: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis. METHODS: Cord and adult blood samples (n = 20 each) were collected and incubated for one hour in either untreated condition or with the addition of lactate in two concentrations (5.5 mmol/l vs. 22 mmol/l). Following incubation, levels of C3a, C5a and sC5b-9, and blood gas parameters were determined. RESULTS: Anaphylatoxin (C3a and C5a) and sC5b-9 levels increased with the addition of lactate in a dose-dependent manner in cord and adult blood (C3a: 1 h, 5.5 mmo/l, 22 mmol/l: 418/498/622 microg/l in cord blood; 1010/1056/1381 microg/l in adult blood, p<0,05; similar results were found for C5a and sC5b-9). CONCLUSION: Lactic acidosis leads to an activation of the entire complement system in neonates and in adults. This activation is dose-dependent and more pronounced in adults as compared to neonates. PMID:11324901

  11. Activation of Human Complement System by Dextran-Coated Iron Oxide Nanoparticles Is Not Affected by Dextran/Fe Ratio, Hydroxyl Modifications, and Crosslinking

    DEFF Research Database (Denmark)

    Wang, Guankui; Chen, Fangfang; Banda, Nirmal K

    2016-01-01

    While having tremendous potential as therapeutic and imaging tools, the clinical use of engineered nanoparticles has been associated with serious safety concerns. Activation of the complement cascade and the release of proinflammatory factors C3a and C5a may contribute to infusion-related reactions......, whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry...... in inciting complement in human serum. Using complement inhibitors and measuring levels of fluid phase markers (sC5b-9, C5a, and Bb), we found that the majority of human complement activation by SPIO is through the alternative pathways (AP). SPIO prepared with high dextran/iron ratio showed some complement...

  12. Evaluation of the Flying Qualities Requirements of MIL-F-8785B (ASG) using the C-5A Airplane

    Science.gov (United States)

    1975-03-20

    10-0 IPIP 1.60 FIURE~ NO3(3.2.2) SH1ORT- PEIIOD WPREgUEN C 106 Requi remen t 3.2.2.1.3 Residual oscillations. Any sustained residual oscillations...lines (.65 Harper-Cooper scale ). For these reasons, the Level 2 requirement that dwnrd be no Its than 0.05 appears to be too stringent. Recommendation It...the forward fuselage at F. S. 610. The signals from the vanes are averaged and scaled to convert from vane angle to angle-of-attack referenced to the

  13. Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis.

    Science.gov (United States)

    Seitz, Maren; Beineke, Andreas; Singpiel, Alena; Willenborg, Jörg; Dutow, Pavel; Goethe, Ralph; Valentin-Weigand, Peter; Klos, Andreas; Baums, Christoph G

    2014-06-01

    Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-) mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3(-/-) mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3(-/-) mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3(-/-) blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR(-/-) mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity.

  14. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease.

    Science.gov (United States)

    Yang, Yue; Cudaback, Eiron; Jorstad, Nikolas L; Hemingway, Jake F; Hagan, Catherine E; Melief, Erica J; Li, Xianwu; Yoo, Tom; Khademi, Shawn B; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk

    2013-09-01

    Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein-expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT-recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT-recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.

  15. Human Development, Human Evolution.

    Science.gov (United States)

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a…

  16. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards an

  17. AcEST: BP913178 [AcEST

    Lifescience Database Archive (English)

    Full Text Available sculus GN=Tns4 PE=2 SV=1 32 0.76 sp|Q29L39|POE_DROPS Protein purity of essence OS=Drosophila pseu... 31 1.7 ...|P79175|C5AR_GORGO C5a anaphylatoxin chemotactic receptor (Fra... 29 6.4 sp|Q9VLT5|POE_DROME Protein purity of essence...RGSFGLALKVQE 471 >sp|Q29L39|POE_DROPS Protein purity of essence OS=Drosophila pse

  18. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  19. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation ...... often mentioned post-human condition....

  20. Human microbiomics

    OpenAIRE

    Rajendhran, J.; P. Gunasekaran

    2010-01-01

    The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity has been demonstrated, which may pave the way for new prophylactic and therapeutic strategies such as bacteriotherapy. The sig...

  1. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  2. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  3. Digital Humanities

    DEFF Research Database (Denmark)

    Brügger, Niels

    2016-01-01

    the humanities for decades, starting with research fields such as humanities computing or computational linguistics in the 1950s, and later new media studies and internet studies. The historical development of digital humanities has been characterized by a focus on three successive, but co-existing types......Digital humanities is an umbrella term for theories, methodologies, and practices related to humanities scholarship that use the digital computer as an integrated and essential part of its research and teaching activities. The computer can be used for establishing, finding, collecting......, and preserving material to study, as an object of study in its own right, as an analytical tool, or for collaborating, and for disseminating results. The term "digital humanities" was coined around 2001, and gained currency within academia in the following years. However, computers had been used within...

  4. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  5. Crucial role of IL1beta and C3a in the in vitro-response of multipotent mesenchymal stromal cells to inflammatory mediators of polytrauma.

    Directory of Open Access Journals (Sweden)

    Nina-Emily Hengartner

    Full Text Available Multipotent mesenchymal stromal cells (MSC exert immune-modulatory effects and support tissue regeneration in various local trauma models. In case of a polytrauma, high amounts of danger-associated molecular patterns are released, leading to a systemic increase of inflammatory mediators. The influence of such a complex inflammatory microenvironment on human MSC is mainly unknown so far. Therefore, we investigated the effects of a defined serum-free polytrauma "cocktail" containing IL beta, IL6, IL8 and the anaphylatoxins C3a and C5a, in concentrations corresponding to those measured in the blood of polytrauma patients, on human MSC in vitro. The polytrauma cocktail induced directed migration of MSC with C3a representing its major soluble chemoattractive agent. Furthermore, the polytrauma cocktail and IL1beta upregulated the expression of MMP1 indicating a potential role of IL1beta to enhance MSC migration in the tissue context. COX2, PTGES and TSG6 were also found to be upregulated upon stimulation with the polytrauma cocktail or IL1beta, but not through other single factors of the polytrauma cocktail in pathophysiologically relevant concentrations. An RNA expression array of 84 inflammation-related genes revealed that both the polytrauma cocktail and IL1beta induced C3, CSF1, TLR3 and various chemokines without major qualitative or quantitative differences. These results indicate that IL1beta is a crucial mediator of the polytrauma cocktail in terms of immune-modulation and MMP1 expression. Thus, upon encountering the primary sterile, inflammatory milieu of a polytrauma, endogenous or systemically transfused MSC might be able to migrate to sites of injury, secrete TSG6 and PGE2 and to influence macrophage biology as observed in local trauma models.

  6. Human Rights and Human Nature

    Directory of Open Access Journals (Sweden)

    Vittorio Possenti

    2013-11-01

    Full Text Available There seems to be two different versions of human rights in Western tradition: say Rationalistic and Christian; the former adopted in revolutionary France, the latter highly developed in Renaissance Spain. Current relativistic criticisms attempt to deny the universality of human rights alleging that this theory has been created in Western countries or it has no strong justification, and therefore cannot have universal approach; but this objection can be dismissed with an alternative justification of human rights.

  7. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg

    2007-01-01

    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  8. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter

    2015-01-01

    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  9. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  10. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre

    2017-01-01

    , and true population genomic studies of Bronze Age populations. Among the emerging areas of aDNA research, the analysis of past epigenomes is set to provide more new insights into human adaptation and disease susceptibility through time. Starting as a mere curiosity, ancient human genetics has become...

  11. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  12. Teaching humanism.

    Science.gov (United States)

    Stern, David T; Cohen, Jordan J; Bruder, Ann; Packer, Barbara; Sole, Allison

    2008-01-01

    As the "passion that animates authentic professionalism," humanism must be infused into medical education and clinical care as a central feature of medicine's professionalism movement. In this article, we discuss a current definition of humanism in medicine. We will also provide detailed descriptions of educational programs intended to promote humanism at a number of medical schools in the United States (and beyond) and identify the key factors that make these programs effective. Common elements of programs that effectively teach humanism include: (1) opportunities for students to gain perspective in the lives of patients; (2) structured time for reflection on those experiences; and (3) focused mentoring to ensure that these events convert to positive, formative learning experiences. By describing educational experiences that both promote and sustain humanism in doctors, we hope to stimulate the thinking of other medical educators and to disseminate the impact of these innovative educational programs to help the profession meet its obligation to provide the public with humanistic physicians.

  13. Human Computation

    CERN Document Server

    CERN. Geneva

    2008-01-01

    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  14. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    In contemporary societies, the humanities are under constant pressure and have to justify their existence. In the ongoing debates, Humboldt’s ideals of ‘Bildung’ and ‘pure science’ are often used to justify the unique function of the humanities of ensuring free research and contributing to a vital...... philosophy. Contrary to Humboldt’s idea that the non-practical is the most practical in the long run, philosophical pragmatism recommends to the humanities to situate knowledge in practices and apply knowledge to practices....

  15. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  16. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    . The first section of this chapter outlines the complete cause-effect pathway, from emissions of toxic substances to intake by the population up to damages in terms of human health effects. Section 2 outlines the framework for assessing human toxicity in LCIA. Section 3 discusses the contributing substances......This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... – demonstrates the importance to account for both outdoor and indoor exposure, including consumer products. Analysing the variations in intake fraction (the fraction of the emitted or applied chemical that is taken in by the consumer and the general population), effect factor and characterisation factor across...

  17. Human influences

    NARCIS (Netherlands)

    Lanen, van H.A.J.; Kasparek, L.; Novicky, O.; Querner, E.P.; Fendeková, M.; Kupczyk, E.

    2004-01-01

    Human activities can cause drought, which was not previously reported (man-induced hydrological drought). Groundwater abstractions for domestic and industrial use are a well-known example of such an environmental change

  18. Human phantom

    CERN Multimedia

    CERN PhotoLab

    1973-01-01

    This human phantom has been received by CERN on loan from the State Committee of the USSR for the Utilization of Atomic Energy. It is used by the Health Physics Group to study personel radiation doses near the accelerators.

  19. Human expunction

    Science.gov (United States)

    Klee, Robert

    2017-10-01

    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  20. Human babesiosis.

    Science.gov (United States)

    Rożej-Bielicka, Wioletta; Stypułkowska-Misiurewicz, Hanna; Gołąb, Elżbieta

    2015-01-01

    Babesiosis is an emerging parasitic, anthropo-zoonotic tick-borne disease, seldom diagnosed in humans. Caused by Protozoa, Babesia (also called Piroplasma) intraerytrocytic piriform microorganism. Infection of vertebrates is transmitted by ticks. Out of more than 100 Babesia species/genotypes described so far, only some were diagnosed in infected humans, mostly B. microti, B. divergens and B. venatorum (Babesia sp. EU1). Infection in humans is often asymptomatic or mild but is of a particular risk for asplenic individuals, those with congenital or acquired immunodeficiencies, and elderly. Infections transmitted with blood and blood products raise concerns in hemotherapy. Epidemiological situation of babesiosis varies around the world. In Europe, no increase in the number of cases was reported, but in the USA its prevalence is increasing and extension of endemic areas is observed. The aim of this publication is to describe the problems connected with the current epidemiological situation, diagnosis and treatment of human babesiosis with regard to clinical status of patients.

  1. Human energy

    OpenAIRE

    2010-01-01

    In the midst of big-oil record profits and growing debate on global warming, the Chevron Corporation launched its “Human Energy” public relations campaign. In television commercials and print advertisements, Chevron portrays itself as a compassionate entity striving to solve the planet’s energy crisis. Yet, the first term in this corporate oxymoron misleadingly reframes the significance of the second, suggesting that the corporation has a renewed focus. In depicting Chevron as a green/human o...

  2. Human Echolocation

    OpenAIRE

    Teng, Santani

    2013-01-01

    The use of active natural echolocation as a mobility aid for blind humans has received increased scientific and popular attention in recent years (Engber, 2006; Kreiser, 2006; NPR, 2011), in part due to a focus on several blind individuals who have developed remarkable expertise. However, perhaps surprisingly, the history of empirical human echolocation research is not much younger than the era of echolocation research (cf. Griffin, 1958). Nevertheless, compared to its bat and cetacean count...

  3. Human ehrlichiosis

    Directory of Open Access Journals (Sweden)

    Đokić Milomir

    2006-01-01

    Full Text Available Background. Human ehrlichiosis is a newly recognized disease. It is a tick-borne disease caused by several bacterial species of the genhus Erlichia. These are small gram-negative pleomorphic cocci, that are obligatory intracellular bacteria. Tick Ixodes is the principle vector in Europe, and Amblyomma americanum in the United States. Bacterial organisms replicate in a tick, and are transmited from infected cells in a vector to the blood cells of animals or humans. Human ehrlichiosis is a name for a group of diseases caused by different species of Ehrlichia. One of them is the disease named human monocytic ehrlichiosis, caused by Ehrlichia chaffeensis, and the other is a human granulocytic ehrlichiosis caused by Anaplasma phagocytophilia. Case report. We reported a 23-year-old patient admitted for the clinical treatment with the symptoms of high febrility (above 40 °C, headache, vomiting, general weakness and exhaustion, but without data on a tick bite. The patient was treated with trimetoprim-sulfamethoxazole for a week when Ehrlichia chaffeensis was confirmed by the immunofluoroscence test, and the therapy contimed with doxacyclin. Conclusion. Human ehrlichiosis is also present in our country, so this disease should be considered everyday, especially in infectology practice.

  4. Complement Activation and STAT4 Expression Are Associated with Early Inflammation in Diabetic Wounds.

    Science.gov (United States)

    Cunnion, Kenji M; Krishna, Neel K; Pallera, Haree K; Pineros-Fernandez, Angela; Rivera, Magdielis Gregory; Hair, Pamela S; Lassiter, Brittany P; Huyck, Ryan; Clements, Mary A; Hood, Antoinette F; Rodeheaver, George T; Cottler, Patrick S; Nadler, Jerry L; Dobrian, Anca D

    2017-01-01

    Diabetic non-healing wounds are a major clinical problem. The mechanisms leading to poor wound healing in diabetes are multifactorial but unresolved inflammation may be a major contributing factor. The complement system (CS) is the most potent inflammatory cascade in humans and contributes to poor wound healing in animal models. Signal transducer and activator of transcription 4 (STAT4) is a transcription factor expressed in immune and adipose cells and contributes to upregulation of some inflammatory chemokines and cytokines. Persistent CS and STAT4 expression in diabetic wounds may thus contribute to chronic inflammation and delayed healing. The purpose of this study was to characterize CS and STAT4 in early diabetic wounds using db/db mice as a diabetic skin wound model. The CS was found to be activated early in the diabetic wounds as demonstrated by increased anaphylatoxin C5a in wound fluid and C3-fragment deposition by immunostaining. These changes were associated with a 76% increase in nucleated cells in the wounds of db/db mice vs. The novel classical CS inhibitor, Peptide Inhibitor of Complement C1 (PIC1) reduced inflammation when added directly or saturated in an acellular skin scaffold, as reflected by reduced CS components and leukocyte infiltration. A significant increase in expression of STAT4 and the downstream macrophage chemokine CCL2 and its receptor CCR2 were also found in the early wounds of db/db mice compared to non-diabetic controls. These studies provide evidence for two new promising targets to reduce unresolved inflammation and to improve healing of diabetic skin wounds.

  5. [Human influenza].

    Science.gov (United States)

    Stock, Ingo

    2006-10-01

    Human influenza is one of the most common human infectious diseases, contributing to approximately one million deaths every year. In Germany, each year between 5.000 and 20.000 individuals die from severe influenza infections. In several countries, the morbidity and mortality of influenza is greatly underestimated. This is reflected by general low immunization rates. The emergence of avian influenza against the background of the scenario of a human influenza pandemic has revived public interest in the disease. According to the World Health Organisation, it is only the question on the beginning of a new influenza pandemic. The virus type of the new pandemic is still uncertain and it is also unclear, if a pandemic spread of the virus may be prevented by consistent controlling of avian influenza.

  6. [Humanized childbirth].

    Science.gov (United States)

    Kuo, Su-Chen

    2005-06-01

    Childbirth is a major event in a family. The expectant parent's perception of the childbirth experience influences his or her development as a parent. Making childbirth a positive and satisfying experience for women is the responsibility of health care providers. Women want to have physical and emotional privacy during labor and delivery, and to experience both in a friendly, comfortable environment. For women expected to undergo normal deliveries, humanized childbirth is one accessible approach. This article explores the definition and evolution of humanized childbirth and the care practice that it involves. It also explores birth plans and birth experiences, and the improvements necessary to routine labor practices to enable women to participate in decision making about their childbirth experiences. The author emphasizes that when health-care providers recognize the value of humanized childbirth and make changes accordingly, the dignity of women's childbirth experiences will be enhanced.

  7. Beyond Humanisms

    Directory of Open Access Journals (Sweden)

    Capurro, Rafael

    2012-01-01

    Full Text Available In the first part of this paper a short history of Western humanisms (Socrates, Pico della Mirandola, Descartes, Kant is presented. As far as these humanisms rest on a fixation of the ‘humanum’ they are metaphysical, although they might radically differ from each other. The second part deals with the present debate on trans- and posthumanism in the context of some breath-taking developments in science and technology.Angeletics, a theory of messengers and messages, intends to give an answer to the leading question of this paper, namely: ‘what does it mean to go beyond humanisms?’ The conclusion exposes briefly an ethics of hospitality and care from an angeletic perspective.

  8. Human IgE-independent systemic anaphylaxis.

    Science.gov (United States)

    Finkelman, Fred D; Khodoun, Marat V; Strait, Richard

    2016-06-01

    Anaphylaxis is a rapidly developing, life-threatening, generalized or systemic allergic reaction that is classically elicited by antigen crosslinking of antigen-specific IgE bound to the high-affinity IgE receptor FcεRI on mast cells and basophils. This initiates signals that induce cellular degranulation with release and secretion of vasoactive mediators, enzymes, and cytokines. However, IgE-independent mechanisms of anaphylaxis have been clearly demonstrated in experimental animals. These include IgG-dependent anaphylaxis, which involves the triggering of mediator release by IgG/antigen complex crosslinking of FcγRs on macrophages, basophils, and neutrophils; anaphylaxis mediated by binding of the complement-derived peptides C3a and C5a to their receptors on mast cells, basophils, and other myeloid cells; and direct activation of mast cells by drugs that interact with receptors on these cells. Here we review the mechanisms involved in these IgE-independent forms of anaphylaxis and the clinical evidence for their human relevance. We conclude that this evidence supports the existence of all 3 IgE-independent mechanisms as important causes of human disease, although practical and ethical considerations preclude their demonstration to the degree of certainty possible with animal models. Furthermore, we cite evidence that different clinical situations can suggest different mechanisms as having a primal role in anaphylaxis and that IgE-dependent and distinct IgE-independent mechanisms can act together to increase anaphylaxis severity. As specific agents become available that can interfere with mechanisms involved in the different types of anaphylaxis, recognition of specific types of anaphylaxis is likely to become important for optimal prophylaxis and therapy.

  9. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  10. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  11. Human Trafficking

    Science.gov (United States)

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  12. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  13. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  14. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    and self-reflective democracy. Contemporary humanities have adopted a new orientation towards practices, and it is not clear how this fits with the ideals of ‘Bildung’ and ‘pure science’. A possible theoretical framework for this orientation towards practices could be found in John Dewey’s pragmatic...

  15. Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.

    Science.gov (United States)

    Zhang, Qiong; Huang, Yinping; Zhang, Keke; Huang, Yanjun; Yan, Yan; Wang, Fan; Wu, Jie; Wang, Xiao; Xu, Zhangye; Chen, Yongtao; Cheng, Xue; Li, Yong; Jiao, Jinyu; Ye, Duyun

    2016-11-01

    With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  17. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  18. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  19. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  20. Human paleoneurology

    CERN Document Server

    2015-01-01

    The book presents an integrative review of paleoneurology, the study of endocranial morphology in fossil species. The main focus is on showing how computed methods can be used to support advances in evolutionary neuroanatomy, paleoanthropology and archaeology and how they have contributed to creating a completely new perspective in cognitive neuroscience. Moreover, thanks to its multidisciplinary approach, the book addresses students and researchers approaching human paleoneurology from different angles and for different purposes, such as biologists, physicians, anthropologists, archaeologists

  1. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  2. Human universe

    CERN Document Server

    Cox, Brian

    2014-01-01

    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  3. In Vitro Desensitization of Human Skin Mast Cells

    Science.gov (United States)

    Zhao, Wei; Gomez, Gregorio; Macey, Matthew; Kepley, Christopher L.

