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Sample records for component c1q mediates

  1. The endothelial deprotection hypothesis for lupus pathogenesis: the dual role of C1q as a mediator of clearance and regulator of endothelial permeability [v2; ref status: indexed, http://f1000r.es/5d5

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    József Prechl

    2015-05-01

    Full Text Available Systemic lupus erythematosus (SLE is a heterogeneous multifactorial systemic autoimmune disease affecting several organs. SLE can start relatively early in life and results in impaired quality of life and shortened life expectancy because of a gradual disease progression leading to cardiovascular, renal and neoplastic disease. The basic mechanisms of the pathogenesis of the disease still remain to be clarified. It is clear that complement proteins play a key and complex role in the development of SLE. Complement component C1q has been known to be a fundamental component of lupus development, but most explanations focus on its role in apoptotic debris removal. Importantly, C1q was recently found to play a key role in the maintenance of vascular endothelial integrity. We suggest that apoptotic products, endothelial cells and extracellular matrix components, which display negatively charged moieties, compete for binding to molecules of the innate humoral immune response, like C1q. Genetic or acquired factors leading to an increased load of apoptotic cell debris and decrease or absence of C1q therefore interfere with the regulation of endothelial permeability and integrity. Furthermore, we suggest that lupus is the net result of an imbalance between the two functions of immune clearance and vascular endothelial integrity maintenance, an imbalance triggered and sustained by autoimmunity, which skews C1q consumption by IgG-mediated complement classical pathway activation on autoantigens. In this triangle of innate clearance, autoimmunity and endothelial integrity, C1q plays a central role. Hence, we interpret the pathogenesis of lupus by identifying three key components, namely innate immune clearance, autoimmunity and endothelial integrity and we establish a link between these components based on the protective role that innate clearance molecules play in endothelial renewal. By including the vasoprotective role of C1q in the interpretation of SLE

  2. The endothelial deprotection hypothesis for lupus pathogenesis: the dual role of C1q as a mediator of clearance and regulator of endothelial permeability [v1; ref status: indexed, http://f1000r.es/50o

    Directory of Open Access Journals (Sweden)

    József Prechl

    2015-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a heterogeneous multifactorial systemic autoimmune disease affecting several organs. SLE can start relatively early in life and results in impaired quality of life and shortened life expectancy because of a gradual disease progression leading to cardiovascular, renal and neoplastic disease. The basic mechanisms of the pathogenesis of the disease still remain to be clarified. It is clear that complement proteins play a key and complex role in the development of SLE. Complement component C1q has been known to be a fundamental component of lupus development, but most explanations focus on its role in apoptotic debris removal. Importantly, C1q was recently found to play a key role in the maintenance of vascular endothelial integrity. We suggest that apoptotic products, endothelial cells and extracellular matrix components, which display negatively charged moieties, compete for binding to molecules of the innate humoral immune response, like C1q. Genetic or acquired factors leading to an increased load of apoptotic cell debris and decrease or absence of C1q therefore interfere with the regulation of endothelial permeability and integrity. Furthermore, we suggest that lupus is the net result of an imbalance between the two functions of immune clearance and vascular endothelial integrity maintenance, an imbalance triggered and sustained by autoimmunity, which skews C1q consumption by IgG-mediated complement classical pathway activation on autoantigens. In this triangle of innate clearance, autoimmunity and endothelial integrity, C1q plays a central role. Hence, we interpret the pathogenesis of lupus by identifying three key components, namely innate immune clearance, autoimmunity and endothelial integrity and we establish a link between these components based on the protective role that innate clearance molecules play in endothelial renewal. By including the vasoprotective role of C1q in the interpretation of SLE

  3. Binding of complement proteins C1q and C4bp to serum amyloid P component (SAP) in solid contra liquid phase

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    Sørensen, Inge Juul; Nielsen, EH; Andersen, Ove

    1996-01-01

    Serum amyloid P component (SAP), a member of the conserved pentraxin family of plasma proteins, binds calcium dependently to its ligands. The authors investigated SAPs interaction with the complement proteins C4b binding protein (C4bp) and C1q by ELISA, immunoelectrophoresis and electron microscopy....... Binding of these proteins to SAP was demonstrated when SAP was immobilized using F(ab')2 anti-SAP, but not when SAP reacted with these proteins in liquid phase; thus the binding to human SAP was markedly phase state dependent. Presaturation of solid phase SAP with heparin, which binds SAP with high...... affinity, did not interfere with the subsequent binding of C4bp or C1q to SAP. In contrast, collagen I and IV showed partial competition with the binding of C1q to SAP. Using fresh serum, immobilized native SAP bound C4bp whereas binding of C1q/C1 could not be demonstrated. Altogether the results indicate...

  4. Identification of a cytochrome P4502E1/Bid/C1q-dependent axis mediating inflammation in adipose tissue after chronic ethanol feeding to mice.

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    Sebastian, Becky M; Roychowdhury, Sanjoy; Tang, Hui; Hillian, Antoinette D; Feldstein, Ariel E; Stahl, Gregory L; Takahashi, Kazue; Nagy, Laura E

    2011-10-14

    Chronic, heavy alcohol exposure results in inflammation in adipose tissue, insulin resistance, and liver injury. Here we have identified a CYP2E1/Bid/C1q-dependent pathway that is activated in response to chronic ethanol and is required for the development of inflammation in adipose tissue. Ethanol feeding for 25 days to wild-type (C57BL/6J) mice increased expression of multiple markers of adipose tissue inflammation relative to pair-fed controls independent of increased body weight or adipocyte size. Ethanol feeding increased the expression of CYP2E1 in adipocytes, but not stromal vascular cells, in adipose tissue and Cyp2e1(-/-) mice were protected from adipose tissue inflammation in response to ethanol. Ethanol feeding also increased the number of TUNEL-positive nuclei in adipose tissue of wild-type mice but not in Cyp2e1(-/-) or Bid (-/-) mice. Apoptosis contributed to adipose inflammation, as the expression of multiple inflammatory markers was decreased in mice lacking the Bid-dependent apoptotic pathway. The complement protein C1q binds to apoptotic cells, facilitating their clearance and activating complement. Making use of C1q-deficient mice, we found that activation of complement via C1q provided the critical link between CYP2E1/Bid-dependent apoptosis and onset of adipose tissue inflammation in response to chronic ethanol. In summary, chronic ethanol increases CYP2E1 activity in adipose, leading to Bid-mediated apoptosis and activation of complement via C1q, finally resulting in adipose tissue inflammation. Taken together, these data identify a novel mechanism for the development of adipose tissue inflammation that likely contributes to the pathophysiological effects of ethanol.

  5. Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy.

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    Zhao, Limei; Shao, Shuai; Chen, Yi; Sun, Ximeng; Sun, Ran; Huang, Jingjing; Zhan, Bin; Zhu, Xinping

    2017-01-01

    As a multicellular parasitic nematode, Trichinella spiralis regulates host immune responses by producing a variety of immunomodulatory molecules to escape from host immune attack, but the mechanisms underlying the immune evasion are not well understood. Here, we identified that T. spiralis calreticulin ( Ts -CRT), a Ca 2+ -binding protein, facilitated T. spiralis immune evasion by interacting with the first component of human classical complement pathway, C1q. In the present study, Ts -CRT was found to be expressed on the surface of different developmental stages of T. spiralis as well as in the secreted products of adult and muscle larval worms. Functional analysis identified that Ts -CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. Moreover, recombinant Ts -CRT (r Ts -CRT) binding to C1q suppressed C1q-induced THP-1-derived macrophages chemotaxis and reduced monocyte-macrophages release of reactive oxygen intermediates (ROIs). Blocking Ts -CRT on the surface of newborn larvae (NBL) of T. spiralis with anti- Ts -CRT antibody increased the C1q-mediated adherence of monocyte-macrophages to larvae and impaired larval infectivity. All of these results suggest that T. spiralis -expressed Ts -CRT plays crucial roles in T. spiralis immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages.

  6. Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: complement component C1q and Prnp polymorphisms

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    Blanchong, Julie A.; Heisey, Dennis M.; Scribner, Kim T.; Libants, Scot V.; Johnson, Chad; Aiken, Judd M.; Langenberg, Julia A.; Samuel, Michael D.

    2009-01-01

    The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case–control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in south-central Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n = 68) and CWD-negative (n = 91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility.

  7. Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

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    Schaefer, S M; Süsal, C; Opelz, G; Döhler, B; Becker, L E; Klein, K; Sickmüller, S; Waldherr, R; Macher-Goeppinger, S; Schemmer, P; Beimler, J; Zeier, M; Morath, C

    2016-02-01

    Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

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    Tahtouh Muriel

    2012-02-01

    Full Text Available Abstract Background In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR, which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand. Methods Recombinant HmC1q (rHmC1q was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques. Results rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia. Conclusions A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal

  9. Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis.

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    Tahtouh, Muriel; Garçon-Bocquet, Annelise; Croq, Françoise; Vizioli, Jacopo; Sautière, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Nagnan-le Meillour, Patricia; Pestel, Joël; Lefebvre, Christophe

    2012-02-22

    In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS) after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR), which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand. Recombinant HmC1q (rHmC1q) was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques. rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia. A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal leech.

  10. Human diploid fibroblasts have receptors for the globular domain of C1Q

    International Nuclear Information System (INIS)

    Bordin, S.; Page, R.C.

    1986-01-01

    The authors showed that mass cultures of fibroblasts grown from gingival explants in DB medium with 10% human serum are enriched in a phenotype that binds C1q with an affinity much higher than the rest of the population. Because of potential biologic importance of C1q receptors, the authors studied whether the interaction between C1q and this phenotype was mediated by the globular or collagenous domains of the molecule. Globular fragments were prepared by digesting C1q with collagenase, and collagenous fragments obtained after pepsin treatment. C1q binding on cells in suspension was determined by reaction with 125 I-C1q as reported. Competition experiments were performed under conditions in which intact 125 I-C1q binding saturated all available receptors. The results showed that collagenous fragments inhibited 20% of the 125 I-C1q binding to high affinity receptors, whereas inhibition by globular fragments was 70%. Unlabeled intact C1q and collagen type 1 were used as controls, and inhibited 92% and 17% of C1q binding, respectively. These studies show that C1q interacts with the fibroblast phenotype expressing high affinity receptors through its globular domain. The authors suggest that at sites of trauma, native C1 may bind to the surface of these cells via the globular domain of C1q, and that this unique phenotype may play an important role in tissue repair

  11. Increased complement C1q level marks active disease in human tuberculosis.

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    Yi Cai

    Full Text Available BACKGROUND: Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. METHODS: Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. RESULTS: C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. CONCLUSIONS: C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.

  12. Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells.

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    Yamada, Masahide; Oritani, Kenji; Kaisho, Tsuneyasu; Ishikawa, Jun; Yoshida, Hitoshi; Takahashi, Isao; Kawamoto, Shinichirou; Ishida, Naoko; Ujiie, Hidetoshi; Masaie, Hiroaki; Botto, Marina; Tomiyama, Yoshiaki; Matsuzawa, Yuji

    2004-01-01

    We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q-deficient mice was higher than that of wild-type mice after intraperitoneal LPS-injection. Because neither globular head of C1q (gC1q) nor collagen-like region of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4 (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS-stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production, another MyD88-dependent TLR-mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR-mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88-deficient mice, indicating that inhibitory effects of C1q on MyD88-independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signals mediated by interactions between invading pathogens and TLR.

  13. Functional C1q is present in the skin mucus of Siberian sturgeon (Acipenser baerii).

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    Fan, Chunxin; Wang, Jian; Zhang, Xuguang; Song, Jiakun

    2015-01-01

    The skin mucus of fish acts as the first line of self-protection against pathogens in the aquatic environment and comprises a number of innate immune components. However, the presence of the critical classical complement component C1q, which links the innate and adaptive immune systems of mammalians, has not been explored in a primitive actinopterygian fish. In this study, we report that C1q is present in the skin mucus of the Siberian sturgeon (Acipenser baerii). The skin mucus was able to inhibit the growth of Escherichia coli. The bacteriostatic activity of the skin mucus was reduced by heating and by pre-incubation with EDTA or mouse anti-human C1q antibody. We also detected C1q protein in skin mucus using the western blot procedure and isolated a cDNA that encodes the Siberian sturgeon C1qC, which had 44.7-51.4% identity with C1qCs in teleosts and tetrapods. A phylogenetic analysis revealed that Siberian sturgeon C1qC lies at the root of the actinopterygian branch and is separate from the tetrapod branch. The C1qC transcript was expressed in many tissues as well as in skin. Our data indicate that C1q is present in the skin mucus of the Siberian sturgeon to protect against water-borne bacteria, and the C1qC found in the sturgeon may represent the primitive form of teleost and tetrapod C1qCs. © 2014 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

  14. Anti-C1q antibodies in systemic lupus erythematosus

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    Orbai, A-M; Truedsson, L; Sturfelt, G

    2015-01-01

    OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

  15. Direct interaction between CD91 and C1q

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    Duus, Karen; Hansen, Erik W; Tacnet, Pascale

    2010-01-01

    . C1q binding to monocytes was shown to be correlated with CD91 expression and could be inhibited by the CD91 chaperone, receptor-associated protein. We also report data showing a direct interaction between CD91 and C1q. The interaction was investigated using various protein interaction assays....... A direct interaction between purified C1q and CD91 was observed both by ELISA and a surface plasmon resonance assay, with either C1q or CD91 immobilized. The interaction showed characteristics of specificity because it was time-dependent, saturable and could be inhibited by known ligands of both CD91 and C...

  16. Analysis of healthy cohorts for single nucleotide polymorphisms in C1q gene cluster

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    MARIA A. RADANOVA

    2015-12-01

    Full Text Available C1q is the first component of the classical pathway of complement activation. The coding region for C1q is localized on chromosome 1p34.1–36.3. Mutations or single nucleotide polymorphisms (SNPs in C1q gene cluster can cause developing of Systemic lupus erythematosus (SLE because of C1q deficiency or other unknown reason. We selected five SNPs located in 7.121 kbp region on chromosome 1, which were previously associated with SLE and/or low C1q level, but not causing C1q deficiency and analyzed them in terms of allele frequencies and genotype distribution in comparison with Hispanic, Asian, African and other Caucasian cohorts. These SNPs were: rs587585, rs292001, rs172378, rs294179 and rs631090. One hundred eighty five healthy Bulgarian volunteers were genotyped for the selected five C1q SNPs by quantative real-time PCR methods. International HapMap Project has been used for information about genotype distribution and allele frequencies of the five SNPs in, Hispanics, Asians, Africans and others Caucasian cohorts. Bulgarian healthy volunteers and another pooled Caucasian cohort had similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, genotype AA of rs172378 was significantly overrepresented in Bulgarians when compared to other healthy Caucasians from USA and UK (60% vs 31%. Genotype distribution of rs172378 in Bulgarians was similar to Greek-Cyriot Caucasians. For all Caucasians the major allele of rs172378 was A. This is the first study analyzing the allele frequencies and genotype distribution of C1q gene cluster SNPs in Bulgarian healthy population.

  17. Transcriptional factor PU.1 regulates decidual C1q expression in early pregnancy in human

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    Priyaa Madhukaran Raj

    2015-02-01

    Full Text Available C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells. Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue- specific. Recently, PU.1 has been shown to regulate C1q gene expression in dendritic cells and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation.

  18. Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord.

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    Tahtouh, Muriel; Croq, Françoise; Vizioli, Jacopo; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Daha, Mohamed R; Pestel, Joël; Lefebvre, Christophe

    2009-02-01

    In vertebrates, central nervous system (CNS) protection is dependent on many immune cells including microglial cells. Indeed, activated microglial cells are involved in neuroinflammation mechanisms by interacting with numerous immune factors. Unlike vertebrates, some lophotrochozoan invertebrates can fully repair their CNS following injury. In the medicinal leech Hirudo medicinalis, the recruitment of microglial cells at the lesion site is essential for sprouting of injured axons. Interestingly, a new molecule homologous to vertebrate C1q was characterized in leech, named HmC1q (for H. medicinalis) and detected in neurons and glial cells. In chemotaxis assays, leech microglial cells were demonstrated to respond to human C1q. The chemotactic activity was reduced when microglia was preincubated with signaling pathway inhibitors (Pertussis Toxin or wortmannin) or anti-human gC1qR antibody suggesting the involvement of gC1qR in C1q-mediated migration in leech. Assays using cells preincubated with NO chelator (cPTIO) showed that C1q-mediated migration was associated to NO production. Of interest, by using anti-HmC1q antibodies, HmC1q released in the culture medium was shown to exhibit a similar chemotactic effect on microglial cells as human C1q. In summary, we have identified, for the first time, a molecule homologous to mammalian C1q in leech CNS. Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms.

  19. Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein.

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    Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M; Di Guilmi, Anne Marie; Frachet, Philippe

    2012-12-14

    C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (K(D) = 0.34-2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response.

  20. Human and Pneumococcal Cell Surface Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Proteins Are Both Ligands of Human C1q Protein*

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    Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M.; Di Guilmi, Anne Marie; Frachet, Philippe

    2012-01-01

    C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (KD = 0.34–2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response. PMID:23086952

  1. C1q Nephropathy: The Unique Underrecognized Pathological Entity

    Directory of Open Access Journals (Sweden)

    Joe Devasahayam

    2015-01-01

    Full Text Available C1q nephropathy is a rare glomerular disease with characteristic mesangial C1q deposition noted on immunofluorescence microscopy. It is histologically defined and poorly understood. Light microscopic features are heterogeneous and comprise minimal change disease (MCD, focal segmental glomerulosclerosis (FSGS, and proliferative glomerulonephritis. Clinical presentation is also diverse, and ranges from asymptomatic hematuria or proteinuria to frank nephritic or nephrotic syndrome in both children and adults. Hypertension and renal insufficiency at the time of diagnosis are common findings. Optimal treatment is not clear and is usually guided by the underlying light microscopic lesion. Corticosteroids are the mainstay of treatment, with immunosuppressive agents reserved for steroid resistant cases. The presence of nephrotic syndrome and FSGS appear to predict adverse outcomes as opposed to favorable outcomes in those with MCD. Further research is needed to establish C1q nephropathy as a universally recognized distinct clinical entity. In this paper, we discuss the current understanding of pathogenesis, histopathology, clinical features, therapeutic options, and outcomes of C1q nephropathy.

  2. Cytoadhesion to gC1qR through Plasmodium falciparum erythrocyte membrane protein 1 in severe malaria

    DEFF Research Database (Denmark)

    Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau

    2016-01-01

    Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed...

  3. Prevalence and clinical significance of anti-C1q antibodies in ...

    African Journals Online (AJOL)

    Asmaa Hegazy

    2012-04-21

    Apr 21, 2012 ... sists of 20 patients with musculoskeletal manifestations, mainly arthritis ... C1q have been found in many different autoimmune diseases, ... improve our diagnostic potential, from these, anti-C1q anti- ... Subjects and methods.

  4. Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency

    DEFF Research Database (Denmark)

    van Schaarenburg, Rosanne A; Schejbel, Lone; Truedsson, Lennart

    2015-01-01

    OBJECTIVE: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can...

  5. Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven

    DEFF Research Database (Denmark)

    Schaller, Monica; Bigler, Cornelia; Danner, Doris

    2009-01-01

    response against C1q at the molecular level, we screened a bone marrow-derived IgGkappa/IgGlambda Fab phage display library from a SLE patient with high anti-C1q Ab titer against purified human C1q. Six Fabs that exhibited strong binding to C1q in ELISA were isolated. The anti-C1q Fabs recognized...... neoepitopes that were only exposed on bound C1q and not present on soluble C1q mapping to different regions of the collagen-like region of C1q. Analysis of the genes encoding the variable H and L chains of the IgG-derived anti-C1q Fab revealed that all the variable H and L chain regions were highly mutated......, with nucleotide and amino acid homologies to the closest germline in the range of 71-97% (average 85 +/- 4) and 72-92% (average 88 +/- 6), respectively. In addition, the variable region of the Fabs exhibited high replacement to silent ratios. The six anti-C1q Fabs were shown to be of high affinity, with a K...

  6. Enhanced Ig production by human peripheral lymphocytes induced by aggregated C1q

    NARCIS (Netherlands)

    Daha, M. R.; Klar, N.; Hoekzema, R.; van Es, L. A.

    1990-01-01

    Because B cells express receptors for C1q, we have investigated the role of C1q in the stimulation of B cells. When B cells were cultured in the presence of C1q that had been frozen, T cells, and suboptimal concentrations of PWM, there was a dose-dependent enhancement of IgM, IgG, and IgA by the B

  7. The C1q family of proteins: insights into the emerging non-traditional functions

    Directory of Open Access Journals (Sweden)

    Berhane eGhebrehiwet

    2012-04-01

    Full Text Available Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders—including autoimmunity, trophoblast migration, preeclampsia and cancer. The results of two recent reports are provided to underscore the critical role C1q plays in health and disease. First is the observation by Singh and colleagues showing that pregnant C1q-/- mice recapitulate the key features of human preeclampsia that correlate with increased fetal death. Treatment of the C1q-/- mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of preeclampsia. Second is the report by Hong et al., which showed that C1q can induce apoptosis of prostate cancer cells by activating the tumor suppressor molecule WW-domain containing oxydoreductase (WWOX or WOX1 and destabilizing cell adhesion. Downregulation of C1q on the other hand enhanced prostate hyperplasia and cancer formation due to failure of WOX1 activation. Recent evidence also shows that C1q belongs to a family of structurally and functionally related TNFα-like family of proteins that may have arisen from a common ancestral gene. Therefore C1q not only shares the diverse functions with the TNF family of proteins, but also explains why C1q has retained some of its ancestral cytokine-like activities. This review is intended to highlight some of the structural and functional aspects of C1q by underscoring the growing list of its non-traditional functions.

  8. Regulation of human lung fibroblast C1q-receptors by transforming growth factor-beta and tumor necrosis factor-alpha.

    Science.gov (United States)

    Lurton, J; Soto, H; Narayanan, A S; Raghu, G

    1999-03-01

    Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are two polypeptide mediators which are believed to play a role in the evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of these two substances on the expression of receptors for collagen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen in human lung fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on C1q binding [Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells, referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF-alpha in serum-free conditions. The levels of mRNA were assessed by in situ hybridization and Northern analysis, and protein levels compared after SDS-polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF-beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively, whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA levels increased to a lesser extent in both cells. These increases were not reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels significantly. They also indicated different subsets of human lung fibroblasts respond differently to inflammatory mediators.

  9. Production and characterization of a murine monoclonal IgM antibody to human C1q receptor (C1qR)

    International Nuclear Information System (INIS)

    Ghebrehiwet, B.

    1986-01-01

    A hybridoma cell line that produces a monoclonal antibody (MAb) to cell surface C1q receptor (C1qr) has been produced by fusion of the P3 x 63-Ag8.653 mouse myeloma cell line with the spleen cells of a CD-1 mouse that had been hyperimmunized with viable Raji cell suspensions (5 x 10 7 cells/inoculum). This MAb, designated II1/D1, is an IgM antibody with lambda-light chain specificity. Radiolabeled or unlabeled, highly purified II1/D1 was used to determine that: a) this antibody competes for C1q binding sites on C1qR-bearing cells; b) the molecule recognized by this MAb is the C1qR; and c) cells that are known to bind C1q also bind II1/D1 in a specific manner. Western blot analysis of solubilized Raji, or U937 cell membranes, showed that the 125 I-MAb detected a major protein band of approximately 85000 m.w. in its unreduced state, indicating that the C1qR is similar, if not identical, in both types of cells. Analyses of 125 I-II/D1 binding experiments revealed that the antibody bound to Raji cells or u937 cells in a specific manner. Uptake of the antibody was saturable, with equilibrium virtually attained within 35 min. Scatchard analysis of the binding data using the intact MAb suggests that the affinity constant K/sub D/ is 2.9 x 10 -10 M, and at apparent saturation, 24.6 ng of the antibody were bound per 2 x 10 6 cells, giving an estimated 7.8 x 10 3 antibody molecules bound per cell. That the II1/D1 antibody is specifically directed to the C1q was further evidenced by an ELISA in which the ability of C1qR-bearing cells to bind the MAb was abrogated by c-C1q in a specific dose-dependent manner

  10. Anti-C1q autoantibodies in patients with neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Yoshikura, Nobuaki; Kimura, Akio; Hayashi, Yuichi; Inuzuka, Takashi

    2017-09-15

    We examined anti-complement C1q (C1q) autoantibody levels in serum and cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting to the same levels as controls during remission. CSF anti-C1q autoantibody levels during the acute phase correlated with several markers reflecting disease severity, Expanded Disability Status Scale worsening, spinal cord lesion length in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum albumin ratios. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Correlation of anti C1Q antibodies with disease activity in patients with systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Riaz, M.O.; Ahmed, T.A.

    2016-01-01

    Objective: To study the correlation of anti C1q antibodies with disease activity in patients with systemic lupus erythematosus (SLE). Study Design: Cross sectional, observational study. Place and Duration of study: The Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Military Hospital, Rawalpindi, Pakistan Institute of Medical Sciences, Islamabad and Benazir Bhutto Hospital, Rawalpindi, from Jan 2012 to Dec 2013. Material and Methods: Patients with a clinical diagnosis of SLE were included in the study on fulfilling revised American College of Rheumatology (ACR) criteria (1997). Main outcome measures were SLE disease activity index (SLEDAI) score and anti C1q antibody levels in serum. SLEDAI scores were calculated for each patient on the basis of physical examination, patient interviews and previous clinical records. Anti C1q antibody levels in the serum were determined by enzyme-linked immunosorbent assay (ELISA) and correlated with the SLEDAI scores by calculating Pearson's correlation coefficient 'r'. The cutoff value for anti C1q antibody positivity in the serum was determined by evaluating the serum levels of anti C1q antibodies in 25 healthy subjects and was 12 U/ml. Results: Six male and forty nine female SLE patients with an age range of 16-47 years (mean 34.5 years) and 8-70 years (mean 31.7 years) respectively were studied. The correlation between anti C1q levels and SLEDAI scores in all patients was demonstrated by calculating the correlation coefficient and was not significant (r=0.19, p=0.14). However, there was an inverse correlation between anti C1q levels and SLEDAI scores in patients with severe disease and this was statistically significant (r=-0.448, p=0.037). The difference in anti C1q antibody positivity between patients with and without nephritis was not significant. The anti C1q antibody levels correlated poorly with anti double stranded deoxyribonucleic acid (dsDNA) antibody positivity. A

  12. A microplate adaptation of the solid-phase C1q immune complex assay

    International Nuclear Information System (INIS)

    Hunt, J.S.; Kennedy, M.P.; Barber, K.E.; McGiven, A.R.

    1980-01-01

    A method has been developed for the detection of C1q binding immune complexes in serum in which microculture plates are used as the solid-phase matrix for adsorption of C1q. This micromethod used only one-tenth of the amount of both C1q and [ 125 I]antihuman immunoglobulin per test and enabled 7 times as many samples to be tested in triplicate in comparison with the number performed in duplicate by the standard tube assay. (Auth.)

  13. Complement protein C1q induces maturation of human dendritic cells

    DEFF Research Database (Denmark)

    Csomor, Eszter; Bajtay, Zsuzsa; Sándor, Noémi

    2007-01-01

    Maturation of dendritic cells (DCs) is known to be induced by several stimuli, including microbial products, inflammatory cytokines and immobilized IgG, as demonstrated recently. Since immune complexes formed in vivo also contain C1q, moreover apoptotic cells and several pathogens fix C1q...... activity of the cells was assessed by measuring cytokine secretion and their ability to activate allogeneic T lymphocytes. Cytokine production by T cells co-cultured with C1q-matured DCs was also investigated. C1q, but not the structurally related mannose-binding lectin was found to bind to imMDC in a dose......-dependent manner and induced NF-kappaB translocation to the nucleus. Immobilized C1q induced maturation of MDCs and enhanced secretion of IL-12 and TNF-alpha, moreover, elevated their T-cell stimulating capacity. As IFN-gamma levels were increased in supernatants of MDC-T cell co-cultures, our data suggest that C1...

  14. Modular organization of proteins containing C1q-like globular domain.

    Science.gov (United States)

    Kishore, U; Reid, K B

    1999-05-01

    The first step in the activation of the classical pathway of complement cascade by immune complexes involves the binding of the six globular heads of C1q to the Fc regions of immunoglobulin G (IgG) or immunoglobulin M (IgM). The globular heads of C1q are located C-terminal to the six triple-helical stalks present in the molecule, each head is considered to be composed of the C-terminal halves (3 x 135 residues) of one A-, one B- and one C-chain. It is not known if the C-terminal globular regions, present in each of the three types of chains, are independently folded modules (with each chain having distinct binding properties towards immunoglobulins) or whether the different binding functions of C1q are dependent upon a globular structure which relies on contributions from all three chains. Recent reports of recombinant production and characterisation of soluble globular head regions of all the three chains indicate that the globular regions of C1q may adopt a modular organization, i.e., each globular head of C1q may be composed of three, structurally and functionally, independent domains, thus retaining multivalency in the form of a heterotrimer. Modules of the same type as the C1q C-terminal module are also found in a variety of noncomplement proteins that include the C-terminal regions of the human type VIII and type X collagens, precerebellin, the chipmunk hibernation proteins, the human endothelial cell protein, multimerin, the serum protein, Acrp-30 which is secreted from mouse adipocytes, and the sunfish inner-ear specific structural protein. The C1q molecule is the only one of these proteins for which, to date, a function has been ascribed to the module. The existence of a shared structural region between C1q and certain collagens may suggest an evolutionarily common ancestral precursor. Various structural and biochemical data suggest that these modules may be responsible for multimerisation through patches of aromatic residues within them.

  15. C1q protein binds to the apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins.

    Science.gov (United States)

    Cai, Yitian; Teo, Boon Heng Dennis; Yeo, Joo Guan; Lu, Jinhua

    2015-09-11

    In infection, complement C1q recognizes pathogen-congregated antibodies and elicits complement activation. Among endogenous ligands, C1q binds to DNA and apoptotic cells, but whether C1q binds to nuclear DNA in apoptotic cells remains to be investigated. With UV irradiation-induced apoptosis, C1q initially bound to peripheral cellular regions in early apoptotic cells. By 6 h, binding concentrated in the nuclei to the nucleolus but not the chromatins. When nucleoli were isolated from non-apoptotic cells, C1q also bound to these structures. In vivo, C1q exists as the C1 complex (C1qC1r2C1s2), and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of the nucleolar proteins nucleolin and nucleophosmin 1. This was inhibited by the C1 inhibitor. The nucleoli are abundant with autoantigens. C1q binding and C1r/C1s degradation of nucleolar antigens during cell apoptosis potentially reduces autoimmunity. These findings help us to understand why genetic C1q and C1r/C1s deficiencies cause systemic lupus erythematosus. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations

    DEFF Research Database (Denmark)

    Schejbel, L; Skattum, L; Hagelberg, S

    2011-01-01

    C1q is the central pattern-recognition molecule in the classical pathway of the complement system and is known to have a key role in the crossroads between adaptive and innate immunity. Hereditary C1q deficiency is a rare genetic condition strongly associated with systemic lupus erythematosus...... and increased susceptibility to bacterial infections. However, the clinical symptoms may vary. For long, the molecular basis of C1q deficiency was ascribed to only six different mutations. In the present report, we describe five new patients with C1q deficiency, present the 12 causative mutations described till...... now and review the clinical spectrum of symptoms found in patients with C1q deficiency. With the results presented here, confirmed C1q deficiency is reported in 64 patients from at least 38 families....

  17. The C1q complement family of synaptic organizers: not just complementary.

    Science.gov (United States)

    Yuzaki, Michisuke

    2017-08-01

    Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity. C1ql2 and C1ql3, released from mossy fibers, determine the synaptic localization of postsynaptic kainate receptors in the hippocampus. C1ql3 also regulates the formation of synapses between the basolateral amygdala and the prefrontal cortex. These findings indicate the diverse functions of C1q family proteins in various brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Complement and alcoholic liver disease: role of C1q in the pathogenesis of ethanol-induced liver injury in mice.

    Science.gov (United States)

    Cohen, Jessica I; Roychowdhury, Sanjoy; McMullen, Megan R; Stavitsky, Abram B; Nagy, Laura E

    2010-08-01

    Complement is involved in the development of alcoholic liver disease in mice; however, the mechanisms for complement activation during ethanol exposure have not been identified. C1q, the recognition subunit of the first complement component, binds to apoptotic cells, thereby activating the classical complement pathway. Because ethanol exposure increases hepatocellular apoptosis, we hypothesized that ethanol-induced apoptosis would lead to activation of complement via the classical pathway. Wild-type and C1qa-/- mice were allowed free access to ethanol-containing diets or pair-fed control diets for 4 or 25 days. Ethanol feeding for 4 days increased apoptosis of Kupffer cells in both wild-type and C1qa-/- mice. Ethanol-induced deposition of C1q and C3b/iC3b/C3c was colocalized with apoptotic Kupffer cells in wild-type, but not C1qa-/-, mice. Furthermore, ethanol-induced increases in tumor necrosis factor-alpha and interleukin-6 expression at this early time point were suppressed in C1q-deficient mice. Chronic ethanol feeding (25 days) increased steatosis, hepatocyte apoptosis, and activity of serum alanine and aspartate aminotransferases in wild-type mice. These markers of hepatocyte injury were attenuated in C1qa-/- mice. In contrast, chronic ethanol (25 days)-induced increases in cytochrome P450 2E1 expression and oxidative stress did not differ between wild-type and C1qa-/- mice. For the first time, these data indicate that ethanol activates the classical complement pathway via C1q binding to apoptotic cells in the liver and that C1q contributes to the pathogenesis of ethanol-induced liver injury. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q.