    2013-01-01

    Desensitization is a clinical procedure whereby incremental doses of a drug are administered over several hours to a sensitive patient until a therapeutic dose and clinical tolerance are achieved. Clinical tolerance may occur in part by attenuating the mast cell response. In the present study, primary human skin mast cells were used to establish and characterize an in vitro model of desensitization. Mast cells in culture were armed with allergen-specific (4-hydroxy-3-nitro-phenylacety and Der p2) and non-specific IgE antibodies, and then desensitized by incremental exposures to 4-hydroxy-3-nitrophenylacety-BSA. This desensitization procedure abrogated the subsequent degranulation response to the desensitizing allergen, to an unrelated allergen, and to IgG anti-FcεRI, but not to C5a, substance P, compound 48/80, and calcium ionophore. Desensitized cells regained their FcεRI-dependent degranulation capability by 24–48 h after free allergen had been removed. Therefore, sensitized human skin mast cells are reversibly desensitized in vitro by exposure to incremental doses of that allergen, which also cross-desensitizes them to an unrelated allergen. PMID:22009002

  4. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  5. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  6. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  7. Human steroidogenesis

    DEFF Research Database (Denmark)

    Andersen, Claus Y; Ezcurra, Diego

    2014-01-01

    steroid concentrations cause alterations in endometrial development, affecting oocyte viability in assisted reproductive technology. Furthermore, it has been proposed that elevated progesterone levels have a negative effect on the reproductive outcome of COS. This may arise from an asynchrony between...... reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

  8. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  9. Platelet adhesion, contact phase coagulation activation, and C5a generation of polyethylene glycol acid-grafted high flux cellulosic membrane with varieties of grafting amounts.

    Science.gov (United States)

    Fushimi, F; Nakayama, M; Nishimura, K; Hiyoshi, T

    1998-10-01

    Grafting of polyethylene glycol chains onto cellulosic membrane can be expected to reduce the interaction between blood (plasma protein and cells) and the membrane surface. Alkylether carboxylic acid (PEG acid) grafted high flux cellulosic membranes for hemodialysis, in which the polyethylene glycol chain bears an alkyl group at one side and a carboxyl group at the other side, have been developed and evaluated. PEG acid-grafted high flux cellulosic membranes with various grafting amounts have been compared with respect to platelet adhesion, the contact phase of blood coagulation, and complement activation in vitro. A new method of quantitating platelet adhesion on hollow-fiber membrane surfaces has been developed, which is based on the determination of lactate dehydrogenase (LDH) activity after lysis of the adhered platelets. PEG acid-grafted high flux cellulosic membranes showed reduced platelet adhesion and complement activation effects in grafting amounts of 200 ppm or higher without detecting adverse effects up to grafting amounts of 850 ppm. The platelet adhesion of a PEG acid-grafted cellulosic membrane depends on both the flux and grafting amounts of the membrane. It is concluded that the grafting of PEG acid onto a cellulosic membrane improves its biocompatibility as evaluated in terms of platelet adhesion, complement activation, and thrombogenicity.

  10. Microglial C5aR (CD88) expression correlates with amyloid-β deposition in murine models of Alzheimer’s Disease

    OpenAIRE

    Ager, Rahasson R.; Fonseca, Maria I.; Chu, Shu-Hui; Sanderson, Sam D.; Taylor, Stephen M; Woodruff, Trent M; Tenner, Andrea J.

    2010-01-01

    Alzheimer Disease (AD), a progressive neurodegenerative disease characterized by the accumulation of amyloid-β protein and neuronal loss, is the leading cause of age-related dementia in the world today. The disease is also associated with neuroinflammation, robust activation of astrocytes and microglia and evidence of activation of the complement system, localized with both fibrillar amyloid-β (fAβ) plaques and tangles. The observations are consistent with a complement dependent component of ...

  11. Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Leeming, Diana J; Veidal, Sanne S; Karsdal, Morten A

    2015-01-01

    Pro-C5 reflects liver hemodynamics, liver function, disease stage and clinically significant portal hypertension (PH). A multimarker model in combination with clinical scores predicted HVPG and separated clinical relevant HVPG thresholds. Plasma Pro-C5 may be suitable for the noninvasive evaluation...

  12. Human Toxocariasis

    Directory of Open Access Journals (Sweden)

    Mehmet Burak Selek

    2013-09-01

    Full Text Available Human toxocariasis is an parasitic infection caused by the ingestion of larvae of dog nematode Toxocara canis and less frequently of cat nematode T.cati. Toxocara eggs, shed to environment by infected dogs' and cats' droppings, become infective by embryonation. Humans, particularly children, can be infected by accidentally ingesting embryonated Toxocara eggs. Larvae hatch in the small intestine, penetrate the intestinal wall and migrate to other parts of body via the bloodstream. It is generally a benign, asymptomatic, and self-limiting disease, although migrating larvae can cause damage to tissues and organs, especially brain involvement can cause severe morbidity. The two main clinical presentations of toxocariasis are visceral larva migrans (VLM (a systemic disease caused by larval migration through major organs and ocular larva migrans (OLM (a disease limited to the eyes and optic nerves. There are also two less-severe syndromes which have recently been described, one mainly in children (covert toxocariasis and the other mainly in adults (common toxocariasis. Diagnosis is usually made by clinical signs/symptoms, epidemiological background of the patient and the use of immunological methods (ELISA or western-blot. On the other hand definitive diagnosis is much more challenging, since it requires the demonstration of larvae via biopsy or autopsy. Most cases of toxocariasis clear up without any treatment. VLM is primarily treated with antihelmintic drugs, such as; albendazole or mebendazole. Treatment of OLM is more difficult and usually consists of measures to prevent progressive damage to the eye like steroids. Laser photocoagulation and cryoretinopexy may also be used to treat severe cases. Since eradicating T.canis infection is difficult due to the complexity of its life cycle, prevention of toxocariasis is always preferred. Toxocara eggs have a strong protective layer which makes the eggs able to survive in the environment for months or

  13. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  14. Detection of a complement-derived chemotactic factor for tumor cells in human inflammatory and neoplastic effusions.

    Science.gov (United States)

    Orr, F. W.; Delikatny, E. J.; Mokashi, S.; Krepart, G. V.; Stiver, H. G.

    1983-01-01

    A chemotactic factor for neoplastic cells can be generated in vitro by incubating human C5 or C5a with leukocytic or pancreatic lysosomal enzymes and is also detectable in experimental inflammatory exudates. The authors therefore sought evidence for the existence of this factor in human effusions. Using the Boyden chamber assay, they detected chemotactic activity for MB-MDA-231 human breast carcinoma cells and Walker ascites tumor cells in human inflammatory and neoplastic exudates, including ascites, pleural effusions, synovial fluids and cerebrospinal fluids. Chemotactic activity was not found in transudates, normal cerebrospinal fluid, or normal serum. Human ovarian adenocarcinoma cells from one of the effusions migrated toward autologous ascites and towards the C5-derived chemotactic factor that had been prepared in vitro. In gel filtration the chemotactic factor behaved generally as a molecule having a molecular weight of approximately 6000 daltons. The activity was blocked after incubation with antiserums directed against C5 but not by antiserums directed against C3 or C4. In vitro, chemotactic activity for tumor cells could be generated by incubating extracts of exudate cells with autologous plasma or with purified C5. The authors conclude that a chemotactic factor for tumor cells can be formed in human effusions and that this factor has properties similar to those of a previously described C5-derived chemotactic factor. PMID:6185003

  15. [Human papillomaviruses].

    Science.gov (United States)

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

  16. Human Development Report 1991: Financing Human Development

    OpenAIRE

    United Nations Development Programme, UNDP

    1991-01-01

    Lack of political commitment rather than financial resources is often the real barrier to human development. This is the main conclusion of Human Development Report 1991 - the second in a series of annual reports on the subject.

  17. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  18. Human-machine interactions

    Science.gov (United States)

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  19. Theory and Realization of Solar Smart Road Lamp Controller based on STC12 C5 A60 AD%基于STC12C5A60AD智能太阳能路灯控制器的原理与实现

    Institute of Scientific and Technical Information of China (English)

    仝新建

    2014-01-01

    基于单片机为核心的智能控制器,设计了太阳能路灯控制器的硬件电路,并提供了系统软件设计。本系统采用PWM三阶段充电法及光控+时控的放电方式,有利于提高充电效率;同时该控制器具有过充、过放、过载、短路等保护措施,可以延长蓄电池使用寿命。%This paper introduces the hardware circuit and software of the intelligent controller based on MCU. This system uses “three-stage PWM charging”mode and “light and time control discharging”mode,which are of great benefits to high charging of efficiency. In addition,the controller has protection measures of overcharge,over discharge,overload and short circuit to extend the service life of bat-tery.

  20. Special Section: Human Rights

    Science.gov (United States)

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  1. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  2. Visualizing Humans by Computer.

    Science.gov (United States)

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  3. The Human/Machine Humanities: A Proposal

    Directory of Open Access Journals (Sweden)

    Ollivier Dyens

    2016-03-01

    Full Text Available What does it mean to be human in the 21st century? The pull of engineering on every aspect of our lives, the impact of machines on how we represent ourselves, the influence of computers on our understanding of free-will, individuality and species, and the effect of microorganisms on our behaviour are so great that one cannot discourse on humanity and humanities without considering their entanglement with technology and with the multiple new dimensions of reality that it opens up. The future of humanities should take into account AI, bacteria, software, viruses (both organic and inorganic, hardware, machine language, parasites, big data, monitors, pixels, swarms systems and the Internet. One cannot think of humanity and humanities as distinct from technology anymore.

  4. From Human Past to Human Future

    OpenAIRE

    Robert G. Bednarik

    2013-01-01

    This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic an...

  5. Decreased synthesis of serum carboxypeptidase N (SCPN) in familial SCPN deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, K.P.; Curd, J.G.; Hugli, T.E.

    1986-01-01

    Serum carboxypeptidase N (SCPN) is the primary inactivator of the C3a, C4a, and C5a anaphylatoxins as well as an inactivator of bradykinin. Thus, SCPN deficiency potentially could result in significant pathophysiologic consequences. Previous studies identified a deficient subject afflicted with frequent episodes of angioedema, and other family members also had SCPN deficiency. To delineate this abnormality further, the fractional catabolic rate (FRC) and enzyme synthesis were determined in three members of the afflicted kindred as well as in five normal persons following the infusion of homogeneous /sup 125/I-SCPN. The mean FCR and synthesis rates for SCPN in the normal subjects were 1.3%/hr and 20,793 U/kg/hr, respectively. Reduced synthesis was concluded to be primarily responsible for the low SCPN levels in the afflicted kindred. The high FRC of SCPN discourages attempted maintenance therapy with infusions of enriched SCPN preparations.

  6. A novel "complement-metabolism-inflammasome axis" as a key regulator of immune cell effector function.

    Science.gov (United States)

    Arbore, Giuseppina; Kemper, Claudia

    2016-07-01

    The inflammasomes are intracellular multiprotein complexes that induce and regulate the generation of the key pro-inflammatory cytokines IL-1β and IL-18 in response to infectious microbes and cellular stress. The activation of inflammasomes involves several upstream signals including classic pattern or danger recognition systems such as the TLRs. Recently, however, the activation of complement receptors, such as the anaphylatoxin C3a and C5a receptors and the complement regulator CD46, in conjunction with the sensing of cell metabolic changes, for instance increased amino acid influx and glycolysis (via mTORC1), have emerged as additional critical activators of the inflammasome. This review summarizes recent advances in our knowledge about complement-mediated inflammasome activation, with a specific focus on a novel "complement - metabolism - NLRP3 inflammasome axis."

  7. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  8. Has Human Evolution Stopped?

    OpenAIRE

    TEMPLETON, Alan R

    2010-01-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important ...

  9. Preference for human eyes in human infants.

    Science.gov (United States)

    Dupierrix, Eve; de Boisferon, Anne Hillairet; Méary, David; Lee, Kang; Quinn, Paul C; Di Giorgio, Elisa; Simion, Francesca; Tomonaga, Masaki; Pascalis, Olivier

    2014-07-01

    Despite evidence supporting an early attraction to human faces, the nature of the face representation in neonates and its development during the first year after birth remain poorly understood. One suggestion is that an early preference for human faces reflects an attraction toward human eyes because human eyes are distinctive compared with other animals. In accord with this proposal, prior empirical studies have demonstrated the importance of the eye region in face processing in adults and infants. However, an attraction for the human eye has never been shown directly in infants. The current study aimed to investigate whether an attraction for human eyes would be present in newborns and older infants. With the use of a preferential looking time paradigm, newborns and 3-, 6-, 9-, and 12-month-olds were simultaneously presented with a pair of nonhuman primate faces (chimpanzees and Barbary macaques) that differed only by the eyes, thereby pairing a face with original nonhuman primate eyes with the same face in which the eyes were replaced by human eyes. Our results revealed that no preference was observed in newborns, but a preference for nonhuman primate faces with human eyes emerged from 3months of age and remained stable thereafter. The findings are discussed in terms of how a preference for human eyes may emerge during the first few months after birth.

  10. Economics of human trafficking.

    Science.gov (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  11. Optimal humanization of 1B4, an anti-CD18 murine monoclonal antibody, is achieved by correct choice of human V-region framework sequences.

    Science.gov (United States)

    Singer, I I; Kawka, D W; DeMartino, J A; Daugherty, B L; Elliston, K O; Alves, K; Bush, B L; Cameron, P M; Cuca, G C; Davies, P

    1993-04-01

    The murine anti-CD18 mAb 1B4 has been humanized using CDR grafting. Three VH (Gal, Jon, and New) and two VL (Rei and Len) human frameworks, whose selection was based exclusively on their sequence identity with m1B4, were used to construct five human gamma 4/kappa recombinant antibodies: Gal/Rei, Gal/Len, Jon/Rei, and New/Rei, and a "hemichimeric" antibody pairing the VH of m1B4 with grafted Rei. Each of these h1B4 constructs completely inhibited the binding of m1B4 to activated human leukocytes with avidities (IC50) ranging from 1.5 to 8.0 nM, compared to 0.5 nM for m1B4. Replacement of three VH residues in the best VH framework, Gal, with the corresponding m1B4 "packing" (nonsolvent exposed) residues gave an h1B4 (mutant Gal/Rei) with the same avidity as m1B4. Avidity correlated with overall percent identity between the human and murine VH frameworks and, in particular, with conservation of "packing" residues. Rei and Len VL frameworks proved to be interchangeable. Further characterization showed that the Gal/Rei prototype was equipotent to m1B4 in blocking adhesion of polymorphonuclear leukocytes and monocytes to human vascular endothelium in vitro, and polymorphonuclear leukocyte extravasation into C5a-injected rabbit or monkey skin sites. Dual-label immunofluorescence microscopy of bone marrow cells with Gal/Rei h1B4 and m1B4 demonstrated that the fine specificity of the combining sites had not been altered by humanization. Reduced immunogenicity was demonstrated in rhesus monkeys that tolerated weekly treatment with h1B4 for 6 wk, whereas m1B4 induced profound anaphylaxis at 3 wk. Anti-1B4 titers in h1B4-treated rhesus were 50 to 66% lower and developed 1 wk later than in m1B4-treated monkeys. Crucially, the anti-h1B4 antibodies were anti-idiotypic while the anti-m1B4 antibodies were directed against constant and framework regions. We conclude that sequence identity searches are sufficient to identify suitable human frameworks for CDR-grafting of m1B4

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-05-15

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

  13. Human assisted robotic exploration

    Science.gov (United States)

    Files, B. T.; Canady, J.; Warnell, G.; Stump, E.; Nothwang, W. D.; Marathe, A. R.

    2016-05-01

    In support of achieving better performance on autonomous mapping and exploration tasks by incorporating human input, we seek here to first characterize humans' ability to recognize locations from limited visual information. Such a characterization is critical to the design of a human-in-the-loop system faced with deciding whether and when human input is useful. In this work, we develop a novel and practical place-recognition task that presents humans with video clips captured by a navigating ground robot. Using this task, we find experimentally that human performance does not seem to depend on factors such as clip length or familiarity with the scene and also that there is significant variability across subjects. Moreover, we find that humans significantly outperform a state-of-the-art computational solution to this problem, suggesting the utility of incorporating human input in autonomous mapping and exploration techniques.

  14. Human Use Index (Future)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  15. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... Directory Cancer Prevention Overview Research Human Papillomavirus (HPV) Vaccines On This Page What are human papillomaviruses? Which ... infections? Can HPV infections be prevented? What HPV vaccines are available? Who should get the HPV vaccines? ...

  16. Human Use Index

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  17. Telling the Human Story.

    Science.gov (United States)

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  18. Human Services Offices

    Data.gov (United States)

    Fairfax County, Virginia — This data contains point features representing the human services offices within Fairfax County.“HS_Region” is the office for each human services region, “DFS_Area”...

  19. Human Resource Accounting System

    Science.gov (United States)

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  20. The Growing Human Population.

    Science.gov (United States)

    Keyfitz, Nathan

    1989-01-01

    Discusses the issue of human population. Illustrates the projections of the growing human population in terms of developed and less developed countries. Describes the family planning programs in several countries. Lists three references for further reading. (YP)

  1. Human bites (image)

    Science.gov (United States)

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  2. Monogenic human obesity syndromes

    National Research Council Canada - National Science Library

    Farooqi, I S; O'Rahilly, S

    2004-01-01

    .... This chapter will consider the human monogenic obesity syndromes that have been characterized to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  3. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007......) article 'Visualizing the mind: Looking at Titian's Flaying of Marsyas', addressing features of the painting not commented on by Hart, and supplementing Hart's (Kleinian) theoretical frame by involving Didier Anzieu's 'skin ego', Slavoj Zizek's concept of the 'non-human', Giorgio Agamben's term...

  4. Human productivity program definition

    Science.gov (United States)

    Cramer, D. B.

    1985-01-01

    The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

  5. Human Resource Management System

    OpenAIRE

    Navaz, A. S. Syed; Fiaz, A. S. Syed; Prabhadevi, C.; V.Sangeetha; Gopalakrishnan,S.

    2013-01-01

    The paper titled HUMAN RESOURCE MANAGEMENT SYSTEM is basically concerned with managing the Administrator of HUMAN RESOURCE Department in a company. A Human Resource Management System, refers to the systems and processes at the intersection between human resource management and information technology. It merges HRM as a discipline and in particular its basic HR activities and processes with the information technology field, whereas the programming of data processing systems evolved into standa...

  6. Human nature and enhancement.

    Science.gov (United States)

    Buchanan, Allen

    2009-03-01

    Appeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good. I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.

  7. Human Document Project

    NARCIS (Netherlands)

    Vries, de J.; Abelmann, L.; Manz, A.; Elwenspoek, M.C.

    2012-01-01

    “The Human Document Project” is a project which tries to answer all of the questions related to preserving information about the human race for tens of generations of humans to come or maybe even for a future intelligence which can emerge in the coming thousands of years. This document mainly focuss

  8. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  9. Has human evolution stopped?

    Science.gov (United States)

    Templeton, Alan R

    2010-07-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  10. (Human) Resourcing For CI

    DEFF Research Database (Denmark)

    Jørgensen, Frances; S., Jacob; Kofoed, Lise Busk

    2005-01-01

    More and more, the ability to compete in today’s market is viewed as being dependent on human capital. One of the most challenging aspects of human resource management involves supplying the organization with the human capital necessary to fulfill its objectives. This task becomes especially...

  11. Human Machine Learning Symbiosis

    Science.gov (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.

    2017-01-01

    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  12. Monogenic human obesity.

    Science.gov (United States)

    Farooqi, I Sadaf

    2008-01-01

    We and others have identified several single gene defects that disrupt the molecules in the leptinmelanocortin pathway causing severe obesity in humans. In this review, we consider these human monogenic obesity syndromes and discuss how far the characterisation of these patients has informed our understanding of the physiological role of leptin and the melanocortins in the regulation of human body weight and neuroendocrine function.

  13. From Human Past to Human Future

    Directory of Open Access Journals (Sweden)

    Robert G. Bednarik

    2013-01-01

    Full Text Available This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic and neural detriments and pathologies. Uniformitarian reasoning based on ontogenic homology suggests that the cognitive abilities of hominins are consistently underrated in the unstable orthodoxies of Pleistocene archaeology. A scientifically guided review establishes developmental trajectories defining recent changes in the human genome and its expressions, which then form the basis of attempts to extrapolate from them into the future. It is suggested that continuing and perhaps accelerating unfavorable genetic changes to the human species, rather than existential threats such as massive disasters, pandemics, or astrophysical events, may become the ultimate peril of humanity.

  14. Humanity at the Edge

    DEFF Research Database (Denmark)

    Svendsen, Mette N.; Gjødsbøl, Iben M.; Dam, Mie S.

    2017-01-01

    At the heart of anthropology and the social sciences lies a notion of human existence according to which humans and animals share the basic need for food, but only humans have the capacity for morality. Based on fieldwork in a pig laboratory, a neonatal intensive care unit (NICU), and a dementia ...... human and animal value and agency with approaches that focus on human experience and virtue ethics, we argue that ‘the human’ at stake in the moral laboratory of feeding precarious lives puts ‘the human’ in anthropology at disposal for moral experimentation....

  15. Jordan Adjusted Human Development

    OpenAIRE

    Ababsa, Myriam

    2014-01-01

    Jordan Human Development Index (HDI) and Adjusted Human Development Index (IHDI) In 1990, the United Nations Development Programme designed a Human Development Index composed of life expectancy at birth, level of education and gross domestic product (GDP) per capita. In 2011, the UNDP ranked Jordan 95th out of 187 countries with a human development index of 0.698, up from 0.591 in 1990, making it the leading medium-range country for human development (fig. VIII.1). In 2010, the inequality adj...

  16. Human Beings And Water

    OpenAIRE

    2016-01-01

    The writer of this paper on this writing is talking about the human beings and water. Water is one of the very fundamentally things that human beings need to keep their lives. Human beings sometimes do not realise that the water is very important for them because they actually cannot live their lives without the present of water. Human beings can keep their lives without rice, but cannot without water. For instances the use of water for human beings are domestic use, cooking, washing, bathing...

  17. Human rights and bioethics.

    Science.gov (United States)

    Barilan, Y M; Brusa, M

    2008-05-01

    In the first part of this article we survey the concept of human rights from a philosophical perspective and especially in relation to the "right to healthcare". It is argued that regardless of meta-ethical debates on the nature of rights, the ethos and language of moral deliberation associated with human rights is indispensable to any ethics that places the victim and the sufferer in its centre. In the second part we discuss the rise of the "right to privacy", particularly in the USA, as an attempt to make the element of personal free will dominate over the element of basic human interest within the structure of rights and when different rights seem to conflict. We conclude by discussing the relationship of human rights with moral values beyond the realm of rights, mainly human dignity, free will, human rationality and response to basic human needs.

  18. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula.

  19. 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 ......-primates and that the bacteria were mainly found in the lungs. In conclusion, complement-dependent binding of Gram-negative bacteria to erythrocyte CR1 decreases phagocytosis and oxidative burst by leukocytes in human whole blood. (C) 2011 Elsevier Ltd. All rights reserved.......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...... were incubated with whole blood using lepirudin as anticoagulant which has no adverse effects on complement. Bacteria free in plasma, bound to erythrocytes or phagocytized by granulocytes and monocytes were quantified using flow cytometry. The effects of the C3 inhibitor compstatin, a C5a receptor...

  20. Human Capital and Sustainability

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2011-01-01

    Full Text Available A study of sustainability needs to consider the role of all forms of capital—natural, biological, social, technological, financial, cultural—and the complex ways in which they interact. All forms of capital derive their value, utility and application from human mental awareness, creativity and social innovation. This makes human capital, including social capital, the central determinant of resource productivity and sustainability. Humanity has entered the Anthropocene Epoch in which human changes have become the predominant factor in evolution. Humanity is itself evolving from animal physicality to social vitality to mental individuality. This transition has profound bearing on human productive capabilities, adaptability, creativity and values, the organization of economy, public policy, social awareness and life styles that determine sustainability. This article examines the linkages between population, economic development, employment, education, health, social equity, cultural values, energy intensity and sustainability in the context of evolving human consciousness. It concludes that development of human capital is the critical determinant of long-term sustainability and that efforts to accelerate the evolution of human consciousness and emergence of mentally self-conscious individuals will be the most effective approach for ensuring a sustainable future. Education is the primary lever. Human choice matters.

  1. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  2. Human organ markets and inherent human dignity.

    Science.gov (United States)

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept.

  3. Chimeras and human dignity.

    Science.gov (United States)

    de Melo-Martín, Inmaculada

    2008-12-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman chimera research threaten human dignity and those who argue that such threat does not exist fail to make their case. I first introduce some of the arguments that have been offered supporting the claim that the creation of certain sorts of chimeras threatens or violates human dignity. I next present opponents' assessments of such arguments. Finally I critically analyze both the critics' and the supporters' claims about whether chimera research threatens human dignity.

  4. Human Performance in Space

    Science.gov (United States)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  5. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  6. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research......Todays expanding digital landscape constitutes an important research object as well as the research environment for the Humanities at the beginning of the 21st century. Taking this state of affairs as a starting point this inaugural lecture presents a vision for how the digital affects...

  7. Advancing Human Rights

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The National Human Rights Action Plan of China (2012-2015) was initiated after the successful conclusion of the National Human Rights Action Plan of China (2009-2010).The Chinese government in late July published an assessment report on the implementation of the plan,elaborating on the full implementation of China's first-ever national program on human rights development,which was drafted in April 2009.

  8. Human hemoglobin genetics

    Energy Technology Data Exchange (ETDEWEB)

    Honig, G.R.; Adams, J.G.

    1986-01-01

    This book contains the following 10 chapters: Introduction; The Human Hemoglobins; The Human Globin Genes; Hemoglobin Synthesis and Globin Gene Expression; The Globin Gene Mutations - A. Mechanisms and Classification; The Globin Gene Mutations - B. Their Phenotypes and Clinical Expression; The Genetics of the Human Globin Gene Loci: Formal Genetics and Gene Linkage; The Geographic Distribution of Globin Gene Variation; Labortory Identification, Screening, Education, and Counseling for Abnormal Hemoglobins and Thalassemias; and Approaches to the Treatment of the Hemoglobin Disorders.

  9. Modern Human Capital Management

    OpenAIRE

    Feldberger, Madita

    2008-01-01

    Title: Modern Human Capital Management Seminar date: 30th of May 2008 Course: Master thesis in Business Administration, 15 ECTS Authors: Madita Feldberger Supervisor: Lars Svensson Keywords: Human capital, SWOT Analysis, Strategic Map, Balanced Scorecard Research Problem: Despite of the success of Human Capital Management (HCM) in research it did not arrive yet in the HR departments of many companies. Numerous firms even have problems to set their strategic goals with focus on HR. The HR Bala...

  10. Robotics for Human Exploration

    Science.gov (United States)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  11. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  12. Human Performance Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — Biochemistry:Improvements in energy metabolism, muscular strength and endurance capacity have a basis in biochemical and molecular adaptations within the human body....

  13. Extraterritorial Human Rights Obligations

    DEFF Research Database (Denmark)

    Amsinck Boie, Hans Nikolaj; Torp, Kristian

    adequately be addressed without including the approach to the problem taken in practice; Corporate Social Responsibility, CSR. The book therefore draws upon the concept of CSR and the approaches developed here and discusses whether states may utilize the CSR-based concept of human rights due diligence...... to fulfil their possible obligations to protect against human rights violations by corporations.......The book addresses the issue of corporate respect for human rights by examining if and how states are obligated to ensure that corporations originating from their jurisdiction respect human rights when they operate abroad. The existence of such a duty is much debated by academics at national...

  14. The psychology of humanness.

    Science.gov (United States)

    Haslam, Nick; Loughnan, Steve; Holland, Elise

    2013-01-01

    This chapter explores the ways in which the concept of "humanness" illuminates a wide and fascinating variety of psychological phenomena. After introducing the concept--everyday understandings of what it is to be human--we present a model of the diverse ways in which humanness can be denied to people. According to this model people may be perceived as lacking uniquely human characteristics, and thus likened to animals, or as lacking human nature, and thus likened to inanimate objects. Both of these forms of dehumanization occur with varying degrees of subtlety, from the explicit uses of derogatory animal metaphors, to stereotypes that ascribe lesser humanness or simpler minds to particular groups, to nonconscious associations between certain humans and nonhumans. After reviewing research on dehumanization through the lens of our model we examine additional topics that the psychology of humanness clarifies, notably the perception of nonhuman animals and the objectification of women. Humanness emerges as a concept that runs an integrating thread through a variety of research literatures.

  15. The Human Toolmaker

    OpenAIRE

    Kassuba, Tanja; Kastner, Sabine

    2014-01-01

    Do you enjoy building airplanes, cars, houses, or robots with Lego blocks? Humans are the only animal species that can create complicated constructions from simple Lego blocks – our Lego building ability is “human-specific,” since it is only found in human beings. What would our closest relatives, apes or monkeys, do with a box of Lego blocks? They would probably chew on them, and lose interest when they find out that they are not edible! Why are humans the only Lego builders in the animal ki...

  16. Photography after the Human

    OpenAIRE

    Zylinska, Joanna

    2016-01-01

    How can we visualise and subsequently reimagine the abstraction that is the extinction of human species while there is still time? The article addresses this question by considering the existence of images – and, in particular, light-induced mechanical images known as photographs – after the human. The “after the human” designation does not just refer to the material disappearance of the human in some kind of distant future, but also to the present imagining of the disappearance of the human ...

  17. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...... in pharmacological management of chronic atrial fibrillation....

  18. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research...

  19. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  20. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century

  1. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  2. Human Capital and Retirement

    NARCIS (Netherlands)

    P. Alders

    1999-01-01

    textabstractThis paper investigates the relation between human capital and retirement when the age of retirement is endogenous. This relation is examined in a life-cycle earnings model. An employee works full time until retirement. The worker accumulates human capital by training- on-the-job and by

  3. Cohabitation: Humans & Agriculture

    NARCIS (Netherlands)

    Woodington, W.

    2012-01-01

    This "designers' manual" is made during the TIDO-course AR0531 Smart & Bioclimatic Design. Cohabitation of humans and agriculture can be used to improve building climate, human health and the state of the world. It affects building design and requires new building components. This manual explains w

  4. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  5. Human Resource Accounting

    Science.gov (United States)

    Woodruff, Robert L., Jr.

    1973-01-01

    An interview is reported which discussed the implications for the hiring, recruiting, screening and development of employees in the light of human resource accounting, here defined as the identification, accumulation and dissemination of information about human resources in dollar terms. (SA)

  6. Hooking Kids with Humanities.

    Science.gov (United States)

    Anstead, Neil L.

    1993-01-01

    Humanitas is part of Collaboratives for Humanities and Arts Teaching (CHART), a nationwide network funded primarily by the Rockefeller Foundation. In 11 large school districts and numerous rural districts, high school teachers, academics, artists, and business and community leaders are cooperating to promote teaching of the arts and humanities.…

  7. The Human Technology

    DEFF Research Database (Denmark)

    Fausing, Bent

    with fundamental human values like intuition, vision and sensing; all the qualities the technology, the industrialisation and rationalisation, or in short modernity, has been criticized for having taken away from human existence. What technology has taken away now comes back through new technology as an aid...

  8. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  9. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  10. Human Rights Guaranteed

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Report says China’s human rights plan successfully implemented According to a detailed assessment report published by China’s State Council Information Office (SCIO),all the measures outlined in the National Human Rights Action Plan of China (2009-10) had been successfully put into place by the end of 2010.

  11. Defects in Human Nature

    Institute of Scientific and Technical Information of China (English)

    黄靓

    2008-01-01

    By tracing the defects of society back to the defects of human nature, humanity's essence is proved to be inherent evil. Man's natural tendency to do evil remain harnessed through the controls and conventions imposed by civilization, however, when rules or civilization are weakened, man' s dark side is unleashed.

  12. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  13. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues its first white paper on human resources The Chinese Government issued a white paper on its human resources on September 10, highlighting the country’s policies to cope with employment pressures and a lack of "high-level innovative talents.

  14. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  15. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  16. Damping Effect of Humans

    DEFF Research Database (Denmark)

    Pedersen, Lars

    Passive humans (sitting or standing) might well be present on flooring-systems, footbridges or other structures that carry humans. An active croud of people might generate structural vibrations, and these might be problematic. The passive crowd of people, however, will interact with the structural...

  17. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  18. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  19. Human Resource Construction

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Centering on strategic objective of reform and development,CIAE formulated its objectives in human resource construction for the 13th Five-year Plan period,and achieved new apparent progress in human resource construction in 2015.1 Implementation of"LONGMA Project"

  20. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  1. Human Rights Improving

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues a white paper on its human rights,highlighting freedom of speech on the Interne The Chinese Government released a white paper on its human rights in 2009 on September 26,highlighting the role of Internet freedom and the country’s efforts in safeguarding citizens’legitimate civil and political rights.

  2. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century lib

  3. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... a shared interdisciplinary research and educational collaboration. As a creative research initiative it focuses on change and innovative thinking. The innovativeness is a result of the strongly interdisciplinary perspective which is at the heart of Designing Human Technologies. Designing Human Technologies...

  4. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...... der mellem Human Relations (Hawthorne-eksperimenter ne) og Neo-Human Relations (behovsteorierne), men i denne fremstilling bruges Human Relations som en samlebetegnelse for begge disse – noget forskellige – forskningstraditioner. De har i dag opnået stor udbredelse og er praktisk talt obligatorisk...

  5. Generation of dendritic cells and macrophages from human induced pluripotent stem cells aiming at cell therapy.

    Science.gov (United States)

    Senju, S; Haruta, M; Matsumura, K; Matsunaga, Y; Fukushima, S; Ikeda, T; Takamatsu, K; Irie, A; Nishimura, Y

    2011-09-01

    This report describes generation of dendritic cells (DCs) and macrophages from human induced pluripotent stem (iPS) cells. iPS cell-derived DC (iPS-DC) exhibited the morphology of typical DC and function of T-cell stimulation and antigen presentation. iPS-DC loaded with cytomegalovirus (CMV) peptide induced vigorous expansion of CMV-specific autologous CD8+ T cells. Macrophages (iPS-MP) with activity of zymosan phagocytosis and C5a-induced chemotaxis were also generated from iPS cells. Genetically modified iPS-MPs were generated by the introduction of expression vectors into undifferentiated iPS cells, isolation of transfectant iPS cell clone and subsequent differentiation. By this procedure, we generated iPS-MP expressing a membrane-bound form of single chain antibody (scFv) specific to amyloid β (Aβ), the causal protein of Alzheimer's disease. The scFv-transfectant iPS-MP exhibited efficient Aβ-specific phagocytosis activity. iPS-MP expressing CD20-specific scFv engulfed and killed BALL-1 B-cell leukemia cells. Anti-BALL-1 effect of iPS-MP in vivo was demonstrated in a xeno-transplantation model using severe combined immunodeficient mice. In addition, we established a xeno-free culture protocol to generate iPS-DC and iPS-MP. Collectively, we demonstrated the possibility of application of iPS-DC and macrophages to cell therapy.

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

    Directory of Open Access Journals (Sweden)

    Sacha Flammier

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

  7. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

    Science.gov (United States)

    Woehrl, Bianca; Brouwer, Matthijs C; Murr, Carmen; Heckenberg, Sebastiaan G B; Baas, Frank; Pfister, Hans W; Zwinderman, Aeilko H; Morgan, B Paul; Barnum, Scott R; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

    2011-10-01

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.

  8. Human to Human Transmission of Brucella Melitensis

    Directory of Open Access Journals (Sweden)

    Patrice Vigeant

    1995-01-01

    Full Text Available Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely mode of transmission in this case.

  9. Human to Human Transmission of Brucella Melitensis

    OpenAIRE

    Patrice Vigeant; Jack Mendelson; Miller, Mark A.

    1995-01-01

    Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely ...

  10. Archaea on human skin.

    Directory of Open Access Journals (Sweden)

    Alexander J Probst

    Full Text Available The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.

  11. Human Power Empirically Explored

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, A.J.

    2011-01-18

    Harvesting energy from the users' muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are convenient and can be environmentally and economically beneficial. This work provides insight into the knowledge required to design human-powered energy systems in consumer products from a scientific perspective. It shows the developments of human-powered products from the first introduction of the BayGen Freeplay radio in 1995 till current products and provides an overview and analysis of 211 human-powered products currently on the market. Although human power is generally perceived as beneficial for the environment, this thesis shows that achieving environmental benefit is only feasible when the environmental impact of additional materials in the energy conversion system is well balanced with the energy demands of the products functionality. User testing with existing products showed a preference for speeds in the range of 70 to 190 rpm for crank lengths from 32 to 95 mm. The muscular input power varied from 5 to 21 W. The analysis of twenty graduation projects from the Faculty of Industrial Design Engineering in the field of human-powered products, offers an interesting set of additional practice based design recommendations. The knowledge based approach of human power is very powerful to support the design of human-powered products. There is substantial potential for improvements in the domains energy conversion, ergonomics and environment. This makes that human power, when applied properly, is environmentally and economically competitive over a wider range of applications than thought previously.

  12. Human pancreas development.

    Science.gov (United States)

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  13. Enhancing human capacities

    CERN Document Server

    Savulescu, Julian; Kahane, Guy

    2011-01-01

    Enhancing Human Capacities is the first to review the very latest scientific developments in human enhancement. It is unique in its examination of the ethical and policy implications of these technologies from a broad range of perspectives. Presents a rich range of perspectives on enhancement from world leading ethicists and scientists from Europe and North America The most comprehensive volume yet on the science and ethics of human enhancement Unique in providing a detailed overview of current and expected scientific advances in this area Discusses both general conceptual and ethical issues

  14. Aluminium in human sweat.

    Science.gov (United States)

    Minshall, Clare; Nadal, Jodie; Exley, Christopher

    2014-01-01

    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  16. Human dignity and bioethics

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš

    2013-01-01

    Full Text Available By opening the field of bioethics followed a new wave of intense debate on the theological, philosophical and legal significance of the concept of human dignity . Exactly ten years ago (December 2003 American bioethicist Ruth Maclin has proposed to divest ourselves of the concept of human dignity because it is vague, useless and redundant and that, without any loss, we can replace it by the ethical principle of personal autonomy. Her article was followed by harsh reactions and opposite views. What is this term in so broad, almost inflationary and opposite use is not a reason to deprive him, but, on the contrary, it shows how important it is and that it should be determined at least outline. As universal values and general concept, the human dignity has no pre-defined and narrow, precise meaning. It is more an evaluation horizon, the guiding principle and regulatory ideas that must constantly define and codify by many guaranted human rights and fundamental freedoms. As generic notion of each reasonable law, it is their foundation and a common denominator, legitimising basis of natural but also of positive law. As intrinsic and static value which means the humaneness, the humanity it is absolute, inherent to every human being without distinction and conditioning, as a unique and unrepeatable creation. In this meaning, the dignity is the obligation and limitation of the state, society and each of us. As an ethical and dynamic category, it is not given to us, but it is assign to us, and it is not in us, but always before us, as a guide of our actions in accordance with virtues, to treat ourselves, each other and the nature in a human way. The century in which we live is named the century of molecular biology and genetic engineering because of the enormous potential but also risks to human dignity. Because of that human dignity has become a central principle in all international documents relating to the human genome, genetics and bioethics, adopted

  17. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  18. Human Capital Tracking Tool -

    Data.gov (United States)

    Department of Transportation — AVS is now required to collect, track, and report on data from the following Flight, Business and Workforce Plan. The Human Resource Management’s Performance Target...

  19. Human Research Program

    Data.gov (United States)

    National Aeronautics and Space Administration — Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance...

  20. Human Papillomavirus (HPV)

    Science.gov (United States)

    ... Español Text Size Email Print Share Human Papillomavirus (HPV) Page Content Article Body According to the Centers ... and how to prevent it. How to Prevent HPV: There are 3 types of HPV vaccine: Cervarix , ...

  1. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  2. Human Emotion Recognition System

    Directory of Open Access Journals (Sweden)

    Dilbag Singh

    2012-08-01

    Full Text Available This paper discusses the application of feature extraction of facial expressions with combination of neural network for the recognition of different facial emotions (happy, sad, angry, fear, surprised, neutral etc... Humans are capable of producing thousands of facial actions during communication that vary in complexity, intensity, and meaning. This paper analyses the limitations with existing system Emotion recognition using brain activity. In this paper by using an existing simulator I have achieved 97 percent accurate results and it is easy and simplest way than Emotion recognition using brain activity system. Purposed system depends upon human face as we know face also reflects the human brain activities or emotions. In this paper neural network has been used for better results. In the end of paper comparisons of existing Human Emotion Recognition System has been made with new one.

  3. Humanism vs. Behaviorism

    Science.gov (United States)

    Hunter, Madeline

    1977-01-01

    Author argues that humanism and behaviorism are not necessarily exclusive of one another, and that principles of behaviorism, when thoughtfully applied, can lead to the achievement of humanistic goals. (RW)

  4. Bridging Humanism and Behaviorism.

    Science.gov (United States)

    Chu, Lily

    1980-01-01

    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  5. BIOETHICS AND HUMAN CLONING

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2011-12-01

    Full Text Available In this paper the authors analyze the process of negotiating and beginning of the United Nations Declaration on Human Cloning as well as the paragraphs of the very Declaration. The negotiation was originally conceived as a clear bioethical debate that should have led to a general agreement to ban human cloning. However, more often it had been discussed about human rights, cultural, civil and religious differences between people and about priorities in case of eventual conflicts between different value systems. In the end, a non-binding Declaration on Human Cloning had been adopted, full of numerous compromises and ambiguous formulations, that relativized the original intention of proposer states. According to authors, it would have been better if bioethical discussion and eventual regulations on cloning mentioned in the following text had been left over to certain professional bodies, and only after the public had been fully informed about it should relevant supranational organizations have taken that into consideration.

  6. Human Resource Planning

    Science.gov (United States)

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  7. Viruses and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  8. CHINESE OF HUMANITY

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Humanism Education in Language Class,Innovative model university English teaching,Analysis on Information Literacy of College English Teachers Based On Net Environment,Cultural Differences between E-C Idioms and Teaching of English Idioms

  9. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  10. Will Technology Humanize Us?

    Science.gov (United States)

    Snider, Robert C.

    1972-01-01

    The author considers the question of whether technology will cause humanization or dehumanization in the schools. He concludes that we can not stop tecchnology; we can only give it direction and purpose. (Author/MS)

  11. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    YIN PUMIN

    2010-01-01

    @@ The Chinese Government issued a white paper on its human resources on September I0, highlighting the coun-try's policies to cope with employ-ment pressures and a lack of "high-level innovative talents."

  12. Statement on Human Cloning

    Science.gov (United States)

    ... ban on efforts to implant a human cloned embryo for the purpose of reproduction. The scientific evidence ... stem cell research, including the use of nuclear transplantation techniques (also known as research or therapeutic cloning), ...