    Science.gov (United States)

    Reid, K B; Bentley, D R; Wood, K J

    1984-09-06

    Normal human C1q is a serum glycoprotein of 460 kDa containing 18 polypeptide chains (6A, 6B, 6C) each 226 amino acids long and each containing an N-terminal collagen-like domain and a C-terminal globular domain. Two unusual forms of C1q have been described: a genetically defective form, which has a molecular mass of approximately 160 kDa and is found in the sera of homozygotes for the defect who show a marked susceptibility to immune complex related disease; a fibroblast form, shown to be synthesized and secreted, in vitro, with a molecular mass of about 800 kDa and with chains approximately 16 kDa greater than those of normal C1q. A higher than normal molecular mass form of C1q has also been described in human colostrum and a form of C1q has been claimed to represent one of the types of Fc receptor on guinea-pig macrophages. To initiate studies, at the genomic level, on these various forms of C1q, and to investigate the possible relation between the C1q genes and the procollagen genes, the complementary DNA corresponding to the B chain of normal C1q has been cloned and characterized.

  20. Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade.

    Science.gov (United States)

    Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini; Mulenga, Albert

    2015-02-01

    In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it's plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate feeding. CRT is a multi-functional protein found in most taxa that is injected into the vertebrate host during tick feeding. Apart from it's current use as a biomarker for human tick bites, role(s) of this protein in tick feeding physiology have not been elucidated. Here we show that annotated functional CRT amino acid motifs are well conserved in tick CRT. However our data show that despite high amino acid identity levels to functionally characterized CRT homologs in other organisms, AamCRT is apparently functionally different. Pichia pastoris expressed recombinant (r) AamCRT bound C1q, the first component of the classical complement system, but it did not inhibit activation of this pathway. This contrast with reports of other parasite CRT that inhibited activation of the classical complement pathway through sequestration of C1q. Furthermore rAamCRT did not bind factor Xa in contrast to reports of parasite CRT binding factor Xa, an important protease in the blood clotting system. Consistent with this observation, rAamCRT did not affect plasma clotting or platelet aggregation. We discuss our findings in the context of tick feeding physiology.

  1. Structure and function of complement protein C1q and its role in the development of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Katarzyna Smykał-Jankowiak

    2009-09-01

    Full Text Available Complement plays an important role in the immune system. Three different pathways of complement activation are known: the classical, alternative, and lectin dependent. They involve more than 30 serum peptides. C1q is the first subcomponent of the classical pathway of complement activation. It is composed of three types of chains, A, B, and C, which form a molecule containing 18 peptides. Each of the chains has a short amino-terminal region followed by a collagen-like region (playing a role in the activation of C1r2C1s2 and a carboxy-terminal head, which binds to immune complexes. Recent studies have shown a great number of ligands for C1q, including aggregated IgG, IgM, human T-cell lymphotropic virus-I (HTLV-I, gp21 peptide, human immunodeficiency virus-1 (HIV-1 gp21 peptide, β-amyloid, fragments of bacterial walls, apoptotic cells, and many others. However, the role of C1q is not only associated with complement activation. It also helps in the removal of immune complexes and necrotic cells, stimulates the production of some cytokines, and modulates the function of lymphocytes. Complete C1q deficiency is a rare genetic disorder. The C1q gene is located on the short arm of chromosome 1. So far, only a few mutations in C1q gene have been reported. The presence of these mutations is strongly associated with recurrent bacterial infections and the development of systemic lupus erythematosus (SLE. Recent clinical studies point to the significance of anti-C1q antibodies in the diagnosis and assessment of lupus nephritis activity.

  2. Characterization of the honeybee venom proteins C1q-like protein and PVF1 and their allergenic potential

    DEFF Research Database (Denmark)

    Russkamp, Dennis; Van Vaerenbergh, Matthias; Etzold, Stefanie

    2018-01-01

    -like protein (C1q) and PDGF/VEGF-like factor 1 (PVF1). C1q and PVF1 were produced as recombinant proteins in insect cells. Their allergenic properties were examined by determining the level of specific IgE antibodies in the sera of HBV-allergic patients (n = 26) as well as by their capacity to activate...... frugiperda insect cells exhibited specific IgE reactivity with approximately 38.5% of sera of HBV-allergic patients. Interestingly, both proteins were unable to activate basophils of the patients, questioning their role in the context of clinically relevant sensitization. Recombinant C1q and PVF1 can build...

  3. Association of anti C1q and ds-DNA levels with the pathogenesis of Lupus Nephritis among SLE patients

    Directory of Open Access Journals (Sweden)

    Zara Sohail

    2018-02-01

    Full Text Available Background: Lupus nephritis (LN is the most common and serious complication associated with SLE and it results in significant morbidity and mortality. It is known by several studies that patients of LN have higher levels of anti-dsDNA and anti-C1q compared with SLE patients without renal involvement. The current study was designed to determine and compare the level of anti-dsDNA and anti-C1q in patients of SLE with and without lupus nephritis in the Pakistani population. This current study was also aimed at providing proof that anti-C1q levels are more prominent in LN/non-LN SLE as compared to anti-dsDNA. This project may help in the determination of results in Pakistan and contribute to the further confirmation of the sensitivity of anti-C1q. Method: The patient samples were collected from Sheikh Zayed hospital, Lahore. These patients were clinically diagnosed by the Rheumatologists as SLE and LN positive on the basis of ACR and SLEDAI scoring criteria. This study was performed and samples were analyzed in the Department of Medical and Laboratory Sciences, Imperial College of Business Study, Lahore on the patient’s serum by ELISA technique. Result: About 38% (12 patients with LN were positive for anti-dsDNA and 31% (9 SLE patients without LN were positive whereas about 38.7% (12 were anti-dsDNA negative in LN cases and 58.6% (17 in SLE without LN. In case of anti-C1q 100% (31 of these LN patients were positive and 93.1% (27 patients SLE without LN showed positive anti C1q results. Only 6.9% (2 patients showed negative results for anti-C1q in LN negative patients Conclusion: The higher levels of anti-C1q suggest that it may be a better diagnostic marker for LN than that of anti-dsDNA and that it can be helpful in the prognosis of SLE patients.

  4. C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases

    Directory of Open Access Journals (Sweden)

    Ruchika Gupta

    2015-01-01

    Full Text Available C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH. Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman′s capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

  5. Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

    Science.gov (United States)

    Olsson, Richard F; Hagelberg, Stefan; Schiller, Bodil; Ringdén, Olle; Truedsson, Lennart; Åhlin, Anders

    2016-06-01

    Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.

  6. DMPD: Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andCTRPs. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17681884 Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs an...ng) (.svg) (.html) (.csml) Show Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andC...TRPs. PubmedID 17681884 Title Adipose tissue as an immunological organ: Toll-like

  7. Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers.

    Science.gov (United States)

    Yuzaki, Michisuke

    2010-07-01

    Several C1q family members, especially the Cbln and C1q-like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)-Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF-Purkinje cell synaptogenesis in vitro and in vivo. Antigen-unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer. © The Author (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    Science.gov (United States)

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

  9. Fc RIIA Genotypes and Its Association with Anti-C1q Autoantibodies in Lupus Nephritis (LN Patients from Western India

    Directory of Open Access Journals (Sweden)

    Vandana Pradhan

    2010-01-01

    Full Text Available To identify Fc RIIA genotypes in Systemic Lupus Erythematosus (SLE patients and their association with anti-C1q antibodies. Methods. Fc RIIA genotyping was done in eighty Indian SLE patients and eighty healthy controls using allele-specific PCR. Anti-C1q antibodies were measured by ELISA. Results. LN patients showed higher SLEDAI (6–32 as compared to SLE patients without renal manifestations and had SLEDAI between 6–23. Fc RIIA polymorphic frequency in SLE patients was R131/H131 (67.5%, R131/R131 (20% and H131/ H131 (12.5% as against that of normal population (62.5%, 10%, and 27.5%, respectively. Sixty two patients (77.5% showed positivity for anti-C1q antibodies. LN patients showed elevated levels of anti-C1q antibodies (258.2u/ml±38.5U/mL as compared to SLE patients without nephritis (134.6±24.6 U/mL. Among anti-C1q positive patients, 71% had R131/H131 genotype, 22.6% had R131/R131 and remaining 6.4%, patients had H131/H131 genotype. All anti-C1q positive patients with R131/R131 genotype had elevated levels of anti-C1q antibodies (>100 U/ml, whereas among anti-C1q negative patients, none had R131/R131 genotype. Conclusion. This first report on Indian SLE patients supports the hypothesis that Fc RIIA R131 variant over expression may constitute a susceptibility factor for development of severe SLE manifestations in LN patients.

  10. "-o C1) (Q

    African Journals Online (AJOL)

    edm deur die Franse Protestamse vlugtelinge. Wat die verstrekte inligting betref, is hoofsaaklik van Charles Weiss se reeds genoemde publika~ sies gebruik gemaak. (a) Brandenburg (na 1701 die koninkryk Pruise). In Brandenburg het keurvors Frederik Willem. (1640-1688) in 1640 die troon bestyg. Deur oorlogsgeweld.

  11. Studies on the pathogenesis of Aleutian disease of mink. X. demonstration of immune complexes by the /sup 125/I-C 1 q binding test after experimental infection

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Peddinghaus, R [Kali-Chemie Pharma G.m.b.H., Hannover (Germany, F.R.). Abt. fuer Experimentelle Pathologie; Meyer zu Schwabedissen, H [Medizinische Hochschule Hannover (Germany, F.R.). Abt. fuer Klinische Immunologie und Bluttransfusionswesen; Kalden, J R [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. und Poliklinik fuer Klinische Immunologie; Trautwein, G; Ueberschaer, S [Tieraerztliche Hochschule Hannover (Germany, F.R.). Inst. fuer Pathologie

    1980-01-01

    Aleutian disease (AD) of mink most closely resembles systemic lupus erythematosus (SLE) in man; both are immune complex disease. In experimental AD serum immune complexes are determined by the /sup 125/J-C 1 q-binding test using human C 1 q. Mink (n = 12) infected intraperitoneally with Aleutian disease virus (ADV), grown in fetal mink kidney cells, developed during the course of infection a mean of /sup 125/I-C 1 q serum binding equivalent to 3.62 +- 1.68 mg./ml. aggr. HGG. (aggregated human immunoglobulin). Sera of mink (n = 8) which were infected with ADV grown in L-cells showed a less marked /sup 125/I-C 1 q binding with a mean equivalent to 2.52 +- 1.43 mg./ml. aggr. HGG. In contrast control animals (n = 8) treated with non-ADV-infected mink epidermal fibroblasts or Eagle's minimal essential medium substituted with fetal calf serum only bound /sup 125/I-C 1 q equivalent to 1.02 +- 0.99 mg./ml. aggr. HGG. In mink infected with ADV propagated in fetal mink kidney cells a constant increase in the /sup 125/I-C 1 q serum binding occurred from the 4th to the 7th and 13th week after ADV infection. Mink which were infected with ADV propagated in mouse L-cells exhibited a different pattern of the /sup 125/I-C 1 q serum binding capacity with a sharp increase from the 4th to the 7th week, followed by a decline towards the 13th week post infection. The serum /sup 125/I-C 1 q binding capacity of all experimental animal groups exhibited at different times of the experiment a significant correlation with the presence of hypergammaglobulinaemia and raised ADV-antibody titers. From the data obtained it appears that the /sup 125/I-C 1 q binding test, utilizing human C 1 q, is a suitable method for the detection of circulating serum immune complexes in mink during the course of ADV-infection.

  12. Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

    Science.gov (United States)

    Juhl, David; Marget, Matthias; Hallensleben, Michael; Görg, Siegfried; Ziemann, Malte

    2017-03-01

    Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The Exosporium of B.cereus Contains a Binding Site for gC1qR/p33: Implication in Spore Attachment and/or Entry.

    Energy Technology Data Exchange (ETDEWEB)

    GHEBREHIWET,B.; TANTRAL, L.; TITMUS, M.A.; PANESSA-WARREN, B.J.; TORTORA, G.T.; WONG, S.S.; WARREN, J.B.

    2008-01-01

    B. cereus, is a member of a genus of aerobic, gram-positive, spore-forming rod-like bacilli, which includes the deadly, B. anthracis. Preliminary experiments have shown that gC1qR binds to B.cereus spores that have been attached to microtiter plates. The present studies were therefore undertaken, to examine if cell surface gC1qR plays a role in B.cereus spore attachment and/or entry. Monolayers of human colon carcinoma (Caco-2) and lung cells were grown to confluency on 6 mm coverslips in shell vials with gentle swirling in a shaker incubator. Then, 2 {micro}l of a suspension of strain SB460 B.cereus spores (3x10{sup 8}/ml, in sterile water), were added and incubated (1-4 h; 36{sup 0} C) in the presence or absence of anti-gC1qR mAb-carbon nanoloops. Examination of these cells by EM revealed that: (1) When B. cereus endospores contacted the apical Caco-2 cell surface, or lung cells, gClqR was simultaneously detectable, indicating upregulation of the molecule. (2) In areas showing spore contact with the cell surface, gClqR expression was often adjacent to the spores in association with microvilli (Caco-2 cells) or cytoskeletal projections (lung cells). (3) Furthermore, the exosporia of the activated and germinating spores were often decorated with mAb-nanoloops. These observations were further corroborated by experiments in which B.cereus spores were readily taken up by monocytes and neutrophils, and this uptake was partially inhibited by mAb 60.11, which recognizes the C1q binding site on gC1qR. Taken together, the data suggest a role, for gC1qR at least in the initial stages of spore attachment and/or entry.

  14. Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction

    International Nuclear Information System (INIS)

    Sjoewall, Christopher; Wetteroe, Jonas; Bengtsson, Torbjoern; Askendal, Agneta; Almroth, Gunnel; Skogh, Thomas; Tengvall, Pentti

    2007-01-01

    C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fcγ receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups

  15. Effect of calcium ions on structure and stability of the C1q-like domain of otolin-1 from human and zebrafish.

    Science.gov (United States)

    Hołubowicz, Rafał; Wojtas, Magdalena; Taube, Michał; Kozak, Maciej; Ożyhar, Andrzej; Dobryszycki, Piotr

    2017-12-01

    Otolin-1 is a collagen-like protein expressed in the inner ear of vertebrates. It provides an organic scaffold for otoliths in fish and otoconia in land vertebrates. In this study, the expression and purification procedure of C1q-like domain of otolin-1 from human and zebrafish was developed. The structure and stability of the proteins were investigated. The results of sedimentation velocity analytical ultracentrifugation and small-angle X-ray scattering indicated that the C1q-like domain of otolin-1 forms stable trimers in solution in the presence of calcium ions. It was also observed that calcium ions influenced the secondary structure of the proteins. C1q-like domains were stabilized by the calcium ions. The human variant was especially affected by the calcium ions. The results indicate the importance of the C1q-like domain for the assembly of the organic matrix of otoliths and otoconia. © 2017 Federation of European Biochemical Societies.

  16. Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

    Science.gov (United States)

    Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

    2015-11-01

    Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Implication of progranulin and C1q/TNF-related protein-3 (CTRP3) on inflammation and atherosclerosis in subjects with or without metabolic syndrome.

    Science.gov (United States)

    Yoo, Hye Jin; Hwang, Soon Young; Hong, Ho Cheol; Choi, Hae Yoon; Yang, Sae Jeong; Choi, Dong Seop; Baik, Sei Hyun; Blüher, Matthias; Youn, Byung-Soo; Choi, Kyung Mook

    2013-01-01

    Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance. We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT). Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = -0.21), diastolic blood pressure (r = -0.21), fasting glucose (r = -0.20), triglyceride (r = -0.34), total cholesterol (r = -0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R(2) = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R(2) = 0.365). Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for

  18. Implication of progranulin and C1q/TNF-related protein-3 (CTRP3 on inflammation and atherosclerosis in subjects with or without metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Hye Jin Yoo

    Full Text Available Progranulin and C1q/TNF-related protein-3 (CTRP3 were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance.We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44 or without metabolic syndrome (n = 83. Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP, interleukin-6 (IL-6, estimated glomerular filtration rate (eGFR, and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT.Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001 and IL-6 (r = 0.30, P = 0.001, whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = -0.21, diastolic blood pressure (r = -0.21, fasting glucose (r = -0.20, triglyceride (r = -0.34, total cholesterol (r = -0.25, eGFR (r = 0.39 and adiponectin (r = 0.26 levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051 and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010. In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R(2 = 0.251. Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R(2 = 0.365.Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in

  19. Identification of expressed genes in cDNA library of hemocytes from the RLO-challenged oyster, Crassostrea ariakensis Gould with special functional implication of three complement-related fragments (CaC1q1, CaC1q2 and CaC3).

    Science.gov (United States)

    Xu, Ting; Xie, Jiasong; Li, Jianming; Luo, Ming; Ye, Shigen; Wu, Xinzhong

    2012-06-01

    A SMARTer™ cDNA library of hemocyte from Rickettsia-like organism (RLO) challenged oyster, Crassostrea ariakensis Gould was constructed. Random clones (400) were selected and single-pass sequenced, resulted in 200 unique sequences containing 96 known genes and 104 unknown genes. The 96 known genes were categorized into 11 groups based on their biological process. Furthermore, we identified and characterized three complement-related fragments (CaC1q1, CaC1q2 and CaC3). Tissue distribution analysis revealed that all of three fragments were ubiquitously expressed in all tissues studied including hemocyte, gills, mantle, digestive glands, gonads and adductor muscle, while the highest level was seen in the hemocyte. Temporal expression profile in the hemocyte monolayers reveled that the mRNA expression levels of three fragments presented huge increase after the RLO incubation at 3 h and 6 h in post-challenge, respectively. And the maximal expression levels at 3 h in post-challenge are about 256, 104 and 64 times higher than the values detected in the control of CaC1q1, CaC1q2 and CaC3, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19

    DEFF Research Database (Denmark)

    Thiel, S; Petersen, Steen Vang; Vorup-Jensen, T

    2000-01-01

    . There is controversy as to whether MBL can utilize C1r and C1s or, inversely, whether C1q can utilize MASP-1 and 2. Serum deficient in C1r produced no complement activation in IgG-coated microwells, whereas activation was seen in mannan-coated microwells. In serum, C1r and C1s were found to be associated only with C1q...

  1. Reduction in erythrocyte-bound complement activation products and titres of anti-C1q antibodies associate with clinical improvement in systemic lupus erythematosus.

    Science.gov (United States)

    Buyon, Jill; Furie, Richard; Putterman, Chaim; Ramsey-Goldman, Rosalind; Kalunian, Kenneth; Barken, Derren; Conklin, John; Dervieux, Thierry

    2016-01-01

    The relationship between cell-bound complement activation products (CB-CAPs: EC4d, EC3d), anti-C1q, soluble complement C3/C4 and disease activity in systemic lupus erythematosus (SLE) was evaluated. Per protocol, at baseline all SLE subjects enrolled in this longitudinal study presented with active disease and elevated CB-CAPs. At each monthly visit, the non-serological (ns) Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG)-2004 index scores were determined as was a random urinary protein to creatinine ratio (uPCR). Short-form 36 (SF-36) questionnaires were also collected. All soluble markers were determined using immunoassays, while EC4d and EC3d were determined using flow cytometry. Statistical analysis consisted of linear mixed models with random intercept and fixed slopes. A total of 36 SLE subjects (mean age 34 years; 94% female) were enrolled and evaluated monthly for an average 11 visits per subject. Clinical improvements were observed during the study, with significant decreases in ns-SELENA-SLEDAI scores, BILAG-2004 index scores and uPCR, and increases in all domains of SF-36 (pimprovements in at least six out of the eight domains of SF-36 and outperformed C3/C4. Anti-dsDNA titres did not correlate with changes in disease activity. These data indicate that CB-CAPs and anti-C1q are helpful in monitoring patients with SLE.

  2. Successful kidney transplantation across a positive complement-dependent cytotoxicity crossmatch by using C1q assay-directed, bortezomib-assisted desensitization

    Science.gov (United States)

    Lee, Juhan; Park, Borae G.; Jeong, Hyang Sook; Park, Youn Hee; Kim, Sinyoung; Kim, Beom Seok; Kim, Hye Jin; Huh, Kyu Ha; Jeong, Hyeon Joo; Kim, Yu Seun

    2017-01-01

    Abstract Rationale: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique. Some patients who fail to achieve negative XM have lost their transplant opportunities, even after receiving sufficient desensitization therapies. Patient concerns: A 57-year-old male with end-stage renal disease secondary to chronic glomerulonephritis was scheduled to have a second transplant from his son, but CDC XM was positive. Diagnoses: Initial CDC XM (Initial T-AHG 1:32) and flow-cytometry XM were positive. Anti-HLA-B59 donor specific antibody was detected by Luminex single antigen assay. Interventions: Herein, we report a successful case of KT across a positive CDC XM (T-AHG 1:8 at the time of transplantation) by using C1q assay-directed, bortezomib-assisted desensitization. After confirming a negative conversion in the C1q donor-specific antibody, we decided to perform KT accepting a positive AHG-CDC XM of 1:8 at the time of transplantation. Outcomes: The posttransplant course was uneventful and a protocol biopsy at 3 months showed no evidence of rejection. The patient had excellent graft function at 12 months posttransplant. Lessons: The results of XM test and solid-phase assay should be interpreted in the context of the individual patient. PMID:28953652

  3. Successful kidney transplantation across a positive complement-dependent cytotoxicity crossmatch by using C1q assay-directed, bortezomib-assisted desensitization: A case report.

    Science.gov (United States)

    Lee, Juhan; Park, Borae G; Jeong, Hyang Sook; Park, Youn Hee; Kim, Sinyoung; Kim, Beom Seok; Kim, Hye Jin; Huh, Kyu Ha; Jeong, Hyeon Joo; Kim, Yu Seun

    2017-09-01

    Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique. Some patients who fail to achieve negative XM have lost their transplant opportunities, even after receiving sufficient desensitization therapies. A 57-year-old male with end-stage renal disease secondary to chronic glomerulonephritis was scheduled to have a second transplant from his son, but CDC XM was positive. Initial CDC XM (Initial T-AHG 1:32) and flow-cytometry XM were positive. Anti-HLA-B59 donor specific antibody was detected by Luminex single antigen assay. Herein, we report a successful case of KT across a positive CDC XM (T-AHG 1:8 at the time of transplantation) by using C1q assay-directed, bortezomib-assisted desensitization. After confirming a negative conversion in the C1q donor-specific antibody, we decided to perform KT accepting a positive AHG-CDC XM of 1:8 at the time of transplantation. The posttransplant course was uneventful and a protocol biopsy at 3 months showed no evidence of rejection. The patient had excellent graft function at 12 months posttransplant. The results of XM test and solid-phase assay should be interpreted in the context of the individual patient.

  4. C1qTNF-related protein 1 improve insulin resistance by reducing phosphorylation of serine 1101 in insulin receptor substrate 1.

    Science.gov (United States)

    Xin, Yaping; Zhang, Dongming; Fu, Yanqin; Wang, Chongxian; Li, Qingju; Tian, Chenguang; Zhang, Suhe; Lyu, Xiaodong

    2017-08-30

    C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

  5. C1q/Tumor Necrosis Factor-related Protein-3 Attenuates Brain Injury after Intracerebral Hemorrhage via AMPK-dependent pathway in Rat

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    Shaohua Wang

    2016-10-01

    Full Text Available C1q/tumor necrosis factor-related protein-3 (CTRP3 is a recently discovered adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP3 in intracerebral hemorrhage (ICH is still mostly unresolved. The aim of the present report was to explore the possible neuroprotective effect of CTRP3 in an ICH rat model and to elucidate the fundamental mechanisms. ICH was induced in rats by intracerebral infusion of autologous arterial blood. The effects of exogenous CTRP3 (recombinant or lentivirus CTRP3 on brain injury were explored on day 7. Treatment with CTRP3 reduced brain edema, protected against disruption of the blood-brain barrier, improved neurological functions, and promoted angiogenesis. Furthermore, CTRP3 greatly intensified phosphorylation of AMP-activated protein kinase (AMPK in addition to expression of hypoxia inducing factor-1α (HIF-1α and vascular endothelial growth factor (VEGF. Finally, the protective effects of CTRP3 could be blocked by either AMPK or VEGF inhibitors. Our findings give the first evidence that CTRP3 is a new proangiogenic and neuroprotective adipokine, which may exert its protective effects at least partly through an AMPK/HIF-1α/ VEGF-dependent pathway, and suggest that CTRP3 may provide a new therapeutic strategy for ICH.

  6. Lower Circulating C1q/TNF-Related Protein-3 (CTRP3 Levels Are Associated with Obesity: A Cross-Sectional Study.

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    Risa M Wolf

    Full Text Available C1q/TNF-related protein-3 (CTRP3 is a novel adipokine that lowers blood glucose levels, reduces liver triglyceride synthesis, and is protective against hepatic steatosis in diet-induced obese mouse models. We hypothesized that higher circulating serum levels of CTRP3 would be associated with a lean body mass index (BMI and a more favorable metabolic profile in humans. The aim of this study was to investigate CTRP3 levels in lean individuals compared to obese individuals.This was a cross-sectional study of obese (n=44 and lean control patients (n=60. Fasting metabolic parameters were measured in all patients and serum CTRP3 levels were measured by ELISA.BMI of the lean group was 21.9 ± 0.2 kg/m2 and obese group was 45.2 ± 1.1 kg/m2. We found significantly lower circulating levels of CTRP3 in obese individuals (405 ± 8.3 vs. 436 ± 6.7 ng/mL, p=0.004 compared to the lean group. Serum CTRP3 levels were inversely correlated with BMI (p=0.001, and triglycerides (p<0.001, and significantly associated with gender (p<0.01, ethnicity (p=0.05, HDL-cholesterol (p<0.01, and adiponectin (p<0.01. We found BMI (p<0.01, gender (p<0.01, and ethnicity (p<0.05 to be significant predictors of CTRP3 levels when controlling for age in multiple regression analysis.CTRP3 is a beneficial adipokine whose circulating levels are significantly lower in obese individuals. Obesity causes dysregulation in adipokine production, including the down-regulation of CTRP3. Lower CTRP3 levels may contribute to the pathophysiology of metabolic disorders associated with obesity. Optimizing CTRP3 levels through novel therapies may improve obesity and its comorbidities.

  7. [C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats].

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    Li, Rong; Yang, Xiaoxia; Yu, Yan; Zhou, Meilan; Tian, Xiujuan; Feng, Shidong; Wang, Hanmin

    2016-11-01

    Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0.5, 5 and 50 mg/kg, respectively. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6, caspase-1 and pyrin domain containing 3 (NLRP3) proteins in the renal tissues of rats. Results Compared with control group, serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group. Compared with the model group, serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups. Moreover, with the increase of the injection dosage of pAd-CTRP6, the suppressive effect was gradually strengthened. Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.

  8. Standardization and application of the solid phase C1q radioimmunoassay using soluble tetanus toxoid-antitetanus immune complexes in sera of patients with chronic polyarthritis and Lupus erythematodes

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    Menzel, E.J.; Steffen, C.; Smolen, J.

    1982-01-01

    Soluble tetanus-antitetanus immune complexes were prepared with affinity-chromatography and gel chromatography. Serial dilutions of these immune complex preparations were tested in a solid phase C1q radioimmunoassay. Soluble immune complexes as well as aggregated human gamma globulin of identical protein concentrations were comparatively investigated. Soluble immune complexes rendered a more sensitive standardization of RIA. According to these observations a relation between μg/ml equivalents of defined tetanus-antitetanus complexes and ng second antibody obtained in C1q-RIA was calculated. Upper limit of mean values and two standard deviations of ng second antibody obtained in investigations of 55 normal sera was designated as 1 unit immune complexes and regarded as border line of negative results. Multiplication of μg/ml immune complex equivalents of 1 unit led to a scale of 1 to 15 units, showing the area of positive results. According to these values a standardization curve was constructed allowing a conversion of ng-second antibody obtained in serum investigations into immune complex units equivalent to defined standard immune complexes. With this curve investigation results of 56 RA sera and 21 SLE sera were expressed in the range of units, making a distinct gradation of positive results and a clear cut separation of positive and negative results possible. SLE sera of patients in acute stage showed highly positive results. (orig.) [de

  9. Standardization and application of the solid phase C1q radioimmunoassay using soluble tetanus toxoid-antitetanus immune complexes in sera of patients with chronic polyarthritis and Lupus erythematodes

    Energy Technology Data Exchange (ETDEWEB)

    Menzel, E J; Steffen, C; Smolen, J

    1982-11-22

    Soluble tetanus-antitetanus immune complexes were prepared with affinity-chromatography and gel chromatography. Serial dilutions of these immune complex preparations were tested in a solid phase C1q radioimmunoassay. Soluble immune complexes as well as aggregated human gamma globulin of identical protein concentrations were comparatively investigated. Soluble immune complexes rendered a more sensitive standardization of RIA. According to these observations a relation between ..mu..g/ml equivalents of defined tetanus-antitetanus complexes and ng second antibody obtained in C1q-RIA was calculated. Upper limit of mean values and two standard deviations of ng second antibody obtained in investigations of 55 normal sera was designated as 1 unit immune complexes and regarded as border line of negative results. Multiplication of ..mu..g/ml immune complex equivalents of 1 unit led to a scale of 1 to 15 units, showing the area of positive results. According to these values a standardization curve was constructed allowing a conversion of ng-second antibody obtained in serum investigations into immune complex units equivalent to defined standard immune complexes. With this curve investigation results of 56 RA sera and 21 SLE sera were expressed in the range of units, making a distinct gradation of positive results and a clear cut separation of positive and negative results possible. SLE sera of patients in acute stage showed highly positive results.

  10. Asociación del anticuerpo anti-C1q con las manifestaciones clínicas, hematológicas e inmunológicas en el Lupus Eritematoso Sistémico : Estudio observacional retrospectivo de 135 casos.

    OpenAIRE

    Córica, María Emilia

    2012-01-01

    : Las concentraciones de anticuerpo anti-C1q están elevadas en los pacientes afectados de LES. Según algunos estudios la presencia de este anticuerpo está asociada a la nefropatía lúpica, sin embargo en otros estudios esta relación no se comprobó. En nuestro trabajo relacionamos la positividad del anticuerpo anti-C1q con las manifestaciones clínicas, hematológicas e inmunológicas de la enfermedad. A diferencia de estudios previos sólo pudimos establecer una relación estadísticamente significa...

  11. Circulating complement-C1q TNF-related protein 1 levels are increased in patients with type 2 diabetes and are associated with insulin sensitivity in Chinese subjects.

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    Xuebo Pan

    Full Text Available BACKGROUND: Complement-C1q TNF-related protein 1 (CTRP1, a member of the CTRP superfamily, possesses anti-inflammatory and anti-diabetic effects in mice. However, the clinical relevance of CTRP1 has been seldom explored. The current study aimed to investigate the association of circulating CTRP1 and type 2 diabetes mellitus (T2DM in a Chinese population. DESIGN AND METHODS: Serum CTRP1 and adiponectin levels of 96 T2DM patients and 85 healthy subjects were determined by ELISA, and their associations with adiposity, glucose and lipid profiles were studied. In a subgroup of this study, the 75-g oral glucose tolerance test (OGTT was performed in 20 healthy and 20 T2DM subjects to evaluate the relationship among serum levels of CTRP1 and adiponectin, insulin secretion and insulin sensitivity. RESULTS: Serum CTRP1 levels were significantly increased in patients with T2DM, compared with healthy controls (p<0.001. Similar to adiponectin, serum levels of CTRP1 were significantly correlated to several parameters involved in glucose metabolism and insulin resistance, and independently associated with fasting glucose levels (p<0.05 after BMI and gender adjustments. Furthermore, CTRP1 levels were positively correlated to insulin secretion, while negatively to insulin sensitivity, as measured by OGTT. CONCLUSION: CTRP1 is a novel adipokine associated with T2DM in humans. The paradoxical increase of serum CTRP1 levels in T2DM subjects may be due to a compensatory response to the adverse glucose and lipid metabolism, which warrants further investigation.

  12. Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

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    Elisa Ramos-Sevillano

    Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

  13. Antibodies Against Complement Components: Relevance for the Antiphospholipid Syndrome-Biomarkers of the Disease and Biopharmaceuticals.