  13. Science and Humanism

    Science.gov (United States)

    Auger, Pierre

    1971-01-01

    Science and humanism are separated so completely as to bring about the creation of two cultures quite distinct from each other within contemporary civilization. Pragmatic, rational attitudes are needed on both sides to bring them together. (DF)

  14. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  15. [Demography and human ecology].

    Science.gov (United States)

    Nazareth, J M

    1993-01-01

    At the end of the 19th century the German biologist Ernest Haekel was the first scientist to use the term ecology, which was defined as the study of relationships of organisms or groups of organisms with the environment and indicated the interdependence of the living world, including plants, animals, and humans. This concept also indicates a continuous process of adaptation of organisms to their external environment. The basic concepts of scientific ecology, which developed at the end of the 19th century, can be attributed to Darwin: the relationships between living beings and the notion of the process of adaptation to their environment. The term human ecology appeared in the early 1920s. Human ecology embodies fundamental ideas: biotype, habitat, community, biocenosis, ecosystem, biomass, interchange and equilibrium, and circulation of energy. The accumulated knowledge about human ecology is broken down using the criteria of topography (ecology of humid forests, deserts, lakes, etc.); followed by the appearance of species; and the variants of classical division: auto ecology (influence of external factors on living beings) and sinecology (the study of groups of associated organisms, i.e., natural, animal, and vegetation communities). The species are considered on the basis of equality or sinecology (all of them have the same interests), while in human ecology a species is determined by its relation to a reference group--autoecology or anthropocentric ecology. In 1911, J. Thompson bridged the gap between biological knowledge and social sciences; in 1921, H. Barrows identified human ecology as a component of geography; in 1925, L. Bernard presented the classification of ecosystems; and in 1936, Ezra Park published his work, Human Ecology, followed in 1945 by the emergence of the Chicago school. Demography and human ecology are intimately connected because population is the result of natural and migratory movements, therefore the two sciences require a methodology

  16. Human Resources Accounting

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 21 st century will be the epoch of knowled ge economy. Knowledge economy is to develop economy on the basis of knowledge will surely become the major resources of economy development. Therefore, human resources accounting which provides such information as the ebb and follow of hu man resources investment, the size of the human resources employment, will bec ome the main stream of accounting the time of knowledge economy. To face China 's reality, to develop economy, and to flourish enterprise...

  17. Human motricity and health

    Directory of Open Access Journals (Sweden)

    Manuel Sérgio Vieira e Cunha

    2008-06-01

    Full Text Available If human motricity science intends to study motor conduct (or actions in which the human being pursues transcendence (or surmounting, it inevitably relates to the large realm of health. What are the aspects it evinces? Transdisciplinarity, solidarity among the various knowledge types (including poetical, complexity, (where the physical is integrated but surmounted and the firm belief that to be healthy is to have in ourselves, alive and working, the capacity for surmounting anything.

  18. Human Happiness Is Sensuous

    Institute of Scientific and Technical Information of China (English)

    吕静

    2003-01-01

    All human happiness is biological happiness. That is strictly scientific. At the risk of being misunderstood. I must make it clearer: all human happiness is sensuous happiness. The spiritualists will misunderstand me. I am sure; the spiritualists and materialists must forever misunderstand each other, because they don’t talk the same language, or mean by the same word different things. Are we, too, in this problem

  19. Evolution and human sexuality.

    Science.gov (United States)

    Gray, Peter B

    2013-12-01

    The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory.

  20. Meeting human needs

    Science.gov (United States)

    Nicogossian, Arnauld E.

    1992-01-01

    The degree of autonomy of future long duration manned missions will emphasize interactions between human operators and automated systems aimed at the most effective allocations of tasks between humans and machines. Knowledge of crewmembers' physical status, encompassing both capabilities and limitations, will also be critical during EVA and planetary roving missions; psychological evaluation and support, with a view to both individual health and group cohesion and productivity, may become a critical consideration. Attention is here given to crewmembers' medical and psychological vulnerabilities.

  1. Human bites - self-care

    Science.gov (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  2. Testing for Human Immunodeficiency Virus

    Science.gov (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  3. A WORLD BEYOND HUMAN

    Directory of Open Access Journals (Sweden)

    David Abram

    2013-12-01

    Full Text Available From an initial project to investigate the relationship between magic and traditional medicine as practiced by shamans in Southern rural Asia, the focus of attention gradually shifted to an awareness of the negotiation traditional medicine people or shamans exert between the human community and the larger community of beings. This attentiveness to a more-than-human world does not occur at a supernatural domain above nature or inside her personal self but is the result of the shaman’s special ability to project her consciousness horizontally to other forms of sensibility with which human existence is interwoven. The ecological function of the shaman is to maintain a constant balance between what is taken and what is given from the human community to the larger community. The spirits of indigenous cultures are not defined in opposition to materiality but are essentially those modes of intelligence or awareness that do not possess a human form. By exploring different landscapes, and the sensibility living in them, a new sensitivity is awoken that allows for communication with those intelligences. However, the drowning of these other voices in Western culture, which reduces otherness to an object, creates an uneasiness that is hardly perceived except as an inability to interact with anything more-than-human and its dire consequences in the form of “civilization’s” destructive behavior.

  4. Genomics of human longevity.

    Science.gov (United States)

    Slagboom, P E; Beekman, M; Passtoors, W M; Deelen, J; Vaarhorst, A A M; Boer, J M; van den Akker, E B; van Heemst, D; de Craen, A J M; Maier, A B; Rozing, M; Mooijaart, S P; Heijmans, B T; Westendorp, R G J

    2011-01-12

    In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial metabolic and cellular features of long-lived families resemble those in animals for whom the lifespan is extended by applying genetic manipulation and, especially, dietary restriction. Candidate gene studies in humans support the notion that human orthologues from longevity genes identified in lower species do contribute to longevity but that the influence of the genetic variants involved is small. Here we discuss how an integration of novel study designs, labour-intensive biobanking, deep phenotyping and genomic research may provide insights into the mechanisms that drive human longevity and healthy ageing, beyond the associations usually provided by molecular and genetic epidemiology. Although prospective studies of humans from the cradle to the grave have never been performed, it is feasible to extract life histories from different cohorts jointly covering the molecular changes that occur with age from early development all the way up to the age at death. By the integration of research in different study cohorts, and with research in animal models, biological research into human longevity is thus making considerable progress.

  5. Human Milk Fortification.

    Science.gov (United States)

    Simmer, Karen

    2015-01-01

    Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15-20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers' instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed composition while monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks' corrected gestational age or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population.

  6. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  7. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  8. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation

    Science.gov (United States)

    Uller, Lena; Mathiesen, Jesper Mosolff; Alenmyr, Lisa; Korsgren, Magnus; Ulven, Trond; Högberg, Thomas; Andersson, Gunnar; Persson, Carl GA; Kostenis, Evi

    2007-01-01

    Background Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit asthma-like pathology. Methods Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histopathology were examined in a mouse asthma model. Results TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited asthma pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia. Conclusion This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban. PMID:17328802

  9. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation

    Directory of Open Access Journals (Sweden)

    Högberg Thomas

    2007-02-01

    Full Text Available Abstract Background Mast cell-derived prostaglandin D2 (PGD2, may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2, a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit asthma-like pathology. Methods Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histopathology were examined in a mouse asthma model. Results TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited asthma pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia. Conclusion This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban.

  10. Why Geo-Humanities

    Science.gov (United States)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  11. [Human ehrlichiosis. Review].

    Science.gov (United States)

    Arraga-Alvarado, C

    1994-12-01

    Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 Ehrlichia canis has been known as a cause of illness in dogs and other canine species, and for a few years it was related with human disease. In 1990, Ehrlichia chaffeensis was isolated from a man suspected of having ehrlichiosis. Partial sequencing of the rRNAS from the human isolate and E. canis, indicated that they are 98.7% related. More recently (May 1994) an "human granulocytic ehrlichiosis" have been reported in USA. PCR amplification and sequence of 16S rDNA, showed that the human isolate was virtually identical to those reported for E. phagocytophila y E. equi, organisms that cause ehrlichiosis in rumiant and in horses. Most patients shows fever, headache, malaise, nausea or vomiting, anorexia and in a minority of cases rash is present. Some of them have complications such as pulmonary infiltrates, gastrointestinal problems, renal dysfunction or failure, hepatoesplenomegaly, neurologic abnormalities, DIC and some times death. Leucopenia, thrombocytopenia and elevated liver enzyme values have been common findings. Tetracycline and cloramphenicol have been using in adults and children as especific theraphy.

  12. The human serum metabolome.

    Directory of Open Access Journals (Sweden)

    Nikolaos Psychogios

    Full Text Available Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca.

  13. Humanity and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available So far our open access publishing company MDPI (Multidisciplinary Digital Publishing Institute has published mainly science, medicine and technology journals. To become a multidisciplinary publisher, we launched the journal Sustainability [1]. More recently, we started to run several social science journals, including Societies [2], Religions [3], Administrative Sciences [4] and Behavioral Sciences [5]. Today we published the first paper [6] of the inaugural issue of Humanities (ISSN 2076-0787. This will be an international open access journal, publishing scholarly papers of high quality across all humanities disciplines. As a publisher, I would like to publish journals surrounding the topics of sustainability and I believe the humanities as a discipline of academic studies are very important. As a scientist, I believed science and technology will only benefit human beings. I was raised in a small village, living a very primitive life in a peasant family: no electricity, no machines, of course no TV and no refrigerator. Now, the life of my children is completely different. Even my own life has completely changed. I have witnessed very rapid changes: more and more machines are used to consume mineral resources and energy and to pollute the environment, in order to produce more and more powerful machines (we are also launching a journal titled Machines, in which the relationship between Man and machine should be an interesting topic.. Machines are more and more like human individuals consuming resources themselves (we are launching a journal titled Resources. [...

  14. NOOSPHERE HUMAN COMMUNITY

    Directory of Open Access Journals (Sweden)

    Novozhilova Elena Olegovna

    2013-01-01

    Full Text Available The author dwells upon typical features of noosphere human communities, assessing prospects and hazards of genetic engineering, namely of recombinant DNA technology. Background: Socio-historical ecology ushers in a new approach to studying society in its relation to nature. This interrelation is regarded as a series of socio-ecological transformations ending up in certain types of socio-ecological systems being formed. One of such historical types is represented by a noosphere human community [1]. Results: A number of characteristic features of this kind of community have been outlined, namely: its existence and functioning on global scale, major role of information in making up social wealth, creation of living matter. Conclusion: The noosphere human community is currently the latest stage in the sequence of historical types of socio-ecological systems. Widespread use of information and genetic technology may enable noosphere people to create in future a totally man-made world superseding evolutionary biosphere.

  15. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    , men også arbejdssociologien, arbejdspsykologien og human resource development. Den første retning udsprang af de såkaldte Hawthorne-eksperimenter og psykologen Elton Mayos bearbejdelse af resultaterne derfra. Den anden er en løsere gruppering bestående af navne som Abraham Maslow og Frederick Herzberg......Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...

  16. [Human pulmonary trichomonoses].

    Science.gov (United States)

    Duboucher, Christophe; Caby, Stéphanie; Chabé, Magali; Gantois, Nausicaa; Delgado-Viscogliosi, Pilar; Pierce, Raymond; Capron, Monique; Dei-Cas, Eduardo; Viscogliosi, Eric

    2007-05-01

    Colonization of human lungs by various Trichomonas species is a frequent occurrence, but is unknown to most physicians. At this site of infection, the parasite develops into an amoeboid form that renders it unrecognizable. For this reason it has been overlooked until recently. Morphological identification is not feasible under these conditions and molecular tools provide the only means of identification. The species involved are not restricted to Trichomonas tenax, a saprophyte of the mouth that is usually cited in the rare cases of pleuropulmonary trichomoniasis reported in the literature. The recent discovery of species previously unknown in humans raises further questions, including the zoonotic potential of these microorganisms and the existence of species of animal origin that have adapted to humans. Anaerobiosis in poorly ventilated alveolar lumen, rather than immunodepression, seems to be the factor that promotes proliferation of this parasite. The diagnosis of trichomoniasis and its treatment by specific drugs will make it possible to evaluate the pathogenicity of these parasites.

  17. Scientists and Human Rights

    Science.gov (United States)

    Makdisi, Yousef

    2012-02-01

    The American Physical Society has a long history of involvement in defense of human rights. The Committee on International Freedom of Scientists was formed in the mid seventies as a subcommittee within the Panel On Public Affairs ``to deal with matters of an international nature that endangers the abilities of scientists to function as scientists'' and by 1980 it was established as an independent committee. In this presentation I will describe some aspects of the early history and the impetus that led to such an advocacy, the methods employed then and how they evolved to the present CIFS responsibility ``for monitoring concerns regarding human rights for scientists throughout the world''. I will also describe the current approach and some sample cases the committee has pursued recently, the interaction with other human rights organizations, and touch upon some venues through which the community can engage to help in this noble cause.

  18. Helicopter human factors

    Science.gov (United States)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  19. Human Systems Design Criteria

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1982-01-01

    the necessary functional qualities but also the needed human qualities. The author's main argument is, that the design process should be a dialectical synthesis of the two points of view: Man as a System Component, and System as Man's Environment. Based on a man's presentation of the state of the art a set...... of design criteria is suggested and their relevance discussed. The point is to focus on the operator rather than on the computer. The crucial question is not to program the computer to work on its own conditions, but to “program” the operator to function on human conditions.......This paper deals with the problem of designing more humanised computer systems. This problem can be formally described as the need for defining human design criteria, which — if used in the design process - will secure that the systems designed get the relevant qualities. That is not only...

  20. Reflections on humanizing biomedicine.

    Science.gov (United States)

    Marcum, James A

    2008-01-01

    Although biomedicine is responsible for the "miracles" of modern medicine, paradoxically it has also led to a quality-of-care crisis in which many patients feel disenfranchised from the health-care industry. To address this crisis, several medical commentators make an appeal for humanizing biomedicine, which has led to shifts in the philosophical boundaries of medical knowledge and practice. In this paper, the metaphysical, epistemological, and ethical boundaries of biomedicine and its humanized versions are investigated and compared to one another. Biomedicine is founded on a metaphysical position of mechanistic monism, an epistemology of objective knowing, and an ethic of emotionally detached concern. In humanizing modern medicine, these boundaries are often shifted to a metaphysical position of dualism/holism, an epistemology of subject knowing, and an ethic of empathic care. In a concluding section, the question is discussed whether these shifts in the philosophical boundaries are adequate to resolve the quality-of-care crisis.

  1. HUMAN MISSION OF EDUCATION

    Directory of Open Access Journals (Sweden)

    Suzana Miovska Spaseva

    2013-06-01

    Full Text Available The article examines the complex role and great responsibility of the education today in development of the moral strength and human values of the children and youth. At the beginning of the article the author reconsiders the pedagogical ideas of Maria Montessori and her concept of education for peace as an instrument for reconstruction of the society and for improvement of the human living. Than the analysis of the moral values in the contemporary society is made and several issues and dilemmas are discussed referring the value disorientation of the youth and the importance of the models of adult’s moral behavior in their search for personal identity. On the basis of this analysis, the human dimension of the education is elaborated enhancing the need for its understanding as support of development, which is based on several crucial elements: love, freedom and spirit of community.

  2. (Human) Resourcing For CI

    DEFF Research Database (Denmark)

    Jørgensen, Frances; S., Jacob; Kofoed, Lise Busk

    2005-01-01

    More and more, the ability to compete in today’s market is viewed as being dependent on human capital. One of the most challenging aspects of human resource management involves supplying the organization with the human capital necessary to fulfill its objectives. This task becomes especially...... challenging in organizations involved in change processes such as Continuous Improvement (CI), as the technical skills traditionally valued are no longer adequate. These companies are faced with the question: “What competencies should our employees possess in order to contribute to our success, given...... the change processes in which we are engaged?” Without a clear picture of the types of competencies required to implement CI, it is impossible for companies to make informed decisions regarding recruitment, hiring, and training of their workforce. The objective of this paper is therefore to define...

  3. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... and technologies relating to performances and experiences, urban design, climate adaptation, etc. The research takes a process-oriented and participatory approach and involves interaction between different user interests and designs. It is based on empirical, typical case- and action research-oriented studies...

  4. Abortion and human rights.

    Science.gov (United States)

    Shaw, Dorothy

    2010-10-01

    Abortion has been a reality in women's lives since the beginning of recorded history, typically with a high risk of fatal consequences, until the last century when evolutions in the field of medicine, including techniques of safe abortion and effective methods of family planning, could have ended the need to seek unsafe abortion. The context of women's lives globally is an important but often ignored variable, increasingly recognised in evolving human rights especially related to gender and reproduction. International and regional human rights instruments are being invoked where national laws result in violations of human rights such as health and life. The individual right to conscientious objection must be respected and better understood, and is not absolute. Health professional organisations have a role to play in clarifying responsibilities consistent with national laws and respecting reproductive rights. Seeking common ground using evidence rather than polarised opinion can assist the future focus.

  5. Human-Robot Interaction

    Science.gov (United States)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta

    2012-01-01

    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  6. Human immune system variation.

    Science.gov (United States)

    Brodin, Petter; Davis, Mark M

    2017-01-01

    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

  7. [Human rights and procreation].

    Science.gov (United States)

    Leroy, F

    1990-04-01

    The impact of procreation on freedom, health and welfare of human beings, is considerable. This relationship, however, is not mirrored in texts devoted to Human Rights. This omission obviously implies a neglect of women's and children's rights. The history of anticonceptive methods exemplifies the struggle for these rights. This conquest, which has lasted two hundred years, is far from completed. Because of the demographic outbreak in Third World countries, an ideological conflict has appeared between first generation Human Rights concerned with individual freedom ("rights of") and those of second generation aiming at social fairness ("rights to"). Adequate political and economic adjustment between North and South is a prerequisite to any balanced compromise that would resolve this conflict through democratic, albeit intensive, birth control.

  8. Monogenic obesity in humans.

    Science.gov (United States)

    Farooqi, I Sadaf; O'Rahilly, Stephen

    2005-01-01

    Until relatively recently, the small number of identifiable inherited human diseases associated with marked obesity were complex, pleiotropic developmental disorders, the molecular basis for which were entirely obscure. The molecular basis for many of these complex syndromes, such as Bardet Beidl syndrome, has been revealed, providing novel insights into processes essential for human hypothalamic function and energy balance. In addition to these discoveries, which were the fruits of positional cloning, the molecular constituents of the signaling pathways responsible for the control of mammalian energy homeostasis have been identified, largely through the study of natural or artificial mutations in mice. We discuss the increasing number of human disorders that result from genetic disruption of the leptin-melanocortin pathways that have been identified. Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged.

  9. Monogenic human obesity syndromes.

    Science.gov (United States)

    Farooqi, I S

    2006-01-01

    Over the past decade we have witnessed a major increase in the scale of scientific activity devoted to the study of energy balance and obesity. This explosion of interest has, to a large extent, been driven by the identification of genes responsible for murine obesity syndromes, and the novel physiological pathways revealed by those genetic discoveries. Others and we have also recently identified several single gene defects causing severe human obesity. Many of these defects have been in molecules identical or similar to those identified as a cause of obesity in rodents. I will review the human monogenic obesity syndromes that have been characterised to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  10. Social cognition in humans

    DEFF Research Database (Denmark)

    Frith, Christopher; Frith, Uta

    2007-01-01

    We review a diversity of studies of human social interaction and highlight the importance of social signals. We also discuss recent findings from social cognitive neuroscience that explore the brain basis of the capacity for processing social signals. These signals enable us to learn about...... the world from others, to learn about other people, and to create a shared social world. Social signals can be processed automatically by the receiver and may be unconsciously emitted by the sender. These signals are non-verbal and are responsible for social learning in the first year of life. Social...... signals can also be processed consciously and this allows automatic processing to be modulated and overruled. Evidence for this higher-level social processing is abundant from about 18 months of age in humans, while evidence is sparse for non-human animals. We suggest that deliberate social signalling...

  11. Human Security Agendas

    Institute of Scientific and Technical Information of China (English)

    Alan Hunter

    2012-01-01

    Ⅰ.IntroductionThe need for governments and international organisations to gain a better understanding of "security" is ever more urgent.For example in the conflict in Libya in early 2011,many security dilemmas were visible:the protection of Libyan civilians,the security of the regime,whether and how the UN or NATO should intervene,whether Europe would be threatened with a massive refugee flow,how to protect or evacuate foreign citizens (including Chinese),how to secure food and medical supplies in the midst of armed conflict.Such events may be termed "complex emergencies" which often raise legal, military and humanitarian issues simultaneously.International law and practice do not provide clear guidelines on such situations,and responses can be random,contingent on a variety of factors.Traditional concepts of security,for example protection of national borders,are certainly still relevant and legally enforceable,but more sophisticated concepts are needed to respond to security dilemmas in today's globalised world.Human security as a concept was first developed within the UN system in the 1990s,and set out,for example,in Human Security Now [1] The first section of this paper tracks the development of Human Security discourse,and also examines the broadening of the "security"concept in recent years.The second section reports on institutions with a specific interest in Human Security,for example within the UN system and in universities.The third section acknowledges some critiques of the Human Security paradigm.The last section reports on new directions that may enrich the Human Security agenda.

  12. Leukotriene B4 potentiates CpG signaling for enhanced cytokine secretion by human leukocytes.

    Science.gov (United States)

    Gaudreault, Eric; Gosselin, Jean

    2009-08-15

    TLRs are known to be important in innate host defense against a variety of microbial infections. In particular, TLR9 has been associated with immune defense against different foreign organisms by recognition of unmethylated DNA sequences. In this report, we provide evidence that leukotriene B(4) (LTB(4)) has the capacity to modulate TLR9 expression on human neutrophils. The effect of LTB(4) was found to be specific, because related leukotrienes such as LTC(4) and LTD(4) or neutrophil agonists IL-8 and C5a failed to modulate TLR9 expression in neutrophils. Using fluorochrome-tagged CpG DNA, we observed that LTB(4) treatment also increased TLR9 ligand binding in neutrophils. Moreover, LTB(4) stimulation potentiates CpG-mediated signaling via an endosome-independent mechanism in human neutrophils, leading to enhanced secretion of proinflammatory cytokines. The increase in cytokine secretion by LTB(4) following CpG stimulation of neutrophils was associated with the activation of TGF-beta-activated kinase (TAK-1) as well as p38 and c-Jun (JNK) kinases. In contrast, in PBMC LTB(4) leads to an increase in cytokine secretion following CpG stimulation but via a MyD88- and endosome-dependent mechanism. As observed in neutrophils, PBMC stimulation with LTB(4) in the presence of CpG also results in enhanced TAK-1, p38, and JNK phosphorylation/activation. These data provide new evidence underlying the immunomodulatory properties of LTB(4) leading to antimicrobial defense.

  13. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  14. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...

  15. On human health.

    Science.gov (United States)

    van Spijk, Piet

    2015-05-01

    If it is true that health is a priority objective of medicine, then medical practice can only be successful if the meaning of the term "health" is known. Various attempts have been made over the years to define health. This paper proposes a new definition. In addition to current health concepts, it also takes into account the distinction between specifically human (great) health and health as the absence of disease and illness-i.e. small health. The feeling of leading a life that makes sense plays a key role in determining specifically human great health.

  16. Handbook of human computation

    CERN Document Server

    Michelucci, Pietro

    2013-01-01

    This volume addresses the emerging area of human computation, The chapters, written by leading international researchers, explore existing and future opportunities to combine the respective strengths of both humans and machines in order to create powerful problem-solving capabilities. The book bridges scientific communities, capturing and integrating the unique perspective and achievements of each. It coalesces contributions from industry and across related disciplines in order to motivate, define, and anticipate the future of this exciting new frontier in science and cultural evolution. Reade

  17. When computers were human

    CERN Document Server

    Grier, David Alan

    2013-01-01

    Before Palm Pilots and iPods, PCs and laptops, the term ""computer"" referred to the people who did scientific calculations by hand. These workers were neither calculating geniuses nor idiot savants but knowledgeable people who, in other circumstances, might have become scientists in their own right. When Computers Were Human represents the first in-depth account of this little-known, 200-year epoch in the history of science and technology. Beginning with the story of his own grandmother, who was trained as a human computer, David Alan Grier provides a poignant introduction to the wider wo

  18. We Are Human Beings

    Science.gov (United States)

    McGee, Andrew

    2016-01-01

    In this paper, I examine Jeff McMahan’s arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients. PMID:26810918

  19. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W

    2010-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...... to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival...... - and healthy survival - to even greater ages....

  20. Understanding digital humanities

    CERN Document Server

    Berry, D

    2012-01-01

    The application of new computational techniques and visualisation technologies in the Arts and Humanities are resulting in fresh approaches and methodologies for the study of new and traditional corpora. This 'computational turn' takes the methods and techniques from computer science to create innovative means of close and distant reading. This book discusses the implications and applications of 'Digital Humanities' and the questions raised when using algorithmic techniques. Key researchers in the field provide a comprehensive introduction to important debates surrounding issues such as th

  1. Artificial human vision.

    Science.gov (United States)

    Dowling, Jason

    2005-01-01

    Can vision be restored to the blind? As early as 1929 it was discovered that stimulating the visual cortex of an individual led to the perception of spots of light, known as phosphenes [1] . The aim of artificial human vision systems is to attempt to utilize the perception of phosphenes to provide a useful substitute for normal vision. Currently, four locations for electrical stimulation are being investigated; behind the retina (subretinal), in front of the retina (epiretinal), the optic nerve and the visual cortex (using intra- and surface electrodes). This review discusses artificial human vision technology and requirements, and reviews the current development projects.

  2. Post-human Viewing

    DEFF Research Database (Denmark)

    Blaagaard, Bolette

    2013-01-01

    to become part of a global cultural flow, thus calling into question the physical connection between viewer and image. This article analyses what happens to that connection when not only the image but also the physical body is mediated and challenged in post-human relations, and examines the ensuing ethical...... implications. The author takes photojournalism and, in particular, mobile phone footage as a starting point for an exploration of the (post-human) body as evidence and sign of authenticity in the modern age of digital communications and journalism....

  3. Ayahuasca and human destiny.

    Science.gov (United States)

    McKenna, Dennis J

    2005-06-01

    In this essay, the author shares his personal reflections gleaned from a lifetime of research with ayahuasca, and speculates on the societal, political, planetary, and evolutionary implications of humanity's aeons-old symbiosis with this shamanic plant. The thesis is developed that at this critical historical juncture, ayahuasca has developed a strategy to broadcast its message to a wider world--a reflection of the urgent need to avert global ecological catastrophe. While ayahuasca has much to teach us, the critical question is, will humanity hear it, and heed it, in time?

  4. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  5. Pragmatic Challenges to Human Rights

    DEFF Research Database (Denmark)

    Schaumburg-Müller, Sten

    2007-01-01

    Pragmatism offers a platform for posing relevant questions. This article uses a pragmatic point of departure to question a natural law conception of human rights and to take a closer look at three pressing human rights problems: The human rights situation in states with little or no state capacity......; the revision and adaptation of human rights law; and the not straightforward relationship betweemn human rights and democracy....

  6. Human automation integration

    NARCIS (Netherlands)

    Barnes, M.; Cosenzo, K.; Galster, s.; Hollnagel, E.; Miller, C.; Parasuraman, R.; Reising, J.; Taylor, R.; Breda, L. van

    2007-01-01

    Many versions of future concept of operations (CONOPS) rely heavily on UMVs. The pressure to take the human out of immediate control of these vehicles is being driven by several factors. These factors include a reduction in cost for the production and maintenance of the vehicle, operational viabilit

  7. Human Work Interaction Design

    DEFF Research Database (Denmark)

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID frame-work, and a sample of 54 papers from workshops, conferences and journals from the period 2009-2014. We group the papers into six topical groups, and then ...

  8. Human Work Interaction Design

    DEFF Research Database (Denmark)

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID framework, and a sample of 54 HWID related papers from workshops, conferences and journals from the period 2009–2014. We group the papers into six topical group...

  9. Biotechnologies and Human Dignity

    Science.gov (United States)

    Sweet, William; Masciulli, Joseph

    2011-01-01

    In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the…

  10. Predictors of human rotation.

    Science.gov (United States)

    Stochl, Jan; Croudace, Tim

    2013-01-01

    Why some humans prefer to rotate clockwise rather than anticlockwise is not well understood. This study aims to identify the predictors of the preferred rotation direction in humans. The variables hypothesised to influence rotation preference include handedness, footedness, sex, brain hemisphere lateralisation, and the Coriolis effect (which results from geospatial location on the Earth). An online questionnaire allowed us to analyse data from 1526 respondents in 97 countries. Factor analysis showed that the direction of rotation should be studied separately for local and global movements. Handedness, footedness, and the item hypothesised to measure brain hemisphere lateralisation are predictors of rotation direction for both global and local movements. Sex is a predictor of the direction of global rotation movements but not local ones, and both sexes tend to rotate clockwise. Geospatial location does not predict the preferred direction of rotation. Our study confirms previous findings concerning the influence of handedness, footedness, and sex on human rotation; our study also provides new insight into the underlying structure of human rotation movements and excludes the Coriolis effect as a predictor of rotation.

  11. Humanizing science education

    Science.gov (United States)

    Donnelly, James F.

    2004-09-01

    This paper argues that the diverse curriculum reform agendas associated with science education are strongly and critically associated with the educational characteristics of the humanities. The article begins with a survey of interpretations of the distinctive contribution which the humanities make to educational purposes. From this survey four general characteristics of the humanities are identified: an appeal to an autonomous self with the right and capacity to make independent judgements and interpretations; indeterminacy in the subject matter of these judgements and interpretations; a focus on meaning, in the context of human responses, actions, and relationships, and especially on the ethical, aesthetic, and purposive; and finally, the possibility of commonality in standards of judgement and interpretation, under conditions of indeterminacy. Inquiry and science technology and society (STS) orientated curriculum development agendas within science education are explored in the light of this analysis. It is argued that the four characteristics identified are central to the educational purposes of these and other less prominent modes of curriculum development in science, though not unproblematically so. In the light of this discussion the prognosis and challenges for science curriculum development are explored.

  12. Learning to Be Human

    Science.gov (United States)

    Macmurray, John

    2012-01-01

    This article presents "Learning to be Human", which John Macmurray delivered on 5 May 1958 as the annual public lecture at Moray House College of Education, now part of Edinburgh University. The key themes of the paper are ones to which Macmurray returned again and again in both his educational and his philosophical writing for over 40 years and…

  13. Human memory search

    NARCIS (Netherlands)

    Davelaar, E.J.; Raaijmakers, J.G.W.; Hills, T.T.; Robbins, T.W.; Todd, P.M.

    2012-01-01

    The importance of understanding human memory search is hard to exaggerate: we build and live our lives based on what whe remember. This chapter explores the characteristics of memory search, with special emphasis on the use of retrieval cues. We introduce the dependent measures that are obtained

  14. Human Memory: The Basics

    Science.gov (United States)

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  15. Parasites and human evolution.

    Science.gov (United States)

    Perry, George H

    2014-01-01

    Our understanding of human evolutionary and population history can be advanced by ecological and evolutionary studies of our parasites. Many parasites flourish only in the presence of very specific human behaviors and in specific habitats, are wholly dependent on us, and have evolved with us for thousands or millions of years. Therefore, by asking when and how we first acquired those parasites, under which environmental and cultural conditions we are the most susceptible, and how the parasites have evolved and adapted to us and we in response to them, we can gain considerable insight into our own evolutionary history. As examples, the tapeworm life cycle is dependent on our consumption of meat, the divergence of body and head lice may have been subsequent to the development of clothing, and malaria hyperendemicity may be associated with agriculture. Thus, the evolutionary and population histories of these parasites are likely intertwined with critical aspects of human biology and culture. Here I review the mechanics of these and multiple other parasite proxies for human evolutionary history and discuss how they currently complement our fossil, archeological, molecular, linguistic, historical, and ethnographic records. I also highlight potential future applications of this promising model for the field of evolutionary anthropology.

  16. Antihumanism in the Humanities.

    Science.gov (United States)

    Schwartz, Joel

    1990-01-01

    Analyzes the antihumanistic elements of Jacques Derrida's theory of deconstruction. Argues that the modern French intellectuals, including Foucault, Derrida, and Lacan, have had an antihumanistic effect on the American social sciences and humanities by rejecting the existence of truth, morality, and rationality. (FMW)

  17. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  18. Human thimet oligopeptidase.

    Science.gov (United States)

    Dando, P M; Brown, M A; Barrett, A J

    1993-01-01

    We have purified human thimet oligopeptidase to homogeneity from erythrocytes, and compared it with the enzyme from rat testis and chicken liver. An antiserum raised against rat thimet oligopeptidase also recognized the human and chicken enzymes, suggesting that the structure of the enzyme has been strongly conserved in evolution. Consistent with this, the properties of the human enzyme were very similar to those for the other species. Thus human thimet oligopeptidase also is a thiol-dependent metallo-oligopeptidase with M(r) about 75,000. Specificity for cleavage of a number of peptides was indistinguishable from that of the rat enzyme, but Ki values for the four potent reversible inhibitors tested were lower. In discussing the results, we consider the determinants of the complex substrate specificity of thimet oligopeptidase. We question whether substrates containing more than 17 amino acid residues are cleaved, as has been suggested. We also point out that the favourable location of a proline residue and a free C-terminus in the substrate may be as important as the hydrophobic residues in the P2, P1 and P3' positions that have been emphasized in the past. Images Figure 1 PMID:8373360

  19. Visible Human Project

    Science.gov (United States)

    ... Library of Medicine thanks the men and the women who will their body to science, thereby enabling medical research and development. Further Information General Information A description of The Visible Human Project ® image data and how to obtain it (includes license ...

  20. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  1. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies dif

  2. Human Power Empirically Explored

    NARCIS (Netherlands)

    Jansen, A.J.

    2011-01-01

    Harvesting energy from the users’ muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are conven

  3. Narratology beyond the Human

    Directory of Open Access Journals (Sweden)

    David Herman

    2014-12-01

    Full Text Available This essay uses Lauren Groff’s 2011 short story “Above and Below” to explore aspects of a narratology beyond the human, considering how ideas developed by scholars of narrative bear on questions about the nature and scope of human-animal relationships in the larger biosphere. Bringing Groff’s text into dialogue with the concept of “self-narratives” as developed by Kenneth J. Gergen and Mary M. Gergen, anthropological research on the ontologies projected by the members of different cultures, and ideas from literary narratology, I discuss how the structure and narration of Groff’s story reveal a fault line between two competing ontologies in the culture of modernity, one parsimonious and the other prolific when it comes to allocating possibilities for selfhood across species lines. More generally, in addition to illuminating how a given self-narrative locates the human agent in a transspecies constellation of selves, a narratology beyond the human can assist with the construction of new, more sustainable individual and collective self-narratives that situate the self within wider webs of creatural life.

  4. Communicating Humanism Nonverbally.

    Science.gov (United States)

    Hillison, John

    1983-01-01

    Discusses the importance of nonverbal communication by counselors in expressing humanistic feeling. Notes that facial expression (i.e., smiling) provides immediate feedback to the observer; use of space (i.e., close proximity) communicates warmth and humaneness; and tone of voice can complement spoken words and give them more meaning. (WAS)

  5. Cultivating human nature

    NARCIS (Netherlands)

    Derksen, Maarten

    2007-01-01

    Evolutionary psychology claims to offer a unified perspective on human nature and culture, which can serve to further the integration of psychology and the social sciences. I describe four approaches to evolutionary psychology, and note increasing attention to the agency of the individual in constru

  6. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  7. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  8. Lessons in Human Relations.

    Science.gov (United States)

    Glenn, Joanne Lozar

    2003-01-01

    Explores the importance of relationship literacy--the ability to create good relationships with others--in the next economy and offers perspectives on how business education instructors can help students develop and improve their human relations skills for business success. (Author/JOW)

  9. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  10. Human health and groundwater

    Science.gov (United States)

    The high quality of most groundwaters, consequent upon the self-purification capacity of subsurface strata, has long been a key factor in human health and wellbeing. More than 50% of the world’s population now rely on groundwater for their supply of drinking water – and in most circumstances a prope...

  11. Humanizing the Secondary School.

    Science.gov (United States)

    Hamilton, Norman K., Ed.; Saylor, J. Galen, Ed.

    These papers, presented during ASCD-sponsored conference, confront educators with issues in and alternatives for making secondary schools a more humanizing experience for students. The contributors and their articles are: Norman K. Hamilton, "Alternatives in Secondary Education"; Thornton B. Monez and Norman L. Bussiere, "The High School in Human…

  12. Humanism in Education

    Science.gov (United States)

    Armstrong, Michael

    2015-01-01

    This is the text of Michael Armstrong's address to the Brian Simon Centenary conference, held at the Institute of Education on 26 March 2015. Michael Armstrong celebrates the humanism that underlay Brian's belief in a common system of education, democratic and non-selective, and finds its counterpart in the creative practice of school children.

  13. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1995-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  14. Hauntings of Human Nature

    DEFF Research Database (Denmark)

    Clasen, Mathias

    2017-01-01

    The central conflicts of Stephen King’s horror novel The Shining are rooted in human nature and reflect evolutionarily recurrent adaptive problems—the problem of balancing conflicting evolved motives, such as motives for selfish status striving versus motives for affiliative nurturing behavior...

  15. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  16. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  17. Human Memory: The Basics

    Science.gov (United States)

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  18. Designers of Human Settlements

    Science.gov (United States)

    Cliff, Ursula

    1976-01-01

    Reviewed herein are the ideas of nine men who have addressed themselves to the problems of human settlements in this century. The ideas reviewed include those of Arnold Toynbee, Lewis Mumford, Hassan Fathy, Buckminster Fuller, Constantinos Doxiadis, Charles Correa, Paul Mwaluko, Robert McNamara and John F. C. Turner. (BT)

  19. The human myotendinous junction

    DEFF Research Database (Denmark)

    Knudsen, A B; Larsen, M; Mackey, Abigail

    2015-01-01

    The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never ...

  20. Haptocorrin in humans

    DEFF Research Database (Denmark)

    Mørkbak, Anne Louise; Nexo, Ebba; Poulsen, Steen Seier

    2007-01-01

    knowledge concerning its function and its distribution in adult and foetal life is limited. In this study, we present data on the tissue expression of haptocorrin and on the relation between analogues on haptocorrin and vitamin B(12) status in humans. Methods: Polyclonal antibodies towards haptocorrin were...

  1. Strengthening Career Human Agency

    Science.gov (United States)

    Chen, Charles P.

    2006-01-01

    Rooted in A. Bandura's (1982, 2001b) social cognitive theory, the notion of human agency has received considerable attention in vocational and career psychology for the last 2 decades, especially with the recent emergence of social constructivist thinking in the field. This article continues in the same direction. In reviewing the notion of human…

  2. Humanism in Education

    Science.gov (United States)

    Armstrong, Michael

    2015-01-01

    This is the text of Michael Armstrong's address to the Brian Simon Centenary conference, held at the Institute of Education on 26 March 2015. Michael Armstrong celebrates the humanism that underlay Brian's belief in a common system of education, democratic and non-selective, and finds its counterpart in the creative practice of school children.

  3. Animal and Human Communication.

    Science.gov (United States)

    Rummel, Lynda

    Several misconceptions regarding the status of human communication systems relative to the systems of other animals are discussed in this paper. Arguments are offered supporting the expansion of the communication discipline to include the study of the communication systems of other species. The "communicative continuity" view which ranks…

  4. Conceptualizations of Human Environments

    Science.gov (United States)

    Moos, Rudolf H.

    1973-01-01

    Presents six major methods by which characteristics of environments have been related to indexes of human functioning: (1) ecological dimensions; (2) behavior settings; (3) dimensions of organizational structure; and, (4) dimensions identifying the collective personal and/or behavioral characteristics of the milieu inhabitants; and two others.…

  5. Radar: Human Safety Net

    Science.gov (United States)

    Ritz, John M.

    2016-01-01

    Radar is a technology that can be used to detect distant objects not visible to the human eye. A predecessor of radar, called the telemobiloscope, was first used to detect ships in the fog in 1904 off the German coast. Many scientists have worked on the development and refinement of radar (Hertz with electromagnetic waves; Popov with determining…

  6. Human Influenza Virus Infections.

    Science.gov (United States)

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  7. Selenium and Human Health

    Directory of Open Access Journals (Sweden)

    M Abedi

    2013-04-01

    Full Text Available Introduction: Selenium is an essential element for human health and it is toxic at high concentrations. Selenium is a constituent component of selenoproteins that have enzymatic and structural roles in human biochemistry. Selenium is a best antioxidant and catalyst for production of thyroid hormone. This element has the key role in the immune function; prevention of AIDS progression and the deactivity of toxins. Furthermore, selenium is essential for sperm motility and can reduce abortions. Selenium deficiency was also associated with adverse mood states. The findings regarding cardiovascular disease risk related to selenium deficiency is unclear, though other conditions such as vascular inflammation, oxidative stress and selenium deficiency can cause this disease too. Moreover, consuming of 60 mg of selenium per day may be associated with reduction of cancer risk. In this study, a review of studies has been performed on the biochemical function of selenium toxicity, and its effects on human health. Furthermore, certain identified cancers associated with selenium have been discussed to absorb more attention to the status of this element and also as a guide for further studies. Selenium plays the dual character (useful and harmful in human health, and then it is necessary to determine the concentration of this element in body fluids and tissues. An appropriate method for routine measurement of selenium in clinical laboratories is electro thermal atomic absorption spectrometry (ETAAS with very low detection limit and good precision.