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    Bećarević, Mirjana

    2017-07-01

    Laboratory criterion for the diagnosis of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPL Abs). Complement system has a role in mediating aPL Abs-induced thrombosis in animal models. The importance of antibodies against complement components (potential biomarkers of APS) and the importance of antibodies with beneficial anti-complement effects in APS (as biopharmaceuticals) are reviewed. Antibodies against complement components described in APS patients, so far, are anti-C1q and anti-factor H Abs, although anti-factor B Abs and anti-C5a Abs were described in animal models of APS. Clinical studies in APS patients are limited to a small number of case reports. Studies that would confirm potential role of Abs against complement components (as potential biomarkers of APS) are lacking. Lack of randomized clinical trials (that would provide complete data for confirmation of beneficial effects of biopharmaceuticals in complement inhibition) in APS is alarming.

  14. Different AMPA receptor subtypes mediate the distinct kinetic components of a biphasic EPSC in hippocampal interneurons

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    Todd eStincic

    2015-05-01

    Full Text Available CA1 hippocampal interneurons at the border between stratum radiatum and stratum lacunosum-moleculare have AMPA receptor (AMPAR-mediated excitatory postsynaptic currents (EPSCs that consist of two distinct phases: a typical fast component (FC, and a highly unusual slow component (SC that persists for hundreds of milliseconds. To determine whether these kinetically distinct components of the EPSC are mediated by distinct AMPAR subpopulations, we examined the relative contributions of GluA2-containing and –lacking AMPARs to the SC. GluA2-containing AMPARs mediated the majority of the FC whereas GluA2-lacking AMPARs preferentially generated the SC. When glutamate uptake through the glial glutamate transporter EAAT1 was inhibited, spill over-mediated AMPAR activation recruited an even slower third kinetic component that persisted for several seconds; however, this spillover-mediated current was mediated predominantly by GluA2-containing AMPARs and therefore was clearly distinct from the SC when uptake is intact. Thus, different AMPAR subpopulations that vary in GluA2 content mediate the distinct components of the AMPAR EPSC. The SC is developmentally downregulated in mice, declining after the second postnatal week. This downregulation affects both GluA2-containing and GluA2-lacking AMPARs mediating the SC, and is not accompanied by developmental changes in the GluA2 content of AMPARs underlying the FC. Thus, the downregulation of the SC appears to be independent of synaptic GluA2 expression, suggesting the involvement of another AMPAR subunit or an auxiliary protein. Our results therefore identify GluA2-dependent and GluA2-independent determinants of the SC: GluA2-lacking AMPARs preferentially contribute to the SC, while the developmental downregulation of the SC is independent of GluA2 content.

  15. Association between Type 2 Diabetes, Obesity and Key Immunological Components of IgE-mediated Inflammation

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    Sokolova Raditsa N.

    2017-06-01

    Full Text Available Background: Changes in lifestyle and obesity in recent decades have brought about a dramatic increase in type 2 diabetes mellitus (DM2 and allergic diseases. Clinical and epidemiological studies associate obesity with epidemics of allergic diseases. The link between obesity and DM2 with immunological components of IgE-mediated allergic inflammation is not yet conclusively established.

  16. Mediated Moderation in Combined Cognitive Behavioral Therapy versus Component Treatments for Generalized Anxiety Disorder

    Science.gov (United States)

    Newman, Michelle G.; Fisher, Aaron J.

    2013-01-01

    Objective: This study examined (a) duration of generalized anxiety disorder (GAD) as a moderator of cognitive behavioral therapy (CBT) versus its components (cognitive therapy and self-control desensitization) and (b) increases in dynamic flexibility of anxious symptoms during the course of psychotherapy as a mediator of this moderation. Degree of…

  17. F(ab'2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement

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    LORENA AGUILAR

    2005-01-01

    Full Text Available Trypanosoma cruzi calreticulin (TcCRT, described in our laboratory, retains several important functional features from its vertebrate homologues. We have shown that recombinant TcCRT inhibits the human complement system when it binds to the collagenous portion of C1q. The generation of classical pathway convertases and membrane attack complexes is thus strongly inhibited. In most T. cruzi-infected individuals, TcCRT is immunogenic and mediates the generation of specific antibodies. By reverting the C1q / TcCRT interaction, a parasite immune evasion strategy, these antibodies contribute to the host / parasite equilibrium. In an in vitro correlate of this situation, we show that the C1q / TcCRT interaction is inhibited by F(ab'2 polyclonal anti-TcCRT IgG fragments. It is therefore feasible that in infected humans anti-TcCRT antibodies participate in reverting an important parasite strategy aimed at inhibiting the classical complement pathway. Thus, membrane-bound TcCRT interacts with the collagenous portion C1q, and this C1q is recognized by the CD91-bound host cell CRT, thus facilitating parasite internalization. Based on our in vitro results, it could be proposed that the in vivo interaction between TcCRT and vertebrate C1q could be inhibited by F(ab'2 fragments anti-rTcCRT or against its S functional domain, thus interfering with the internalization process

  18. The Tlo Proteins Are Stoichiometric Components of Candida albicans Mediator Anchored via the Med3 Subunit

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    Zhang, Anda; Petrov, Kostadin O.; Hyun, Emily R.; Liu, Zhongle; Gerber, Scott A.

    2012-01-01

    The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo proteins in addition to the Mediator-associated population. Coexpression and copurification of Tloα12 and caMed3 in Escherichia coli established a direct physical interaction between the two proteins. We have also made a C. albicans med3Δ/Δ strain and purified an intact Mediator from this strain. The analysis of the composition of the med3Δ Mediator shows that it lacks a Tlo subunit. Regarding Mediator function, the med3Δ/Δ strain serves as a substitute for the difficult-to-make tloΔ/Δ C. albicans strain. A potential role of the TLO and MED3 genes in virulence is supported by the inability of the med3Δ/Δ strain to form normal germ tubes. This study of caMediator structure provides initial clues to the mechanism of action of the Tlo genes and a platform for further mechanistic studies of caMediator's involvement in gene regulatory patterns that underlie pathogenesis. PMID:22562472

  19. Mediated moderation in combined cognitive behavioral therapy versus component treatments for generalized anxiety disorder.

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    Newman, Michelle G; Fisher, Aaron J

    2013-06-01

    This study examined (a) duration of generalized anxiety disorder (GAD) as a moderator of cognitive behavioral therapy (CBT) versus its components (cognitive therapy and self-control desensitization) and (b) increases in dynamic flexibility of anxious symptoms during the course of psychotherapy as a mediator of this moderation. Degree of dynamic flexibility in daily symptoms was quantified as the inverse of spectral power due to daily to intradaily oscillations in four-times-daily diary data (Fisher, Newman, & Molenaar, 2011). This was a secondary analysis of the data of Borkovec, Newman, Pincus, and Lytle (2002). Seventy-six participants with a principle diagnosis of GAD were assigned randomly to combined CBT (n = 24), cognitive therapy (n = 25), or self-control desensitization (n = 27). Duration of GAD moderated outcome such that those with longer duration showed greater reliable change from component treatments than they showed from CBT, whereas those with shorter duration fared better in response to CBT. Decreasing predictability in daily and intradaily oscillations of anxiety symptoms during therapy reflected less rigidity and more flexible responding. Increases in flexibility over the course of therapy fully mediated the moderating effect of GAD duration on condition, indicating a mediated moderation process. Individuals with longer duration of GAD may respond better to more focused treatments, whereas those with shorter duration of GAD may respond better to a treatment that offers more coping strategies. Importantly, the mechanism by which this moderation occurs appears to be the establishment of flexible responding during treatment.

  20. The Role of Cgrp-Receptor Component Protein (Rcp in Cgrp-Mediated Signal Transduction

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    M. A. Prado

    2001-01-01

    Full Text Available The calcitonin gene-related peptide (CGRP-receptor component protein (RCP is a 17-kDa intracellular peripheral membrane protein required for signal transduction at CGRP receptors. To determine the role of RCP in CGRP-mediated signal transduction, RCP was depleted from NIH3T3 cells using antisense strategy. Loss of RCP protein correlated with loss of cAMP production by CGRP in the antisense cells. In contrast, loss of RCP had no effect on CGRP-mediated binding; therefore RCP is not acting as a chaperone for the CGRP receptor. Instead, RCP is a novel signal transduction molecule that couples the CGRP receptor to the cellular signal transduction machinery. RCP thus represents a prototype for a new class of signal transduction proteins that are required for regulation of G protein-coupled receptors.

  1. Human Milk Components Modulate Toll-Like Receptor–Mediated Inflammation12

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    He, YingYing; Lawlor, Nathan T

    2016-01-01

    Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2′-fucosyllactose attenuate TLR4 signaling; 3′-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. PMID:26773018

  2. Vibrio cholerae interactions with Mytilus galloprovincialis hemocytes mediated by serum components.

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    Laura eCanesi

    2013-12-01

    Full Text Available Edible bivalves (e.g., mussels, oysters can accumulate large amount of bacteria in their tissues and act as passive carriers of pathogens to humans. Bacterial persistence inside bivalves depends, at least in part, on hemolymph anti-bacterial activity that is exerted by both serum soluble factors and phagocytic cells (i.e., the hemocytes. It was previously shown that Mytilus galloprovincialis hemolymph serum contains opsonins that mediate D-mannose-sensitive interactions between hemocytes and V. cholerae O1 El Tor bacteria that carry the Mannose–Sensitive Hemagglutinin (MSHA. These opsonins enhance phagocytosis and killing of vibrios by facilitating their binding to hemocytes. Since V. cholerae strains not carrying the MSHA ligand (O1 classical, non O1/O139 are present in coastal water and can be entrapped by mussels, we studied whether in mussel serum, in addition to opsonins directed towards MSHA, other components can mediate opsonization of these bacteria. By comparing interactions of O1 classical and non O1/O139 strains with hemocytes in ASW and serum, it was found that M. galloprovincialis serum contains components that increase by at approximately two fold their adhesion to, association with and killing by hemocytes. Experiments conducted with high and low molecular mass fractions obtained by serum ultrafiltration indicated that these compounds have molecular mass higher than 5000 Da. Serum exposure to high temperature (80°C abolished its opsonizing capability suggesting that the involved serum active components are of protein nature. Further studies are needed to define the chemical properties and specificity of both the involved bacterial ligands and hemolymph opsonins. This information will be central not only to better understand V. cholerae ecology, but also to improve current bivalve depuration practices and properly protect human health.

  3. A Mediation Analysis on the Relationship of Physical Fitness Components, Obesity, and Academic Performance in Children.

    Science.gov (United States)

    Muntaner-Mas, Adrià; Pere, Palou; Vidal-Conti, Josep; Esteban-Cornejo, Irene

    2018-04-20

    To examine the relationship between a battery of obesity indicators and physical fitness components with academic performance in children and to explore the combined and mediation role of the physical fitness components in the relationship between obesity and academic performance in children. A cross-sectional study including data from 250 Spanish schoolchildren (Balearic Islands) between 10 and 12 years of age (mean age, 10.98 ± 0.76 years) was conducted. Obesity measures (body mass index, body fat, waist circumference, hip circumference, and waist-to-height ratio), physical fitness components (cardiorespiratory fitness, muscular fitness, and speed-agility), and academic performance (Spanish language, Catalan language, English language, natural sciences, social sciences, arts, physical education, religion, and grade point average [GPA]) were collected. All obesity measures were negatively related to at least 3 of the 10 academic indicators, including GPA (β range, -0.135 to -0.229; all P fitness and speed-agility were positively related to all academic indicators (β range, 0.182 to 0.350; all P fitness with 3 academic indicators (β range, 0.143 to 0.253; all P fit had better academic performance than their unfit peers (score +0.75; P = .001). The association between body mass index and GPA was mediated by cardiorespiratory fitness and speed-agility. This investigation contributes to the current knowledge by adding evidence about the crucial role of physical fitness in terms of academic performance rather than obesity status, suggesting that physical fitness may ameliorate the negative influence of obesity on academic performance. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Chaperone-mediated autophagy components are upregulated in sporadic inclusion-body myositis muscle fibres.

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    Cacciottolo, M; Nogalska, A; D'Agostino, C; Engel, W K; Askanas, V

    2013-12-01

    Sporadic inclusion-body myositis (s-IBM) is an age-associated degenerative muscle disease. Characteristic features are muscle-fibre vacuolization and intramuscle-fibre accumulations of multiprotein aggregates, which may result from the demonstrated impairments of the 26S proteasome and autophagy. Chaperone-mediated autophagy (CMA) is a selective form of lysosomal degradation targeting proteins carrying the KFERQ motif. Lysosome-associated membrane protein type 2A (LAMP2A) and the heat-shock cognate protein 70 (Hsc70) constitute specific CMA components. Neither CMA components nor CMA activity has been studied in normal or disease human muscle, to our knowledge. We studied CMA components by immunocytochemistry, immunoblots, real-time PCR and immunoprecipitation in: (a) 16 s-IBM, nine aged-matched normal and nine disease control muscle biopsies; and (b) cultured human muscle fibres (CHMFs) with experimentally inhibited activities of either the 26S proteasome or autophagy. Compared with age-matched controls, in s-IBM muscle, LAMP2A and Hsc70 were on a given transverse section accumulated as aggregates in approximately 5% of muscle fibres, where they (a) colocalized with each other and α-synuclein (α-syn), a CMA-targeted protein; and (b) were bound to each other and to α-syn by immunoprecipitation. By immunoblots, LAMP2A was increased sevenfold P pathogenic aspect in s-IBM. © 2013 British Neuropathological Society.

  5. Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction

    International Nuclear Information System (INIS)

    Bauer, G

    2011-01-01

    Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.

  6. Resting sympathetic activity is associated with the sympathetically mediated component of energy expenditure following a meal.

    Science.gov (United States)

    Limberg, Jacqueline K; Malterer, Katherine R; Matzek, Luke J; Levine, James A; Charkoudian, Nisha; Miles, John M; Joyner, Michael J; Curry, Timothy B

    2017-08-01

    Individuals with high plasma norepinephrine (NE) levels at rest have a smaller reduction in resting energy expenditure (REE) following β -adrenergic blockade. If this finding extends to the response to a meal, it could have important implications for the role of the sympathetic nervous system in energy balance and weight gain. We hypothesized high muscle sympathetic nerve activity (MSNA) would be associated with a low sympathetically mediated component of energy expenditure following a meal. Fourteen young, healthy adults completed two visits randomized to continuous saline (control) or intravenous propranolol to achieve systemic β -adrenergic blockade. Muscle sympathetic nerve activity and REE were measured (indirect calorimetry) followed by a liquid mixed meal (Ensure). Measures of energy expenditure continued every 30 min for 5 h after the meal and are reported as an area under the curve (AUC). Sympathetic support of energy expenditure was calculated as the difference between the AUC during saline and β -blockade (AUC P ropranolol -AUC S aline , β -REE) and as a percent (%) of control (AUC P ropranolol ÷AUC S aline  × 100). β -REE was associated with baseline sympathetic activity, such that individuals with high resting MSNA (bursts/100 heart beats) and plasma NE had the greatest sympathetically mediated component of energy expenditure following a meal (MSNA: β -REE R  =   -0.58, P =  0.03; %REE R  = -0.56, P =  0.04; NE: β -REE R  = -0.55, P  = 0.0535; %REE R  = -0.54, P  = 0.0552). Contrary to our hypothesis, high resting sympathetic activity is associated with a greater sympathetically mediated component of energy expenditure following a liquid meal. These findings may have implications for weight maintenance in individuals with varying resting sympathetic activity. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  7. Complement-fixing antibodies against denatured HLA and MICA antigens are associated with antibody mediated rejection.

    Science.gov (United States)

    Cai, Junchao; Terasaki, Paul I; Zhu, Dong; Lachmann, Nils; Schönemann, Constanze; Everly, Matthew J; Qing, Xin

    2016-02-01

    We have found antibodies against denatured HLA class I antigens in the serum of allograft recipients which were not significantly associated with graft failure. It is unknown whether transplant recipients also have denatured HLA class II and MICA antibodies. The effects of denatured HLA class I, class II, and MICA antibodies on long-term graft outcome were further investigated based on their ability to fix complement c1q. In this 4-year retrospective cohort study, post-transplant sera from 975 kidney transplant recipients were tested for antibodies against denatured HLA/MICA antigens and these antibodies were further classified based on their ability to fix c1q. Thirty percent of patients had antibodies against denatured HLA class I, II, or MICA antigens. Among them, 8.5% and 21.5% of all patients had c1q-fixing and non c1q-fixing antibodies respectively. There was no significant difference on graft survival between patients with or without antibodies against denatured HLA/MICA. However, when these antibodies were further classified according to their ability to fix c1q, patients with c1q-fixing antibodies had a significantly lower graft survival rate than patients without antibodies or patients with non c1q-fixing antibodies (p=0.008). In 169 patients who lost renal grafts, 44% of them had c1q-fixing antibodies against denatured HLA/MICA antigens, which was significantly higher than that in patients with functioning renal transplants (25%, pantibodies were more significantly associated with graft failure caused by AMR (72.73%) or mixed AMR/CMR (61.9%) as compared to failure due to CMR (35.3%) or other causes (39.2%) (p=0.026). Transplant recipients had antibodies against denatured HLA class I, II, and MICA antigens. However, only c1q-fixing antibodies were associated with graft failure which was related to antibody mediated rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Identification of Aspergillus fumigatus Surface Components That Mediate Interaction of Conidia and Hyphae With Human Platelets.

    Science.gov (United States)

    Rambach, Günter; Blum, Gerhard; Latgé, Jean-Paul; Fontaine, Thierry; Heinekamp, Thorsten; Hagleitner, Magdalena; Jeckström, Hanna; Weigel, Günter; Würtinger, Philipp; Pfaller, Kristian; Krappmann, Sven; Löffler, Jürgen; Lass-Flörl, Cornelia; Speth, Cornelia

    2015-10-01

    Platelets were recently identified as a part of innate immunity. They are activated by contact with Aspergillus fumigatus; putative consequences include antifungal defense but also thrombosis, excessive inflammation, and thrombocytopenia. We aimed to identify those fungal surface structures that mediate interaction with platelets. Human platelets were incubated with Aspergillus conidia and hyphae, isolated wall components, or fungal surface mutants. Interaction was visualized microscopically; activation was quantified by flow cytometry of specific markers. The capacity of A. fumigatus conidia to activate platelets is at least partly due to melanin, because this effect can be mimicked with "melanin ghosts"; a mutant lacking melanin showed reduced platelet stimulating potency. In contrast, conidial hydrophobin masks relevant structures, because an A. fumigatus mutant lacking the hydrophobin protein induced stronger platelet activation than wild-type conidia. A. fumigatus hyphae also contain surface structures that interact with platelets. Wall proteins, galactomannan, chitin, and β-glucan are not the relevant hyphal components; instead, the recently identified fungal polysaccharide galactosaminogalactan potently triggered platelet activation. Conidial melanin and hydrophobin as well as hyphal galactosaminogalactan represent important pathogenicity factors that modulate platelet activity and thus might influence immune responses, inflammation, and thrombosis in infected patients. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Do Emotional Components of Alexithymia Mediate the Interplay between Cyberbullying Victimization and Perpetration?

    Science.gov (United States)

    Wachs, Sebastian; Bilz, Ludwig; Fischer, Saskia M; Wright, Michelle F

    2017-12-08

    A substantial amount of research has revealed that cyberbully-victims have more emotional and behavioral problems than either cyberbullying victims or perpetrators. However, until now, little research has been conducted into the factors that contribute to the interplay between cyberbullying victimization and perpetration. The purpose of this study was to examine the relationship between cyberbullying victimization, perpetration, and two emotional components of alexithymia, namely difficulties in identifying and describing one's own feelings. Self-report questions were administered to 1549 adolescents between 12 and 18 years old ( M = 14.51; SD = 1.68; 42.1% ( n = 652) male) from Germany and Thailand. Results showed that cyberbullying victimization and alexithymia are associated with cyberbullying perpetration. Moreover, alexithymia mediated the associations between cyberbullying victimization and adolescents' cyberbullying perpetration. Consequently, we suggest that the ability to describe and identify one's own feelings might be important for understanding the link between cyberbullying, victimization, and perpetration. The results may help develop prevention and intervention programs focused on reducing cyberbullying.

  10. Do Emotional Components of Alexithymia Mediate the Interplay between Cyberbullying Victimization and Perpetration?

    Science.gov (United States)

    Wachs, Sebastian; Bilz, Ludwig; Fischer, Saskia M.; Wright, Michelle F.

    2017-01-01

    A substantial amount of research has revealed that cyberbully-victims have more emotional and behavioral problems than either cyberbullying victims or perpetrators. However, until now, little research has been conducted into the factors that contribute to the interplay between cyberbullying victimization and perpetration. The purpose of this study was to examine the relationship between cyberbullying victimization, perpetration, and two emotional components of alexithymia, namely difficulties in identifying and describing one’s own feelings. Self-report questions were administered to 1549 adolescents between 12 and 18 years old (M = 14.51; SD = 1.68; 42.1% (n = 652) male) from Germany and Thailand. Results showed that cyberbullying victimization and alexithymia are associated with cyberbullying perpetration. Moreover, alexithymia mediated the associations between cyberbullying victimization and adolescents’ cyberbullying perpetration. Consequently, we suggest that the ability to describe and identify one’s own feelings might be important for understanding the link between cyberbullying, victimization, and perpetration. The results may help develop prevention and intervention programs focused on reducing cyberbullying. PMID:29292720

  11. Do Emotional Components of Alexithymia Mediate the Interplay between Cyberbullying Victimization and Perpetration?

    Directory of Open Access Journals (Sweden)

    Sebastian Wachs

    2017-12-01

    Full Text Available A substantial amount of research has revealed that cyberbully-victims have more emotional and behavioral problems than either cyberbullying victims or perpetrators. However, until now, little research has been conducted into the factors that contribute to the interplay between cyberbullying victimization and perpetration. The purpose of this study was to examine the relationship between cyberbullying victimization, perpetration, and two emotional components of alexithymia, namely difficulties in identifying and describing one’s own feelings. Self-report questions were administered to 1549 adolescents between 12 and 18 years old (M = 14.51; SD = 1.68; 42.1% (n = 652 male from Germany and Thailand. Results showed that cyberbullying victimization and alexithymia are associated with cyberbullying perpetration. Moreover, alexithymia mediated the associations between cyberbullying victimization and adolescents’ cyberbullying perpetration. Consequently, we suggest that the ability to describe and identify one’s own feelings might be important for understanding the link between cyberbullying, victimization, and perpetration. The results may help develop prevention and intervention programs focused on reducing cyberbullying.

  12. The Relationship between Listening Comprehension of Text and Sentences in Preschoolers: Specific or Mediated by Lower and Higher Level Components?

    Science.gov (United States)

    Florit, Elena; Roch, Maja; Levorato, M. Chiara

    2013-01-01

    Two studies explored the relation between listening comprehension of text and listening comprehension of sentences in preschoolers aged 4 to 5 years, 11 months. The first study analyzed this relationship taking into account the role of lower level components, namely, word knowledge and verbal working memory, as possible mediators. These components…

  13. Glutamatergic activation of anterior cingulate cortex mediates the affective component of visceral pain memory in rats.

    Science.gov (United States)

    Yan, Ni; Cao, Bing; Xu, Jiahe; Hao, Chun; Zhang, Xu; Li, Ying

    2012-01-01

    Studies of both humans and animals suggest that anterior cingulate cortex (ACC) is important for processing pain perception. We identified that perigenul ACC (pACC) sensitization and enhanced visceral pain in a visceral hypersensitive rat in previous studies. Pain contains both sensory and affective dimensions. Teasing apart the mechanisms that control the neural pathways mediating pain affect and sensation in nociceptive behavioral response is a challenge. In this study, using a rodent visceral pain assay that combines the colorectal distension (CRD)-induced visceromotor response (VMR) with the conditioning place avoidance (CPA), we measured a learned behavior that directly reflects the affective component of visceral pain. When CRD was paired with a distinct environment context, the rats spent significantly less time in this compartment on the post-conditioning test days as compared with the pre-conditioning day. Effects were lasted for 14 days. Bilateral pACC lesion significantly reduced CPA scores without reducing acute visceral pain behaviors (CRD-induced VMR). Bilateral administration of non-NMDA receptor antagonist CNQX or NMDA receptor antagonist AP5 into the pACC decreased the CPA scores. AP5 or CNQX at dose of 400 mM produced about 70% inhibition of CRD-CPA in the day 1, 4 and 7, and completely abolished the CPA in the day 14 after conditioning. We concluded that neurons in the pACC are necessary for the "aversiveness" of visceral nociceptor stimulation. pACC activation is critical for the memory processing involved in long-term negative affective state and prediction of aversive stimuli by contextual cue. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Testing the Causal Mediation Component of Dodge's Social Information Processing Model of Social Competence and Depression

    Science.gov (United States)

    Possel, Patrick; Seemann, Simone; Ahrens, Stefanie; Hautzinger, Martin

    2006-01-01

    In Dodge's model of "social information processing" depression is the result of a linear sequence of five stages of information processing ("Annu Rev Psychol" 44: 559-584, 1993). These stages follow a person's reaction to situational stimuli, such that each stage of information processing mediates the relationship between earlier and later stages.…

  15. Role of Host Type IA Phosphoinositide 3-Kinase Pathway Components in Invasin-Mediated Internalization of Yersinia enterocolitica.

    Science.gov (United States)

    Dowd, Georgina C; Bhalla, Manmeet; Kean, Bernard; Thomas, Rowan; Ireton, Keith

    2016-06-01

    Many bacterial pathogens subvert mammalian type IA phosphoinositide 3-kinase (PI3K) in order to induce their internalization into host cells. How PI3K promotes internalization is not well understood. Also unclear is whether type IA PI3K affects different pathogens through similar or distinct mechanisms. Here, we performed an RNA interference (RNAi)-based screen to identify components of the type IA PI3K pathway involved in invasin-mediated entry of Yersinia enterocolitica, an enteropathogen that causes enteritis and lymphadenitis. The 69 genes targeted encode known upstream regulators or downstream effectors of PI3K. A similar RNAi screen was previously performed with the food-borne bacterium Listeria monocytogenes The results of the screen with Y. enterocolitica indicate that at least nine members of the PI3K pathway are needed for invasin-mediated entry. Several of these proteins, including centaurin-α1, Dock180, focal adhesion kinase (FAK), Grp1, LL5α, LL5β, and PLD2 (phospholipase D2), were recruited to sites of entry. In addition, centaurin-α1, FAK, PLD2, and mTOR were required for remodeling of the actin cytoskeleton during entry. Six of the human proteins affecting invasin-dependent internalization also promote InlB-mediated entry of L. monocytogenes Our results identify several host proteins that mediate invasin-induced effects on the actin cytoskeleton and indicate that a subset of PI3K pathway components promote internalization of both Y. enterocolitica and L. monocytogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. Visualizing solvent mediated phase transformation behavior of carbamazepine polymorphs by principal component analysis

    DEFF Research Database (Denmark)

    Tian, Fang; Rades, Thomas; Sandler, Niklas

    2008-01-01

    The purpose of this research is to gain a greater insight into the hydrate formation processes of different carbamazepine (CBZ) anhydrate forms in aqueous suspension, where principal component analysis (PCA) was applied for data analysis. The capability of PCA to visualize and to reveal simplified...

  17. Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.

    Directory of Open Access Journals (Sweden)

    Hanqian Mao

    2016-09-01

    Full Text Available The exon junction complex (EJC is an RNA binding complex comprised of the core components Magoh, Rbm8a, and Eif4a3. Human mutations in EJC components cause neurodevelopmental pathologies. Further, mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly. Yet despite the requirement of these genes for neurodevelopment, the pathogenic mechanisms linking EJC dysfunction to microcephaly remain poorly understood. Here we employ mouse genetics, transcriptomic and proteomic analyses to demonstrate that haploinsufficiency for each of the 3 core EJC components causes microcephaly via converging regulation of p53 signaling. Using a new conditional allele, we first show that Eif4a3 haploinsufficiency phenocopies aberrant neurogenesis and microcephaly of Magoh and Rbm8a mutant mice. Transcriptomic and proteomic analyses of embryonic brains at the onset of neurogenesis identifies common pathways altered in each of the 3 EJC mutants, including ribosome, proteasome, and p53 signaling components. We further demonstrate all 3 mutants exhibit defective splicing of RNA regulatory proteins, implying an EJC dependent RNA regulatory network that fine-tunes gene expression. Finally, we show that genetic ablation of one downstream pathway, p53, significantly rescues microcephaly of all 3 EJC mutants. This implicates p53 activation as a major node of neurodevelopmental pathogenesis following EJC impairment. Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease.

  18. Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

    International Nuclear Information System (INIS)

    Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M.

    1991-01-01

    Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37 degree C. A functional fibrinogen-binding component (M r , 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with 125 I-fibrinogen. Fibrinogen degradation did not occur at 4 degree C but did occur at 22 and 37 degree C. When bacteria and iodinated fibrinogen were incubated at 37 degree C, two major fibrinogen fragments (M r , 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M r , 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M r -120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-α-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate

  19. Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M. (Univ. of Alabama at Birmingham (USA))

    1991-01-01

    Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37{degree}C. A functional fibrinogen-binding component (M{sub r}, 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with {sup 125}I-fibrinogen. Fibrinogen degradation did not occur at 4{degree}C but did occur at 22 and 37{degree}C. When bacteria and iodinated fibrinogen were incubated at 37{degree}C, two major fibrinogen fragments (M{sub r}, 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M{sub r}, 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M{sub r}-120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-{alpha}-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate.

  20. Hypochlorous acid-mediated oxidation of lipid components and antioxidants present in low-density lipoproteins

    DEFF Research Database (Denmark)

    Pattison, David I; Hawkins, Clare Louise; Davies, Michael Jonathan

    2003-01-01

    Oxidation of low-density lipoproteins (LDL) is believed to contribute to the increased uptake of LDL by macrophages, which is an early event in atherosclerosis. Hypochlorous acid (HOCl) has been implicated as one of the major oxidants involved in these processes. In a previous study, the rates...... of reaction of HOCl with the reactive sites in proteins were investigated (Pattison, D. I., and Davies, M. J. (2001) Chem. Res. Toxicol. 14, 1453-1464). The work presented here expands on those studies to determine absolute second-order rate constants for the reactions of HOCl with various lipid components...... nitrogen- and carbon-centered radicals. Subsequent reactions of these species may induce oxidation of the LDL lipid component. In contrast, phosphoryl-choline reacted much more slowly (k Reaction of HOCl with 3-pentenoic acid was used as a model of lipid double bonds...

  1. Optimization of components in high-yield synthesis of block copolymer-mediated gold nanoparticles

    International Nuclear Information System (INIS)

    Ray, Debes; Aswal, Vinod Kumar

    2012-01-01

    The optimization to achieve stable and high-yield gold nanoparticles in block copolymer-mediated synthesis has been examined. Gold nanoparticles are synthesized using block copolymer P85 in gold salt HAuCl 4 ·3H 2 O solution. This method usually has a very limited yield which does not simply increase with the increase in the gold salt concentration. We show that the yield can be enhanced by increasing the block copolymer concentration but is limited to the factor by which the concentration is increased. On the other hand, the presence of an additional reductant (trisodium citrate) in 1:1 molar ratio with gold salt enhances the yield by manyfold. In this case (with additional reductant), the stable and high-yield nanoparticles having size about 14 nm can be synthesized at very low block copolymer concentrations. These nanoparticles thus can be efficiently used for their application such as for adsorption of proteins.

  2. Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.

    Science.gov (United States)

    Mao, Suifang; Shah, Alok S; Moninger, Thomas O; Ostedgaard, Lynda S; Lu, Lin; Tang, Xiao Xiao; Thornell, Ian M; Reznikov, Leah R; Ernst, Sarah E; Karp, Philip H; Tan, Ping; Keshavjee, Shaf; Abou Alaiwa, Mahmoud H; Welsh, Michael J

    2018-02-06

    Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gα i and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. Copyright © 2018 the Author(s). Published by PNAS.

  3. Cumulative organic anion transporter-mediated drug-drug interaction potential of multiple components in salvia miltiorrhiza (danshen) preparations.

    Science.gov (United States)

    Wang, Li; Venitz, Jürgen; Sweet, Douglas H

    2014-12-01

    To evaluate organic anion transporter-mediated drug-drug interaction (DDI) potential for individual active components of Danshen (Salvia miltiorrhiza) vs. combinations using in vitro and in silico approaches. Inhibition profiles for single Danshen components and combinations were generated in stably-expressing human (h)OAT1 and hOAT3 cells. Plasma concentration-time profiles for compounds were estimated from in vivo human data using an i.v. two-compartment model (with first-order elimination). The cumulative DDI index was proposed as an indicator of DDI potential for combination products. This index was used to evaluate the DDI potential for Danshen injectables from 16 different manufacturers and 14 different lots from a single manufacturer. The cumulative DDI index predicted in vivo inhibition potentials, 82% (hOAT1) and 74% (hOAT3), comparable with those observed in vitro, 72 ± 7% (hOAT1) and 81 ± 10% (hOAT3), for Danshen component combinations. Using simulated unbound Cmax values, a wide range in cumulative DDI index between manufacturers, and between lots, was predicted. Many products exhibited a cumulative DDI index > 1 (50% inhibition). Danshen injectables will likely exhibit strong potential to inhibit hOAT1 and hOAT3 function in vivo. The proposed cumulative DDI index might improve prediction of DDI potential of herbal medicines or pharmaceutical preparations containing multiple components.

  4. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  5. Examining causal components and a mediating process underlying self-generated health arguments for exercise and smoking cessation.