  8. Towards International Humanism

    Science.gov (United States)

    Huxley, Julian

    1971-01-01

    The basic task before the educational profession today is to study and understand the evolutionary-humanist revolution, to follow up its educational implications; and to enable as many as possible of the world's growing minds to be illuminated by its new vision of human destiny. (Author/JB)

  9. Recombinant human milk proteins.

    Science.gov (United States)

    Lönnerdal, Bo

    2006-01-01

    Human milk provides proteins that benefit newborn infants. They not only provide amino acids, but also facilitate the absorption of nutrients, stimulate growth and development of the intestine, modulate immune function, and aid in the digestion of other nutrients. Breastfed infants have a lower prevalence of infections than formula-fed infants. Since many women in industrialized countries choose not to breastfeed, and an increasing proportion of women in developing countries are advised not to breastfeed because of the risk of HIV transmission, incorporation of recombinant human milk proteins into infant foods is likely to be beneficial. We are expressing human milk proteins known to have anti-infective activity in rice. Since rice is a normal constituent of the diet of infants and children, limited purification of the proteins is required. Lactoferrin has antimicrobial and iron-binding activities. Lysozyme is an enzyme that is bactericidal and also acts synergistically with lactoferrin. These recombinant proteins have biological activities identical to their native counterparts. They are equally resistant to heat processing, which is necessary for food applications, and to acid and proteolytic enzymes which are needed to maintain their biological activity in the gastrointestinal tract of infants. These recombinant human milk proteins may be incorporated into infant formulas, baby foods and complementary foods, and used with the goal to reduce infectious diseases.

  10. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of hu

  11. Disability and Human Supports

    Directory of Open Access Journals (Sweden)

    Jeff McNair

    2015-01-01

    Full Text Available This article provides a brief overview of models of disability growing out of the field of disability studies and leading to a call for interventions going beyond a simply medical model approach. A brief discussion of human supports/services is provided such that readers engaged in the development of services/supports can base them on best principles.

  12. Human herpesviruses and MS

    DEFF Research Database (Denmark)

    Christensen, Tove

    2007-01-01

    Environmental factors operate on a background of genetic susceptibility in MS pathogenesis; the human herpesviruses (HHV) are likely candidates for such factors. HHV share a number of properties: they are almost ubiquitous, they are highly prevalent worldwide, they all cause latent infections...

  13. Children Are Human Beings

    Science.gov (United States)

    Bossard, James H. S.

    2017-01-01

    The basic assumption underlying this article is that the really significant changes in human history are those that occur, not in the mechanical gadgets which men use nor in the institutionalized arrangements by which they live, but in their attitudes and in the values which they accept. The revolutions of the past that have had the greatest…

  14. Ubiquitous Human Computing

    OpenAIRE

    Zittrain, Jonathan L.

    2008-01-01

    Ubiquitous computing means network connectivity everywhere, linking devices and systems as small as a thumb tack and as large as a worldwide product distribution chain. What could happen when people are so readily networked? This short essay explores issues arising from two possible emerging models of ubiquitous human computing: fungible networked brainpower and collective personal vital sign monitoring.

  15. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Lopes, Arminda; Ørngreen, Rikke

    This book constitutes the thoroughly refereed post-conference proceedings of the Third IFIP WG 13.6 Working Conference on Human Work Interaction Design, HWID 2012, held in Copenhagen, Denmark, in December 2012. The 16 revised papers presented were carefully selected for inclusion in this volume...

  16. Human-Centered Aspects

    NARCIS (Netherlands)

    Kulyk, O.; Kosara, R.; Urquiza, J.; Wassink, I.; Kerren, A.; Ebert, A.; Meyer, J.

    2007-01-01

    Humans have remarkable perceptual capabilities. These capabilities are heavily underestimated in current visualizations. Often, this is due to the lack of an in-depth user study to set the requirements for optimal visualizations. The designer does not understand what kind of information should be vi

  17. Human Learning and Memory

    Science.gov (United States)

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  18. Making Human Beings Human: Bioecological Perspectives on Human Development. The SAGE Program on Applied Developmental Science

    Science.gov (United States)

    Bronfenbrenner, Urie, Ed.

    2004-01-01

    To a greater extent than any other species, human beings create the environments that, in turn, shape their own development. This book endeavors to demonstrate that human beings can also develop those environments to optimize their most constructive genetic potentials. What makes human beings human, therefore, is both the potential to shape their…

  19. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  20. Human-Robot Interaction

    Science.gov (United States)

    Sandor, Aniko; Cross, E. Vincent, II; Chang, Mai Lee

    2015-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces affect the human's ability to perform tasks effectively and efficiently when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. For efficient and effective remote navigation of a rover, a human operator needs to be aware of the robot's environment. However, during teleoperation, operators may get information about the environment only through a robot's front-mounted camera causing a keyhole effect. The keyhole effect reduces situation awareness which may manifest in navigation issues such as higher number of collisions, missing critical aspects of the environment, or reduced speed. One way to compensate for the keyhole effect and the ambiguities operators experience when they teleoperate a robot is adding multiple cameras and including the robot chassis in the camera view. Augmented reality, such as overlays, can also enhance the way a person sees objects in the environment or in camera views by making them more visible. Scenes can be augmented with integrated telemetry, procedures, or map information. Furthermore, the addition of an exocentric (i.e., third-person) field of view from a camera placed in the robot's environment may provide operators with the additional information needed to gain spatial awareness of the robot. Two research studies investigated possible mitigation approaches to address the keyhole effect: 1) combining the inclusion of the robot chassis in the camera view with augmented reality overlays, and 2) modifying the camera

  1. Helicopter Human Factors

    Science.gov (United States)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  2. Helicopter Human Factors

    Science.gov (United States)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  3. The science of unitary human beings and interpretive human science.

    Science.gov (United States)

    Reeder, F

    1993-01-01

    Natural science and human science are identified as the bases of most nursing theories and research programs. Natural science has been disclaimed by Martha Rogers as the philosophy of science that undergirds her work. The question remains, is the science of unitary human beings an interpretive human science? The author explores the works of Rogers through a dialectic with two human scientists' works. Wilhelm Dilthey's works represent the founding or traditional view, and Jurgen Habermas' works represent a contemporary, reconstructionist view. The ways Rogerian thought contributes to human studies but is distinct from traditional and reconstructionist human sciences are illuminated.

  4. 面向真实世界的测试函数Ⅱ%Theory and Realization of Solar Smart Road Lamp Controller based on STC12 C5 A60 AD

    Institute of Scientific and Technical Information of China (English)

    彭复明

    2014-01-01

    This paper introduces the hardware circuit and software of the intelligent controller based on MCU. This system uses “three-stage PWM charging”mode and “light and time control discharging”mode,which are of great benefits to high charging of efficiency. In addition,the controller has protection measures of overcharge,over discharge,overload and short circuit to extend the service life of bat-tery.%针对目前无约束优化测试函数的全局最优解坐标是人为设置的现状,介绍了一种面向真实世界的测试函数,它的全局最优解可能为零,但对应的坐标是未知的。最优解坐标必须输入一个指定的网站,它自动计算最优解,可以保证最优解的真实性,优化数据的可信度将会大大提高。

  5. Digitalization of the human mind

    Directory of Open Access Journals (Sweden)

    Mr.Sc. Drita Mehmeti

    2013-06-01

    Full Text Available The human faces with various problems already in its first steps in live, and carriers of such life situations are found in various ages which bring new currents in the way of life. Starting from the ancient Greek thought, the human and its mind made the centre of the world, already orienting the Western thought towards the study of the human mind (namely human reason, since it made the key tool for human survival. Although human problems have been discussed throughout various ages, they have not been able to resolve in full the human problems, and therefore, the same issues were taken by the representatives of the socalled “critical theory”, who used the theory to criticize the way of live Western civilization was offering, known as digitalization of the human mind. The human problems are addressed in a poly-dimensional manner. The factors affecting the human mind are: industrial civilization, technical progress, automation, overtly influence of machinery on humans, substitution of cultural values, which in sum have developed a new World Order, where the ruler is technology. In the modern world, the human fails to recognize himself, since he is out of himself and lives according to the rules set forth by the “remote control”. In the flow of this kind of livelihood, human alienates, or in other words, the human goes out of himself, trying to adapt maximally to the requirements of the new way of life.

  6. Human Integration Design Processes (HIDP)

    Science.gov (United States)

    Boyer, Jennifer

    2014-01-01

    The purpose of the Human Integration Design Processes (HIDP) document is to provide human-systems integration design processes, including methodologies and best practices that NASA has used to meet human systems and human rating requirements for developing crewed spacecraft. HIDP content is framed around human-centered design methodologies and processes in support of human-system integration requirements and human rating. NASA-STD-3001, Space Flight Human-System Standard, is a two-volume set of National Aeronautics and Space Administration (NASA) Agency-level standards established by the Office of the Chief Health and Medical Officer, directed at minimizing health and performance risks for flight crews in human space flight programs. Volume 1 of NASA-STD-3001, Crew Health, sets standards for fitness for duty, space flight permissible exposure limits, permissible outcome limits, levels of medical care, medical diagnosis, intervention, treatment and care, and countermeasures. Volume 2 of NASASTD- 3001, Human Factors, Habitability, and Environmental Health, focuses on human physical and cognitive capabilities and limitations and defines standards for spacecraft (including orbiters, habitats, and suits), internal environments, facilities, payloads, and related equipment, hardware, and software with which the crew interfaces during space operations. The NASA Procedural Requirements (NPR) 8705.2B, Human-Rating Requirements for Space Systems, specifies the Agency's human-rating processes, procedures, and requirements. The HIDP was written to share NASA's knowledge of processes directed toward achieving human certification of a spacecraft through implementation of human-systems integration requirements. Although the HIDP speaks directly to implementation of NASA-STD-3001 and NPR 8705.2B requirements, the human-centered design, evaluation, and design processes described in this document can be applied to any set of human-systems requirements and are independent of reference

  7. The effects of human resource flexibility on human resources development

    Directory of Open Access Journals (Sweden)

    SeidMehdi Veise

    2014-08-01

    Full Text Available Human resources are the primary factor for development of competitiveness and innovation and reaching competitive advantage and they try to improve corporate capabilities through various characteristics such as value creation, scarcity and difficulty of imitation. This paper investigates the effect of human resource flexibility and its dimensions on human resource development and its dimensions. The survey was conducted using descriptive-correlation method that intended to describe how human resource flexibility was effective on human resource development. Questionnaire was tool of data collection. The statistical population included one hundred employees of the Electric Company in Ilam province, thus census method was used. Reliability of the questionnaire was measured via Cronbach's alpha equal to 0.96. The findings revealed that flexibility and its dimensions were effective on human resource development and dimensions of it. As a result, human resource flexibility should be considered for development of human resources and employees with the highest flexibility should be selected.

  8. Survey Relationship between Human Resources Roles and Human Resources Competencies

    Directory of Open Access Journals (Sweden)

    Hasan Darvish

    2012-09-01

    Full Text Available This study evaluates relationship between Human resources roles and Human resources competencies in Iranian Petroleum Company. For this study, we were looking for answers to these questions: What are the new required Human Resources competencies For Contemporary organizations? And For Gain these competencies what roles should be played by Human Resources? The study had one main hypothesis and four minor hypotheses. Research method was descriptive, and regression and correlation tests were used to determine the relationship between variables. The populations of this study were managers of Iranian Petroleum Company. This Research showed that Human resources roles have significant effect on Human resources competencies; Strategic partner, Employee champion, and Change agent had significant relationship with all of Human resource competencies; Administrative expert had not significant relationship with none of the Human resource competencies.

  9. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    morphine via high pressure liquid chromatography (HPLC). The HPLC peak corresponding to an authentic morphine standard had its morphine level determined via radioimmune assay. The identity of this material was established by Q-TOF-MS analysis. RESULTS: Each glioma exhibited an endogenous morphine presence....... Tumor extractions demonstrated a molecular mass of 286.14 da, identical to authentic morphine. Subsequent fragmentation analysis of this molecule revealed fragment masses of 129.01 da, 183.09 da and 201.07 da, corresponding to authentic morphine fragments. This material was not found in any......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  10. [PALEOPATHOLOGY OF HUMAN REMAINS].

    Science.gov (United States)

    Minozzi, Simona; Fornaciari, Gino

    2015-01-01

    Many diseases induce alterations in the human skeleton, leaving traces of their presence in ancient remains. Paleopathological examination of human remains not only allows the study of the history and evolution of the disease, but also the reconstruction of health conditions in the past populations. This paper describes the most interesting diseases observed in skeletal samples from the Roman Imperial Age necropoles found in urban and suburban areas of Rome during archaeological excavations in the last decades. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumours, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, the palaeopathological study allowed to highlight the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

  11. Human Actions Made Tangible

    DEFF Research Database (Denmark)

    Buur, Jacob; Caglio, Agnese; Jensen, Lars Christian

    2014-01-01

    projects, it remains a challenge to investigate in detail how people interact with all of their body. Analysis of full-body movement is time consuming, notation techniques are rare, and findings are difficult to share between members of a design team. In this paper we propose tangible video analysis......, a method developed to engage people from different backgrounds in collaboratively analysing videos with the help of physical objects. We will present one of these tools, Action Scrabble, for analysing temporal organisation of human actions. We work with a case of skilled forklift truck driving....... By backtracking our design research experiments, we will unfold how and why the tangible tool succeeds in engaging designers with varied analysis experience to collaboratively focus on human action structures – and even find video analysis fun!...

  12. Philanthropy and Human Rights

    DEFF Research Database (Denmark)

    Larsen, Øjvind

    2013-01-01

    written about philanthropy from a political, sociological, anthropological and managerial perspective. However, an essential question remains: what does philanthropy mean? In a Greek context, philanthropy is connected to a friendly act towards one’s owns close connections such as family or fellow citizens......, and normally utilized to promote one’s own prestige in the city-state. In Roman context, universal humanism, humanitas, was invented. This universal perspective was also supported by Christianity. It is this universal concept of philanthropy which is the foundation for the different philanthropic traditions...... in Germany, England, France and USA. In each tradition is developed special features of the concept of philanthropy. The four traditions are summarized in the UN universal human rights, which has become the common normative reference for global philanthropy. In this way philanthropy has become, in a modern...

  13. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2015-01-01

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of transnational business governance interactions (TBGI) analytical framework.1 The article identifies and discusses dimensions of interaction...... and components of regulatory governance which characterize the Guiding Principles, focusing in particular on rule formation and implementation. The article notes that the Guiding Principles actively enrolled other actors for the rule-making process, ensuring support in a politically and legally volatile field...... in several areas of relevance to transnational business governance interaction and indicates the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational business governance suggests that this form...

  14. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of Transnational Business Governance Interactions (TBGI) analytical framework (Eberlein et al. 2014). The article identifies and discusses...... dimensions of interaction and components of regulatory governance which characterise the Guiding Principles, focusing in particular on the rule formation and implementation. The article notes that the Guiding Principles actively enrolled other actors for the rule-making process ensuring support...... that the UN Guiding Principles are unique in several respects of relevance to transnational business governance interaction and indicate the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational...

  15. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...... and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus...

  16. Ancient human microbiomes.

    Science.gov (United States)

    Warinner, Christina; Speller, Camilla; Collins, Matthew J; Lewis, Cecil M

    2015-02-01

    Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and we therefore lack a foundation for characterizing this change. High-throughput sequencing has opened up new opportunities in the field of paleomicrobiology, allowing us to investigate the evolution of the complex microbial ecologies that inhabit our bodies. By focusing on recent coprolite and dental calculus research, we explore how emerging research on ancient human microbiomes is changing the way we think about ancient disease and how archaeological studies can contribute to a medical understanding of health and nutrition today.

  17. Is human fecundity changing?

    DEFF Research Database (Denmark)

    Smarr, Melissa M; Sapra, Katherine J; Gemmill, Alison

    2017-01-01

    Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is, therefore, fundamental for understanding human health at the population level. Given the absence of a population (bio)marker, fecundity is assessed indirectly by various individual-based (e.g. semen...... quality, ovulation) or couple-based (e.g. time-to-pregnancy) endpoints. Population monitoring of fecundity is challenging, and often defaults to relying on rates of births (fertility) or adverse outcomes such as genitourinary malformations and reproductive site cancers. In light of reported declines...... in semen quality and fertility rates in some global regions among other changes, the question as to whether human fecundity is changing needs investigation. We review existing data and novel methodological approaches aimed at answering this question from a transdisciplinary perspective. The existing...

  18. Serotonin in human skin

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Qiying Gong; Guiming Li

    2005-01-01

    In this review the authors summarize data of a potential role for serotonin in human skin physiology and pathology. The uncovering of endogenous serotonin synthesis and its transformation to melatonin underlines a putative important role of this pathway in melanocyte physiology and pathology. Pathways of the biosynthesis and biodegradation of serotonin have been characterized in human beings and its major cellular populations. Moreover, receptors of serotonin are expressed on keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. And the widespread expression of a cutaneous seorotoninergic system indicates considerable selectivity of action to facilitate intra-, auto-, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner. Melatonin, in turn, can also act as a hormone, neurotransmitter, cytokine, biological modifier and immunomodulator. Thus, Serotonin local synthesis and cellular localization could thus become of great importance in the diagnosis and management of cutaneous pathology.

  19. Posthumanism: beyond humanism?

    Science.gov (United States)

    Valera, Luca

    2014-01-01

    The focal point of posthumanism consists not as such in an a-critical acceptance of the technological promises - like there is for transhumanism - but in a total contamination and hybridization of human beings with other living beings and machines (these are the two main forms of contamination). The change of perspective untaken by posthumanism would be, thus, a paradigmatic shift in anthropology. As with ecologism, posthumanism, in order to obtain total contamination and man's openness to otherness, proposes the elimination and the fluidification of boundaries, thus even denying man's identity, and, with it, the very possibility of openness. However, by denying the identity, one denies the condition of possibility of thought, just as it has been manifested in history until now: hence we understand how, primarily, posthumanism is not configured as an adequate philosophical reflection, but as a narrative that takes origin from certain requirements, which are eminently human, and that discloses its deeply anthropogenic roots.

  20. Human-Forest Relationships

    DEFF Research Database (Denmark)

    Ritter, Eva; Dauksta, D.

    2012-01-01

    The relationship between human beings and forests has been important for the development of society. It is based on various productive, ecological, social and cultural functions of forests. The cultural functions, including the spiritual and symbolic role of forests, are often not addressed...... problems. To achieve a deeper understanding of the dependency of society on forests, it is necessary to recognise the role of forests in our consciousness of being human. Giving a historical overview about the cultural bonds between people and forests, the first part of the paper puts focus on non-productive...... with the same attention as the other functions. The aim of this paper is to put a stronger emphasis on the fact that the acknowledgement of cultural bonds is needed in the discussion of sustainable development. Forest should not only be considered as a technical means to solve environmental and economic...

  1. Animals, Humans and Sociability

    Directory of Open Access Journals (Sweden)

    Enrica Tedeschi

    2016-06-01

    Full Text Available This article discusses animal studies from the point of view of sociability as an “inter-subjective field of action” and as an agent and builder of society (“doing society”. In sociology, the zoological connection has availed of the theory of borders and critical realism, but, above all, of constructionism, in its interactionist and ethno-methodological sense and both focused on social micro-interaction. The construction of the identity of social actors (both human and animal is especially evident in interaction regarding play, games, sport, daily life and work. In these spheres, analyses shed light on ambivalent and contradictory human experiences that clash with the dominant culture, while highlighting practical resistance against speciesism, which it is well worth to bring to the attention of future research, using open, mixed methodologies.

  2. Fractionating human intelligence.

    Science.gov (United States)

    Hampshire, Adam; Highfield, Roger R; Parkin, Beth L; Owen, Adrian M

    2012-12-20

    What makes one person more intellectually able than another? Can the entire distribution of human intelligence be accounted for by just one general factor? Is intelligence supported by a single neural system? Here, we provide a perspective on human intelligence that takes into account how general abilities or "factors" reflect the functional organization of the brain. By comparing factor models of individual differences in performance with factor models of brain functional organization, we demonstrate that different components of intelligence have their analogs in distinct brain networks. Using simulations based on neuroimaging data, we show that the higher-order factor "g" is accounted for by cognitive tasks corecruiting multiple networks. Finally, we confirm the independence of these components of intelligence by dissociating them using questionnaire variables. We propose that intelligence is an emergent property of anatomically distinct cognitive systems, each of which has its own capacity.

  3. Hyaluronan in human malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: Veli-Matti.Kosma@uef.fi [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  4. Strategies of Human Mating

    Directory of Open Access Journals (Sweden)

    David M. Buss

    2006-12-01

    Full Text Available Modern humans have inherited the mating strategies that led to the success of their ancestors. These strategies include long-term mating, short-term mating, extra-pair mating, mate poaching, and mate guarding. This article presents empirical evidence supporting evolution-based hypotheses about the complexities of these mating strategies. Since men and women historically confronted different adaptive problems in the mating domain, the sexes differ profoundly in evolved strategic solutions. These differences include possessing different mate preferences, different desires for short-term mating, and differences in the triggers that evoke sexual jealousy. The study of human mating is one of the “success stories” of evolutionary psychology.

  5. Human herpesvirus 8 – A novel human pathogen

    Directory of Open Access Journals (Sweden)

    Edelman Daniel C

    2005-09-01

    Full Text Available Abstract In 1994, Chang and Moore reported on the latest of the gammaherpesviruses to infect humans, human herpesvirus 8 (HHV-8 1. This novel herpesvirus has and continues to present challenges to define its scope of involvement in human disease. In this review, aspects of HHV-8 infection are discussed, such as, the human immune response, viral pathogenesis and transmission, viral disease entities, and the virus's epidemiology with an emphasis on HHV-8 diagnostics.