    Science.gov (United States)

    Baldwin, Austin S; Rothman, Alexander J; Vander Weg, Mark W; Christensen, Alan J

    2013-12-01

    Self-persuasion-generating one's own arguments for engaging in a specific behavior-can be an effective strategy to promote health behavior change, yet the causal processes that explain why it is effective are not well-specified. We sought to elucidate specific causal components and a mediating process of self-persuasion in two health behavior domains: physical activity and smoking. In two experiments, participants were randomized to write or read arguments about regular exercise (Study 1: N = 76; college students) or smoking cessation (Study 2: N = 107; daily smokers). In Study 2, we also manipulated the argument content (matched vs. mismatched participants' own concerns about smoking) to isolate its effect from the effect of argument source (self vs. other). Study outcomes included participants' reports of argument ratings, attitudes, behavioral intentions (Studies 1 & 2), and cessation attempts at 1 month (Study 2). In Study 1, self-generated arguments about exercise were evaluated more positively than other arguments (p = .01, d = .63), and this biased processing mediated the self-generated argument effect on attitudes toward exercise (β = .08, 95% CI = .01, .18). In Study 2, the findings suggested that biased processing occurs because self-generated argument content matches people's own health concerns and not because of the argument source (self vs. other). In addition, self-generated arguments indirectly led to greater behavior change intentions (Studies 1 & 2) and a greater likelihood of a smoking cessation attempt (Study 2). The findings elucidate a causal component and a mediating process that explain why self-persuasion and related behavior change interventions, such as motivational interviewing, are effective. Findings also suggest that self-generated arguments may be an efficient way to deliver message interventions aimed at changing health behaviors.

  6. Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.

    Science.gov (United States)

    Donson, Andrew M; Apps, John; Griesinger, Andrea M; Amani, Vladimir; Witt, Davis A; Anderson, Richard C E; Niazi, Toba N; Grant, Gerald; Souweidane, Mark; Johnston, James M; Jackson, Eric M; Kleinschmidt-DeMasters, Bette K; Handler, Michael H; Tan, Aik-Choon; Gore, Lia; Virasami, Alex; Gonzalez-Meljem, Jose Mario; Jacques, Thomas S; Martinez-Barbera, Juan Pedro; Foreman, Nicholas K; Hankinson, Todd C

    2017-09-01

    Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  7. Structural white-matter connections mediating distinct behavioral components of spatial neglect in right brain-damaged patients.

    Science.gov (United States)

    Vaessen, Maarten J; Saj, Arnaud; Lovblad, Karl-Olof; Gschwind, Markus; Vuilleumier, Patrik

    2016-04-01

    Spatial neglect is a neuropsychological syndrome in which patients fail to perceive and orient to stimuli located in the space contralateral to the lesioned hemisphere. It is characterized by a wide heterogeneity in clinical symptoms which can be grouped into distinct behavioral components correlating with different lesion sites. Moreover, damage to white-matter (WM) fiber tracts has been suggested to disconnect brain networks that mediate different functions associated with spatial cognition and attention. However, it remains unclear what WM pathways are associated with functionally dissociable neglect components. In this study we examined nine patients with a focal right hemisphere stroke using a series of neuropsychological tests and diffusion tensor imaging (DTI) in order to disentangle the role of specific WM pathways in neglect symptoms. First, following previous work, the behavioral test scores of patients were factorized into three independent components reflecting perceptual, exploratory, and object-centered deficits in spatial awareness. We then examined the structural neural substrates of these components by correlating indices of WM integrity (fractional anisotropy) with the severity of deficits along each profile. Several locations in the right parietal and frontal WM correlated with neuropsychological scores. Fiber tracts projecting from these locations indicated that posterior parts of the superior longitudinal fasciculus (SLF), as well as nearby callosal fibers connecting ipsilateral and contralateral parietal areas, were associated with perceptual spatial deficits, whereas more anterior parts of SLF and inferior fronto-occipital fasciculus (IFOF) were predominantly associated with object-centered deficits. In addition, connections between frontal areas and superior colliculus were found to be associated with the exploratory deficits. Our results provide novel support to the view that neglect may result from disconnection lesions in distributed

  8. Assemblage structure: an overlooked component of human-mediated species movements among freshwater ecosystems

    Directory of Open Access Journals (Sweden)

    D. Andrew R. Drake

    2014-04-01

    many influential factors (e.g., demographic and genetic stochasticity, environmental variability, composition of recipient ecosystems that will help refine an understanding of establishment risk following the human-mediated movement of species. 

  9. Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo.

    Science.gov (United States)

    Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

    2017-07-12

    The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo.

  10. Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration

    Directory of Open Access Journals (Sweden)

    Guang-shuai Li

    2016-01-01

    Full Text Available Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8ß and complement factor D in the nerve regeneration conditioned fluid and each varied at different time points. These findings suggest that all these complement components have a functional role in nerve regeneration.

  11. A component of retinal light adaptation mediated by the thyroid hormone cascade.

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    Diana E Bedolla

    Full Text Available Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3 are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2-3 months of age kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4-8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation.

  12. A component of retinal light adaptation mediated by the thyroid hormone cascade.

    Science.gov (United States)

    Bedolla, Diana E; Torre, Vincent

    2011-01-01

    Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2-3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4-8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation.

  13. Influence of electron-phonon interaction on soliton mediated spin-charge conversion effects in two-component polymer model

    International Nuclear Information System (INIS)

    Sergeenkov, S.; Moraes, F.; Furtado, C.; Araujo-Moreira, F.M.

    2010-01-01

    By mapping a Hubbard-like model describing a two-component polymer in the presence of strong enough electron-phonon interactions (κ) onto the system of two coupled nonlinear Schroedinger equations with U(2) symmetry group, some nontrivial correlations between topological solitons mediated charge Q and spin S degrees of freedom are obtained. Namely, in addition to a charge fractionalization and reentrant like behavior of both Q(κ) and S(κ), the model also predicts a decrease of soliton velocity with κ as well as spin-charge conversion effects which manifest themselves through an explicit S(Q,Ω) dependence (with Ω being a mixing angle between spin-up and spin-down electron amplitudes). A possibility to observe the predicted effects in low-dimensional systems with charge and spin soliton carriers is discussed.

  14. Using network component analysis to dissect regulatory networks mediated by transcription factors in yeast.

    Directory of Open Access Journals (Sweden)

    Chun Ye

    2009-03-01

    Full Text Available Understanding the relationship between genetic variation and gene expression is a central question in genetics. With the availability of data from high-throughput technologies such as ChIP-Chip, expression, and genotyping arrays, we can begin to not only identify associations but to understand how genetic variations perturb the underlying transcription regulatory networks to induce differential gene expression. In this study, we describe a simple model of transcription regulation where the expression of a gene is completely characterized by two properties: the concentrations and promoter affinities of active transcription factors. We devise a method that extends Network Component Analysis (NCA to determine how genetic variations in the form of single nucleotide polymorphisms (SNPs perturb these two properties. Applying our method to a segregating population of Saccharomyces cerevisiae, we found statistically significant examples of trans-acting SNPs located in regulatory hotspots that perturb transcription factor concentrations and affinities for target promoters to cause global differential expression and cis-acting genetic variations that perturb the promoter affinities of transcription factors on a single gene to cause local differential expression. Although many genetic variations linked to gene expressions have been identified, it is not clear how they perturb the underlying regulatory networks that govern gene expression. Our work begins to fill this void by showing that many genetic variations affect the concentrations of active transcription factors in a cell and their affinities for target promoters. Understanding the effects of these perturbations can help us to paint a more complete picture of the complex landscape of transcription regulation. The software package implementing the algorithms discussed in this work is available as a MATLAB package upon request.

  15. Parental problem drinking and anxiety disorder symptoms in adult offspring: examining the mediating role of anxiety sensitivity components.

    Science.gov (United States)

    MacPherson, P S; Stewart, S H; McWilliams, L A

    2001-01-01

    Preliminary studies have implicated childhood exposure to parental problem drinking as a possible factor in the development of anxiety sensitivity (AS). The present retrospective study was designed to examine the role of exposure to distressing parental problem drinking behaviors, over and above the role of parental alcoholism, in the development of various AS components (psychological, physical, and social concerns) in the offspring. We also examined the possible mediating role of AS components in explaining relations between parental drinking problems and anxiety-related symptoms in the adult offspring. A sample of 213 university students provided retrospective reports of both distress related to parental drinking [Children of Alcoholics Screening Test (CAST)] and parental alcoholism [maternal and paternal forms of the Short Michigan Alcoholism Screening Test (SMAST)]. Participants also reported on their own current AS levels [AS Index (ASI)], general anxiety symptoms [State-Trait Anxiety Inventory-Trait subscale (STAI-T)], and lifetime history of uncued panic attacks [Panic Attack Questionnaire-Revised (PAQ-R)]. Scores on the CAST predicted AS psychological and physical concerns (but not social concerns) over and above participant gender and parental alcoholism measured by the SMASTs. Moreover, AS psychological concerns proved a consistent modest mediator of the relations between parental problem drinking on the CAST and both general anxiety and uncued panic outcomes in the offspring. Thus, exposure to distressing parental problem drinking behavior may be one factor that contributes to elevated AS psychological concerns in the child, which in turn may contribute to the development of anxiety disorder symptoms in the offspring.

  16. The components of the unique Zur regulon of Cupriavidus metallidurans mediate cytoplasmic zinc handling.

    Science.gov (United States)

    Bütof, Lucy; Schmidt-Vogler, Christopher; Herzberg, Martin; Große, Cornelia; Nies, Dietrich H

    2017-08-14

    Zinc is an essential trace element and at the same time it is toxic at high concentrations. In the beta-proteobacterium Cupriavidus metallidurans the highly efficient removal of surplus zinc from the periplasm is responsible for its outstanding metal resistance. Rather than having a typical Zur-dependent, high-affinity ATP-binding cassette transporter of the ABC protein superfamily for zinc uptake at low concentrations, C. metallidurans instead has the secondary zinc importer ZupT of the ZRT/IRT (ZIP) family. It is important to understand, therefore, how this zinc-resistant bacterium copes when it is exposed to low zinc concentrations. Members of the Zur regulon in C. metallidurans were identified by comparing the transcriptomes of a Δ zur mutant and its parent strain. The consensus sequence of the Zur-binding box was derived for the zupTp promoter-regulatory region using a truncation assay. The motif was used to predict possible Zur-boxes upstream of Zur regulon members. Binding of Zur to these boxes was confirmed. Two Zur-boxes upstream of the cobW 1 gene, encoding a putative zinc chaperone, proved to be required for complete repression of cobW 1 and its downstream genes in cells cultivated in mineral salts medium. A Zur box upstream of each of zur-cobW 2 , cobW 3 and zupT permitted low-expression level of these genes plus their up-regulation under zinc starvation conditions. This demonstrates a compartmentalization of zinc homeostasis in C. metallidurans with the periplasm being responsible for removal of surplus zinc and cytoplasmic components for management of zinc as an essential co-factor, with both compartments connected by ZupT. Importance Elucidating zinc homeostasis is necessary to understand both host-pathogen interactions and performance of free-living bacteria in their natural environment. Escherichia coli acquires zinc under low zinc concentrations by the Zur-controlled ZnuABC importer of the ABC superfamily, and this was also the paradigm for other

  17. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    Science.gov (United States)

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  18. SAF-A forms a complex with BRG1 and both components are required for RNA polymerase II mediated transcription.

    Directory of Open Access Journals (Sweden)

    Dzeneta Vizlin-Hodzic

    Full Text Available BACKGROUND: Scaffold attachment factor A (SAF-A participates in the regulation of gene expression by organizing chromatin into transcriptionally active domains and by interacting directly with RNA polymerase II. METHODOLOGY: Here we use co-localization, co-immunoprecipitation (co-IP and in situ proximity ligation assay (PLA to identify Brahma Related Gene 1 (BRG1, the ATP-driven motor of the human SWI-SNF chromatin remodeling complex, as another SAF-A interaction partner in mouse embryonic stem (mES cells. We also employ RNA interference to investigate functional aspects of the SAF-A/BRG1 interaction. PRINCIPAL FINDINGS: We find that endogenous SAF-A protein interacts with endogenous BRG1 protein in mES cells, and that the interaction does not solely depend on the presence of mRNA. Moreover the interaction remains intact when cells are induced to differentiate. Functional analyses reveal that dual depletion of SAF-A and BRG1 abolishes global transcription by RNA polymerase II, while the nucleolar RNA polymerase I transcription machinery remains unaffected. CONCLUSIONS: We demonstrate that SAF-A interacts with BRG1 and that both components are required for RNA Polymerase II Mediated Transcription.

  19. The Mediator Roles of Life Satisfaction and Self-Esteem between the Affective Components of Psychological Well-Being and the Cognitive Symptoms of Problematic Internet Use

    Science.gov (United States)

    Senol-Durak, Emre; Durak, Mithat

    2011-01-01

    The factors associated with cognitions about problematic Internet use have been empirically tested in various studies. The aim of the present study was to examine the mediator roles of both life satisfaction and self-esteem between affective components of subjective well-being and cognitions about problematic Internet use. For this purpose, the…

  20. Evaluating cis-2,6-Dimethylpiperidide (cis-DMP) as a Base Component in Lithium-Mediated Zincation Chemistry

    Science.gov (United States)

    Armstrong, David R; Garden, Jennifer A; Kennedy, Alan R; Leenhouts, Sarah M; Mulvey, Robert E; O'Keefe, Philip; O'Hara, Charles T; Steven, Alan

    2013-01-01

    Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N′,N′-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N

  1. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Science.gov (United States)

    Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

    2013-01-01

    We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  2. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Directory of Open Access Journals (Sweden)

    Peizhen Hu

    Full Text Available We reported (PLoS One 6 (12:e28670, 2011 that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1 expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  3. A pp32-retinoblastoma protein complex modulates androgen receptor-mediated transcription and associates with components of the splicing machinery

    International Nuclear Information System (INIS)

    Adegbola, Onikepe; Pasternack, Gary R.

    2005-01-01

    We have previously shown pp32 and the retinoblastoma protein interact. pp32 and the retinoblastoma protein are nuclear receptor transcriptional coregulators: the retinoblastoma protein is a coactivator for androgen receptor, the major regulator of prostate cancer growth, while pp32, which is highly expressed in prostate cancer, is a corepressor of the estrogen receptor. We now show pp32 increases androgen receptor-mediated transcription and the retinoblastoma protein modulates this activity. Using affinity purification and mass spectrometry, we identify members of the pp32-retinoblastoma protein complex as PSF and nonO/p54nrb, proteins implicated in coordinate regulation of nuclear receptor-mediated transcription and splicing. We show that the pp32-retinoblastoma protein complex is modulated during TPA-induced K562 differentiation. Present evidence suggests that nuclear receptors assemble multiprotein complexes to coordinately regulate transcription and mRNA processing. Our results suggest that pp32 and the retinoblastoma protein may be part of a multiprotein complex that coordinately regulates nuclear receptor-mediated transcription and mRNA processing

  4. Capsular Polysaccharide is a Main Component of Mycoplasma ovipneumoniae in the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells.

    Science.gov (United States)

    Jiang, Zhongjia; Song, Fuyang; Li, Yanan; Xue, Di; Deng, Guangcun; Li, Min; Liu, Xiaoming; Wang, Yujiong

    2017-01-01

    Mycoplasma ovipneumoniae ( M. ovipneumoniae ) is characterized as an etiological agent of primary atypical pneumonia that specifically infects sheep and goat. In an attempt to better understand the pathogen-host interaction between the invading M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory responses against capsular polysaccharide (designated as CPS) of M. ovipneumoniae using sheep bronchial epithelial cells cultured in an air-liquid interface (ALI) model. Results showed that CPS derived from M. ovipneumoniae could activate toll-like receptor- (TLR-) mediated inflammatory responses, along with an elevated expression of nuclear factor kappa B (NF- κ B), activator protein-1 (AP-1), and interferon regulatory factor 3 (IRF3) as well as various inflammatory-associated mediators, representatively including proinflammatory cytokines, such as IL1 β , TNF α , and IL8, and anti-inflammatory cytokines such as IL10 and TGF β of TLR signaling cascade. Mechanistically, the CPS-induced inflammation was TLR initiated and was mediated by activations of both MyD88-dependent and MyD88-independent signaling pathways. Of importance, a blockage of CPS with specific antibody led a significant reduction of M. ovipneumoniae -induced inflammatory responses in sheep bronchial epithelial cells. These results suggested that CPS is a key virulent component of M. ovipneumoniae , which may play a crucial role in the inflammatory response induced by M. ovipneumoniae infections.

  5. Capsular Polysaccharide is a Main Component of Mycoplasma ovipneumoniae in the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Zhongjia Jiang

    2017-01-01

    Full Text Available Mycoplasma ovipneumoniae (M. ovipneumoniae is characterized as an etiological agent of primary atypical pneumonia that specifically infects sheep and goat. In an attempt to better understand the pathogen-host interaction between the invading M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory responses against capsular polysaccharide (designated as CPS of M. ovipneumoniae using sheep bronchial epithelial cells cultured in an air-liquid interface (ALI model. Results showed that CPS derived from M. ovipneumoniae could activate toll-like receptor- (TLR- mediated inflammatory responses, along with an elevated expression of nuclear factor kappa B (NF-κB, activator protein-1 (AP-1, and interferon regulatory factor 3 (IRF3 as well as various inflammatory-associated mediators, representatively including proinflammatory cytokines, such as IL1β, TNFα, and IL8, and anti-inflammatory cytokines such as IL10 and TGFβ of TLR signaling cascade. Mechanistically, the CPS-induced inflammation was TLR initiated and was mediated by activations of both MyD88-dependent and MyD88-independent signaling pathways. Of importance, a blockage of CPS with specific antibody led a significant reduction of M. ovipneumoniae-induced inflammatory responses in sheep bronchial epithelial cells. These results suggested that CPS is a key virulent component of M. ovipneumoniae, which may play a crucial role in the inflammatory response induced by M. ovipneumoniae infections.

  6. Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

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    Kazuaki Yamanaka

    Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

  7. ResDE Two-Component Regulatory System Mediates Oxygen Limitation-Induced Biofilm Formation by Bacillus amyloliquefaciens SQR9.

    Science.gov (United States)

    Zhou, Xuan; Zhang, Nan; Xia, Liming; Li, Qing; Shao, Jiahui; Shen, Qirong; Zhang, Ruifu

    2018-04-15

    Efficient biofilm formation and root colonization capabilities facilitate the ability of beneficial plant rhizobacteria to promote plant growth and antagonize soilborne pathogens. Biofilm formation by plant-beneficial Bacillus strains is triggered by environmental cues, including oxygen deficiency, but the pathways that sense these environmental signals and regulate biofilm formation have not been thoroughly elucidated. In this study, we showed that the ResDE two-component regulatory system in the plant growth-promoting rhizobacterium Bacillus amyloliquefaciens strain SQR9 senses the oxygen deficiency signal and regulates biofilm formation. ResE is activated by sensing the oxygen limitation-induced reduction of the NAD + /NADH pool through its PAS domain, stimulating its kinase activity, and resulting in the transfer of a phosphoryl group to ResD. The phosphorylated ResD directly binds to the promoter regions of the qoxABCD and ctaCDEF operons to improve the biosynthesis of terminal oxidases, which can interact with KinB to activate biofilm formation. These results not only revealed the novel regulatory function of the ResDE two-component system but also contributed to the understanding of the complicated regulatory network governing Bacillus biofilm formation. This research may help to enhance the root colonization and the plant-beneficial efficiency of SQR9 and other Bacillus rhizobacteria used in agriculture. IMPORTANCE Bacillus spp. are widely used as bioinoculants for plant growth promotion and disease suppression. The exertion of their plant-beneficial functions is largely dependent on their root colonization, which is closely related to their biofilm formation capabilities. On the other hand, Bacillus is the model bacterium for biofilm study, and the process and molecular network of biofilm formation are well characterized (B. Mielich-Süss and D. Lopez, Environ Microbiol 17:555-565, 2015, https://doi.org/10.1111/1462-2920.12527; L. S. Cairns, L. Hobley, and

  8. Complement component C1r mediated cleavage of the heavy chain of the major histocompatibility class I antigens

    DEFF Research Database (Denmark)

    Eriksson, H; Nissen, Mogens Holst

    1992-01-01

    Apart from cleaving C1s, we demonstrate for the first time that: 1) at concentrations found in serum, the activated forms of the complement components C1r in addition to C1s can cleave the heavy chain of MHC class I antigens, 2) the cleavage by C1r and C1s is seemingly dependent upon a native con......-chain of MHC class I was shown to take place between the alpha 2- and alpha 3- domains as estimated by the Con A-Sepharose precipitation pattern on SDS-PAGE. The alpha 1/alpha 2 fragment was still shown to interact with beta 2-microglobulin as shown by immunoprecipitation....

  9. Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone Andrographolide, the active component of Andrographis paniculata

    Science.gov (United States)

    Yang, Shuo; Evens, Andrew M.; Prachand, Sheila; Singh, Amareshwar T.K; Bhalla, Savita; David, Kevin; Gordon, Leo I.

    2010-01-01

    Purpose Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, anti-viral and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines. Experimental Design We studied the Burkitt p53 mutated Ramos cell line, the mantle-cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1 and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL. Results We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin-V/propidium iodide (PI) in the presence and absence of the antioxidant N-acetyl-L-cysteine (NAC), the glutathione-depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by PARP cleavage and activation of caspases 3, 8 and 9. We measured BAX conformational change, and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEFBax−/−/Bak−/−), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and in patient samples. Conclusions Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted. PMID:20798229

  10. Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.

    Science.gov (United States)

    Peluso, John J

    2011-08-01

    Various ovarian cell types including granulosa cells and ovarian surface epithelial cells express the progesterone (P4) binding protein, progesterone receptor membrane component-1 (PGRMC1). PGRMC1 is also expressed in ovarian tumors. PGRMC1 plays an essential role in promoting the survival of both normal and cancerous ovarian cell in vitro. Given the clinical significance of factors that regulate the viability of ovarian cancer, this review will focus on the role of PGRMC1 in ovarian cancer, while drawing insights into the mechanism of PGRMC1's action from cell lines derived from healthy ovaries as well as ovarian tumors. Studies using PGRMC1siRNA demonstrated that P4's ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1. To confirm the importance of PGRMC1, the ability of PGRMC1-deplete ovarian cancer cell lines to form tumors in intact nude mice was assessed. Compared to PGRMC1-expressing ovarian cancer cells, PGRMC1-deplete ovarian cancer cells formed tumors in fewer mice (80% compared to 100% for controls). Moreover, the number of tumors derived from PGRMC1-deplete ovarian cancer cells was 50% of that observed in controls. Finally, the tumors that formed from PGRMC1-deplete ovarian cancer cells were about a fourth the size of tumors derived from ovarian cancer cells with normal levels of PGRMC1. One reason for PGRMC1-deplete tumors being smaller is that they had a poorly developed microvasculature system. How PGRMC1 regulates cell viability and in turn tumor growth is not known but part of the mechanism likely involves the regulation of genes that promote cell survival and inhibit apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling

    Science.gov (United States)

    Barrington, Chloe L.; Katsanis, Nicholas

    2017-01-01

    The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT) proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS) complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh) dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure. PMID:28291807

  12. The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    Sarah C Goetz

    Full Text Available The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure.

  13. Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling.

    Science.gov (United States)

    Shi, Haojun; Fang, Winston; Liu, Minda; Fu, Deliang

    2017-10-01

    Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. © 2017 UICC.

  14. Progesterone receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine-induced matrix metalloproteinase 9 activity in vitro.

    Science.gov (United States)

    Allen, Terrence K; Feng, Liping; Grotegut, Chad A; Murtha, Amy P

    2014-02-01

    Progesterone (P4) and the progestin, 17α-hydroxyprogesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical progesterone receptor (PGR) but instead a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyprogesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyprogesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small interfering RNA. Our findings highlight a possible novel role of PGRMC1 in mediating the effects of MPA and in modulating cytokine-induced MMP-9 activity in cytotrophoblast cells in vitro.

  15. Mutation of the Streptococcus gordonii Thiol-Disulfide Oxidoreductase SdbA Leads to Enhanced Biofilm Formation Mediated by the CiaRH Two-Component Signaling System.

    Directory of Open Access Journals (Sweden)

    Lauren Davey

    Full Text Available Streptococcus gordonii is a commensal inhabitant of human oral biofilms. Previously, we identified an enzyme called SdbA that played an important role in biofilm formation by S. gordonii. SdbA is thiol-disulfide oxidoreductase that catalyzes disulfide bonds in secreted proteins. Surprisingly, inactivation of SdbA results in enhanced biofilm formation. In this study we investigated the basis for biofilm formation by the ΔsdbA mutant. The results revealed that biofilm formation was mediated by the interaction between the CiaRH and ComDE two-component signalling systems. Although it did not affect biofilm formation by the S. gordonii parent strain, CiaRH was upregulated in the ΔsdbA mutant and it was essential for the enhanced biofilm phenotype. The biofilm phenotype was reversed by inactivation of CiaRH or by the addition of competence stimulating peptide, the production of which is blocked by CiaRH activity. Competition assays showed that the enhanced biofilm phenotype also corresponded to increased oral colonization in mice. Thus, the interaction between SdbA, CiaRH and ComDE affects biofilm formation both in vitro and in vivo.

  16. Divergent mechanisms underlie Smad4-mediated positive regulation of the three genes encoding the basement membrane component laminin-332 (laminin-5)

    International Nuclear Information System (INIS)

    Zboralski, Dirk; Böckmann, Miriam; Zapatka, Marc; Hoppe, Sabine; Schöneck, Anna; Hahn, Stephan A; Schmiegel, Wolff; Schwarte-Waldhoff, Irmgard

    2008-01-01

    Functional inactivation of the tumor suppressor Smad4 in colorectal and pancreatic carcinogenesis occurs coincident with the transition to invasive growth. Breaking the basement membrane (BM) barrier, a prerequisite for invasive growth, can be due to tumor induced proteolytic tissue remodeling or to reduced synthesis of BM molecules by incipient tumor cells. Laminin-332 (laminin-5), a heterotrimeric BM component composed of α3-, β3- and γ2-chains, has recently been identified as a target structure of Smad4 and represents the first example for expression control of an essential BM component by a tumor and invasion suppressor. Biochemically Smad4 is a transmitter of signals of the TGFβ superfamily of cytokines. We have reported previously, that Smad4 functions as a positive transcriptional regulator of constitutive and of TGFβ-induced transcription of all three genes encoding Laminin-332, LAMA3, LAMB3 and LAMC2. Promoter-reporter constructs harboring 4 kb upstream regions, each of the three genes encoding Laminin-322 as well as deletion and mutations constructs were established. Promoter activities and TGFβ induction were assayed through transient transfections in Smad4-negative human cancer cells and their stable Smad4-positive derivatives. Functionally relevant binding sites were subsequently confirmed through chromatin immunoprecipitation. Herein, we report that Smad4 mediates transcriptional regulation through three different mechanisms, namely through Smad4 binding to a functional SBE site exclusively in the LAMA3 promoter, Smad4 binding to AP1 (and Sp1) sites presumably via interaction with AP1 family components and lastly a Smad4 impact on transcription of AP1 factors. Whereas Smad4 is essential for positive regulation of all three genes, the molecular mechanisms are significantly divergent between the LAMA3 promoter as compared to the LAMB3 and LAMC2 promoters. We hypothesize that this divergence in modular regulation of the three promoters may lay the

  17. Post-intervention effects on screen behaviours and mediating effect of parental regulation: the HEalth In Adolescents study - a multi-component school-based randomized controlled trial

    NARCIS (Netherlands)

    Bergh, I.H.; van Stralen, M.M.; Bjelland, M.; Grydeland, M.; Lien, N.; Klepp, K.I.; Anderssen, S.A.; Ommundsen, Y.

    2014-01-01

    Background: To improve effectiveness of future screen behaviour interventions, one needs to know whether an intervention works via the proposed mediating mechanisms and whether the intervention is equally effective among subgroups. Parental regulation is identified as a consistent correlate of

  18. Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade

    OpenAIRE

    Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini; Mulenga, Albert

    2015-01-01

    In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it’s plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate fee...

  19. Immunoregulation of Neutrophil Extracellular Trap Formation by Endothelial-Derived p33 (gC1q Receptor)

    DEFF Research Database (Denmark)

    Neumann, Ariane; Papareddy, Praveen; Westman, Johannes

    2018-01-01

    The formation of neutrophil extracellular traps (NETs) is a host defence mechanism, known to facilitate the entrapment and growth inhibition of many bacterial pathogens. It has been implicated that the translocation of myeloperoxidase (MPO) from neutrophilic granules to the nucleus is crucial to ...

  20. MED25 is a mediator component of HNF4α-driven transcription leading to insulin secretion in pancreatic beta-cells.

    Directory of Open Access Journals (Sweden)

    Eun Hee Han

    Full Text Available Unique nuclear receptor Hepatocyte Nuclear Factor 4α (HNF4α is an essential transcriptional regulator for early development and proper function of pancreatic ß-cells, and its mutations are monogenic causes of a dominant inherited form of diabetes referred to as Maturity Onset Diabetes of the Young 1 (MODY1. As a gene-specific transcription factor, HNF4α exerts its function through various molecular interactions, but its protein recruiting network has not been fully characterized. Here we report the identification of MED25 as one of the HNF4α binding partners in pancreatic ß-cells leading to insulin secretion which is impaired in MODY patients. MED25 is one of the subunits of the Mediator complex that is required for induction of RNA polymerase II transcription by various transcription factors including nuclear receptors. This HNF4α-MED25 interaction was initially identified by a yeast-two-hybrid method, confirmed by in vivo and in vitro analyses, and proven to be mediated through the MED25-LXXLL motif in a ligand-independent manner. Reporter-gene based transcription assays and siRNA/shRNA-based gene silencing approaches revealed that this interaction is crucial for full activation of HNF4α-mediated transcription, especially expression of target genes implicated in glucose-stimulated insulin secretion. Selected MODY mutations at the LXXLL motif binding pocket disrupt these interactions and cause impaired insulin secretion through a 'loss-of-function' mechanism.

  1. Salicylic acid is an indispensable component of the Ny-1 resistance-gene-mediated response against Potato virus Y infection in potato.

    Science.gov (United States)

    Baebler, Š; Witek, K; Petek, M; Stare, K; Tušek-Žnidarič, M; Pompe-Novak, M; Renaut, J; Szajko, K; Strzelczyk-Żyta, D; Marczewski, W; Morgiewicz, K; Gruden, K; Hennig, J

    2014-03-01

    The purpose of the study was to investigate the role of salicylic acid (SA) signalling in Ny-1-mediated hypersensitive resistance (HR) of potato (Solanum tuberosum L.) to Potato virus Y (PVY). The responses of the Ny-1 allele in the Rywal potato cultivar and transgenic NahG-Rywal potato plants that do not accumulate SA were characterized at the cytological, biochemical, transcriptome, and proteome levels. Analysis of noninoculated and inoculated leaves revealed that HR lesions started to develop from 3 d post inoculation and completely restricted the virus spread. At the cytological level, features of programmed cell death in combination with reactive oxygen species burst were observed. In response to PVY infection, SA was synthesized de novo. The lack of SA accumulation in the NahG plants led to the disease phenotype due to unrestricted viral spreading. Grafting experiments show that SA has a critical role in the inhibition of PVY spreading in parenchymal tissue, but not in vascular veins. The whole transcriptome analysis confirmed the central role of SA in orchestrating Ny-1-mediated responses and showed that the absence of SA leads to significant changes at the transcriptome level, including a delay in activation of expression of genes known to participate in defence responses. Moreover, perturbations in the expression of hormonal signalling genes were detected, shown as a switch from SA to jasmonic acid/ethylene signalling. Viral multiplication in the NahG plants was accompanied by downregulation of photosynthesis genes and activation of multiple energy-producing pathways.

  2. New cobalt-mediated radical polymerization (CMRP of methyl methacrylate initiated by two single-component dinuclear β-diketone cobalt (II catalysts.

    Directory of Open Access Journals (Sweden)

    Feng Bao

    Full Text Available Two dinuclear cobalt complexes based on bis-diketonate ligands (ligand 1: 3,3'-(1,3-phenylenebis(1-phenylpropane-1,3-dione; ligand 2: 3,3'-(1,4-phenylenebis(1-phenylpropane-1,3-dione were successfully synthesized. The two neutral catalysts all showed satisfactory activities in the cobalt-mediated radical polymerization (CMRP of methyl methacrylate (MMA with the common initiator of azodiisobutyronitrile (AIBN. The resulting polymerizations have all of the characteristics of a living polymerization and displayed linear semilogarithmic kinetic plots, a linear correlation between the number-average molecular weight and the monomer conversion, and low polydispersities. Mono- or dicomponent low polydispersity polymers could be obtained by using the two dinuclear catalysts under proper reaction conditions. All these improvements facilitate the implementation of the acrylate CMRP and open the door to the scale-up of the syntheses and applications of the multicomponent low polydispersity polymers.

  3. HER2 monoclonal antibodies that do not interfere with receptor heterodimerization-mediated signaling induce effective internalization and represent valuable components for rational antibody-drug conjugate design.

    Science.gov (United States)

    de Goeij, Bart E C G; Peipp, Matthias; de Haij, Simone; van den Brink, Edward N; Kellner, Christian; Riedl, Thilo; de Jong, Rob; Vink, Tom; Strumane, Kristin; Bleeker, Wim K; Parren, Paul W H I

    2014-01-01

    The human epidermal growth factor receptor (HER)2 provides an excellent target for selective delivery of cytotoxic drugs to tumor cells by antibody-drug conjugates (ADC) as has been clinically validated by ado-trastuzumab emtansine (Kadcyla(TM)). While selecting a suitable antibody for an ADC approach often takes specificity and efficient antibody-target complex internalization into account, the characteristics of the optimal antibody candidate remain poorly understood. We studied a large panel of human HER2 antibodies to identify the characteristics that make them most suitable for an ADC approach. As a model toxin, amenable to in vitro high-throughput screening, we employed Pseudomonas exotoxin A (ETA') fused to an anti-kappa light chain domain antibody. Cytotoxicity induced by HER2 antibodies, which were thus non-covalently linked to ETA', was assessed for high and low HER2 expressing tumor cell lines and correlated with internalization and downmodulation of HER2 antibody-target complexes. Our results demonstrate that HER2 antibodies that do not inhibit heterodimerization of HER2 with related ErbB receptors internalize more efficiently and show greater ETA'-mediated cytotoxicity than antibodies that do inhibit such heterodimerization. Moreover, stimulation with ErbB ligand significantly enhanced ADC-mediated tumor kill by antibodies that do not inhibit HER2 heterodimerization. This suggests that the formation of HER2/ErbB-heterodimers enhances ADC internalization and subsequent killing of tumor cells. Our study indicates that selecting HER2 ADCs that allow piggybacking of HER2 onto other ErbB receptors provides an attractive strategy for increasing ADC delivery and tumor cell killing capacity to both high and low HER2 expressing tumor cells.

  4. Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

    Directory of Open Access Journals (Sweden)

    T.I. Omotayo

    2015-04-01

    Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

  5. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP.

    Science.gov (United States)

    Yeom, Miji; Lee, HansongI; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

    2018-03-23

    Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

  6. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP

    Directory of Open Access Journals (Sweden)

    Miji Yeom

    2018-03-01

    Full Text Available Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1 and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

  7. A plant small polypeptide is a novel component of DNA-binding protein phosphatase 1-mediated resistance to plum pox virus in Arabidopsis.

    Science.gov (United States)

    Castelló, María José; Carrasco, Jose Luis; Navarrete-Gómez, Marisa; Daniel, Jacques; Granot, David; Vera, Pablo

    2011-12-01

    DNA-binding protein phosphatases (DBPs) have been identified as a novel class of plant-specific regulatory factors playing a role in plant-virus interactions. NtDBP1 from tobacco (Nicotiana tabacum) was shown to participate in transcriptional regulation of gene expression in response to virus infection in compatible interactions, and AtDBP1, its closest relative in the model plant Arabidopsis (Arabidopsis thaliana), has recently been found to mediate susceptibility to potyvirus, one of the most speciose taxa of plant viruses. Here, we report on the identification of a novel family of highly conserved small polypeptides that interact with DBP1 proteins both in tobacco and Arabidopsis, which we have designated DBP-interacting protein 2 (DIP2). The interaction of AtDIP2 with AtDBP1 was demonstrated in vivo by bimolecular fluorescence complementation, and AtDIP2 was shown to functionally interfere with AtDBP1 in yeast. Furthermore, reducing AtDIP2 gene expression leads to increased susceptibility to the potyvirus Plum pox virus and to a lesser extent also to Turnip mosaic virus, whereas overexpression results in enhanced resistance. Therefore, we describe a novel family of conserved small polypeptides in plants and identify AtDIP2 as a novel host factor contributing to resistance to potyvirus in Arabidopsis.

  8. Storage of the complement components C4, C3, and C 3-activator in the human liver as PAS-negative globular hyaline bodies.

    Science.gov (United States)

    Storch, W; Riedel, H; Trautmann, B; Justus, J; Hiemann, D

    1982-01-01

    Liver biopsies of a 58-year-old clinically healthy patient with a hepatomegaly and intracisternal PAS-negative globular hyaline bodies were immunofluorescent-optically examined for the content of the complement components C 1 q, C 4, C 9, C 1-inactivator, C 3-activator. Further examinations were performed for fibrinogen, IgG, IgA, IgM, IgD, IgE, L-chain (type chi and lambda), alpha 1-antitrypsin, alpha 1-fetoprotein, alpha 1- and alpha 2-glycoprotein, cholinesterase, ceruloplasmin, myoglobin, hemopexin, HBsAg and HBsAg. Th inclusion bodies reacted with antisera against the complement components C 4, C 3 and C 3-activator, as also identified by double immunofluorescence. Probably this is a disturbance of the protein metabolism of the liver cell with abnormal complement storage in the presence of normal total complement and normal complement components in the serum.

  9. Cytoprotective effects of Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage)

    International Nuclear Information System (INIS)

    Kim, Sang Chan; Byun, Sung Hui; Yang, Chae Ha; Kim, Chul Young; Kim, Jin Woong; Kim, Sang Geon

    2004-01-01

    Glycyrrhizae radix has been popularly used as one of the oldest and most frequently employed botanicals in herbal medicine in Asian countries, and currently occupies an important place in food products. Cadmium (Cd) induces both apoptotic and non-apoptotic cell death, in which alterations in cellular sulfhydryls participate. In the present study, we determined the effects of G. radix extract (GRE) and its representative active components on cell death induced by Cd and explored the mechanistic basis of cytoprotective effects of G. radix. Incubation of H4IIE cells with GRE inhibited cell death induced by 10 μM Cd. Also, GRE effectively blocked Cd (1 μM)-induced cell death potentiated by buthionine sulfoximine (BSO) without restoration of cellular GSH. GRE prevented both apoptotic and non-apoptotic cell injury induced by Cd (10 μM) or Cd (0.3-1 μM) + BSO. Inhibition of Cd-induced cell injury by pretreatment of cells with GRE suggested that the cytoprotective effect result from alterations in the levels of the protein(s) responsible for cell viability. GRE inhibited mitochondrial Bad translocation by Cd or Cd+BSO, and caused restoration of mitochondrial Bcl xL and cytochrome c levels. Cd-induced poly(ADP-ribose)polymerase cleavage in control cells or in cells deprived of sulfhydryls was prevented by GRE treatment. Among the major components present in GRE, liquiritigenin, but not liquiritin, isoliquiritigenin or glycyrrhizin, exerted cytoprotective effect. These results demonstrated that GRE blocked Cd-induced cell death by inhibiting the apoptotic processes involving translocation of Bad into mitochondria, decreases in mitochondrial Bcl xL and cytochrome c, and poly(ADP-ribose)polymerase cleavage

  10. CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations.

    Science.gov (United States)

    Basavarajappa, Balapal S; Subbanna, Shivakumar

    2014-02-01

    Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as "Spice" or "K2" to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared with vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice. © 2013 Wiley Periodicals, Inc.

  11. Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily regulated by the two-component system ArcBA through antagonizing the H-NS mediated repression.

    Science.gov (United States)

    Deng, Ziqing; Shan, Yue; Pan, Qing; Gao, Xiang; Yan, Aixin

    2013-01-01

    The gadE-mdtEF operon encodes a central acid resistance regulator GadE and two multidrug efflux proteins MdtEF. Although transcriptional regulation of gadE in the context of acid resistance under the aerobic growth environment of Escherichia coli has been extensively studied, regulation of the operon under the physiologically relevant environment of anaerobic growth and its effect on the expression of the multidrug efflux proteins MdtEF in the operon has not been disclosed. Our previous study revealed that anaerobic induction of the operon was dependent on ArcA, the response regulator of the ArcBA two-component system, in the M9 glucose minimal medium. However, the detailed regulatory mechanism remains unknown. In this study, we showed that anaerobic activation of mdtEF was driven by the 798 bp unusually long gadE promoter. Deletion of evgA, ydeO, rpoS, and gadX which has been shown to activate the gadE expression during acid stresses under aerobic condition did not have a significant effect on the anaerobic activation of the operon. Rather, anaerobic activation of the operon was largely dependent on the global regulator ArcA and a GTPase MnmE. Under aerobic condition, transcription of gadE was repressed by the global DNA silencer H-NS in M9 minimal medium. Interestingly, under anaerobic condition, while ΔarcA almost completely abolished transcription of gadE-mdtEF, further deletion of hns in ΔarcA mutant restored the transcription of the full-length PgadE-lacZ, and P1- and P3-lacZ fusions, suggesting an antagonistic effect of ArcA on the H-NS mediated repression. Taken together, we conclude that the anaerobic activation of the gadE-mdtEF was primarily mediated by the two-component system ArcBA through antagonizing the H-NS mediated repression.

  12. Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily regulated by the two-component system ArcBA through antagonizing the H-NS mediated repression

    Directory of Open Access Journals (Sweden)

    Ziqing eDeng

    2013-07-01

    Full Text Available The gadE-mdtEF operon encodes a central acid resistance regulator GadE and two multidrug efflux proteins MdtEF. Although transcriptional regulation of gadE in the context of acid resistance under the aerobic growth environment of E. coli has been extensively studied, regulation of the operon under the physiologically relevant environment of anaerobic growth and its effect on the expression of the multidrug efflux proteins MdtEF has not been disclosed. Our previous study revealed that anaerobic induction of the operon was dependent on ArcA, the response regulator of the ArcBA two-component system, in the M9 glucose minimal medium. However, the detailed regulatory mechanism remains unknown. In this study, we showed that anaerobic activation of mdtEF was driven by the 798bp unusually long gadE promoter. Deletion of evgA, ydeO, rpoS, and gadX which has been shown to activate the gadE expression during acid stresses under aerobic condition did not have a significant effect on the anaerobic activation of the operon. Rather, anaerobic activation of the operon was largely dependent on the global regulator ArcA and a GTPase MnmE. Under aerobic condition, transcription of gadE was repressed by the global DNA silencer H-NS in M9 minimal medium. Interestingly, under anaerobic condition, while ΔarcA almost completely abolished transcription of gadE-mdtEF, further deletion of hns in ΔarcA mutant restored the transcription of the full length PgadE-lacZ, and P1- and P3-lacZ fusions, suggesting an antagonistic effect of ArcA on the H-NS mediated repression. Taken together, we conclude that the anaerobic activation of the gadE-mdtEF was primarily mediated by the two-component system ArcBA through antagonizing the H-NS mediated repression.

  13. Characterization of the CrbS/R Two-Component System in Pseudomonas fluorescens Reveals a New Set of Genes under Its Control and a DNA Motif Required for CrbR-Mediated Transcriptional Activation

    Directory of Open Access Journals (Sweden)

    Edgardo Sepulveda

    2017-11-01

    Full Text Available The CrbS/R system is a two-component signal transduction system that regulates acetate utilization in Vibrio cholerae, P. aeruginosa, and P. entomophila. CrbS is a hybrid histidine kinase that belongs to a recently identified family, in which the signaling domain is fused to an SLC5 solute symporter domain through aSTAC domain. Upon activation by CrbS, CrbR activates transcription of the acs gene, which encodes an acetyl-CoA synthase (ACS, and the actP gene, which encodes an acetate/solute symporter. In this work, we characterized the CrbS/R system in Pseudomonas fluorescens SBW25. Through the quantitative proteome analysis of different mutants, we were able to identify a new set of genes under its control, which play an important role during growth on acetate. These results led us to the identification of a conserved DNA motif in the putative promoter region of acetate-utilization genes in the Gammaproteobacteria that is essential for the CrbR-mediated transcriptional activation of genes under acetate-utilizing conditions. Finally, we took advantage of the existence of a second SLC5-containing two-component signal transduction system in P. fluorescens, CbrA/B, to demonstrate that the activation of the response regulator by the histidine kinase is not dependent on substrate transport through the SLC5 domain.

  14. Other components

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    This chapter includes descriptions of electronic and mechanical components which do not merit a chapter to themselves. Other hardware requires mention because of particularly high tolerance or intolerance of exposure to radiation. A more systematic analysis of radiation responses of structures which are definable by material was given in section 3.8. The components discussed here are field effect transistors, transducers, temperature sensors, magnetic components, superconductors, mechanical sensors, and miscellaneous electronic components

  15. Electronic components

    CERN Document Server

    Colwell, Morris A

    1976-01-01

    Electronic Components provides a basic grounding in the practical aspects of using and selecting electronics components. The book describes the basic requirements needed to start practical work on electronic equipment, resistors and potentiometers, capacitance, and inductors and transformers. The text discusses semiconductor devices such as diodes, thyristors and triacs, transistors and heat sinks, logic and linear integrated circuits (I.C.s) and electromechanical devices. Common abbreviations applied to components are provided. Constructors and electronics engineers will find the book useful

  16. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  17. Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone's antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 mutations.

    Science.gov (United States)

    Peluso, John J; Romak, Jonathan; Liu, Xiufang

    2008-02-01

    Progesterone (P4) receptor membrane component-1 (PGRMC1) and its binding partner, plasminogen activator inhibitor 1 RNA binding protein (PAIRBP1) are thought to form a complex that functions as membrane receptor for P4. The present investigations confirm PGRMC1's role in this membrane receptor complex by demonstrating that depleting PGMRC1 with PGRMC1 small interfering RNA results in a 60% decline in [(3)H]P4 binding and the loss of P4's antiapoptotic action. Studies conducted on partially purified GFP-PGRMC1 fusion protein indicate that [(3)H]P4 specifically binds to PGRMC1 at a single site with an apparent K(d) of about 35 nm. In addition, experiments using various deletion mutations reveal that the entire PGRMC1 molecule is required for maximal [(3)H]P4 binding and P4 responsiveness. Analysis of the binding data also suggests that the P4 binding site is within a segment of PGRMC1 that is composed of the transmembrane domain and the initial segment of the C terminus. Interestingly, PAIRBP1 appears to bind to the C terminus between amino acids 70-130, which is distal to the putative P4 binding site. Taken together, these data provide compelling evidence that PGRMC1 is the P4 binding protein that mediates P4's antiapoptotic action. Moreover, the deletion mutation studies indicate that each domain of PGRMC1 plays an essential role in modulating PGRMC1's capacity to both bind and respond to P4. Additional studies are required to more precisely delineate the role of each PGRMC1 domain in transducing P4's antiapoptotic action.

  18. The Green Tea Component (--Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

    Directory of Open Access Journals (Sweden)

    Jee-Youn Kim

    Full Text Available The green tea component (--epigallocatechin-3-gallate (EGCG has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose polymerase (PARP, activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As treatment significantly induced production of reactive oxygen species (ROS, which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK, which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

  19. The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

    Science.gov (United States)

    Kim, Jee-Youn; Choi, Ji-Young; Lee, Hyeon-Ju; Byun, Catherine Jeonghae; Park, Jung-Hyun; Park, Jae Hoon; Cho, Ho-Seong; Cho, Sung-Jin; Jo, Sangmee Ahn; Jo, Inho

    2015-01-01

    The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

  20. Principal components

    NARCIS (Netherlands)

    Hallin, M.; Hörmann, S.; Piegorsch, W.; El Shaarawi, A.

    2012-01-01

    Principal Components are probably the best known and most widely used of all multivariate analysis techniques. The essential idea consists in performing a linear transformation of the observed k-dimensional variables in such a way that the new variables are vectors of k mutually orthogonal

  1. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  2. Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice.

    Science.gov (United States)

    Wei, Zhikui; Lei, Xia; Petersen, Pia S; Aja, Susan; Wong, G William

    2014-04-01

    Transgenic overexpression of CTRP9, a secreted hormone downregulated in obesity, confers striking protection against diet-induced obesity and type 2 diabetes. However, the physiological relevance of this adiponectin-related plasma protein remains undefined. Here, we used gene targeting to establish the metabolic function of CTRP9 in a physiological context. Mice lacking CTRP9 were obese and gained significantly more body weight when fed standard laboratory chow. Increased food intake, due in part to upregulated expression of hypothalamic orexigenic neuropeptides, contributed to greater adiposity in CTRP9 knockout mice. Although the frequency of food intake remained unchanged, CTRP9 knockout mice increased caloric intake by increasing meal size and decreasing satiety ratios. The absence of CTRP9 also resulted in peripheral tissue insulin resistance, leading to increased fasting insulin levels, impaired hepatic insulin signaling, and reduced insulin tolerance. Increased expression of lipogenic genes, combined with enhanced caloric intake, contributed to hepatic steatosis in CTRP9 knockout mice. Loss of CTRP9 also resulted in reduced skeletal muscle AMPK activation and mitochondrial content. Together, these results provide the genetic evidence for a physiological role of CTRP9 in controlling energy balance via central and peripheral mechanisms.

  3. Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice

    OpenAIRE

    Wei, Zhikui; Lei, Xia; Petersen, Pia S.; Aja, Susan; Wong, G. William

    2014-01-01

    Transgenic overexpression of CTRP9, a secreted hormone downregulated in obesity, confers striking protection against diet-induced obesity and type 2 diabetes. However, the physiological relevance of this adiponectin-related plasma protein remains undefined. Here, we used gene targeting to establish the metabolic function of CTRP9 in a physiological context. Mice lacking CTRP9 were obese and gained significantly more body weight when fed standard laboratory chow. Increased food intake, due in ...

  4. Autoantibodies against protective molecules-C1q, C-reactive protein, serum amyloid P, mannose-binding lectin, and apolipoprotein A1 - Prevalence in systemic lupus erythematosus

    NARCIS (Netherlands)

    Shoenfeld, Yehuda; Szyper-Kravitz, Martine; Witte, Torsten; Doria, Andrea; Tsutsumi, Akito; Tatsuya, Abe; Dayer, Jean-Michel; Roux-Lombard, Pascale; Fontao, Lionel; Kallenberg, Cees G. M.; Bijl, Marc; Matthias, Torsten; Fraser, Abigail; Zandman-Goddard, Gisele; Blank, Miri; Gilburd, Boris; Meroni, Pier Luigi; Shoenfeld, Y; Gershwin, ME

    2007-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of several autoantibodies. Among the multiple factors involved in SLE development, apoptotic defects and impaired clearance of cellular debris have gained considerable interest, as they contribute to

  5. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  6. The complement system at the embryo implantation site: friend or foe?

    Directory of Open Access Journals (Sweden)

    Roberta eBulla

    2012-03-01

    Full Text Available An inflammatory-like process and vascular remodeling represent the main changes that occur in decidua in the early phase of pregnancy. These changes are partly induced by trophoblast cells that colonize the decidua and are also contributed by the complement system. C1q is one of the component components produced at feto-maternal interface that serves an important function in placental development. Decidual endothelial cells synthesize and express C1q on the cell surface where it acts as a molecular bridge between endovascular trophoblast and endothelial cells. C1q is also produced by extravillous trophoblast and is used to favor trophoblast migration through the decidua. C7 is another component produced and expressed on the membrane of endothelial cells and is involved in the control of the proinflammatory effect of the terminal complement complex. Defective expression of C1q by trophoblast is associated with impaired trophoblast invasion of decidua and may have important implications in pregnancy disorders such as preeclampsia characterized by reduced vascular remodeling. Local control of complement activation by several complement regulators including cell-bound C7 is critical to prevent complement-mediated tissue damage as suggested by recent data showing an association of preeclampsia with mutations in the genes encoding for some complement regulators.

  7. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  8. Axionic mirage mediation

    International Nuclear Information System (INIS)

    Nakamura, Shuntaro; Okumura, Ken-ichi; Yamaguchi, Masahiro

    2008-01-01

    Although mirage mediation is one of the most plausible mediation mechanisms of supersymmetry breaking, it suffers from two crucial problems. One is the μ/Bμ problem, and the second is the cosmological one. The former stems from the fact that the B parameter tends to be comparable with the gravitino mass, which is 2 orders of magnitude larger than the other soft masses. The latter problem is caused by the decay of the modulus whose branching ratio into the gravitino pair is sizable. In this paper, we propose a model of mirage mediation, in which Peccei-Quinn symmetry is incorporated. In this axionic mirage mediation, it is shown that the Peccei-Quinn symmetry breaking scale is dynamically determined around 10 10 GeV to 10 12 GeV due to the supersymmetry breaking effects, and the μ problem can be solved naturally. Furthermore, in our model, the lightest supersymmetric particle (LSP) is the axino, that is, the superpartner of the axion. The overabundance of the LSPs due to decays of the modulus/gravitino, which is the most serious cosmological difficulty in the mirage mediation, can be avoided if the axino is sufficiently light. The next-LSPs (NLSPs) produced by the gravitino decay eventually decay into the axino LSPs, yielding the dominant component of the axinos remaining today. It is shown that the axino with a mass of O(100) MeV is naturally realized, which can constitute the dark matter of the Universe, with a free-streaming length of the order of 0.1 Mpc. The saxion, the real scalar component of the axion supermultiplet, can also be cosmologically harmless due to the dilution of the modulus decay. The lifetime of the NLSP is relatively long, but much shorter than 1 sec, when the big-bang nucleosynthesis commences. The decay of the NLSP would provide intriguing collider signatures

  9. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  10. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  11. Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression.

    Science.gov (United States)

    Maes, Michael; Ringel, Karl; Kubera, Marta; Berk, Michael; Rybakowski, Janusz

    2012-02-01

    Depression is characterized by inflammation and cell-mediated immune (CMI) activation and autoimmune reactions directed against a multitude of self-epitopes. There is evidence that the inflammatory response in depression causes dysfunctions in the metabolism of 5-HT, e.g. lowering the 5-HT precursor tryptophan, and upregulating 5-HT receptor mRNA. This study has been undertaken to examine autoimmune activity directed against 5-HT in relation to CMI activation and inflammation. 5-HT antibodies were examined in major depressed patients (n=109) versus normal controls (n=35) in relation to serum neopterin and lysozyme, and plasma pro-inflammatory cytokines (PIC), i.e. interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of fatigue and somatic symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%). Patients with positive 5-HT antibodies showed increased serum neopterin and lysozyme, and plasma TNFα and IL-1; higher scores on the HDRS and FF scales, and more somatic symptoms, including malaise and neurocognitive dysfunctions. There was a significant association between autoimmune activity to 5-HT and the number of previous depressive episodes. The autoimmune reactions directed against 5-HT might play a role in the pathophysiology of depression and the onset of severe depression. The strong association between autoimmune activity against 5-HT and inflammation/CMI activation is explained by multiple, reciprocal pathways between these factors. Exposure to previous depressive episodes increases the incidence of autoimmune activity directed against 5-HT, which in turn may increase the likelihood to develop new depressive episodes. These findings suggest that sensitization

  12. Components of Adenovirus Genome Packaging

    Science.gov (United States)

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

    Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging. PMID:27721809

  13. Mitigating component performance variation

    Science.gov (United States)

    Gara, Alan G.; Sylvester, Steve S.; Eastep, Jonathan M.; Nagappan, Ramkumar; Cantalupo, Christopher M.

    2018-01-09

    Apparatus and methods may provide for characterizing a plurality of similar components of a distributed computing system based on a maximum safe operation level associated with each component and storing characterization data in a database and allocating non-uniform power to each similar component based at least in part on the characterization data in the database to substantially equalize performance of the components.

  14. The Use of Propensity Scores in Mediation Analysis

    Science.gov (United States)

    Jo, Booil; Stuart, Elizabeth A.; MacKinnon, David P.; Vinokur, Amiram D.

    2011-01-01

    Mediation analysis uses measures of hypothesized mediating variables to test theory for how a treatment achieves effects on outcomes and to improve subsequent treatments by identifying the most efficient treatment components. Most current mediation analysis methods rely on untested distributional and functional form assumptions for valid…

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

    Science.gov (United States)

    Cai, Qing; Li, Yuanyuan; Pei, Gang

    2017-03-24

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

  16. Two component systems: physiological effect of a third component.

    Directory of Open Access Journals (Sweden)

    Baldiri Salvado

    Full Text Available Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS. These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK and by a response regulator (RR that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call "third component" on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.

  17. Reusable Component Services

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Reusable Component Services (RCS) is a super-catalog of components, services, solutions and technologies that facilitates search, discovery and collaboration in...

  18. Software component quality evaluation

    Science.gov (United States)

    Clough, A. J.

    1991-01-01

    The paper describes a software inspection process that can be used to evaluate the quality of software components. Quality criteria, process application, independent testing of the process and proposed associated tool support are covered. Early results indicate that this technique is well suited for assessing software component quality in a standardized fashion. With automated machine assistance to facilitate both the evaluation and selection of software components, such a technique should promote effective reuse of software components.

  19. Reactor component automatic grapple

    International Nuclear Information System (INIS)

    Greenaway, P.R.

    1982-01-01

    A grapple for handling nuclear reactor components in a medium such as liquid sodium which, upon proper seating and alignment of the grapple with the component as sensed by a mechanical logic integral to the grapple, automatically seizes the component. The mechanical logic system also precludes seizure in the absence of proper seating and alignment. (author)

  20. Repurposing learning object components

    NARCIS (Netherlands)

    Verbert, K.; Jovanovic, J.; Gasevic, D.; Duval, E.; Meersman, R.

    2005-01-01

    This paper presents an ontology-based framework for repurposing learning object components. Unlike the usual practice where learning object components are assembled manually, the proposed framework enables on-the-fly access and repurposing of learning object components. The framework supports two

  1. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  2. Micro dynamics in mediation

    OpenAIRE

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  3. Protein- mediated enamel mineralization

    Science.gov (United States)

    Moradian-Oldak, Janet

    2012-01-01

    Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth. PMID:22652761

  4. Supply chain components

    OpenAIRE

    Vieraşu, T.; Bălăşescu, M.

    2011-01-01

    In this article I will go through three main logistics components, which are represented by: transportation, inventory and facilities, and the three secondary logistical components: information, production location, price and how they determine performance of any supply chain. I will discuss then how these components are used in the design, planning and operation of a supply chain. I will also talk about some obstacles a supply chain manager may encounter.

  5. Supply chain components

    Directory of Open Access Journals (Sweden)

    Vieraşu, T.

    2011-01-01

    Full Text Available In this article I will go through three main logistics components, which are represented by: transportation, inventory and facilities, and the three secondary logistical components: information, production location, price and how they determine performance of any supply chain. I will discuss then how these components are used in the design, planning and operation of a supply chain. I will also talk about some obstacles a supply chain manager may encounter.

  6. Control component retainer

    International Nuclear Information System (INIS)

    Walton, L.A.; King, R.A.

    1983-01-01

    An apparatus is described for retaining an undriven control component assembly disposed in a fuel assembly in a nuclear reactor of the type having a core grid plate. The first part of the mechanism involves a housing for the control component and the second part is a brace with a number of arms that reach under the grid plate. The brace and the housing are coupled together to firmly hold the control components in place even under strong flows of th coolant

  7. Component design for LMFBR's

    International Nuclear Information System (INIS)

    Fillnow, R.H.; France, L.L.; Zerinvary, M.C.; Fox, R.O.

    1975-01-01

    Just as FFTF has prototype components to confirm their design, FFTF is serving as a prototype for the design of the commercial LMFBR's. Design and manufacture of critical components for the FFTF system have been accomplished primarily using vendors with little or no previous experience in supplying components for high temperature sodium systems. The exposure of these suppliers, and through them a multitude of subcontractors, to the requirements of this program has been a necessary and significant step in preparing American industry for the task of supplying the large mechanical components required for commercial LMFBR's

  8. Hot gas path component

    Science.gov (United States)

    Lacy, Benjamin Paul; Kottilingam, Srikanth Chandrudu; Porter, Christopher Donald; Schick, David Edward

    2017-09-12

    Various embodiments of the disclosure include a turbomachine component. and methods of forming such a component. Some embodiments include a turbomachine component including: a first portion including at least one of a stainless steel or an alloy steel; and a second portion joined with the first portion, the second portion including a nickel alloy including an arced cooling feature extending therethrough, the second portion having a thermal expansion coefficient substantially similar to a thermal expansion coefficient of the first portion, wherein the arced cooling feature is located within the second portion to direct a portion of a coolant to a leakage area of the turbomachine component.

  9. Transcription regulation by the Mediator complex.

    Science.gov (United States)

    Soutourina, Julie

    2018-04-01

    Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

  10. Components of Sexual Identity

    Science.gov (United States)

    Shively, Michael G.; DeCecco, John P.

    1977-01-01

    This paper examines the four components of sexual identity: biological sex, gender identity, social sex-role, and sexual orientation. Theories about the development of each component and how they combine and conflict to form the individual's sexual identity are discussed. (Author)

  11. Towards Cognitive Component Analysis

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Ahrendt, Peter; Larsen, Jan

    2005-01-01

    Cognitive component analysis (COCA) is here defined as the process of unsupervised grouping of data such that the ensuing group structure is well-aligned with that resulting from human cognitive activity. We have earlier demonstrated that independent components analysis is relevant for representing...

  12. C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

    Science.gov (United States)

    Viglietti, D; Gosset, C; Loupy, A; Deville, L; Verine, J; Zeevi, A; Glotz, D; Lefaucheur, C

    2016-05-01

    Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. GCS component development cycle

    Science.gov (United States)

    Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos; Pi, Marti

    2012-09-01

    The GTC1 is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). First light was at 13/07/2007 and since them it is in the operation phase. The GTC control system (GCS) is a distributed object & component oriented system based on RT-CORBA8 and it is responsible for the management and operation of the telescope, including its instrumentation. GCS has used the Rational Unified process (RUP9) in its development. RUP is an iterative software development process framework. After analysing (use cases) and designing (UML10) any of GCS subsystems, an initial component description of its interface is obtained and from that information a component specification is written. In order to improve the code productivity, GCS has adopted the code generation to transform this component specification into the skeleton of component classes based on a software framework, called Device Component Framework. Using the GCS development tools, based on javadoc and gcc, in only one step, the component is generated, compiled and deployed to be tested for the first time through our GUI inspector. The main advantages of this approach are the following: It reduces the learning curve of new developers and the development error rate, allows a systematic use of design patterns in the development and software reuse, speeds up the deliverables of the software product and massively increase the timescale, design consistency and design quality, and eliminates the future refactoring process required for the code.

  14. 2-component heating systems

    Energy Technology Data Exchange (ETDEWEB)

    Radtke, W

    1987-03-01

    The knowledge accumulated only recently of the damage to buildings and the hazards of formaldehyde, radon and hydrocarbons has been inducing louder calls for ventilation, which, on their part, account for the fact that increasing importance is being attached to the controlled ventilation of buildings. Two-component heating systems provide for fresh air and thermal comfort in one. While the first component uses fresh air blown directly and controllably into the rooms, the second component is similar to the Roman hypocaustic heating systems, meaning that heated outer air is circulating under the floor, thus providing for hot surfaces and thermal comfort. Details concerning the two-component heating system are presented along with systems diagrams, diagrams of the heating system and tables identifying the respective costs. Descriptions are given of the two systems components, the fast heat-up, the two-component made, the change of air, heat recovery and control systems. Comparative evaluations determine the differences between two-component heating systems and other heating systems. Conclusive remarks are dedicated to energy conservation and comparative evaluations of costs. (HWJ).

  15. Replaceable LMFBR core components

    International Nuclear Information System (INIS)

    Evans, E.A.; Cunningham, G.W.

    1976-01-01

    Much progress has been made in understanding material and component performance in the high temperature, fast neutron environment of the LMFBR. Current data have provided strong assurance that the initial core component lifetime objectives of FFTF and CRBR can be met. At the same time, this knowledge translates directly into the need for improved core designs that utilize improved materials and advanced fuels required to meet objectives of low doubling times and extended core component lifetimes. An industrial base for the manufacture of quality core components has been developed in the US, and all procurements for the first two core equivalents for FFTF will be completed this year. However, the problem of fabricating recycled plutonium while dramatically reducing fabrication costs, minimizing personnel exposure, and protecting public health and safety must be addressed

  16. Explosive Components Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The 98,000 square foot Explosive Components Facility (ECF) is a state-of-the-art facility that provides a full-range of chemical, material, and performance analysis...

  17. Histone modifications influence mediator interactions with chromatin

    Science.gov (United States)

    Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

    2011-01-01

    The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

  18. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2011-09-01

    Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

  19. Component fragility research program

    International Nuclear Information System (INIS)

    Tsai, N.C.; Mochizuki, G.L.; Holman, G.S.

    1989-11-01

    To demonstrate how ''high-level'' qualification test data can be used to estimate the ultimate seismic capacity of nuclear power plant equipment, we assessed in detail various electrical components tested by the Pacific Gas ampersand Electric Company for its Diablo Canyon plant. As part of our Phase I Component Fragility Research Program, we evaluated seismic fragility for five Diablo Canyon components: medium-voltage (4kV) switchgear; safeguard relay board; emergency light battery pack; potential transformer; and station battery and racks. This report discusses our Phase II fragility evaluation of a single Westinghouse Type W motor control center column, a fan cooler motor controller, and three local starters at the Diablo Canyon nuclear power plant. These components were seismically qualified by means of biaxial random motion tests on a shaker table, and the test response spectra formed the basis for the estimate of the seismic capacity of the components. The seismic capacity of each component is referenced to the zero period acceleration (ZPA) and, in our Phase II study only, to the average spectral acceleration (ASA) of the motion at its base. For the motor control center, the seismic capacity was compared to the capacity of a Westinghouse Five-Star MCC subjected to actual fragility tests by LLNL during the Phase I Component Fragility Research Program, and to generic capacities developed by the Brookhaven National Laboratory for motor control center. Except for the medium-voltage switchgear, all of the components considered in both our Phase I and Phase II evaluations were qualified in their standard commercial configurations or with only relatively minor modifications such as top bracing of cabinets. 8 refs., 67 figs., 7 tabs

  20. Refractory alloy component fabrication

    International Nuclear Information System (INIS)

    Young, W.R.