  6. Den humane teknologi

    DEFF Research Database (Denmark)

    Fausing, Bent

    2008-01-01

    Artiklen undersøger hverdagsæstetikkens forestillinger om teknologi i tv-reklamer, nærmere bestemt to mobiltelefoner fra Nokia. Nokias slogan er som bekendt: "Nokia -connecting people". Hvilken funktion tilskrives denne succes-teknologi via billeder, narrativer, lyde, interaktioner og affekter? M...... så ofte nævnte post-humane tilstand, er konklusionen. Udgivelsesdato: 14.9.08...

  7. Den humane teknologi

    DEFF Research Database (Denmark)

    Fausing, Bent

    2008-01-01

    Artiklen undersøger hverdagsæstetikkens forestillinger om teknologi i tv-reklamer, nærmere bestemt to mobiltelefoner fra Nokia. Nokias slogan er som bekendt: "Nokia -connecting people". Hvilken funktion tilskrives denne succes-teknologi via billeder, narrativer, lyde, interaktioner og affekter? M...... så ofte nævnte post-humane tilstand, er konklusionen. Udgivelsesdato: 14.9.08...

  8. Retroviruses and human disease.

    OpenAIRE

    1987-01-01

    Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Qu...

  9. [The process of humanization].

    Science.gov (United States)

    Durali, T

    1999-01-01

    As Stefan Zweig expressed the situation of mankind succinctly: There are key moments in history (Sternstunden der Menschheit). Because of their paramount importance their events are minimal. Moreover, among them there are those which are greater in calibre than the ones quoted in Stefan Zweig's Sternstunden der Menschheit. These are the turning points of history. At first glance we can enumerate four major events: first and foremost, the enormous shift of certain communities from food-gathering to agriculture around 8000 BC mainly in Southwest Asia (Mesopotamia). Second, the introduction of the writing system at circa 3500 BC by the Sumerians again in Southwest Asia. Last but not least that tremendous innovation, maybe the greatest in history, once more in western Asia, the emergence of monotheistic religions based on revelation, and the origination of philosophy-science within the realm of the Antique Aegean civilization. Man's basic reality is biotic. He shares this very particularity with all other living beings of this world. Livingness, so far as we know, is a peculiarity of our planet, the Earth. The unfolding of livingness and ultimately the emergence of man as a living being is apparently covered by evolution. Hominization is the biotic, whereas humanization represents the cultural (or spiritual) aspect of becoming the human being. Hominization and humanization complement one another to bring about the human wholeness. Hominization, or put it in another way, the evolutionary aspect is, indeed, not the beginning of the story. There still remains a lower layer, in the ontological sense of the team, to be tackled; and that is the physical one. Just as with every living thing, man's most fundamental building blocks are of a physico-chemical-i.e. subatomic, atomic and molecular-nature.

  10. Ancient human microbiomes

    OpenAIRE

    Warinner, C.; Speller, C; Collins, M.; Lewis Jr., C.

    2015-01-01

    Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and theref...

  11. Recombinant Human Enterovirus 71

    OpenAIRE

    2004-01-01

    Two human enterovirus 71 (HEV71) isolates were identified from hand, foot and mouth disease patients with genome sequences that had high similarity to HEV71 (>93%) at 5´ UTR, P1, and P2 and coxsackievirus A16 (CV-A16, >85%) at P3 and 3´UTR. Intertypic recombination is likely to have occurred between HEV71 and CV-A16 or an as-yet to be described CV-A16-like virus.

  12. Strategic Human Resources Management

    OpenAIRE

    Marta Muqaj

    2016-01-01

    Strategic Human Resources Management (SHRM) represents an important and sensitive aspect of the functioning and development of a company, business, institution, state, public or private agency of a country. SHRM is based on a point of view of the psychological practices, especially by investing on empowerment, broad training and teamwork. This way it remains the primary resource to maintain stability and competitiveness. SHRM has lately evolved on fast and secure steps, and the transformation...

  13. Structure of Human Adenovirus

    OpenAIRE

    Nemerow, Glen R.; Phoebe L Stewart; Reddy, Vijay S.

    2012-01-01

    A detailed structural analysis of the entire human adenovirus capsid has been stymied by the complexity and size of this 150 MDa macromolecular complex. Over the past 10 years, the steady improvements in viral genome manipulation concomitant with advances in crystallographic techniques and data processing software has allowed structure determination of this virus by X-ray diffraction at 3.5 Å resolution. The virus structure revealed the location, folds, and interactions of major and minor (ce...

  14. Understanding Human Carboxylesterase 2

    OpenAIRE

    Lamego, Joana

    2012-01-01

    Dissertation presented to obtain the Ph.D degree in Engineering and Technology Sciences, Biotechnology The first barrier oral drugs and prodrugs encounter prior to reaching an organism’s systemic circulation is the gastrointestinal (GI) tract, specifically the intestine, which is the primary section for absorption. Therefore, it is fundamental to understand the permeability of the therapeutic agent as well as its potential metabolism by human enterocytes, since biotransformatio...

  15. Literature as a Humanity

    Science.gov (United States)

    Levi, Albert William

    1976-01-01

    Attempts a brief summary of the American critical scene for the period 1935-1965 in order to indicate the serial prominence of 1) a sociological, 2) a New-Critical, and 3) a Marxist moment in literary criticism. Sets out to assert that for any literary work to be taught as a humanity is to bring to bear upon it the arts of communication,…

  16. Human Islet Amyloid Polypeptide

    DEFF Research Database (Denmark)

    Kosicka, Iga

    2014-01-01

    Diabetes mellitus type II is a metabolic disease affecting millions of people worldwide. The disease is associated with occurence of insoluble, fibrillar, protein aggregates in islets of Langerhans in the pancreas - islet amyloid. The main constituent of these protein fibers is the human islet...... of diabetes type II, while revealing the structure(s) of islet amyloid fibrils is necessary for potential design of therapeutic agents....

  17. Is dissection humane?

    OpenAIRE

    Hasan, Tabinda

    2011-01-01

    Dissection is being jeopardized in the modern medical education. It has unrelentingly faced the lashes of time and has been the scapegoat for numerous convenient curricula reforms and subjective biases. The cadaver is unparallel in establishing core knowledge among the medical community and it needs to be appreciated in a new light in the “cyber anatomy” realm of today. This article elucidates the medical and ethical validity of continuing human body dissection in medicine which outweighs all...

  18. Multichannel Human Body Communication

    Science.gov (United States)

    Przystup, Piotr; Bujnowski, Adam; Wtorek, Jerzy

    2016-01-01

    Human Body Communication is an attractive alternative for traditional wireless communication (Bluetooth, ZigBee) in case of Body Sensor Networks. Low power, high data rates and data security makes it ideal solution for medical applications. In this paper, signal attenuation for different frequencies, using FR4 electrodes, has been investigated. Performance of single and multichannel transmission with frequency modulation of analog signal has been tested. Experiment results show that HBC is a feasible solution for transmitting data between BSN nodes.

  19. Science and Human Experience

    Science.gov (United States)

    Cooper, Leon N.

    2015-01-01

    Part I. Science and Society: 1. Science and human experience; 2. Does science undermine our values?; 3. Can science serve mankind?; 4. Modern science and contemporary discomfort: metaphor and reality; 5. Faith and science; 6. Art and science; 7. Fraud in science; 8. Why study science? The keys to the cathedral; 9. Is evolution a theory? A modest proposal; 10. The silence of the second; 11. Introduction to Copenhagen; 12. The unpaid debt; Part II. Thought and Consciousness: 13. Source and limits of human intellect; 14. Neural networks; 15. Thought and mental experience: the Turing test; 16. Mind as machine: will we rubbish human experience?; 17. Memory and memories: a physicist's approach to the brain; 18. On the problem of consciousness; Part III. On the Nature and Limits of Science: 19. What is a good theory?; 20. Shall we deconstruct science?; 21. Visible and invisible in physical theory; 22. Experience and order; 23. The language of physics; 24. The structure of space; 25. Superconductivity and other insoluble problems; 26. From gravity to light and consciousness: does science have limits?

  20. Oxytocin promotes human ethnocentrism.

    Science.gov (United States)

    De Dreu, Carsten K W; Greer, Lindred L; Van Kleef, Gerben A; Shalvi, Shaul; Handgraaf, Michel J J

    2011-01-25

    Human ethnocentrism--the tendency to view one's group as centrally important and superior to other groups--creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence.

  1. Human Viruses and Cancer

    Directory of Open Access Journals (Sweden)

    Abigail Morales-Sánchez

    2014-10-01

    Full Text Available The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  2. Psychophysics of human echolocation.

    Science.gov (United States)

    Schörnich, Sven; Wallmeier, Ludwig; Gessele, Nikodemus; Nagy, Andreas; Schranner, Michael; Kish, Daniel; Wiegrebe, Lutz

    2013-01-01

    The skills of some blind humans orienting in their environment through the auditory analysis of reflections from self-generated sounds have received only little scientific attention to date. Here we present data from a series of formal psychophysical experiments with sighted subjects trained to evaluate features of a virtual echo-acoustic space, allowing for rigid and fine-grain control of the stimulus parameters. The data show how subjects shape both their vocalisations and auditory analysis of the echoes to serve specific echo-acoustic tasks. First, we show that humans can echo-acoustically discriminate target distances with a resolution of less than 1 m for reference distances above 3.4 m. For a reference distance of 1.7 m, corresponding to an echo delay of only 10 ms, distance JNDs were typically around 0.5 m. Second, we explore the interplay between the precedence effect and echolocation. We show that the strong perceptual asymmetry between lead and lag is weakened during echolocation. Finally, we show that through the auditory analysis of self-generated sounds, subjects discriminate room-size changes as small as 10%.In summary, the current data confirm the practical efficacy of human echolocation, and they provide a rigid psychophysical basis for addressing its neural foundations.

  3. Mapping the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Cantor, Charles R.

    1989-06-01

    The following pages aim to lay a foundation for understanding the excitement surrounding the ''human genome project,'' as well as to convey a flavor of the ongoing efforts and plans at the Human Genome Center at the Lawrence Berkeley Laboratory. Our own work, of course, is only part of a broad international effort that will dramatically enhance our understanding of human molecular genetics before the end of this century. In this country, the bulk of the effort will be carried out under the auspices of the Department of Energy and the National Institutes of Health, but significant contributions have already been made both by nonprofit private foundations and by private corporation. The respective roles of the DOE and the NIH are being coordinated by an inter-agency committee, the aims of which are to emphasize the strengths of each agency, to facilitate cooperation, and to avoid unnecessary duplication of effort. The NIH, for example, will continue its crucial work in medical genetics and in mapping the genomes of nonhuman species. The DOE, on the other hand, has unique experience in managing large projects, and its national laboratories are repositories of expertise in physics, engineering, and computer science, as well as the life sciences. The tools and techniques the project will ultimately rely on are thus likely to be developed in multidisciplinary efforts at laboratories like LBL. Accordingly, we at LBL take great pride in this enterprise -- an enterprise that will eventually transform our understanding of ourselves.

  4. Cocoa and human health.

    Science.gov (United States)

    Ellam, Samantha; Williamson, Gary

    2013-01-01

    Cocoa is a dry, powdered, nonfat component product prepared from the seeds of the Theobroma cacao L. tree and is a common ingredient of many food products, particularly chocolate. Nutritionally, cocoa contains biologically active substances that may affect human health: flavonoids (epicatechin and oligomeric procyanidins), theobromine, and magnesium. Theobromine and epicatechin are absorbed efficiently in the small intestine, and the nature of their conjugates and metabolites are now known. Oligomeric procyanidins are poorly absorbed in the small intestine, but catabolites are very efficiently absorbed after microbial biotransformation in the colon. A significant number of studies, using in vitro and in vivo approaches, on the effects of cocoa and its constituent flavonoids have been conducted. Most human intervention studies have been performed on cocoa as an ingredient, whereas many in vitro studies have been performed on individual components. Approximately 70 human intervention studies have been carried out on cocoa and cocoa-containing products over the past 12 years, with a variety of endpoints. These studies indicate that the most robust biomarkers affected are endothelial function, blood pressure, and cholesterol level. Mechanistically, supporting evidence shows that epicatechin affects nitric oxide synthesis and breakdown (via inhibition of nicotinamide adenine di-nucleotide phosphate oxidase) and the substrate arginine (via inhibition of arginase), among other targets. Evidence further supports cocoa as a biologically active ingredient with potential benefits on biomarkers related to cardiovascular disease. However, the calorie and sugar content of chocolate and its contribution to the total diet should be taken into account in intervention studies.

  5. Human African trypanosomiasis.

    Science.gov (United States)

    Lejon, Veerle; Bentivoglio, Marina; Franco, José Ramon

    2013-01-01

    Human African trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-Saharan Africa. The disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite Trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. The disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal of the blood-brain barrier. African trypanosomiasis, which leads to severe neuroinflammation, is fatal without treatment, but the available drugs are toxic and complicated to administer. The choice of medication is determined by the infecting parasite subspecies and disease stage. Clinical features include a constellation of nonspecific symptoms and signs with evolving neurological and psychiatric alterations and characteristic sleep-wake disturbances. Because of the clinical profile variability and insidiously progressive central nervous system involvement, disease staging is currently based on cerebrospinal fluid examination, which is usually performed after the finding of trypanosomes in blood or other body fluids. No vaccine being available, control of human African trypanosomiasis relies on diagnosis and treatment of infected patients, assisted by vector control. Better diagnostic tools and safer, easy to use drugs are needed to facilitate elimination of the disease.

  6. Human evolution and cognition.

    Science.gov (United States)

    Tattersall, Ian

    2010-09-01

    Human beings are distinguished from all other organisms by their symbolic way of processing information about the world. This unique cognitive style is qualitatively different from all the earlier hominid cognitive styles, and is not simply an improved version of them. The hominid fossil and archaeological records show clearly that biological and technological innovations have typically been highly sporadic, and totally out of phase, since the invention of stone tools some 2.5 million years ago. They also confirm that this pattern applied in the arrival of modern cognition: the anatomically recognizable species Homo sapiens was well established long before any population of it began to show indications of behaving symbolically. This places the origin of symbolic thought in the realms of exaptation, whereby new structures come into existence before being recruited to new uses, and of emergence, whereby entire new levels of complexity are achieved through new combinations of attributes unremarkable in themselves. Both these phenomena involve entirely routine evolutionary processes; special as we human beings may consider ourselves, there was nothing special about the way we came into existence. Modern human cognition is a very recent acquisition; and its emergence ushered in an entirely new pattern of technological (and other behavioral) innovation, in which constant change results from the ceaseless exploration of the potential inherent in our new capacity.

  7. Securing Humanity - Situating 'Human Security' as Concept and Discourse

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2005-01-01

    markdownabstractAbstract The label ‘human security’ (HS) has attracted much attention since the 1994 Human Development Report, but there are numerous conflicting definitions and agendas and widespread scepticism. The Ogata-Sen Commission report Human Security Now has proposed a unified yet

  8. Securing Humanity - Situating 'Human Security' as Concept and Discourse

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2005-01-01

    markdownabstractAbstract The label ‘human security’ (HS) has attracted much attention since the 1994 Human Development Report, but there are numerous conflicting definitions and agendas and widespread scepticism. The Ogata-Sen Commission report Human Security Now has proposed a unified yet flexibl

  9. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, Byron E.; Barzon, Luisa; Pijlman, Gorben P.; Fuente, de la José; Rizzoli, Annapaola; Wammes, Linda J.; Takken, Willem; Rij, van Ronald P.; Papa, Anna

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex i

  10. Human dignity according to international instruments on human rights

    Directory of Open Access Journals (Sweden)

    José Pablo Alzina de Aguilar

    2011-01-01

    Full Text Available According to international instruments on human rights, the dignity of the human person is the foundation of human rights, and both human dignity and human rights are inherent to the human being, universal and inviolable. This understanding of human dignity is not a fruitless truism, but the solid foundation on which to build a world community under the rule of the new ius gentium: the International Law for Humankind. Moreover, it is the clue to answer many questions raised by the new world of globalization and of the exponential growth of international rules.Consequently, there is a need to a common doctrine on a notion of human dignity which will allow the implementation and adjudication of the aforementioned instruments, at the service of the human person and in conformity with the juridical conscience which they reflect. Philosophy of Law concepts which can be traced back to Aristotle provide that notion. According to these concepts, the demanding nature of “human dignity” sustains the notion of “legal personhood”, and both notions pertain to the realm of Law and Right, not of Morale and Values. Thus, human dignity and human rights are and must be, respectively, a basic principle and a necessary part of any Law system, including international law

  11. Human-centered Computing: Toward a Human Revolution

    OpenAIRE

    Jaimes, Alejandro; Gatica-Perez, Daniel; Sebe, Nicu; Thomas S. Huang

    2007-01-01

    Human-centered computing studies the design, development, and deployment of mixed-initiative human-computer systems. HCC is emerging from the convergence of multiple disciplines that are concerned both with understanding human beings and with the design of computational artifacts.

  12. Human Provenancing: It's Elemental…

    Science.gov (United States)

    Meier-Augenstein, Wolfram; Kemp

    2009-04-01

    Forensic science already uses a variety of methods often in combination to determine a deceased person's identity if neither personal effects nor next of kin (or close friends) can positively identify the victim. While disciplines such as forensic anthropology are able to work from a blank canvass as it were and can provide information on age, gender and ethnical grouping, techniques such as DNA profiling do rely on finding a match either in a database or a comparative sample presumed to be an ante-mortem sample of the victim or from a putative relation. Chances for either to succeed would be greatly enhanced if information gained from a forensic anthropological examination and, circumstances permitting a facial reconstruction could be linked to another technique that can work from a blank canvass or at least does not require comparison to a subject specific database. With the help of isotope ratio mass spectrometry even the very atoms from which a body is made can be used to say something about a person that will help to focus human identification using traditional techniques such as DNA, fingerprints and odontology. Stable isotope fingerprinting works on the basis that almost all chemical elements and in particular the so-called light elements such as carbon (C) that comprise most of the human body occur naturally in different forms, namely isotopes. 2H isotope abundance values recorded by the human body through food and drink ultimately reflect averaged isotopic composition of precipitation or ground water. Stable isotope analysis of 2H isotopic composition in different human tissue such as hair, nails, bone and teeth enables us to construct a time resolved isotopic profile or ‘fingerprint' that may not necessarily permit direct identification of a murder victim or mass disaster victim but in conjunction with forensic anthropological information will provide sufficient intelligence to construct a profile for intelligence lead identification stating where a

  13. Administrative Aspects of Human Experimentation.

    Science.gov (United States)

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  14. Consolidated Human Activities Database (CHAD)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Consolidated Human Activity Database (CHAD) contains data obtained from human activity studies that were collected at city, state, and national levels. CHAD is...

  15. Cell encoding recombinant human erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Beck, A.K.; Withy, R.M.; Zabrecky, J.R.; Masiello, N.C.

    1990-09-04

    This patent describes a C127 cell transformed with a recombinant DNA vector. It comprises: a DNA sequence encoding human erythropoietin, the transformed cell being capable of producing N-linked and O-linked glycosylated human erythropoietin.

  16. Human pheromones and sexual attraction.

    Science.gov (United States)

    Grammer, Karl; Fink, Bernhard; Neave, Nick

    2005-02-01

    Olfactory communication is very common amongst animals, and since the discovery of an accessory olfactory system in humans, possible human olfactory communication has gained considerable scientific interest. The importance of the human sense of smell has by far been underestimated in the past. Humans and other primates have been regarded as primarily 'optical animals' with highly developed powers of vision but a relatively undeveloped sense of smell. In recent years this assumption has undergone major revision. Several studies indicate that humans indeed seem to use olfactory communication and are even able to produce and perceive certain pheromones; recent studies have found that pheromones may play an important role in the behavioural and reproduction biology of humans. In this article we review the present evidence of the effect of human pheromones and discuss the role of olfactory cues in human sexual behaviour.

  17. National Human Genome Research Institute

    Science.gov (United States)

    ... the Director Organization Reports & Publications Español The National Human Genome Research Institute conducts genetic and genomic research, funds ... Landscape Social Media Videos Image Gallery Fact Sheets Human Genome Project Clinical Studies Genomic Careers DNA Day Calendar ...

  18. Humanities Education in Chinese Universities.

    Science.gov (United States)

    Rosen, Stanley; Chengxu, Wang, Eds.

    1986-01-01

    In China, humanities studies include languages, history, philosophy, economics, law, political science, business, and education. Changes and trends in humanities education at the post-secondary level are discussed. (RM)

  19. Human Exposure Database System (HEDS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Human Exposure Database System (HEDS) provides public access to data sets, documents, and metadata from EPA on human exposure. It is primarily intended for...

  20. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

    Directory of Open Access Journals (Sweden)

    Carlos Wong-Baeza

    2015-01-01

    Full Text Available Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice.

  1. Human Milk-Treatment and Quality of Banked Human Milk.

    Science.gov (United States)

    Picaud, Jean-Charles; Buffin, Rachel

    2017-03-01

    The aim of human milk banks is to deliver safe and high quality donor human milk. Treatment of human milk has to destroy most microorganisms while preserving immunological and nutrient components, which is obtained when using low time low temperature pasteurization. However it destroys bile-simulated lipase, reduces lactoferrin, lysozyme, immunoglobulins, and bactericidal capacity of human milk. New methods are under investigation such as high temperature short time pasteurization, high pressure processing, or ultraviolet irradiation. They have been tested in experimental conditions and there are promising results, but they have to be tested in real conditions in human milk bank.

  2. Human Rights and Public Education

    Science.gov (United States)

    Bowring, Bill

    2012-01-01

    This article attempts a contrast to the contribution by Hugh Starkey. Rather than his account of the inexorable rise of human rights discourse, and of the implementation of human rights standards, human rights are here presented as always and necessarily scandalous and highly contested. First, I explain why the UK has lagged so far behind its…

  3. Leadership in a Humane Organization

    Science.gov (United States)

    Dimitrov, Danielle

    2015-01-01

    Purpose: The purpose of this paper is to explore the way leadership influences an organization to become humane through its features and behaviors; as well as the organizational circumstances in which humane leadership can be nurtured. The first empirical case study, in the fields of Human Resource Development (HRD) and hospitality management, to…

  4. Measuring human behaviour with radar

    NARCIS (Netherlands)

    Dorp, Ph. van

    2001-01-01

    The paper presents human motion measurements with the experimental Frequency Modulated Continuous Wave(FMCW) radar at TNO-FEL. The aim of these measurements is to analyse the Doppler velocity spectrum of humans. These analysis give insight in measuring human behaviour with radar for security applica

  5. Human walking estimation with radar

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.

    2003-01-01

    Radar can be used to observe humans that are obscured by objects such as walls. These humans cannot be visually observed. The radar measurements are used to animate an obscured human in virtual reality. This requires detailed information about the motion. The radar measurements give detailed informa

  6. Human Rights and the Statistician.

    Science.gov (United States)

    Spirer, Herbert F.

    Statisticians can help to improve human rights reporting. The statistician's approach to measurement, summary, and interpretation is needed to understand and help reduce human rights violations. Statistical problems in the measurement and analysis of human rights violations include: lack of agreement on the definition; great difficulties in…

  7. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  8. Human Rights and Public Education

    Science.gov (United States)

    Bowring, Bill

    2012-01-01

    This article attempts a contrast to the contribution by Hugh Starkey. Rather than his account of the inexorable rise of human rights discourse, and of the implementation of human rights standards, human rights are here presented as always and necessarily scandalous and highly contested. First, I explain why the UK has lagged so far behind its…

  9. Leadership in a Humane Organization

    Science.gov (United States)

    Dimitrov, Danielle

    2015-01-01

    Purpose: The purpose of this paper is to explore the way leadership influences an organization to become humane through its features and behaviors; as well as the organizational circumstances in which humane leadership can be nurtured. The first empirical case study, in the fields of Human Resource Development (HRD) and hospitality management, to…

  10. NASA Space Human Factors Program

    Science.gov (United States)

    1992-01-01

    This booklet briefly and succinctly treats 23 topics of particular interest to the NASA Space Human Factors Program. Most articles are by different authors who are mainly NASA Johnson or NASA Ames personnel. Representative topics covered include mental workload and performance in space, light effects on Circadian rhythms, human sleep, human reasoning, microgravity effects and automation and crew performance.

  11. Humanism and science: a reaction.

    Science.gov (United States)

    Wampold, Bruce E

    2012-12-01

    Authors in this section have noted that humanism is intrinsic to psychotherapy, although disagreements remain. One of the disagreements is about the role of science in humanism. In this reaction, I contend that humanism, as discussed in these articles, is a legitimate theory to be subjected to scientific scrutiny. (c) 2012 APA, all rights reserved.

  12. Community College Humanities Review, 1999.

    Science.gov (United States)

    Scheper, George L., Ed.

    1999-01-01

    This special issue of the Community College Humanities Review contains articles generated by National Endowment for the Humanities Summer Institutes, held over several years. The institutes provided opportunities for academics from a variety of humanities disciplines and types of institutions to interact over an extended period of common study of…

  13. Human walking estimation with radar

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.

    2003-01-01

    Radar can be used to observe humans that are obscured by objects such as walls. These humans cannot be visually observed. The radar measurements are used to animate an obscured human in virtual reality. This requires detailed information about the motion. The radar measurements give detailed

  14. Lysophosphatidic Acid Regulation and Roles in Human Prostate Cancer

    Science.gov (United States)

    2006-08-01

    Received 23 June 2005 C©2005 Biochemical Society Glycoconjugate Journal 20, 39–47, 2004 C© 2004 Kluwer Academic Publishers. Manufactured in The Netherlands...neuroblastoma, lymphoma, and ovarian cancer cells [105,106]. Thus, antibod- ies against specific gangliosides have received consideration as...is nearly as effective a chemoattractant for DC as are C5a and CCL19 [34]. Like T cells, DC express CCR7 and migrate in response to its ligands CCL19

  15. Human myoblast genome therapy

    Institute of Scientific and Technical Information of China (English)

    Peter K Law; Leo A Bockeria; Choong-Chin Liew; Danlin M Law; Ping Lu; Eugene KW Sim; Khawja H Haider; Lei Ye; Xun Li; Margarita N Vakhromeeva; Ilia I Berishvili

    2006-01-01

    Human Myoblast Genome Therapy (HMGT) is a platform technology of cell transplantation, nuclear transfer, and tissue engineering. Unlike stem cells, myoblasts are differentiated, immature cells destined to become muscles. Myoblasts cultured from satellite cells of adult muscle biopsies survive, develop, and function to revitalize degenerative muscles upon transplantation. Injection injury activates regeneration of host myofibers that fuse with the engrafted myoblasts, sharing their nuclei in a common gene pool of the syncytium. Thus, through nuclear transfer and complementation, the normal human genome can be transferred into muscles of patients with genetic disorders to achieve phenotype repair or disease prevention. Myoblasts are safe and efficient gene transfer vehicles endogenous to muscles that constitute 50% of body weight. Results of over 280 HMGT procedures on Duchenne Muscular Dystrophy (DMD) subjects in the past 15 years demonstrated absolute safety. Myoblast-injected DMD muscles showed improved histology.Strength increase at 18 months post-operatively averaged 123%. In another application of HMGT on ischemic cardiomyopathy, the first human myoblast transfer into porcine myocardium revealed that it was safe and effective. Clinical trials on approximately 220 severe cardiomyopathy patients in 15 countries showed a <10% mortality. Most subjects received autologous cells implanted on the epicardial surface during coronory artery bypass graft, or injected on the endomyocardial surface percutaneously through guiding catheters. Significant increases in left ventricular ejection fraction, wall thickness, and wall motion have been reported, with reduction in perfusion defective areas, angina, and shortness of breath. As a new modality of treatment for disease in the skeletal muscle or myocardium, HMGT emerged as safe and effective. Large randomized multi-center trials are under way to confirm these preliminary results. The future of HMGT is bright and exciting

  16. [Humanism and medicine].

    Science.gov (United States)

    Kahn, Axel

    2002-03-30

    WITH THE PROGRESS MADE IN KNOWLEDGE AND TECHNIQUES: Therapeutic efficacy has advanced. However, interrogations concerning the control of the power that is conferred and the new obligations towards patients that stem from this progress have emerged and, further to the sinister ethical deviations in medical research and testing, and the supreme temptation that is represented by the money involved, questioning has increased. THE NUREMBERG CODE: Promulgated in December 1947, is the founder text of modern biomedical ethics. Subsequently completed by numerous other international conventions, it established the principle of voluntary, informed consent, therefore confirming the autonomy of the patient and the respect that is due from the physicians. However, questions arise not only regarding the foetus and embryo, but also regarding those reaching the end of their lives. CONCERNING EMBRYOS: No contradiction is apparent between the singularity of the human embryo and the use of embryos destined to be destroyed in highly scientific and moral quality research projects. With regard to the development of methods for producing cloned human embryos, it appears to be associated with greater risks than establishing urgent and necessary steps towards fulfilling the promises of regenerating medicine. Last but not least, deviations in reproductive biology and clinical trials conducted in this field, with relentless procreation and "human studies", must be denounced. AT THE OTHER END OF LIFE: It is worrying to note the apparent facility with which our societies consider that old age is an indignity. To call knowledge a 'power' is to consider that such power can be used not only to relieve suffering but also to manipulate others. The humanistic finality of an intention is not sufficient to guarantee neither its benignity nor its morality.

  17. Ringing public human talent

    Directory of Open Access Journals (Sweden)

    Guillermo Augusto José Díaz Samper

    2013-12-01

    Full Text Available In this article we will see how the human talent, by misionalidad, has established his duty to be on the need to attract the best service delivery and quality of life of personnel testing it has resorted to various strategies of management. But the media can go against this fundamental purpose, and represent an adverse and contrary to the institution actually starting, the disseminating a discourse of violence characterized by the friend / enemy, and irrationality passionality braking going against their own initiatives opposition.

  18. Errors in Human Performance

    Science.gov (United States)

    1980-08-15

    activities. Internatin , f - Studie, 1979, _ 5-24. Collins, A. h., & Loftus, E. F. A spreading activation theory of seman- tic processing. k fl _j-ej w...rea-daAm i_=E1jJh. Providence, R.I.: Brown University Press, 1967. LaBerge, D., & Samuels, S. J. Toward a theory of automatic information processing...Report, November, 1979. Norman, D. A. Er n human pefg ce (Tech. Rep. 8004). University of California, San Diego, July 1980. Norman, D. A. Post Freudian

  19. HUMAN MACHINE COOPERATIVE TELEROBOTICS

    Energy Technology Data Exchange (ETDEWEB)

    William R. Hamel; Spivey Douglass; Sewoong Kim; Pamela Murray; Yang Shou; Sriram Sridharan; Ge Zhang; Scott Thayer; Rajiv V. Dubey

    2003-06-30

    The remediation and deactivation and decommissioning (D&D) of nuclear waste storage tanks using telerobotics is one of the most challenging tasks faced in environmental cleanup. Since a number of tanks have reached the end of their design life and some of them have leaks, the unstructured, uncertain and radioactive environment makes the work inefficient and expensive. However, the execution time of teleoperation consumes ten to hundred times that of direct contact with an associated loss in quality. Thus, a considerable effort has been expended to improve the quality and efficiency of telerobotics by incorporating into teleoperation and robotic control functions such as planning, trajectory generation, vision, and 3-D modeling. One example is the Robot Task Space Analyzer (RTSA), which has been developed at the Robotics and Electromechanical Systems Laboratory (REMSL) at the University of Tennessee in support of the D&D robotic work at the Oak Ridge National Laboratory and the National Energy Technology Laboratory. This system builds 3-D models of the area of interest in task space through automatic image processing and/or human interactive manual modeling. The RTSA generates a task plan file, which describes the execution of a task including manipulator and tooling motions. The high level controller of the manipulator interprets the task plan file and executes the task automatically. Thus, if the environment is not highly unstructured, a tooling task, which interacts with environment, will be executed in the autonomous mode. Therefore, the RTSA not only increases the system efficiency, but also improves the system reliability because the operator will act as backstop for safe operation after the 3-D models and task plan files are generated. However, unstructured conditions of environment and tasks necessitate that the telerobot operates in the teleoperation mode for successful execution of task. The inefficiency in the teleoperation mode led to the research

  20. Photosensitive human syndromes.

    Science.gov (United States)

    Spivak, Graciela; Hanawalt, Philip C

    2015-06-01

    Photosensitivity in humans can result from defects in repair of light-induced DNA lesions, from photoactivation of chemicals (including certain medications) with sunlight to produce toxic mediators, and by immune reactions to sunlight exposures. Deficiencies in DNA repair and the processing of damaged DNA during replication and transcription may result in mutations and genomic instability. We will review current understanding of photosensitivity to short wavelength ultraviolet light (UV) due to genetic defects in particular DNA repair pathways; deficiencies in some are characterized by an extremely high incidence of cancer in sun-exposed tissues, while in others no cancers have been reported.

  1. Book Review: Human Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.

    2013-11-01

    This well written report reviews the evidence for variation in human sensitivity to ionizing radiation from epidemiological, clinical, animal, and experimental studies. The report also considers the mechanism(s) of radiation sensitivity and the ethical implications of current and potential knowledge that might be gained in the future. The report is concisely written, considers a large number of historical as well as recent studies, and features a ‘ bullet like ’ summary at the end of each chapter that captures the salient points.

  2. [Human brown adipose tissue].

    Science.gov (United States)

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  3. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  4. Human workload in aviation

    Science.gov (United States)

    Kantowitz, Barry H.; Casper, Patricia A.

    1988-01-01

    The application of human-factors analysis techniques to the evaluation of aircraft-crew workloads is discussed in an introductory overview. Consideration is given to the importance of workload for safety, crew size, automation, and certification; the definition and measurement of workload, physical vs mental workloads, subjective ratings, secondary tasks, biocybernetic measures, and attention and workload. Recent studies of pilot and ATC workloads are reviewed, and typical data are presented in graphs. Future trends are discussed, and it is predicted that increased cockpit automation will eventually require new methods to maintain operator attention rather than reduce workload.

  5. HUMAN CONNECTOME PROJECT (HCP)

    OpenAIRE

    Shashank Shekhar Tiwari*, Shivani Joshi, Tanvi Mittal, Shruti Jain

    2016-01-01

    This project deals with the nervous system and its function in brain. Here connectome means the microscopic neural connectivity and its mapping between all the neurons present in the brain which further represents their graphical representation on the visual screen also which will further help us to zoom into a region to explore the cells and the functions depending on it and taking this one step ahead the memory implementation in human brain so it will be used as a memory unit except the fac...

  6. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  7. Mentoring Human Performance - 12480

    Energy Technology Data Exchange (ETDEWEB)

    Geis, John A.; Haugen, Christian N. [CALIBRE Systems, Inc., Alexandria, Virginia (United States)

    2012-07-01

    Although the positive effects of implementing a human performance approach to operations can be hard to quantify, many organizations and industry areas are finding tangible benefits to such a program. Recently, a unique mentoring program was established and implemented focusing on improving the performance of managers, supervisors, and work crews, using the principles of Human Performance Improvement (HPI). The goal of this mentoring was to affect behaviors and habits that reliably implement the principles of HPI to ensure continuous improvement in implementation of an Integrated Safety Management System (ISMS) within a Conduct of Operations framework. Mentors engaged with personnel in a one-on-one, or one-on-many dialogue, which focused on what behaviors were observed, what factors underlie the behaviors, and what changes in behavior could prevent errors or events, and improve performance. A senior management sponsor was essential to gain broad management support. A clear charter and management plan describing the goals, objectives, methodology, and expected outcomes was established. Mentors were carefully selected with senior management endorsement. Mentors were assigned to projects and work teams based on the following three criteria: 1) knowledge of the work scope; 2) experience in similar project areas; and 3) perceived level of trust they would have with project management, supervision, and work teams. This program was restructured significantly when the American Reinvestment and Recovery Act (ARRA) and the associated funding came to an end. The program was restructured based on an understanding of the observations, attributed successes and identified shortfalls, and the consolidation of those lessons. Mentoring the application of proven methods for improving human performance was shown effective at increasing success in day-to-day activities and increasing confidence and level of skill of supervisors. While mentoring program effectiveness is difficult to

  8. Nanotechnology and human health

    CERN Document Server

    Malsch, Ineke

    2013-01-01

    Addressing medium- and long-term expectations for human health, this book reviews current scientific and technical developments in nanotechnology for biomedical, agrofood, and environmental applications. This collection of perspectives on the ethical, legal, and societal implications of bionanotechnology provides unique insight into contemporary technological developments. Readers with a technical background will benefit from the overview of the state-of-the-art research in their field, while readers with a social science background will benefit from the discussion of realistic prospects of na

  9. RNA in human sperm

    Institute of Scientific and Technical Information of China (English)

    Rui Pires Martins; Stephen A. Krawetz

    2005-01-01

    We have yet to develop a fundamental understanding of the molecular complexities of human spermatozoa. This encompasses the unique packaging and structure of the sperm genome along with their paternally derived RNAs in preparation for their delivery to the egg. The diversity of these transcripts is vast, including several anti-sense molecules resembling known regulatory micro-RNAs. The field is still grasping with its delivery to the oocyte at fertilization and possible significance. It remains tempting to analogize them to maternally-derived transcripts active in early embryo patterning. Irrespective of their role in the embryo, their use as a means to assess male factor infertility is promising.

  10. Artificial intelligence: Human effects

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, M.; Narayanan, A.

    1984-01-01

    This book presents an up-to-date study of the interaction between the fast-growing discipline of artificial intelligence and other human endeavors. The volume explores the scope and limitations of computing, and presents a history of the debate on the possibility of machines achieving intelligence. The authors offer a state-of-the-art survey of Al, concentrating on the ''mind'' (language understanding) and the ''body'' (robotics) of intelligent computing systems.

  11. Human herpes simplex labialis.

    Science.gov (United States)

    Fatahzadeh, M; Schwartz, R A

    2007-11-01

    Humans are the natural host for eight of more than 80 known herpes viruses. Infections with herpes simplex virus type 1 (HSV-1) are ubiquitous worldwide and highly transmissible. Herpes simplex labialis (HSL) is the best-recognized recrudescent infection of the lips and perioral tissues caused by HSV-1. Facial lesions of HSL may be unsightly, frequent outbreaks unpleasant, and the infection itself more severe locally and systemically in immunocompromised people. This article highlights the pathogenesis, clinical presentation, diagnostic features and management issues for HSL.

  12. Human Love, Boundless Love

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ On August 15,a special charity performance was carried on in Malaysia by IPC Shopping Services(M)Sdn Bhd,an Ecommerce company based on Malaysia.It was special for"May 12 Earthquake"in China's Sichuan Province.and special for those suffering children in the disaster.Months have past,but moving and touching stories happened during the earthquake encourage the people alive to create a better life and never give up hopes.What the post-earthquake construction left to us is the human love and boundless love,which is also the theme of the"8.15 Yu Miao Charity Performance".

  13. Visual Analysis of Humans

    CERN Document Server

    Moeslund, Thomas B

    2011-01-01

    This unique text/reference provides a coherent and comprehensive overview of all aspects of video analysis of humans. Broad in coverage and accessible in style, the text presents original perspectives collected from preeminent researchers gathered from across the world. In addition to presenting state-of-the-art research, the book reviews the historical origins of the different existing methods, and predicts future trends and challenges. This title: features a Foreword by Professor Larry Davis; contains contributions from an international selection of leading authorities in the field; includes

  14. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  15. Biological Databases for Human Research

    Institute of Scientific and Technical Information of China (English)

    Dong Zou; Lina Ma; Jun Yu; Zhang Zhang

    2015-01-01

    The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation.

  16. Biological Databases for Human Research

    Science.gov (United States)

    Zou, Dong; Ma, Lina; Yu, Jun; Zhang, Zhang

    2015-01-01

    The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation. PMID:25712261

  17. Timescales of Massive Human Entrainment

    CERN Document Server

    Fusaroli, Riccardo; Mislove, Alan; Paxton, Alexandra; Matlock, Teenie; Dale, Rick

    2014-01-01

    The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We demonstrate that large scale human entrainment may hold across a number of distinct scales, in an exquisitely time locked fashion. Using a large scale database of human communication data, we analyze and describe three different time scales of human entrainment in electronic media. We sought a distinct shared experience that provided a test bed for quantifying large scale human entrainment. We conducted a detailed investigation of the real time unfolding of human entrainment, as expressed by the content and patterns of hundreds of thousands of messages on Twitter, during the 2012 US presidential debates. By time locking these data sources, we quantify the real time impact of the debate on human attention. We show that social behavior covaries second by second to the interactional dynamics...

  18. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .

  19. [A cyborg is only human].

    Science.gov (United States)

    Schermer, Maartje H N

    2013-01-01

    New biomedical technologies make it possible to replace parts of the human body or to substitute its functions. Examples include artificial joints, eye lenses and arterial stents. Newer technologies use electronics and software, for example in brain-computer interfaces such as retinal implants and the exoskeleton MindWalker. Gradually we are creating cyborgs: hybrids of man and machine. This raises the question: are cyborgs still humans? It is argued that they are. First, because employing technology is a typically human characteristic. Second, because in western thought the human mind, and not the body, is considered to be the seat of personhood. However, it has been argued by phenomenological philosophers that the body is more than just an object but is also a subject, important for human identity. From this perspective, we can appreciate that a bionic body does not make one less human, but it does influence the experience of being human.

  20. Predicting Human Cooperation.

    Directory of Open Access Journals (Sweden)

    John J Nay

    Full Text Available The Prisoner's Dilemma has been a subject of extensive research due to its importance in understanding the ever-present tension between individual self-interest and social benefit. A strictly dominant strategy in a Prisoner's Dilemma (defection, when played by both players, is mutually harmful. Repetition of the Prisoner's Dilemma can give rise to cooperation as an equilibrium, but defection is as well, and this ambiguity is difficult to resolve. The numerous behavioral experiments investigating the Prisoner's Dilemma highlight that players often cooperate, but the level of cooperation varies significantly with the specifics of the experimental predicament. We present the first computational model of human behavior in repeated Prisoner's Dilemma games that unifies the diversity of experimental observations in a systematic and quantitatively reliable manner. Our model relies on data we integrated from many experiments, comprising 168,386 individual decisions. The model is composed of two pieces: the first predicts the first-period action using solely the structural game parameters, while the second predicts dynamic actions using both game parameters and history of play. Our model is successful not merely at fitting the data, but in predicting behavior at multiple scales in experimental designs not used for calibration, using only information about the game structure. We demonstrate the power of our approach through a simulation analysis revealing how to best promote human cooperation.