    1984-01-01

    Purpose of this report is to describe joining procedures, primarily welding techniques, which were developed to construct reliable refractory alloy components and systems for advanced space power systems. Two systems, the Nb-1Zr Brayton Cycle Heat Receiver and the T-111 Alloy Potassium Boiler Development Program, are used to illustrate typical systems and components. Particular emphasis is given to specific problems which were eliminated during the development efforts. Finally, some thoughts on application of more recent joining technology are presented. 78 figures

  1. Impact test of components

    International Nuclear Information System (INIS)

    Borsoi, L.; Buland, P.; Labbe, P.

    1987-01-01

    Stops with gaps are currently used to support components and piping: it is simple, low cost, efficient and permits free thermal expansion. In order to keep the nonlinear nature of stops, such design is often modeled by beam elements (for the component) and nonlinear springs (for the stops). This paper deals with the validity and the limits of these models through the comparison of computational and experimental results. The experimental results come from impact laboratory tests on a simplified mockup. (orig.)

  2. Nordic Mediation Reseach

    DEFF Research Database (Denmark)

    A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden.......A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden....

  3. Bayesian Mediation Analysis

    OpenAIRE

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  4. Multiscale principal component analysis

    International Nuclear Information System (INIS)

    Akinduko, A A; Gorban, A N

    2014-01-01

    Principal component analysis (PCA) is an important tool in exploring data. The conventional approach to PCA leads to a solution which favours the structures with large variances. This is sensitive to outliers and could obfuscate interesting underlying structures. One of the equivalent definitions of PCA is that it seeks the subspaces that maximize the sum of squared pairwise distances between data projections. This definition opens up more flexibility in the analysis of principal components which is useful in enhancing PCA. In this paper we introduce scales into PCA by maximizing only the sum of pairwise distances between projections for pairs of datapoints with distances within a chosen interval of values [l,u]. The resulting principal component decompositions in Multiscale PCA depend on point (l,u) on the plane and for each point we define projectors onto principal components. Cluster analysis of these projectors reveals the structures in the data at various scales. Each structure is described by the eigenvectors at the medoid point of the cluster which represent the structure. We also use the distortion of projections as a criterion for choosing an appropriate scale especially for data with outliers. This method was tested on both artificial distribution of data and real data. For data with multiscale structures, the method was able to reveal the different structures of the data and also to reduce the effect of outliers in the principal component analysis

  5. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  6. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  7. Mediated electrochemical oxidation of organic wastes using a Co(III) mediator in a neutral electrolyte

    International Nuclear Information System (INIS)

    Balazs, G.B.; Lewis, P.R.

    1999-01-01

    An electrochemical cell with a Co(III) mediator and neutral pH anolyte provides efficient destruction of organic and mixed wastes. The organic waste is concentrated in the anolyte reservoir, where the cobalt mediator oxidizes the organics and insoluble radioactive species and is regenerated at the anode until all organics are converted to carbon dioxide and destroyed. The neutral electrolyte is non-corrosive, and thus extends the lifetime of the cell and its components. 2 figs

  8. Optical CDMA components requirements

    Science.gov (United States)

    Chan, James K.

    1998-08-01

    Optical CDMA is a complementary multiple access technology to WDMA. Optical CDMA potentially provides a large number of virtual optical channels for IXC, LEC and CLEC or supports a large number of high-speed users in LAN. In a network, it provides asynchronous, multi-rate, multi-user communication with network scalability, re-configurability (bandwidth on demand), and network security (provided by inherent CDMA coding). However, optical CDMA technology is less mature in comparison to WDMA. The components requirements are also different from WDMA. We have demonstrated a video transport/switching system over a distance of 40 Km using discrete optical components in our laboratory. We are currently pursuing PIC implementation. In this paper, we will describe the optical CDMA concept/features, the demonstration system, and the requirements of some critical optical components such as broadband optical source, broadband optical amplifier, spectral spreading/de- spreading, and fixed/programmable mask.

  9. Solid state lighting component

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Thomas; Keller, Bernd; Tarsa, Eric; Ibbetson, James; Morgan, Frederick; Dowling, Kevin; Lys, Ihor

    2017-10-17

    An LED component according to the present invention comprising an array of LED chips mounted on a submount with the LED chips capable of emitting light in response to an electrical signal. The array can comprise LED chips emitting at two colors of light wherein the LED component emits light comprising the combination of the two colors of light. A single lens is included over the array of LED chips. The LED chip array can emit light of greater than 800 lumens with a drive current of less than 150 milli-Amps. The LED chip component can also operate at temperatures less than 3000 degrees K. In one embodiment, the LED array is in a substantially circular pattern on the submount.

  10. An integrated magnetics component

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an integrated magnetics component comprising a magnetically permeable core comprising a base member extending in a horizontal plane and first, second, third and fourth legs protruding substantially perpendicularly from the base member. First, second, third...... and fourth output inductor windings are wound around the first, second, third and fourth legs, respectively. A first input conductor of the integrated magnetics component has a first conductor axis and extends in-between the first, second, third and fourth legs to induce a first magnetic flux through a first...... flux path of the magnetically permeable core. A second input conductor of the integrated magnetics component has a second coil axis extending substantially perpendicularly to the first conductor axis to induce a second magnetic flux through a second flux path of the magnetically permeable core...

  11. Cognitive Component Analysis

    DEFF Research Database (Denmark)

    Feng, Ling

    2008-01-01

    This dissertation concerns the investigation of the consistency of statistical regularities in a signaling ecology and human cognition, while inferring appropriate actions for a speech-based perceptual task. It is based on unsupervised Independent Component Analysis providing a rich spectrum...... of audio contexts along with pattern recognition methods to map components to known contexts. It also involves looking for the right representations for auditory inputs, i.e. the data analytic processing pipelines invoked by human brains. The main ideas refer to Cognitive Component Analysis, defined...... as the process of unsupervised grouping of generic data such that the ensuing group structure is well-aligned with that resulting from human cognitive activity. Its hypothesis runs ecologically: features which are essentially independent in a context defined ensemble, can be efficiently coded as sparse...

  12. Electronic components and systems

    CERN Document Server

    Dennis, W H

    2013-01-01

    Electronic Components and Systems focuses on the principles and processes in the field of electronics and the integrated circuit. Covered in the book are basic aspects and physical fundamentals; different types of materials involved in the field; and passive and active electronic components such as capacitors, inductors, diodes, and transistors. Also covered in the book are topics such as the fabrication of semiconductors and integrated circuits; analog circuitry; digital logic technology; and microprocessors. The monograph is recommended for beginning electrical engineers who would like to kn

  13. General gauge mediation

    International Nuclear Information System (INIS)

    Meade, Patrick; Seiberg, Nathan; Shih, David

    2009-01-01

    We give a general definition of gauge mediated supersymmetry breaking which encompasses all the known gauge mediation models. In particular, it includes both models with messengers as well as direct mediation models. A formalism for computing the soft terms in the generic model is presented. Such a formalism is necessary in strongly-coupled direct mediation models where perturbation theory cannot be used. It allows us to identify features of the entire class of gauge mediation models and to distinguish them from specific signatures of various subclasses. (author)

  14. Validating Timed Component Contracts

    DEFF Research Database (Denmark)

    Le Guilly, Thibaut; Liu, Shaoying; Olsen, Petur

    2015-01-01

    This paper presents a technique for testing software components with contracts that specify functional behavior, synchronization, as well as timing behavior. The approach combines elements from unit testing with model-based testing techniques for timed automata. The technique is implemented...... in an online testing tool, and we demonstrate its use on a concrete use case....

  15. Euler principal component analysis

    NARCIS (Netherlands)

    Liwicki, Stephan; Tzimiropoulos, Georgios; Zafeiriou, Stefanos; Pantic, Maja

    Principal Component Analysis (PCA) is perhaps the most prominent learning tool for dimensionality reduction in pattern recognition and computer vision. However, the ℓ 2-norm employed by standard PCA is not robust to outliers. In this paper, we propose a kernel PCA method for fast and robust PCA,

  16. Hybrid wars’ information component

    Directory of Open Access Journals (Sweden)

    T. A. Nevskaya

    2015-01-01

    Full Text Available The war of the new generation - hybrid war, the information component which is directed not so much on the direct destruction of the enemy, how to achieve the goals without warfare. Fighting in the information field is no less important than immediate military action.

  17. ITER plasma facing components

    International Nuclear Information System (INIS)

    Kuroda, T.; Vieider, G.; Akiba, M.

    1991-01-01

    This document summarizes results of the Conceptual Design Activities (1988-1990) for the International Thermonuclear Experimental Reactor (ITER) project, namely those that pertain to the plasma facing components of the reactor vessel, of which the main components are the first wall and the divertor plates. After an introduction and an executive summary, the principal functions of the plasma-facing components are delineated, i.e., (i) define the low-impurity region within which the plasma is produced, (ii) absorb the electromagnetic radiation and charged-particle flux from the plasma, and (iii) protect the blanket/shield components from the plasma. A list of critical design issues for the divertor plates and the first wall is given, followed by discussions of the divertor plate design (including the issues of material selection, erosion lifetime, design concepts, thermal and mechanical analysis, operating limits and overall lifetime, tritium inventory, baking and conditioning, safety analysis, manufacture and testing, and advanced divertor concepts) and the first wall design (armor material and design, erosion lifetime, overall design concepts, thermal and mechanical analysis, lifetime and operating limits, tritium inventory, baking and conditioning, safety analysis, manufacture and testing, an alternative first wall design, and the limiters used instead of the divertor plates during start-up). Refs, figs and tabs

  18. Spain's nuclear components industry

    International Nuclear Information System (INIS)

    Kaibel, E.

    1985-01-01

    Spanish industrial participation in supply of components for nuclear power plants has grown steadily over the last fifteen years. The share of Spanish companies in work for the five second generation nuclear power plants increased to 50% of total capital investments. The necessity to maintain Spanish technology and production in the nuclear field is emphasized

  19. The market for components

    International Nuclear Information System (INIS)

    Simon, M.; Stoelzl, D.

    1986-01-01

    The offers of the German nuclear components industry are shown at the examples of some masterpieces of engineering and their delivery capacities. Then, the success achieved with exports up to now are referred to. The forecast includes the demand, the side conditions of the technical competition, and the pricing and financing situation. (UA) [de

  20. Bayesian Independent Component Analysis

    DEFF Research Database (Denmark)

    Winther, Ole; Petersen, Kaare Brandt

    2007-01-01

    In this paper we present an empirical Bayesian framework for independent component analysis. The framework provides estimates of the sources, the mixing matrix and the noise parameters, and is flexible with respect to choice of source prior and the number of sources and sensors. Inside the engine...

  1. Component-oriented programming

    NARCIS (Netherlands)

    Bosch, J; Szyperski, C; Weck, W; Buschmann, F; Buchmann, AP; Cilia, MA

    2003-01-01

    This report covers the eighth Workshop on Component-Oriented Programming (WCOP). WCOP has been affiliated with ECOOP since its inception in 1996. The report summarizes the contributions made by authors of accepted position papers as well as those made by all attendees of the workshop sessions.

  2. Bayesian dynamic mediation analysis.

    Science.gov (United States)

    Huang, Jing; Yuan, Ying

    2017-12-01

    Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Auxin-dependent compositional change in Mediator in ARF7- and ARF19-mediated transcription.

    Science.gov (United States)

    Ito, Jun; Fukaki, Hidehiro; Onoda, Makoto; Li, Lin; Li, Chuanyou; Tasaka, Masao; Furutani, Masahiko

    2016-06-07

    Mediator is a multiprotein complex that integrates the signals from transcription factors binding to the promoter and transmits them to achieve gene transcription. The subunits of Mediator complex reside in four modules: the head, middle, tail, and dissociable CDK8 kinase module (CKM). The head, middle, and tail modules form the core Mediator complex, and the association of CKM can modify the function of Mediator in transcription. Here, we show genetic and biochemical evidence that CKM-associated Mediator transmits auxin-dependent transcriptional repression in lateral root (LR) formation. The AUXIN/INDOLE 3-ACETIC ACID 14 (Aux/IAA14) transcriptional repressor inhibits the transcriptional activity of its binding partners AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 by making a complex with the CKM-associated Mediator. In addition, TOPLESS (TPL), a transcriptional corepressor, forms a bridge between IAA14 and the CKM component MED13 through the physical interaction. ChIP assays show that auxin induces the dissociation of MED13 but not the tail module component MED25 from the ARF7 binding region upstream of its target gene. These findings indicate that auxin-induced degradation of IAA14 changes the module composition of Mediator interacting with ARF7 and ARF19 in the upstream region of their target genes involved in LR formation. We suggest that this regulation leads to a quick switch of signal transmission from ARFs to target gene expression in response to auxin.

  4. Developing a Model Component

    Science.gov (United States)

    Fields, Christina M.

    2013-01-01

    The Spaceport Command and Control System (SCCS) Simulation Computer Software Configuration Item (CSCI) is responsible for providing simulations to support test and verification of SCCS hardware and software. The Universal Coolant Transporter System (UCTS) was a Space Shuttle Orbiter support piece of the Ground Servicing Equipment (GSE). The initial purpose of the UCTS was to provide two support services to the Space Shuttle Orbiter immediately after landing at the Shuttle Landing Facility. The UCTS is designed with the capability of servicing future space vehicles; including all Space Station Requirements necessary for the MPLM Modules. The Simulation uses GSE Models to stand in for the actual systems to support testing of SCCS systems during their development. As an intern at Kennedy Space Center (KSC), my assignment was to develop a model component for the UCTS. I was given a fluid component (dryer) to model in Simulink. I completed training for UNIX and Simulink. The dryer is a Catch All replaceable core type filter-dryer. The filter-dryer provides maximum protection for the thermostatic expansion valve and solenoid valve from dirt that may be in the system. The filter-dryer also protects the valves from freezing up. I researched fluid dynamics to understand the function of my component. The filter-dryer was modeled by determining affects it has on the pressure and velocity of the system. I used Bernoulli's Equation to calculate the pressure and velocity differential through the dryer. I created my filter-dryer model in Simulink and wrote the test script to test the component. I completed component testing and captured test data. The finalized model was sent for peer review for any improvements. I participated in Simulation meetings and was involved in the subsystem design process and team collaborations. I gained valuable work experience and insight into a career path as an engineer.

  5. Demonstration and evaluation of a method for assessing mediated moderation.

    Science.gov (United States)

    Morgan-Lopez, Antonio A; MacKinnon, David P

    2006-02-01

    Mediated moderation occurs when the interaction between two variables affects a mediator, which then affects a dependent variable. In this article, we describe the mediated moderation model and evaluate it with a statistical simulation using an adaptation of product-of-coefficients methods to assess mediation. We also demonstrate the use of this method with a substantive example from the adolescent tobacco literature. In the simulation, relative bias (RB) in point estimates and standard errors did not exceed problematic levels of +/- 10% although systematic variability in RB was accounted for by parameter size, sample size, and nonzero direct effects. Power to detect mediated moderation effects appears to be severely compromised under one particular combination of conditions: when the component variables that make up the interaction terms are correlated and partial mediated moderation exists. Implications for the estimation of mediated moderation effects in experimental and nonexperimental research are discussed.

  6. Factor structure underlying components of allostatic load.

    Directory of Open Access Journals (Sweden)

    Jeanne M McCaffery

    Full Text Available Allostatic load is a commonly used metric of health risk based on the hypothesis that recurrent exposure to environmental demands (e.g., stress engenders a progressive dysregulation of multiple physiological systems. Prominent indicators of response to environmental challenges, such as stress-related hormones, sympatho-vagal balance, or inflammatory cytokines, comprise primary allostatic mediators. Secondary mediators reflect ensuing biological alterations that accumulate over time and confer risk for clinical disease but overlap substantially with a second metric of health risk, the metabolic syndrome. Whether allostatic load mediators covary and thus warrant treatment as a unitary construct remains to be established and, in particular, the relation of allostatic load parameters to the metabolic syndrome requires elucidation. Here, we employ confirmatory factor analysis to test: 1 whether a single common factor underlies variation in physiological systems associated with allostatic load; and 2 whether allostatic load parameters continue to load on a single common factor if a second factor representing the metabolic syndrome is also modeled. Participants were 645 adults from Allegheny County, PA (30-54 years old, 82% non-Hispanic white, 52% female who were free of confounding medications. Model fitting supported a single, second-order factor underlying variance in the allostatic load components available in this study (metabolic, inflammatory and vagal measures. Further, this common factor reflecting covariation among allostatic load components persisted when a latent factor representing metabolic syndrome facets was conjointly modeled. Overall, this study provides novel evidence that the modeled allostatic load components do share common variance as hypothesized. Moreover, the common variance suggests the existence of statistical coherence above and beyond that attributable to the metabolic syndrome.

  7. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  8. Adaptable component frameworks

    DEFF Research Database (Denmark)

    Katajainen, Jyrki; Simonsen, Bo

    2009-01-01

    The CPH STL is a special edition of the STL, the containers and algorithms part of the C++ standard library. The specification of the generic components of the STL is given in the C++ standard. Any implementation of the STL, e.g. the one that ships with your standard-compliant C++ compiler, should...... for vector, which is undoubtedly the most used container of the C++ standard library. In particular, we specify the details of a vector implementation that is safe with respect to referential integrity and strong exception safety. Additionally, we report the experiences and lessons learnt from...... the development of component frameworks which we hope to be of benefit to persons engaged in the design and implementation of generic software libraries....

  9. Causal mediation analysis with multiple mediators.

    Science.gov (United States)

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  10. Components of laboratory accreditation.

    Science.gov (United States)

    Royal, P D

    1995-12-01

    Accreditation or certification is a recognition given to an operation or product that has been evaluated against a standard; be it regulatory or voluntary. The purpose of accreditation is to provide the consumer with a level of confidence in the quality of operation (process) and the product of an organization. Environmental Protection Agency/OCM has proposed the development of an accreditation program under National Environmental Laboratory Accreditation Program for Good Laboratory Practice (GLP) laboratories as a supplement to the current program. This proposal was the result of the Inspector General Office reports that identified weaknesses in the current operation. Several accreditation programs can be evaluated and common components identified when proposing a structure for accrediting a GLP system. An understanding of these components is useful in building that structure. Internationally accepted accreditation programs provide a template for building a U.S. GLP accreditation program. This presentation will discuss the traditional structure of accreditation as presented in the Organization of Economic Cooperative Development/GLP program, ISO-9000 Accreditation and ISO/IEC Guide 25 Standard, and the Canadian Association for Environmental Analytical Laboratories, which has a biological component. Most accreditation programs are managed by a recognized third party, either privately or with government oversight. Common components often include a formal review of required credentials to evaluate organizational structure, a site visit to evaluate the facility, and a performance evaluation to assess technical competence. Laboratory performance is measured against written standards and scored. A formal report is then sent to the laboratory indicating accreditation status. Usually, there is a scheduled reevaluation built into the program. Fee structures vary considerably and will need to be examined closely when building a GLP program.

  11. Fabricating nuclear components

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    Activities of the Nuclear Engineering Division of Vickers Ltd., particularly fabrication of long slim tubular components for power reactors and the construction of irradiation loops and rigs, are outlined. The processes include hydraulic forming for fabrication of various types of tubes and outer cases of fuel transfer buckets, various specialised welding operations including some applications of the TIG process, and induction brazing of specialised assemblies. (U.K.)

  12. Components of the environment

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    This report of the Ministry of the Environment of the Slovak Republic deals with the components of the environment. The results of monitoring of air (emission situation), ambient air quality, atmospheric precipitation, tropospheric ozone, water (surface water, groundwater resources, waste water and drinking water), geological factors (geothermal energy, fuel deposits, ore deposits, non-metallic ore deposits), soil (area statistics, soil contamination. soil reaction and active extractable aluminium, soil erosion), flora and fauna (national strategy of biodiversity protection) are presented

  13. Ionitriding of Weapon Components

    Science.gov (United States)

    1974-01-01

    and documented tho production sequences required for the case- hardening of AISI 4140 and Nitralloy 13514 steels. Determination of processina...depths were established experimentally for Nitralloy 135M and for AISI 4140 steels. These steels are commonly used for the manufacture of nitrlded...weapons components. A temperature of 050F, upper limit for lonitrlding, was selected for the Nitralloy 135M to keep treatment times short. Since AISI 4140

  14. Components of QCD

    International Nuclear Information System (INIS)

    Sivers, D.

    1979-10-01

    Some aspects of a simple strategy for testing the validity of QCD perturbation theory are examined. The importance of explicit evaluation of higher-order contributions is illustrated by considering Z 0 decays. The recent progress toward understanding exclusive processes in QCD is discussed and some simple examples are given of how to isolate and test the separate components of the perturbation expansion in a hypothetical series of jet experiments

  15. Optimized Kernel Entropy Components.

    Science.gov (United States)

    Izquierdo-Verdiguier, Emma; Laparra, Valero; Jenssen, Robert; Gomez-Chova, Luis; Camps-Valls, Gustau

    2017-06-01

    This brief addresses two main issues of the standard kernel entropy component analysis (KECA) algorithm: the optimization of the kernel decomposition and the optimization of the Gaussian kernel parameter. KECA roughly reduces to a sorting of the importance of kernel eigenvectors by entropy instead of variance, as in the kernel principal components analysis. In this brief, we propose an extension of the KECA method, named optimized KECA (OKECA), that directly extracts the optimal features retaining most of the data entropy by means of compacting the information in very few features (often in just one or two). The proposed method produces features which have higher expressive power. In particular, it is based on the independent component analysis framework, and introduces an extra rotation to the eigen decomposition, which is optimized via gradient-ascent search. This maximum entropy preservation suggests that OKECA features are more efficient than KECA features for density estimation. In addition, a critical issue in both the methods is the selection of the kernel parameter, since it critically affects the resulting performance. Here, we analyze the most common kernel length-scale selection criteria. The results of both the methods are illustrated in different synthetic and real problems. Results show that OKECA returns projections with more expressive power than KECA, the most successful rule for estimating the kernel parameter is based on maximum likelihood, and OKECA is more robust to the selection of the length-scale parameter in kernel density estimation.

  16. Mediated electrochemical hazardous waste destruction

    International Nuclear Information System (INIS)

    Hickman, R.G.; Farmer, J.C.; Wang, F.T.

    1992-03-01

    There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing an electrochemical process, based upon mediated electrochemical oxidation (MEO), that converts toxic organic components of mixed waste to water, carbon dioxide, and chloride or chloride precipitates. Aggressive oxidizer ions such as Ag 2+ , Co 3+ , or Fe 3+ are produced at an anode. These can attack organic molecules directly, and may also produce hydroxyl free radicals that promote destruction. Solid and liquid radioactive waste streams containing only inorganic radionuclide forms may be treated with existing technology and prepared for final disposal. The coulombic efficiency of the process has been determined, as well as the destruction efficiency for ethylene glycol, a surrogate waste. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient- temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag(II) has been used as a mediator in this process. Fe(III) and Co(III) are attractive alternatives to Ag(II) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is toxic heavy metal. Quantitative data have been obtained for the complete oxidation of ethylene glycol by Fe(III) and Co(III). Though ethylene glycol is a nonhalogenated organic, these data have enabled us to make direct comparisons of activities of Fe(III) and Co(III) with Ag(II). Very good quantitative data for the oxidation of ethylene glycol by Ag(II) had already been collected

  17. Flexible Mediation Analysis With Multiple Mediators.

    Science.gov (United States)

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    This study analyzes how a group of ‘mediators’ in a large, multinational company adapted a computer-mediated communication technology (a ‘virtual workspace’) to the organizational context (and vice versa) by modifying features of the technology, providing ongoing support for users, and promoting...... appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology will be established and used in an organization. However, this study also indicates that the process...... of technology-use mediation is more complex and indeterminate than earlier literature suggests. In particular, we want to draw attention to the fact that advanced computer-mediated communication technologies are equivocal and that technology-use mediation consequently requires ongoing sensemaking (Weick 1995)....

  19. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9......In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors...... to the basal transcription machinery. Mediator was initially isolated from Saccharomyces cerevisiae based on its ability to render a RNA polymerase II in vitro transcription system responsive to activators. Additionally, structural studies have revealed striking structural similarities between S. cerevisiae...

  20. Applied mediation analyses

    DEFF Research Database (Denmark)

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart...... disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation...

  1. Immunologically mediated oral diseases

    OpenAIRE

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  2. Implementing general gauge mediation

    International Nuclear Information System (INIS)

    Carpenter, Linda M.; Dine, Michael; Festuccia, Guido; Mason, John D.

    2009-01-01

    Recently there has been much progress in building models of gauge mediation, often with predictions different than those of minimal gauge mediation. Meade, Seiberg, and Shih have characterized the most general spectrum which can arise in gauge-mediated models. We discuss some of the challenges of building models of general gauge mediation, especially the problem of messenger parity and issues connected with R symmetry breaking and CP violation. We build a variety of viable, weakly coupled models which exhibit some or all of the possible low energy parameters.

  3. Reinforced seal component

    International Nuclear Information System (INIS)

    Jeanson, G.M.; Odent, R.P.

    1980-01-01

    The invention concerns a seal component of the kind comprising a soft sheath and a flexible reinforcement housed throughout the entire length of the sheath. The invention enables O ring seals to be made capable of providing a radial seal, that is to say between two sides or flat collars of two cylindrical mechanical parts, or an axial seal, that is to say between two co-axial axisymmetrical areas. The seal so ensured is relative, but it remains adequately sufficient for many uses, for instance, to ensure the separation of two successive fixed blading compartments of axial compressors used in gas diffusion isotope concentration facilities [fr

  4. Electronic components and technology

    CERN Document Server

    Sangwine, Stephen

    2007-01-01

    Most introductory textbooks in electronics focus on the theory while leaving the practical aspects to be covered in laboratory courses. However, the sooner such matters are introduced, the better able students will be to include such important concerns as parasitic effects and reliability at the very earliest stages of design. This philosophy has kept Electronic Components and Technology thriving for two decades, and this completely updated third edition continues the approach with a more international outlook.Not only does this textbook introduce the properties, behavior, fabrication, and use

  5. Autonomous component carrier selection

    DEFF Research Database (Denmark)

    Garcia, Luis Guilherme Uzeda; Pedersen, Klaus; Mogensen, Preben

    2009-01-01

    management and efficient system operation. Due to the expected large number of user-deployed cells, centralized network planning becomes unpractical and new scalable alternatives must be sought. In this article, we propose a fully distributed and scalable solution to the interference management problem...... in local areas, basing our study case on LTE-Advanced. We present extensive network simulation results to demonstrate that a simple and robust interference management scheme, called autonomous component carrier selection allows each cell to select the most attractive frequency configuration; improving...... the experience of all users and not just the few best ones; while overall cell capacity is not compromised....

  6. Impedance of accelerator components

    International Nuclear Information System (INIS)

    Corlett, J.N.

    1996-05-01

    As demands for high luminosity and low emittance particle beams increase, an understanding of the electromagnetic interaction of these beams with their vacuum chamber environment becomes more important in order to maintain the quality of the beam. This interaction is described in terms of the wake field in time domain, and the beam impedance in frequency domain. These concepts are introduced, and related quantities such as the loss factor are presented. The broadband Q = 1 resonator impedance model is discussed. Perturbation and coaxial wire methods of measurement of real components are reviewed

  7. Complement-Mediated Enhancement of Monocyte Adhesion to Endothelial Cells by HLA Antibodies, and Blockade by a Specific Inhibitor of the Classical Complement Cascade, TNT003

    Science.gov (United States)

    Valenzuela, Nicole M.; Thomas, Kimberly A.; Mulder, Arend; Parry, Graham C.; Panicker, Sandip; Reed, Elaine F.

    2017-01-01

    Background Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling. Methods Primary human aortic endothelial cells (HAEC) were stimulated with HLA class I antibodies in the presence of intact human serum complement. C3a and C5a generation, endothelial P-selectin expression, and adhesion of human primary and immortalized monocytes (Mono Mac 6) were measured. Alternatively, HAEC or monocytes were directly stimulated with purified C3a or C5a. Classical complement activation was inhibited by pretreatment of complement with an anti-C1s antibody (TNT003). Results Treatment of HAEC with HLA antibody and human complement increased the formation of C3a and C5a. Monocyte recruitment by human HLA antibodies was enhanced in the presence of intact human serum complement or purified C3a or C5a. Specific inhibition of the classical complement pathway using TNT003 or C1q-depleted serum significantly reduced adhesion of monocytes in the presence of human complement. Conclusions Despite persistent endothelial viability in the presence of HLA antibodies and complement, upstream complement anaphylatoxin production exacerbates endothelial exocytosis and leukocyte recruitment. Upstream inhibition of classical complement may be therapeutic to dampen mononuclear cell recruitment and endothelial activation characteristic of microvascular inflammation during AMR. PMID:28640789

  8. Interactions between photodegradation components

    Directory of Open Access Journals (Sweden)

    Abdollahi Yadollah

    2012-09-01

    Full Text Available Abstract Background The interactions of p-cresol photocatalytic degradation components were studied by response surface methodology. The study was designed by central composite design using the irradiation time, pH, the amount of photocatalyst and the p-cresol concentration as variables. The design was performed to obtain photodegradation % as actual responses. The actual responses were fitted with linear, two factor interactions, cubic and quadratic model to select an appropriate model. The selected model was validated by analysis of variance which provided evidences such as high F-value (845.09, very low P-value (2 = 0.999, adjusted R-squared (Radj2 = 0.998, predicted R-squared (Rpred2 = 0.994 and the adequate precision (95.94. Results From the validated model demonstrated that the component had interaction with irradiation time under 180 min of the time while the interaction with pH was above pH 9. Moreover, photocatalyst and p-cresol had interaction at minimal amount of photocatalyst (p-cresol. Conclusion These variables are interdependent and should be simultaneously considered during the photodegradation process, which is one of the advantages of the response surface methodology over the traditional laboratory method.

  9. Prognostics for Microgrid Components

    Science.gov (United States)

    Saxena, Abhinav

    2012-01-01

    Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

  10. [Effects decomposition in mediation analysis: a numerical example].

    Science.gov (United States)

    Zugna, Daniela; Richiardi, Lorenzo

    2018-01-01

    Mediation analysis aims to decompose the total effect of the exposure on the outcome into a direct effect (unmediated) and an indirect effect (mediated by a mediator). When the interest also lies on understanding whether the exposure effect differs in different sub-groups of study population or under different scenarios, the mediation analysis needs to be integrated with interaction analysis. In this setting it is necessary to decompose the total effect not only into two components, the direct and indirect effects, but other two components linked to interaction. The interaction between the exposure and the mediator in their effect on the outcome could indeed act through the effect of the exposure on the mediator or through the mediator when the mediator is not totally explained by the exposure. We describe options for decomposition, proposed in literature, of the total effect and we illustrate them through a hypothetical example of the effect of age at diagnosis of cancer on survival, mediated and unmediated by the therapeutical approach, and a numerical example.

  11. Teaching Mediated Public Relations.

    Science.gov (United States)

    Kent, Michael L.

    2001-01-01

    Discusses approaches to teaching a mediated public relations course, emphasizing the World Wide Web. Outlines five course objectives, assignments and activities, evaluation, texts, and lecture topics. Argues that students mastering these course objectives will understand ethical issues relating to media use, using mediated technology in public…

  12. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    of handling multiple, fluid realities with multiple, fluid methods. Empirically, the paper works with mediation in fashion - that is efforts the active shaping of relations between producer and consumer through communication, marketing and PR. Fashion mediation is by no means simple, but organise complex...

  13. The Mediated Transparent Society

    DEFF Research Database (Denmark)

    Backer, Lise

    2001-01-01

    in the mediated transparent society. The paper concludes that, based on these analyses, the mediated panopticism working on the business segment is not an effective disciplinary apparatus, which can guarantee that business corporations are carrying out important ecological or ethical improvements....

  14. Laccase/Mediator Systems

    NARCIS (Netherlands)

    Hilgers, Roelant; Vincken, Jean Paul; Gruppen, Harry; Kabel, Mirjam A.

    2018-01-01

    Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it

  15. Atomic Force Microscope Mediated Chromatography

    Science.gov (United States)

    Anderson, Mark S.

    2013-01-01

    The atomic force microscope (AFM) is used to inject a sample, provide shear-driven liquid flow over a functionalized substrate, and detect separated components. This is demonstrated using lipophilic dyes and normal phase chromatography. A significant reduction in both size and separation time scales is achieved with a 25-micron-length column scale, and one-second separation times. The approach has general applications to trace chemical and microfluidic analysis. The AFM is now a common tool for ultra-microscopy and nanotechnology. It has also been demonstrated to provide a number of microfluidic functions necessary for miniaturized chromatography. These include injection of sub-femtoliter samples, fluidic switching, and sheardriven pumping. The AFM probe tip can be used to selectively remove surface layers for subsequent microchemical analysis using infrared and tip-enhanced Raman spectroscopy. With its ability to image individual atoms, the AFM is a remarkably sensitive detector that can be used to detect separated components. These diverse functional components of microfluidic manipulation have been combined in this work to demonstrate AFM mediated chromatography. AFM mediated chromatography uses channel-less, shear-driven pumping. This is demonstrated with a thin, aluminum oxide substrate and a non-polar solvent system to separate a mixture of lipophilic dyes. In conventional chromatographic terms, this is analogous to thin-layer chromatography using normal phase alumina substrate with sheardriven pumping provided by the AFM tip-cantilever mechanism. The AFM detection of separated components is accomplished by exploiting the variation in the localized friction of the separated components. The AFM tip-cantilever provides the mechanism for producing shear-induced flows and rapid pumping. Shear-driven chromatography (SDC) is a relatively new concept that overcomes the speed and miniaturization limitations of conventional liquid chromatography. SDC is based on a

  16. The multitalented Mediator complex.

    Science.gov (United States)

    Carlsten, Jonas O P; Zhu, Xuefeng; Gustafsson, Claes M

    2013-11-01

    The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Music, radio and mediatization

    DEFF Research Database (Denmark)

    Michelsen, Morten; Krogh, Mads

    2016-01-01

    of mediatization where media as such seem to be ascribed agency. Instead, we consider historical accounts of music–radio in order to address the complex nonlinearity of concrete processes of mediatization as they take place in the multiple meetings between a decentred notion of radio and musical life.......Mediatization has become a key concept for understanding the relations between media and other cultural and social fields. Contributing to the discussions related to the concept of mediatization, this article discusses how practices of radio and music(al life) influence each other. We follow Deacon......’s and Stanyer’s advice to supplement the concept of mediatization with ‘a series of additional concepts at lower levels of abstraction’ and suggest, in this respect, the notion of heterogeneous milieus of music–radio. Hereby, we turn away from the all-encompassing perspectives related to the concept...

  18. Food Components and Supplements

    DEFF Research Database (Denmark)

    Parlesak, Alexandr

    2012-01-01

    The major part of food consists of chemical compounds that can be used for energy production, biological synthesis, or maintenance of metabolic processes by the host. These components are defined as nutrients, and can be categorized into macronutrients (proteins, carbohydrates, triglycerides......, and alcohol), minerals, and micronutrients. The latter category comprises 13 vitamins and a hand full of trace elements. Many micronutrients are used as food supplements and are ingested at doses exceeding the amounts that can be consumed along with food by a factor of 10–100. Both macro- and micronutrients...... can interact with enzyme systems related to xenobiotic metabolism either by regulation of their expression or direct interference with their enzymatic activity. During food consumption, we consume a wide range of xenobiotics along with the consumable food, either as an original part of the food (e...

  19. Sprayed skin turbine component

    Science.gov (United States)

    Allen, David B

    2013-06-04

    Fabricating a turbine component (50) by casting a core structure (30), forming an array of pits (24) in an outer surface (32) of the core structure, depositing a transient liquid phase (TLP) material (40) on the outer surface of the core structure, the TLP containing a melting-point depressant, depositing a skin (42) on the outer surface of the core structure over the TLP material, and heating the assembly, thus forming both a diffusion bond and a mechanical interlock between the skin and the core structure. The heating diffuses the melting-point depressant away from the interface. Subsurface cooling channels (35) may be formed by forming grooves (34) in the outer surface of the core structure, filling the grooves with a fugitive filler (36), depositing and bonding the skin (42), then removing the fugitive material.

  20. Food Components and Supplements

    DEFF Research Database (Denmark)

    Parlesak, Alexandr

    2012-01-01

    acting as carcinogens) to health-protective effects (e.g., flavonoids ameliorating detrimental effects of mitochondrial oxidative stress). In particular, secondary plant metabolites along with vitamins, specific types of macronutrients and live bacteria (probiotics) as well as substances promoting.......g., secondary plant metabolites such as flavonoids), or as contaminants that enter the food chain at different stages or during the food production process. For these components, a wide spectrum of biological effects was observed that ranges from health-threatening impacts (e.g., polycyclic aromatic amines....... The supplements and contaminants can compete directly with drug oxidation, induce or suppress the expression of xenobiotic-metabolizing enzymes, change the bioavailability of drugs, and, in the case of live bacteria, bring in their own xenobiotic metabolism, including cytochrome P450 (CYP) activity. In numerous...

  1. Component failure data handbook

    International Nuclear Information System (INIS)

    Gentillon, C.D.

    1991-04-01

    This report presents generic component failure rates that are used in reliability and risk studies of commercial nuclear power plants. The rates are computed using plant-specific data from published probabilistic risk assessments supplemented by selected other sources. Each data source is described. For rates with four or more separate estimates among the sources, plots show the data that are combined. The method for combining data from different sources is presented. The resulting aggregated rates are listed with upper bounds that reflect the variability observed in each rate across the nuclear power plant industry. Thus, the rates are generic. Both per hour and per demand rates are included. They may be used for screening in risk assessments or for forming distributions to be updated with plant-specific data

  2. High thermal load component

    International Nuclear Information System (INIS)

    Fuse, Toshiaki; Tachikawa, Nobuo.

    1996-01-01

    A cooling tube made of a pure copper is connected to the inner portion of an armour (heat resistant member) made of an anisotropic carbon/carbon composite (CFC) material. The CFC material has a high heat conductivity in longitudinal direction of fibers and has low conductivity in perpendicular thereto. Fibers extending in the armour from a heat receiving surface just above the cooling tube are directly connected to the cooling tube. A portion of the fibers extending from a heat receiving surface other than portions not just above the cooling tube is directly bonded to the cooling tube. Remaining fibers are disposed so as to surround the cooling tube. The armour and the cooling tube are soldered using an active metal flux. With such procedures, high thermal load components for use in a thermonuclear reactor are formed, which are excellent in a heat removing characteristic and hardly causes defects such as crackings and peeling. (I.N.)

  3. Impedance and component heating

    CERN Document Server

    Métral, E; Mounet, N; Pieloni, T; Salvant, B

    2015-01-01

    The impedance is a complex function of frequency, which represents, for the plane under consideration (longitudinal, horizontal or vertical), the force integrated over the length of an element, from a “source” to a “test” wave, normalized by their charges. In general, the impedance in a given plane is a nonlinear function of the test and source transverse coordinates, but it is most of the time sufficient to consider only the first few linear terms. Impedances can influence the motion of trailing particles, in the longitudinal and in one or both transverse directions, leading to energy loss, beam instabilities, or producing undesirable secondary effects such as excessive heating of sensitive components at or near the chamber wall, called beam-induced RF heating. The LHC performance limitations linked to impedances encountered during the 2010-2012 run are reviewed and the currently expected situation during the HL-LHC era is discussed.

  4. Complement and thrombosis in the antiphospholipid syndrome.

    Science.gov (United States)

    Oku, Kenji; Nakamura, Hiroyuki; Kono, Michihiro; Ohmura, Kazumasa; Kato, Masaru; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Amengual, Olga; Atsumi, Tatsuya

    2016-10-01

    The involvement of complement activation in the pathophysiology of antiphospholipid syndrome (APS) was first reported in murine models of antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously reported that complement activation is prevalent and may function as a source of procoagulant cell activation in the sera of APS patients. Recently, autoantibodies against C1q, a component of complement 1, were reported to be correlated with complement activation in systemic lupus erythematosus. These antibodies target neoepitopes of deformed C1q bound to various molecules (i.e., anionic phospholipids) and induce accelerated complement activation. We found that anti-C1q antibodies are more frequently detected in primary APS patients than in control patients and in refractory APS patients with repeated thrombotic events. The titer of anti-C1q antibodies was significantly higher in refractory APS patients than in APS patients without flare. The binding of C1q to anionic phospholipids may be associated with the surge in complement activation in patients with anti-C1q antibodies when triggered by 'second-hit' biological stressors such as infection. Such stressors will induce overexpression of anionic phospholipids, with subsequent increases in deformed C1q that is targeted by anti-C1q antibodies. Copyright © 2016. Published by Elsevier B.V.

  5. A classical regression framework for mediation analysis: fitting one model to estimate mediation effects.

    Science.gov (United States)

    Saunders, Christina T; Blume, Jeffrey D

    2017-10-26

    Mediation analysis explores the degree to which an exposure's effect on an outcome is diverted through a mediating variable. We describe a classical regression framework for conducting mediation analyses in which estimates of causal mediation effects and their variance are obtained from the fit of a single regression model. The vector of changes in exposure pathway coefficients, which we named the essential mediation components (EMCs), is used to estimate standard causal mediation effects. Because these effects are often simple functions of the EMCs, an analytical expression for their model-based variance follows directly. Given this formula, it is instructive to revisit the performance of routinely used variance approximations (e.g., delta method and resampling methods). Requiring the fit of only one model reduces the computation time required for complex mediation analyses and permits the use of a rich suite of regression tools that are not easily implemented on a system of three equations, as would be required in the Baron-Kenny framework. Using data from the BRAIN-ICU study, we provide examples to illustrate the advantages of this framework and compare it with the existing approaches. © The Author 2017. Published by Oxford University Press.

  6. Pin Component Technology (V1.0) and Its C Interface

    National Research Council Canada - National Science Library

    Hissam, Scott; Ivers, James; Plakosh, Daniel; Wallnau, Kurt C

    2005-01-01

    .... Pin implements the container idiom for software components. Containers provide a pre-fabricated "shell" in which custom code executes and through which all interactions between custom code and its external environment are mediated...

  7. Initial Ada components evaluation

    Science.gov (United States)

    Moebes, Travis

    1989-01-01

    The SAIC has the responsibility for independent test and validation of the SSE. They have been using a mathematical functions library package implemented in Ada to test the SSE IV and V process. The library package consists of elementary mathematical functions and is both machine and accuracy independent. The SSE Ada components evaluation includes code complexity metrics based on Halstead's software science metrics and McCabe's measure of cyclomatic complexity. Halstead's metrics are based on the number of operators and operands on a logical unit of code and are compiled from the number of distinct operators, distinct operands, and total number of occurrences of operators and operands. These metrics give an indication of the physical size of a program in terms of operators and operands and are used diagnostically to point to potential problems. McCabe's Cyclomatic Complexity Metrics (CCM) are compiled from flow charts transformed to equivalent directed graphs. The CCM is a measure of the total number of linearly independent paths through the code's control structure. These metrics were computed for the Ada mathematical functions library using Software Automated Verification and Validation (SAVVAS), the SSE IV and V tool. A table with selected results was shown, indicating that most of these routines are of good quality. Thresholds for the Halstead measures indicate poor quality if the length metric exceeds 260 or difficulty is greater than 190. The McCabe CCM indicated a high quality of software products.

  8. Radiation damage in components

    International Nuclear Information System (INIS)

    Takano, Tomehachi

    1977-01-01

    The performance change of typical capacitors and resistors in electronic components by Co-60 γ-irradiation from the 1320 Ci source was examined in the range of 10 5 to 10 8 R. Specifically, the characteristic change during irradiation and the recovery after irradiation were continuously observed. The capacity change is +2.4% at maximum in ceramic and metallized paper capacitors, and -2.4% at maximum in mylar and paper capacitors. It is also +-0.4% at maximum in mica and polystyrene capacitors. Some of these capacitors showed the recovery of the capacity change, but the others did not. Dielectric loss varied by 15% at larger dose in some capacitors, and the recovery was not observed. While, the insulation resistance of the resistors of 10 15 Ω or more lowered to 10 13 Ω or less after 10 to 30 sec. irradiation, but recovered soon nearly to the initial values after irradiation was interrupted. The resistance change of carbon film resistors is about 0.2 to 2%, and recovered to the initial values in 100 hours after irradiation. The resistance change of composition resistors is large over the range of -13 to +35%, besides, no sign of recovery was seen. In carbon film resistors, the surface insulated type indicated far better results which are assumed to be caused by the selection of element materials and the forming of coating materials. (Wakatsuki, Y.)

  9. General resonance mediation

    International Nuclear Information System (INIS)

    McGarrie, Moritz

    2012-07-01

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for σ(visible → hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  10. General resonance mediation

    Energy Technology Data Exchange (ETDEWEB)

    McGarrie, Moritz

    2012-07-15

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for {sigma}(visible {yields} hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  11. Positively deflected anomaly mediation

    International Nuclear Information System (INIS)

    Okada, Nobuchika

    2002-01-01

    We generalize the so-called 'deflected anomaly mediation' scenario to the case where threshold corrections of heavy messengers to the sparticle squared masses are positive. A concrete model realizing this scenario is also presented. The tachyonic slepton problem can be fixed with only a pair of messengers. The resultant sparticle mass spectrum is quite different from that in the conventional deflected anomaly mediation scenario, but is similar to the one in the gauge mediation scenario. The lightest sparticle is mostly B-ino

  12. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  13. Component-based development process and component lifecycle

    NARCIS (Netherlands)

    Crnkovic, I.; Chaudron, M.R.V.; Larsson, S.

    2006-01-01

    The process of component- and component-based system development differs in many significant ways from the "classical" development process of software systems. The main difference is in the separation of the development process of components from the development process of systems. This fact has a

  14. Mediated electrochemical hazardous waste destruction

    International Nuclear Information System (INIS)

    Hickman, R.G.; Farmer, J.C.; Wang, F.T.

    1991-08-01

    There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing electrochemical processes that convert the toxic organic components of mixed waste to water, carbon dioxide, an innocuous anions such as chloride. Aggressive oxidizer ions such as Ag 2+ or Ce +4 are produced at an anode. These can attack the organic molecules directly. They can also attack water which yields hydroxyl free radicals that in turn attack the organic molecules. The condensed (i.e., solid and/or liquid) effluent streams contain the inorganic radionuclide forms. These may be treated with existing technology and prepared for final disposal. Kinetics and the extent of destruction of some toxic organics have been measured. Depending on how the process is operated, coulombic efficiency can be nearly 100%. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient-temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag (2) has been used as a mediator in this process. Fe(6) and Co(3) are attractive alternatives to Ag(2) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is a toxic heavy metal. Quantitative data has been obtained for the complete oxidation of ethylene glycol by Fe(6) and Co(3). Though ethylene glycol is a nonhalogenated organic, this data has enabled us to make direct comparisons of activities of Fe(6) and Co(3) with Ag(2). Very good quantitative data for the oxidation of ethylene glycol by Ag(2) had already been collected. 4 refs., 6 figs

  15. GOATS - Orbitology Component

    Science.gov (United States)

    Haber, Benjamin M.; Green, Joseph J.

    2010-01-01

    The GOATS Orbitology Component software was developed to specifically address the concerns presented by orbit analysis tools that are often written as stand-alone applications. These applications do not easily interface with standard JPL first-principles analysis tools, and have a steep learning curve due to their complicated nature. This toolset is written as a series of MATLAB functions, allowing seamless integration into existing JPL optical systems engineering modeling and analysis modules. The functions are completely open, and allow for advanced users to delve into and modify the underlying physics being modeled. Additionally, this software module fills an analysis gap, allowing for quick, high-level mission analysis trades without the need for detailed and complicated orbit analysis using commercial stand-alone tools. This software consists of a series of MATLAB functions to provide for geometric orbit-related analysis. This includes propagation of orbits to varying levels of generalization. In the simplest case, geosynchronous orbits can be modeled by specifying a subset of three orbit elements. The next case is a circular orbit, which can be specified by a subset of four orbit elements. The most general case is an arbitrary elliptical orbit specified by all six orbit elements. These orbits are all solved geometrically, under the basic problem of an object in circular (or elliptical) orbit around a rotating spheroid. The orbit functions output time series ground tracks, which serve as the basis for more detailed orbit analysis. This software module also includes functions to track the positions of the Sun, Moon, and arbitrary celestial bodies specified by right ascension and declination. Also included are functions to calculate line-of-sight geometries to ground-based targets, angular rotations and decompositions, and other line-of-site calculations. The toolset allows for the rapid execution of orbit trade studies at the level of detail required for the

  16. Making mediation work.

    Science.gov (United States)

    Arif, Zeba

    2016-10-26

    Mediation can be an effective way of solving conflict between staff members. It signifies a willingness for people to work together to discuss their differences in a constructive way, before going down the official grievance route.

  17. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2004-01-01

    Implementation of new computer-mediated communication (CMC) systems in organizations is a complex socio-technical endeavour, involving the mutual adaptation of technology and organization over time. Drawing on the analytic concept of sensemaking, this paper provides a theoretical perspective...... that deepens our understanding of how organizations appropriate new electronic communication media. The paper analyzes how a group of mediators in a large, multinational company adapted a new web-based CMC technology (a virtual workspace) to the local organizational context (and vice versa) by modifying...... features of the technology, providing ongoing support for users, and promoting appropriate conventions of use. We found that these mediators exerted considerable influence on how the technology was established and used in the organization. The mediators were not neutral facilitators of a well...

  18. Understanding Mediation Support

    OpenAIRE

    Lanz, David; Pring, Jamie; von Burg, Corinne; Zeller, Mathias

    2017-01-01

    Recent decades have witnessed increasing institutionalization of mediation support through the establishment of mediation support structures (MSS) within foreign ministries and secretariats of multilateral organizations. This study sheds light on this trend and aims to better understand the emergence, design and development of different MSS. This study analyzes six MSS, namely those established in the United Nations (UN), the Organization for Security and Co-operation in Europe (OSCE), the Eu...

  19. ENVIRONMENTAL CONFLICT MEDIATION

    Directory of Open Access Journals (Sweden)

    GABRIELA G. MIHUT

    2011-04-01

    Full Text Available At a time of global economic crisis followed by resource crisis, a period in which the world seeks alternative resources through eco-investment, environmental conflicts are inevitable. Romania is among the few countries that do not pay enough attention to environmental conflicts and to the advantages to of solving them through mediation procedure. The present paper deals with areas in which conflicts can be applied in environmental mediation and its benefits.

  20. Towards Prognostics for Electronics Components

    Data.gov (United States)

    National Aeronautics and Space Administration — Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is...

  1. Independent component analysis: recent advances

    OpenAIRE

    Hyv?rinen, Aapo

    2013-01-01

    Independent component analysis is a probabilistic method for learning a linear transform of a random vector. The goal is to find components that are maximally independent and non-Gaussian (non-normal). Its fundamental difference to classical multi-variate statistical methods is in the assumption of non-Gaussianity, which enables the identification of original, underlying components, in contrast to classical methods. The basic theory of independent component analysis was mainly developed in th...

  2. Statistics of Shared Components in Complex Component Systems

    Science.gov (United States)

    Mazzolini, Andrea; Gherardi, Marco; Caselle, Michele; Cosentino Lagomarsino, Marco; Osella, Matteo

    2018-04-01

    Many complex systems are modular. Such systems can be represented as "component systems," i.e., sets of elementary components, such as LEGO bricks in LEGO sets. The bricks found in a LEGO set reflect a target architecture, which can be built following a set-specific list of instructions. In other component systems, instead, the underlying functional design and constraints are not obvious a priori, and their detection is often a challenge of both scientific and practical importance, requiring a clear understanding of component statistics. Importantly, some quantitative invariants appear to be common to many component systems, most notably a common broad distribution of component abundances, which often resembles the well-known Zipf's law. Such "laws" affect in a general and nontrivial way the component statistics, potentially hindering the identification of system-specific functional constraints or generative processes. Here, we specifically focus on the statistics of shared components, i.e., the distribution of the number of components shared by different system realizations, such as the common bricks found in different LEGO sets. To account for the effects of component heterogeneity, we consider a simple null model, which builds system realizations by random draws from a universe of possible components. Under general assumptions on abundance heterogeneity, we provide analytical estimates of component occurrence, which quantify exhaustively the statistics of shared components. Surprisingly, this simple null model can positively explain important features of empirical component-occurrence distributions obtained from large-scale data on bacterial genomes, LEGO sets, and book chapters. Specific architectural features and functional constraints can be detected from occurrence patterns as deviations from these null predictions, as we show for the illustrative case of the "core" genome in bacteria.

  3. Statistics of Shared Components in Complex Component Systems

    Directory of Open Access Journals (Sweden)

    Andrea Mazzolini

    2018-04-01

    Full Text Available Many complex systems are modular. Such systems can be represented as “component systems,” i.e., sets of elementary components, such as LEGO bricks in LEGO sets. The bricks found in a LEGO set reflect a target architecture, which can be built following a set-specific list of instructions. In other component systems, instead, the underlying functional design and constraints are not obvious a priori, and their detection is often a challenge of both scientific and practical importance, requiring a clear understanding of component statistics. Importantly, some quantitative invariants appear to be common to many component systems, most notably a common broad distribution of component abundances, which often resembles the well-known Zipf’s law. Such “laws” affect in a general and nontrivial way the component statistics, potentially hindering the identification of system-specific functional constraints or generative processes. Here, we specifically focus on the statistics of shared components, i.e., the distribution of the number of components shared by different system realizations, such as the common bricks found in different LEGO sets. To account for the effects of component heterogeneity, we consider a simple null model, which builds system realizations by random draws from a universe of possible components. Under general assumptions on abundance heterogeneity, we provide analytical estimates of component occurrence, which quantify exhaustively the statistics of shared components. Surprisingly, this simple null model can positively explain important features of empirical component-occurrence distributions obtained from large-scale data on bacterial genomes, LEGO sets, and book chapters. Specific architectural features and functional constraints can be detected from occurrence patterns as deviations from these null predictions, as we show for the illustrative case of the “core” genome in bacteria.

  4. Unblockable Compositions of Software Components

    DEFF Research Database (Denmark)

    Dong, Ruzhen; Faber, Johannes; Liu, Zhiming

    2012-01-01

    We present a new automata-based interface model describing the interaction behavior of software components. Contrary to earlier component- or interface-based approaches, the interface model we propose specifies all the non-blockable interaction behaviors of a component with any environment...... composition of interface models preserves unblockable sequences of provided services....

  5. mma: An R Package for Mediation Analysis with Multiple Mediators

    OpenAIRE

    Qingzhao Yu; Bin Li

    2017-01-01

    Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous...

  6. PIC Activation through Functional Interplay between Mediator and TFIIH.

    Science.gov (United States)

    Malik, Sohail; Molina, Henrik; Xue, Zhu

    2017-01-06

    The multiprotein Mediator coactivator complex functions in large part by controlling the formation and function of the promoter-bound preinitiation complex (PIC), which consists of RNA polymerase II and general transcription factors. However, precisely how Mediator impacts the PIC, especially post-recruitment, has remained unclear. Here, we have studied Mediator effects on basal transcription in an in vitro transcription system reconstituted from purified components. Our results reveal a close functional interplay between Mediator and TFIIH in the early stages of PIC development. We find that under conditions when TFIIH is not normally required for transcription, Mediator actually represses transcription. TFIIH, whose recruitment to the PIC is known to be facilitated by the Mediator, then acts to relieve Mediator-induced repression to generate an active form of the PIC. Gel mobility shift analyses of PICs and characterization of TFIIH preparations carrying mutant XPB translocase subunit further indicate that this relief of repression is achieved through expending energy via ATP hydrolysis, suggesting that it is coupled to TFIIH's established promoter melting activity. Our interpretation of these results is that Mediator functions as an assembly factor that facilitates PIC maturation through its various stages. Whereas the overall effect of the Mediator is to stimulate basal transcription, its initial engagement with the PIC generates a transcriptionally inert PIC intermediate, which necessitates energy expenditure to complete the process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Component Reification in Systems Modelling

    DEFF Research Database (Denmark)

    Bendisposto, Jens; Hallerstede, Stefan

    When modelling concurrent or distributed systems in Event-B, we often obtain models where the structure of the connected components is specified by constants. Their behaviour is specified by the non-deterministic choice of event parameters for events that operate on shared variables. From a certain......? These components may still refer to shared variables. Events of these components should not refer to the constants specifying the structure. The non-deterministic choice between these components should not be via parameters. We say the components are reified. We need to address how the reified components get...... reflected into the original model. This reflection should indicate the constraints on how to connect the components....

  8. Component Composition Using Feature Models

    DEFF Research Database (Denmark)

    Eichberg, Michael; Klose, Karl; Mitschke, Ralf

    2010-01-01

    interface description languages. If this variability is relevant when selecting a matching component then human interaction is required to decide which components can be bound. We propose to use feature models for making this variability explicit and (re-)enabling automatic component binding. In our...... approach, feature models are one part of service specifications. This enables to declaratively specify which service variant is provided by a component. By referring to a service's variation points, a component that requires a specific service can list the requirements on the desired variant. Using...... these specifications, a component environment can then determine if a binding of the components exists that satisfies all requirements. The prototypical environment Columbus demonstrates the feasibility of the approach....

  9. Analysis of multiparty mediation processes

    NARCIS (Netherlands)

    Vuković, Siniša

    2013-01-01

    Crucial challenges for multiparty mediation processes include the achievement of adequate cooperation among the mediators and consequent coordination of their activities in the mediation process. Existing literature goes only as far as to make it clear that successful mediation requires necessary

  10. Plant Mediator complex and its critical functions in transcription regulation.

    Science.gov (United States)

    Yang, Yan; Li, Ling; Qu, Li-Jia

    2016-02-01

    The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted. © 2015 Institute of Botany, Chinese Academy of Sciences.

  11. HUMAN COMMUNICATION AS MEDIATING THE UNITS OF PARAMETERISED ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Josip Stepanic

    2004-06-01

    Full Text Available Human communication is prevalently a mediated process. Mediators are units of environment, which are attributed functions within the local value set. They are utilised in such a way as to optimise the change of human states. In this article, a mediator-centred interpretation of the human communication is given. The interpretation follows closely the concept of mediated interaction developed within physics. It is conjectured that collection of mediators, which the humans use, has a well-defined average. The averaged collection permits reliable interpretation as a human communication spectrum. Relation of the intensity of a spectral component with regard to different senses, and with regard to intensity of interaction is discussed.

  12. Mediation: The Wise Advocacy

    Directory of Open Access Journals (Sweden)

    Towseef Ahmad

    2016-01-01

    Full Text Available AbstractAdversarial litigation is not the only means of resolving disputes and settling of claims. There are various options. Alternative means of dispute resolution can save money and time, and can help to anchor and resolve the dispute while exploring valuable good offices, amicable approaches and facilitation. Mediation, as used in law, is a process of managing negotiation by a neutral third party in the form of Alternative Dispute Resolution (ADR, as a convenient way of resolving disputes between two or more parties with speediation processes. On the sidelines typically, a neutral third party, the mediator assists the parties to negotiate a settlement. The term “mediation” broadly refers to any instance in which a neutral third party helps others to reach an amicable and mutually acceptable agreement. More specifically, mediation has a structure, timetable and dynamic approaches that “ordinary” negotiations usually lack. The process helps the parties to flourish the healthy ideas which are different and distinct from the legal rights in a Court of law. It is well known in International Law also and disputants can submit their disputes to mediation in a variety of matters such as commercial, legal, diplomatic, workplace, community and family matters, which assumes a great significance and it is bricolaged within the framework of this article.Keywords: Adversarial, Litigation, Mediation, Negotiation and Amicable.

  13. R2 effect-size measures for mediation analysis

    Science.gov (United States)

    Fairchild, Amanda J.; MacKinnon, David P.; Taborga, Marcia P.; Taylor, Aaron B.

    2010-01-01

    R2 effect-size measures are presented to assess variance accounted for in mediation models. The measures offer a means to evaluate both component paths and the overall mediated effect in mediation models. Statistical simulation results indicate acceptable bias across varying parameter and sample-size combinations. The measures are applied to a real-world example using data from a team-based health promotion program to improve the nutrition and exercise habits of firefighters. SAS and SPSS computer code are also provided for researchers to compute the measures in their own data. PMID:19363189

  14. R2 effect-size measures for mediation analysis.

    Science.gov (United States)

    Fairchild, Amanda J; Mackinnon, David P; Taborga, Marcia P; Taylor, Aaron B

    2009-05-01

    R(2) effect-size measures are presented to assess variance accounted for in mediation models. The measures offer a means to evaluate both component paths and the overall mediated effect in mediation models. Statistical simulation results indicate acceptable bias across varying parameter and sample-size combinations. The measures are applied to a real-world example using data from a team-based health promotion program to improve the nutrition and exercise habits of firefighters. SAS and SPSS computer code are also provided for researchers to compute the measures in their own data.

  15. Immunologically mediated oral diseases.

    Science.gov (United States)

    Jimson, Sudha; Balachader, N; Anita, N; Babu, R

    2015-04-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  16. Immunologically mediated oral diseases

    Directory of Open Access Journals (Sweden)

    Sudha Jimson

    2015-01-01

    Full Text Available Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  17. Causal mediation analysis with multiple causally non-ordered mediators.

    Science.gov (United States)

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  18. Mediator kinase module and human tumorigenesis.

    Science.gov (United States)

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  19. SBA Network Components & Software Inventory

    Data.gov (United States)

    Small Business Administration — SBA’s Network Components & Software Inventory contains a complete inventory of all devices connected to SBA’s network including workstations, servers, routers,...

  20. Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle

    DEFF Research Database (Denmark)

    Astrup, A; Simonsen, L; Bülow, J

    1989-01-01

    The thermic effect of carbohydrate has a component mediated by the sympathoadrenal system but of unknown anatomical localization. We have studied the contribution of skeletal muscle to the thermic effect of a carbohydrate-rich natural meal (115 g of carbohydrate, approximately 80% of energy...... postprandially and coinciding with the peak in arterial epinephrine. The present study provides evidence of a facultative thermogenic component in skeletal muscle, mediated by epinephrine via beta 2-adrenoreceptors. However, it also points to a nonmuscle component mediated through beta 1-adrenoceptors...... by norepinephrine released from the sympathetic nervous system. Consequently, the sympathoadrenal system seems to play a physiological role in the daily energy balance....

  1. WRKY Transcription Factors: Key Components in Abscisic Acid Signaling

    Science.gov (United States)

    2011-01-01

    networks that take inputs from numerous stimuli and that they are involved in mediating responses to numerous phytohormones including salicylic acid ... jasmonic acid , ABA and GA. These roles in multiple signalling pathways may in turn partly explain the pleiotropic effects commonly seen when TF genes are...Review article WRKY transcription factors: key components in abscisic acid signalling Deena L. Rushton1, Prateek Tripathi1, Roel C. Rabara1, Jun Lin1

  2. Components selection for ageing management

    International Nuclear Information System (INIS)

    Mingiuc, C.; Vidican, D.

    2002-01-01

    Full text: The paper presents a synthesis of methods and activities realized for the selection of critical components to assure plant safety and availability (as electricity supplier). There are presented main criteria for selection, screening process. For the resulted categories of components shall be applied different category of maintenance (condition oriented, scheduled or corrective), function of the importance and financial effort necessary to fulfil the task. 1. Systems and components screening for plant safety assurance For the systems selection, from Safety point of view, was necessary first, to define systems which are dangerous in case of failure (mainly by rupture/ release of radioactivity) and the safety systems which have to mitigate the effects. This is realized based on accident analysis (from Safety Report). Also where taken in to account the 4 basic Safety Principles: 'Reactor shut down; Residual heat removal; Radioactivity products confinement; NPP status monitoring in normal and accident conditions'. Following step is to establish safety support systems, which have to action to assure main safety systems operation. This could be realized based on engineering judgement, or on PSA Level I analysis. Finally shall be realized chains of the support systems, which have to work, till primary systems. For the critical components selection, was realized a Failure Mode and Effect Analysis (FMEA), considering the components effects of failures, on system safety function. 2. Systems and components screening for plant availability assurance The work was realized in two steps: Systems screening; Components screening The systems screening, included: General, analyze of the plant systems list and the definition of those which clearly have to run continue to assure the nominal power; Realization of a complex diagram to define interdependence between the systems (e.g. PHT and auxiliaries, moderator and auxiliaries, plant electrical diagram); Fill of special

  3. Mediation analysis with time varying exposures and mediators.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

    2017-06-01

    In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

  4. Multiple mediation analysis of the relationship between rapid naming and reading

    DEFF Research Database (Denmark)

    Poulsen, Mads; Juul, Holger; Elbro, Carsten

    2015-01-01

    It is well established that rapid automatised naming (RAN) correlates with reading ability. Despite several attempts, no single component process (mediator) has been identified that fully accounts for the correlation. The present paper estimated the explanatory value of several mediators....... The influence of the mediators on the RAN-reading correlation was estimated as indirect effects in mediation analyses. Phonological awareness and letter knowledge significantly mediated the RAN-reading relationship, each accounted for a moderate part of the correlation between RAN and reading fluency. Thus...

  5. APS beamline standard components handbook

    International Nuclear Information System (INIS)

    Kuzay, T.M.

    1992-01-01

    It is clear that most Advanced Photon Source (APS) Collaborative Access Team (CAT) members would like to concentrate on designing specialized equipment related to their scientific programs rather than on routine or standard beamline components. Thus, an effort is in progress at the APS to identify standard and modular components of APS beamlines. Identifying standard components is a nontrivial task because these components should support diverse beamline objectives. To assist with this effort, the APS has obtained advice and help from a Beamline Standardization and Modularization Committee consisting of experts in beamline design, construction, and operation. The staff of the Experimental Facilities Division identified various components thought to be standard items for beamlines, regardless of the specific scientific objective of a particular beamline. A generic beamline layout formed the basis for this identification. This layout is based on a double-crystal monochromator as the first optical element, with the possibility of other elements to follow. Pre-engineering designs were then made of the identified standard components. The Beamline Standardization and Modularization Committee has reviewed these designs and provided very useful input regarding the specifications of these components. We realize that there will be other configurations that may require special or modified components. This Handbook in its current version (1.1) contains descriptions, specifications, and pre-engineering design drawings of these standard components. In the future, the APS plans to add engineering drawings of identified standard beamline components. Use of standard components should result in major cost reductions for CATs in the areas of beamline design and construction

  6. Structure of Energetic Particle Mediated Shocks Revisited

    International Nuclear Information System (INIS)

    Mostafavi, P.; Zank, G. P.; Webb, G. M.

    2017-01-01

    The structure of collisionless shock waves is often modified by the presence of energetic particles that are not equilibrated with the thermal plasma (such as pickup ions [PUIs] and solar energetic particles [SEPs]). This is relevant to the inner and outer heliosphere and the Very Local Interstellar Medium (VLISM), where observations of shock waves (e.g., in the inner heliosphere) show that both the magnetic field and thermal gas pressure are less than the energetic particle component pressures. Voyager 2 observations revealed that the heliospheric termination shock (HTS) is very broad and mediated by energetic particles. PUIs and SEPs contribute both a collisionless heat flux and a higher-order viscosity. We show that the incorporation of both effects can completely determine the structure of collisionless shocks mediated by energetic ions. Since the reduced form of the PUI-mediated plasma model is structurally identical to the classical cosmic ray two-fluid model, we note that the presence of viscosity, at least formally, eliminates the need for a gas sub-shock in the classical two-fluid model, including in that regime where three are possible. By considering parameters upstream of the HTS, we show that the thermal gas remains relatively cold and the shock is mediated by PUIs. We determine the structure of the weak interstellar shock observed by Voyager 1 . We consider the inclusion of the thermal heat flux and viscosity to address the most general form of an energetic particle-thermal plasma two-fluid model.

  7. Structure of Energetic Particle Mediated Shocks Revisited

    Energy Technology Data Exchange (ETDEWEB)

    Mostafavi, P.; Zank, G. P. [Department of Space Science, University of Alabama in Huntsville, Huntsville, AL 35899 (United States); Webb, G. M. [Center for Space Plasma and Aeronomic Research (CSPAR), University of Alabama in Huntsville, Huntsville, AL 35899 (United States)

    2017-05-20

    The structure of collisionless shock waves is often modified by the presence of energetic particles that are not equilibrated with the thermal plasma (such as pickup ions [PUIs] and solar energetic particles [SEPs]). This is relevant to the inner and outer heliosphere and the Very Local Interstellar Medium (VLISM), where observations of shock waves (e.g., in the inner heliosphere) show that both the magnetic field and thermal gas pressure are less than the energetic particle component pressures. Voyager 2 observations revealed that the heliospheric termination shock (HTS) is very broad and mediated by energetic particles. PUIs and SEPs contribute both a collisionless heat flux and a higher-order viscosity. We show that the incorporation of both effects can completely determine the structure of collisionless shocks mediated by energetic ions. Since the reduced form of the PUI-mediated plasma model is structurally identical to the classical cosmic ray two-fluid model, we note that the presence of viscosity, at least formally, eliminates the need for a gas sub-shock in the classical two-fluid model, including in that regime where three are possible. By considering parameters upstream of the HTS, we show that the thermal gas remains relatively cold and the shock is mediated by PUIs. We determine the structure of the weak interstellar shock observed by Voyager 1 . We consider the inclusion of the thermal heat flux and viscosity to address the most general form of an energetic particle-thermal plasma two-fluid model.

  8. When Memories are Mediated

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    that are mediated through stories: told and retold as oral stories through generations, as myths or sagas, or remediated as contemporary documentary film accounts or more fictional film accounts. In these processes of retelling acts of violence, transformations of meanings across time, cultural, social...

  9. Mediated Cultural Memories

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    generations. Acts of mass violence also construct a sort of looking glass of culturally dominant memories that are mediated through stories: retold as oral stories through generations, as myths or sagas, or remediated in contemporary documentary or fiction films. In these processes of retelling acts...

  10. Cultural mediation in museums

    Directory of Open Access Journals (Sweden)

    Gherghina Boda

    2017-12-01

    Full Text Available If we perceive the museum not only as a place of storing and conserving the patrimony, but also of transmitting it, then we can also see it as a mediator through which cultures can become collective patrimony. Tightly connected to patrimonial appropriation, mediation appears from this perspective as a process and not an end, as it manifests itself in animation, communication and making knowledge popular in relation to a precise patrimony. That is why we can see cultural mediation as a transmission, as a transformation, as an action or social project which aims at creating social bonds, the museum thus being not only a place of meeting for the public with the objects exposed, but also as a place of meeting between different cultures. Thus, cultural mediation presents itself as the most efficient means for access to culture of all categories of the public, situated as the crossroads of culture, continuous education and entertainment and is inscribed in the field of informal education.

  11. The Bensberg Mediation Model

    Directory of Open Access Journals (Sweden)

    Raluca - Marilena Mihalcioiu

    2011-05-01

    Full Text Available The basis of the conflict through the mediation represents the objectives and procedures ofmediation, mediation of a conflict. The conflict will not be disclosed to others, but the parties will be creditedthe authority to resolve the conflict, the conflict among themselves with the help of a mediator. The disputeshould be resolved by the parties with help of a third party. The parties in conflict (it may be several personsare jointly responsible for the solution. They seek together a way that leads to long-term settlement of theconflict. The assumption of responsibility in this process strengthens the confidence and the importance oftheir decision. Important is that losers usually have no peace, because they are out for revenge. Winners don’tneed peace. If both parties lose, remains disappointing, with the understanding of which the conflict isresolved, will understand each other better developed. Reconciliation is therefore a longer-term goal.Conflicts also help to clarify roles. The paper presents Bensberg Model of Mediation, because this isdeveloped as a win win solution and his possible implementation in Romanian schools.

  12. Secure coupling of hardware components

    NARCIS (Netherlands)

    Hoepman, J.H.; Joosten, H.J.M.; Knobbe, J.W.

    2011-01-01

    A method and a system for securing communication between at least a first and a second hardware components of a mobile device is described. The method includes establishing a first shared secret between the first and the second hardware components during an initialization of the mobile device and,

  13. Generic component failure data base

    International Nuclear Information System (INIS)

    Eide, S.A.; Calley, M.B.

    1992-01-01

    This report discusses comprehensive component generic failure data base which has been developed for light water reactor probabilistic risk assessments. The Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR) was used to generate component failure rates. Using this approach, most of the failure rates are based on actual plant data rather then existing estimates

  14. Active components in food supplements

    NARCIS (Netherlands)

    Siemelink M; Jansen EHJM; Piersma AH; Opperhuizen A; LEO

    2000-01-01

    The growing food supplement market, where supplements are both more diverse and more easily available (e.g. through Internet) formed the backdrop to the inventory of the active components in food supplements. The safety of an increased intake of food components via supplements was also at issue

  15. Component reliability for electronic systems

    CERN Document Server

    Bajenescu, Titu-Marius I

    2010-01-01

    The main reason for the premature breakdown of today's electronic products (computers, cars, tools, appliances, etc.) is the failure of the components used to build these products. Today professionals are looking for effective ways to minimize the degradation of electronic components to help ensure longer-lasting, more technically sound products and systems. This practical book offers engineers specific guidance on how to design more reliable components and build more reliable electronic systems. Professionals learn how to optimize a virtual component prototype, accurately monitor product reliability during the entire production process, and add the burn-in and selection procedures that are the most appropriate for the intended applications. Moreover, the book helps system designers ensure that all components are correctly applied, margins are adequate, wear-out failure modes are prevented during the expected duration of life, and system interfaces cannot lead to failure.

  16. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  17. Mediation analysis with multiple versions of the mediator.

    Science.gov (United States)

    Vanderweele, Tyler J

    2012-05-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

  18. Component Fragility Research Program: Phase 1 component prioritization

    International Nuclear Information System (INIS)

    Holman, G.S.; Chou, C.K.

    1987-06-01

    Current probabilistic risk assessment (PRA) methods for nuclear power plants utilize seismic ''fragilities'' - probabilities of failure conditioned on the severity of seismic input motion - that are based largely on limited test data and on engineering judgment. Under the NRC Component Fragility Research Program (CFRP), the Lawrence Livermore National Laboratory (LLNL) has developed and demonstrated procedures for using test data to derive probabilistic fragility descriptions for mechanical and electrical components. As part of its CFRP activities, LLNL systematically identified and categorized components influencing plant safety in order to identify ''candidate'' components for future NRC testing. Plant systems relevant to safety were first identified; within each system components were then ranked according to their importance to overall system function and their anticipated seismic capacity. Highest priority for future testing was assigned to those ''very important'' components having ''low'' seismic capacity. This report describes the LLNL prioritization effort, which also included application of ''high-level'' qualification data as an alternate means of developing probabilistic fragility descriptions for PRA applications

  19. Formalization in Component Based Development

    DEFF Research Database (Denmark)

    Holmegaard, Jens Peter; Knudsen, John; Makowski, Piotr

    2006-01-01

    We present a unifying conceptual framework for components, component interfaces, contracts and composition of components by focusing on the collection of properties or qualities that they must share. A specific property, such as signature, functionality behaviour or timing is an aspect. Each aspect...... may be specified in a formal language convenient for its purpose and, in principle, unrelated to languages for other aspects. Each aspect forms its own semantic domain, although a semantic domain may be parameterized by values derived from other aspects. The proposed conceptual framework is introduced...

  20. Current Directions in Mediation Analysis

    Science.gov (United States)

    MacKinnon, David P.; Fairchild, Amanda J.

    2010-01-01

    Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables. PMID:20157637

  1. Current Directions in Mediation Analysis

    OpenAIRE

    MacKinnon, David P.; Fairchild, Amanda J.

    2009-01-01

    Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables.

  2. Dissociation in mediation

    Directory of Open Access Journals (Sweden)

    Daniela Muraru

    2008-01-01

    Full Text Available This paper approaches several texts that are part of the so-called discourse of mediation, adopting a pragma-dialectical perspective of the theory of dissociation. It is an attempt to identify the uses of dissociative patterns, with special emphasis on the indicators of dissociation. The paper investigates the various uses of the concept of dissociation as a discursive technique in the argumentation on the different aspects that are involved in international conflict, such as the discussion of the notion of peace. The purpose is to identify the role of dissociation, as a device strategically used by the mediator to help the parties minimize the disagreement space, and come to a conflict resolution.

  3. [Mediation in schools].

    Science.gov (United States)

    Mickley, Angela

    2006-01-01

    In this article the guiding questions concern the objectives and effectiveness of introducing mediation into an existing school culture of dominance, competition and selection. In addition the necessity will be shown of combining conflict resolution with organisational development and the introduction of a consensual ethics and behaviour code to attain sustainable results in creating a constructive and healthy school environment. Given scarce resources and little time the decisive role of artistic methods will be looked at in providing young people with flexible methods of expressing and negotiating their interests in a changing environment of values and power structures. Some aspects of the development of nonviolent communication, conflict resolution and mediation methods in schools in Germany will be focused on with special emphasis on the type of intervention used and its long term sustainable effects.

  4. Church mediation - een vak apart

    NARCIS (Netherlands)

    Annelies Klinefelter; dr Hans A.J. Jonker

    2009-01-01

    Welke rol kan mediation in de kerk spelen in de diverse geledingen en specifieke activiteiten? In dit artikel wordt ingegaan op kerkelijke conflicten, gelaagdheid in church mediation, en specifieke dilemma's van church mediation. Daarnaast komen enkele benaderingen aan bod zoals: helende

  5. The Mediatization of Philanthropy

    OpenAIRE

    Mitchell, Matthew

    2014-01-01

    This study seeks to better understand the motivations and mechanics of individuals contributing to nonprofits organizations today.  Through the prism of our highly mediatized (Hjarvard, 2008) social environment, this study examines the individual motivations and actions of cause-champions running in the 2013 NYC marathon and fundraising through social media and offline on behalf of the Michael J Fox Foundation (MJFF).  To gain the necessary detail and understanding of these micro-actions of a...

  6. Teachers as mediators

    DEFF Research Database (Denmark)

    Dorf, Hans; Kelly, Peter; Hohmann, Ulrike

    2012-01-01

    Within the context of lower secondary English teaching in South West England, this study identifies in broad terms the competing goals between which English teachers mediate and the explicit and hidden tensions that result. To understand the interactions of competing goals, teachers’ goal...... and cultural influences on practice. Yet the teachers observed moved smoothly between goal-oriented behaviours in a continuous and comfortable style, easily and without reflecting any tensions between them. Thus, this article elaborates an account of situated English teaching....

  7. mma: An R Package for Mediation Analysis with Multiple Mediators

    Directory of Open Access Journals (Sweden)

    Qingzhao Yu

    2017-04-01

    Full Text Available Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous, exposure, or mediation variables. With these definitions, multiple mediators of different types can be considered simultaneously, and the indirect effects carried by individual mediators can be separated from the total effect. Moreover, the derived mediation analysis can be performed with general predictive models. That is, the relationships among variables can be modeled using not only generalized linear models but also nonparametric models such as the Multiple Additive Regression Trees. Therefore, more complicated variable transformations and interactions can be considered in analyzing the mediation effects. The proposed method is realized by the R package 'mma'. We illustrate in this paper the proposed method and how to use 'mma' to estimate mediation effects and make inferences.

  8. Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Yang, Hwai-I

    2017-05-01

    Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

  9. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  10. Lopsided Gauge Mediation

    CERN Document Server

    De Simone, Andrea; Giudice, Gian Francesco; Pappadopulo, Duccio; Rattazzi, Riccardo

    2011-01-01

    It has been recently pointed out that the unavoidable tuning among supersymmetric parameters required to raise the Higgs boson mass beyond its experimental limit opens up new avenues for dealing with the so called $\\mu$-$B_\\mu$ problem of gauge mediation. In fact, it allows for accommodating, with no further parameter tuning, large values of $B_\\mu$ and of the other Higgs-sector soft masses, as predicted in models where both $\\mu$ and $B_\\mu$ are generated at one-loop order. This class of models, called Lopsided Gauge Mediation, offers an interesting alternative to conventional gauge mediation and is characterized by a strikingly different phenomenology, with light higgsinos, very large Higgs pseudoscalar mass, and moderately light sleptons. We discuss general parametric relations involving the fine-tuning of the model and various observables such as the chargino mass and the value of $\\tan\\beta$. We build an explicit model and we study the constraints coming from LEP and Tevatron. We show that in spite of ne...

  11. Three-component homeostasis control

    Science.gov (United States)

    Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

    2014-03-01

    Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

  12. Component Processes in Analogical Reasoning

    Science.gov (United States)

    Sternberg, Robert J.

    1977-01-01

    Describes alternative theoretical positions regarding (a) the component information processes used in analogical reasoning and (b) strategies for combining these processes. Also presents results from three experiments on analogical reasoning. (Author/RK)

  13. Passive Microwave Components and Antennas

    DEFF Research Database (Denmark)

    State-of-the-art microwave systems always require higher performance and lower cost microwave components. Constantly growing demands and performance requirements of industrial and scientific applications often make employing traditionally designed components impractical. For that reason, the design...... and development process remains a great challenge today. This problem motivated intensive research efforts in microwave design and technology, which is responsible for a great number of recently appeared alternative approaches to analysis and design of microwave components and antennas. This book highlights...... techniques. Modelling and computations in electromagnetics is a quite fast-growing research area. The recent interest in this field is caused by the increased demand for designing complex microwave components, modeling electromagnetic materials, and rapid increase in computational power for calculation...

  14. Metallurgical Laboratory and Components Testing

    Data.gov (United States)

    Federal Laboratory Consortium — In the field of metallurgy, TTC is equipped to run laboratory tests on track and rolling stock components and materials. The testing lab contains scanning-electron,...

  15. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    for zinc binding by the investigated amino acids, peptides and proteins. The thiol group or imidazole group containing amino acids, peptides and proteins which exhibited strong zinc binding ability were further selected for interacting with zinc salts in relation to zinc absorption. The interactions...... between the above selected food components and zinc citrate or zinc phytate will lead to the enhanced solubility of zinc citrate or zinc phytate. The main driving force for this observed solubility enhancement is the complex formation between zinc and investigated food components as revealed by isothermal...... titration calorimetry and quantum mechanical calculations. This is due to the zinc binding affinity of the relatively softer ligands (investigated food components) will become much stronger than citrate or phytate when they present together in aqueous solution. This mechanism indicates these food components...

  16. Komitmen Sebagai Mediator Pengaruh Iklim Inovatif Dan Kecocokan Individu‐Tim Terhadap Kinerja

    OpenAIRE

    Sugiyanto, -

    2009-01-01

    In the long term, the purpose of the research is to build an understanding of the organizational commitment as an important mediator of the effects of various antecedents on performance. The commitment as a mediator has been studied in various levels of workplace: Low, medium, and high technologies. The current study tested a theoretical model of the components of organizational commitment as mediators, innovative climate and person‐team fit as antecedents, whereas its consequence was perform...

  17. Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

    OpenAIRE

    Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Herv?; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

    2015-01-01

    Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation i...

  18. Komitmen Sebagai Mediator Pengaruh Iklim Inovatif dan Kecocokan Individu‐Tim Terhadap Kinerja

    OpenAIRE

    Sugiyanto, -

    2015-01-01

    In the long term, the purpose of the research is to build an understanding of the organizational commitment as an important mediator of the effects of various antecedents on performance. The commitment as a mediator has been studied in various levels of workplace: Low, medium, and high technologies. The current study tested a theoretical model of the components of organizational commitment as mediators, innovative climate and person‐team fit as antecedents, whereas its consequence...

  19. Immunomodulatory Effects Mediated by Dopamine

    Science.gov (United States)

    Alvarez-Herrera, Samantha; Pérez-Sánchez, Gilberto; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Flores-Gutierrez, Enrique Octavio; Quintero-Fabián, Saray

    2016-01-01

    Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers. PMID:27795960

  20. Immunomodulatory Effects Mediated by Dopamine

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2016-01-01

    Full Text Available Dopamine (DA, a neurotransmitter in the central nervous system (CNS, has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R and D2-like receptors (D2R, D3R, and D4R. The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS, there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

  1. Radiation effects in optical components

    International Nuclear Information System (INIS)

    Friebele, E.J.

    1987-01-01

    This report discusses components of high performance optical devices may be exposed to high energy radiation environments during their lifetime. The effect of these adverse environments depends upon a large number of parameters associated with the radiation (nature, energy, dose, dose rate, etc.) or the system (temperature, optical performance requirements, optical wavelength, optical power, path length, etc.), as well as the intrinsic susceptibility of the optical component itself to degradation

  2. Multiview Bayesian Correlated Component Analysis

    DEFF Research Database (Denmark)

    Kamronn, Simon Due; Poulsen, Andreas Trier; Hansen, Lars Kai

    2015-01-01

    are identical. Here we propose a hierarchical probabilistic model that can infer the level of universality in such multiview data, from completely unrelated representations, corresponding to canonical correlation analysis, to identical representations as in correlated component analysis. This new model, which...... we denote Bayesian correlated component analysis, evaluates favorably against three relevant algorithms in simulated data. A well-established benchmark EEG data set is used to further validate the new model and infer the variability of spatial representations across multiple subjects....

  3. A Review of Peer-Mediated Social Interaction Interventions for Students with Autism in Inclusive Settings

    Science.gov (United States)

    Watkins, Laci; O'Reilly, Mark; Kuhn, Michelle; Gevarter, Cindy; Lancioni, Giulio E.; Sigafoos, Jeff; Lang, Russell

    2015-01-01

    This review addresses the use of peer-mediated interventions (PMI) to improve the social interaction skills of students with autism spectrum disorder (ASD) in inclusive settings. The purpose of this review is to (a) identify the characteristics and components of peer-mediated social interaction interventions, (b) evaluate the effectiveness of PMI…

  4. A UML/OCL framework for design of mediated data federations

    NARCIS (Netherlands)

    Balsters, H.

    2003-01-01

    This paper describes a general semantic framework for precise specification of so-called mediating systems; such systems provide for tight coupling on a global level of a collection of heterogeneous component databases to a federated database. A mediating system maps in a uniform and systematic

  5. Mediation Analysis of an Adolescent HIV/STI/Pregnancy Prevention Intervention

    Science.gov (United States)

    Glassman, Jill R.; Franks, Heather M.; Baumler, Elizabeth R.; Coyle, Karin K.

    2014-01-01

    Most interventions designed to prevent HIV/STI/pregnancy risk behaviours in young people have multiple components based on psychosocial theories (e.g. social cognitive theory) dictating sets of mediating variables to influence to achieve desired changes in behaviours. Mediation analysis is a method for investigating the extent to which a variable…

  6. Multiple Mediation Analysis of the Relationship between Rapid Naming and Reading

    Science.gov (United States)

    Poulsen, Mads; Juul, Holger; Elbro, Carsten

    2015-01-01

    It is well established that rapid automatised naming (RAN) correlates with reading ability. Despite several attempts, no single component process (mediator) has been identified that fully accounts for the correlation. The present paper estimated the explanatory value of several mediators for the RAN--reading correlation. One hundred and sixty-nine…

  7. Youth Engagement and Suicide Risk: Testing a Mediated Model in a Canadian Community Sample

    Science.gov (United States)

    Ramey, Heather L.; Busseri, Michael A.; Khanna, Nishad; Rose-Krasnor, Linda

    2010-01-01

    Suicide is a leading cause of death among adolescents in many industrialized countries. We report evidence from a mediation model linking greater youth activity engagement, spanning behavioral and psychological components, with lower suicide risk through five hypothesized intrapersonal and interpersonal mediating factors. Self-report survey data…

  8. What carries a mediation process? Configural analysis of mediation.

    Science.gov (United States)

    von Eye, Alexander; Mun, Eun Young; Mair, Patrick

    2009-09-01

    Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

  9. Component protection based automatic control

    International Nuclear Information System (INIS)

    Otaduy, P.J.

    1992-01-01

    Control and safety systems as well as operation procedures are designed on the basis of critical process parameters limits. The expectation is that short and long term mechanical damage and process failures will be avoided by operating the plant within the specified constraints envelopes. In this paper, one of the Advanced Liquid Metal Reactor (ALMR) design duty cycles events is discussed to corroborate that the time has come to explicitly make component protection part of the control system. Component stress assessment and aging data should be an integral part of the control system. Then transient trajectory planning and operating limits could be aimed at minimizing component specific and overall plant component damage cost functions. The impact of transients on critical components could then be managed according to plant lifetime design goals. The need for developing methodologies for online transient trajectory planning and assessment of operating limits in order to facilitate the explicit incorporation of damage assessment capabilities to the plant control and protection systems is discussed. 12 refs

  10. Urban Songlines as Mediator

    DEFF Research Database (Denmark)

    Corlin, Anne

    2016-01-01

    The aim of this paper is to present an investigation of the method The Urban Songlines Book and how it works as a mediator for mapping the experienced space. The method contains a combination of aerial maps, photographs, and interviews as a way to understand the respondent´s use, relations...... and experiences of their neighborhood and the city. Through a presentation of the origin of the method, a description of the conducted study, and an analysis of the process in relation to theories about participatory design, social design, ANT and architectural sociology, the paper reveals how this method...

  11. Sociocultural mediators of remembering

    DEFF Research Database (Denmark)

    Wagoner, Brady; Gillespie, Alex

    2014-01-01

    , questioning and deferring contribute to the transformation and conventionalization of the material. These diverse sociocultural mediators are integrated into a partially coherent recollection by participants self-reflecting, or as Bartlett termed it, turning around upon their schemas. We demonstrate...... that this self-reflection is both a social and a psychological process, occurring because participants are responding to their own utterances in the same way that they respond to the utterances of other people. These empirical findings are used to make a case for using discursive data to look not only...

  12. DNA-Mediated Electrochemistry

    Science.gov (United States)

    Gorodetsky, Alon A.; Buzzeo, Marisa C.

    2009-01-01

    The base pair stack of DNA has been demonstrated as a medium for long range charge transport chemistry both in solution and at DNA-modified surfaces. This chemistry is exquisitely sensitive to structural perturbations in the base pair stack as occur with lesions, single base mismatches, and protein binding. We have exploited this sensitivity for the development of reliable electrochemical assays based on DNA charge transport at self-assembled DNA monolayers. Here we discuss the characteristic features, applications, and advantages of DNA-mediated electrochemistry. PMID:18980370

  13. Holographic Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Benini, Francesco; /Princeton U.; Dymarsky, Anatoly; /Stanford U., ITP; Franco, Sebastian; /Santa Barbara, KITP; Kachru, Shamit; Simic, Dusan; /Stanford U., ITP /SLAC; Verlinde, Herman; /Princeton, Inst. Advanced Study

    2009-06-19

    We discuss gravitational backgrounds where supersymmetry is broken at the end of a warped throat, and the SUSY-breaking is transmitted to the Standard Model via gauginos which live in (part of) the bulk of the throat geometry. We find that the leading effect arises from splittings of certain 'messenger mesons,' which are adjoint KK-modes of the D-branes supporting the Standard Model gauge group. This picture is a gravity dual of a strongly coupled field theory where SUSY is broken in a hidden sector and transmitted to the Standard Model via a relative of semi-direct gauge mediation.

  14. Mechanical design of machine components

    CERN Document Server

    Ugural, Ansel C

    2015-01-01

    Mechanical Design of Machine Components, Second Edition strikes a balance between theory and application, and prepares students for more advanced study or professional practice. It outlines the basic concepts in the design and analysis of machine elements using traditional methods, based on the principles of mechanics of materials. The text combines the theory needed to gain insight into mechanics with numerical methods in design. It presents real-world engineering applications, and reveals the link between basic mechanics and the specific design of machine components and machines. Divided into three parts, this revised text presents basic background topics, deals with failure prevention in a variety of machine elements and covers applications in design of machine components as well as entire machines. Optional sections treating special and advanced topics are also included.Key Features of the Second Edition:Incorporates material that has been completely updated with new chapters, problems, practical examples...

  15. Towards Prognostics for Electronics Components

    Science.gov (United States)

    Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

    2013-01-01

    Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  16. Automated cleaning of electronic components

    International Nuclear Information System (INIS)

    Drotning, W.; Meirans, L.; Wapman, W.; Hwang, Y.; Koenig, L.; Petterson, B.

    1994-01-01

    Environmental and operator safety concerns are leading to the elimination of trichloroethylene and chlorofluorocarbon solvents in cleaning processes that remove rosin flux, organic and inorganic contamination, and particulates from electronic components. Present processes depend heavily on these solvents for manual spray cleaning of small components and subassemblies. Use of alternative solvent systems can lead to longer processing times and reduced quality. Automated spray cleaning can improve the quality of the cleaning process, thus enabling the productive use of environmentally conscious materials, while minimizing personnel exposure to hazardous materials. We describe the development of a prototype robotic system for cleaning electronic components in a spray cleaning workcell. An important feature of the prototype system is the capability to generate the robot paths and motions automatically from the CAD models of the part to be cleaned, and to embed cleaning process knowledge into the automatically programmed operations

  17. 45 CFR 16.18 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 16.18 Section 16.18 Public Welfare... BOARD § 16.18 Mediation. (a) In cases pending before the Board. If the Board decides that mediation... mediation techniques and will provide or assist in selecting a mediator. The mediator may take any steps...

  18. Mediating Effects of Working Memory in the Relation Between Rapid Automatized Naming and Chinese Reading Comprehension.

    Science.gov (United States)

    Weng, Xiaoqian; Li, Guangze; Li, Rongbao

    2016-08-01

    This study examined the mediating role of working memory (WM) in the relation between rapid automatized naming (RAN) and Chinese reading comprehension. Three tasks assessing differentially visual and verbal components of WM were programmed by E-prime 2.0. Data collected from 55 Chinese college students were analyzed using correlations and hierarchical regression methods to determine the connection among RAN, reading comprehension, and WM components. Results showed that WM played a significant mediating role in the RAN-reading relation and that auditory WM made stronger contributions than visual WM. Taking into account of the multi-component nature of WM and the specificity of Chinese reading processing, this study discussed the mediating powers of the WM components, particularly auditory WM, further clarifying the possible components involved in the RAN-reading relation and thus providing some insight into the complicated Chinese reading process.

  19. Data Mediation with Enterprise Level Security

    Directory of Open Access Journals (Sweden)

    Kevin E. Foltz

    2017-10-01

    Full Text Available Enterprise Level Security (ELS is an architecture for enabling information sharing with strong security guarantees. It is built upon basic tenets and concepts that shape its component technologies and implementation. One challenge in sharing information is that the source and recipient of the information may use different units, protocols, data formats, or tools to process information. As a result, a transformation of the data is needed before the recipient can use the information. These conversions introduce potential security weaknesses into an ELS system, so an approach for enterprise-wide mediation is required. Methods in common use today, such as a man-in-the-middle (MITM translation and an online mediation service, do not preserve the basic ELS tenets and concepts. This paper examines these existing approaches and compares them with two new approaches designed to preserve ELS security. It looks at the complete picture of security, performance, and ease of implementation, offering a framework for choosing the best mediation approach based on the data sharing context.

  20. Diverse exocytic pathways for mast cell mediators.

    Science.gov (United States)

    Xu, Hao; Bin, Na-Ryum; Sugita, Shuzo

    2018-04-17

    Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells respond to environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g. proteases, amines, and cytokines). Many of these mediators are stored in granules/lysosomes and rely on intricate degranulation processes for release. Mast cell stabilizers (e.g. sodium cromoglicate), which prevent such degranulation processes, have therefore been clinically employed to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators that rely on overlapping but distinct mechanisms for release. This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells. We also discuss strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Explanation components as interactive tools

    Energy Technology Data Exchange (ETDEWEB)

    Wahlster, W.

    1983-01-01

    The ability to explain itself is probably the most important criterion of the user-friendliness of interactive systems. Explanation aids in the form of simple help functions do not meet this criterion. The reasons for this are outlined. More promising is an explanation component which can give the user intelligible and context-oriented explanations. The essential requirement for this is the development of knowledge-based interactive systems using artificial intelligence methods and techniques. The authors report on experiences with the development of explanation components, in particular a number of examples from the HAM-ANS project. 12 references.

  2. Radioactive resistance of EEPROM components

    International Nuclear Information System (INIS)

    Loncar, B.; Novakovic, D.; Stankovic, S.; Osmokrovic, P.

    1999-01-01

    The aim of this paper is to examine the resistance of EEPROM components under the influence of gamma radiation. This paper is significant for military industry and space technology. Therefore the analysis of the degradation mechanisms of these components as well as the possibilities to increase their radiation resistance have been considered by many authors. Total dose results are presented for 28C64C EEPROM there is evidence that the first failure appeared for 1000 Gy total dose level. The obtained result are analyzed and explained theoretically via the interaction of gamma radiation with oxide layer. (author)

  3. Space storable propulsion components development

    Science.gov (United States)

    Hagler, R., Jr.

    1982-01-01

    The current development status of components to control the flow of propellants (liquid fluorine and hydrazine) in a demonstration space storable propulsion system is discussed. The criteria which determined the designs for the pressure regulator, explosive-actuated valves, propellant shutoff valve, latching solenoid-actuated valve and propellant filter are presented. The test philosophy that was followed during component development is outlined. The results from compatibility demonstrations for reusable connectors, flange seals, and CRES/Ti-6Al4V transition tubes and the evaluations of processes for welding (hand-held TIG, automated TIG, and EB), cleaning for fluorine service, and decontamination after fluorine exposure are described.

  4. Radiation effects on eye components

    Science.gov (United States)

    Durchschlag, H.; Fochler, C.; Abraham, K.; Kulawik, B.

    1999-08-01

    The most important water-soluble components of the vertebrate eye (lens proteins, aqueous humor, vitreous, hyaluronic acid, ascorbic acid) have been investigated in aqueous solution, after preceding X- or UV-irradiation. Spectroscopic, chromatographic, electrophoretic, hydrodynamic and analytic techniques have been applied, to monitor several radiation damages such as destruction of aromatic and sulfur-containing amino acids, aggregation, crosslinking, dissociation, fragmentation, and partial unfolding. Various substances were found which were able to protect eye components effectively against radiation, some of them being also of medical relevance.

  5. Latent semantics as cognitive components

    DEFF Research Database (Denmark)

    Petersen, Michael Kai; Mørup, Morten; Hansen, Lars Kai

    2010-01-01

    Cognitive component analysis, defined as an unsupervised learning of features resembling human comprehension, suggests that the sensory structures we perceive might often be modeled by reducing dimensionality and treating objects in space and time as linear mixtures incorporating sparsity...... emotional responses can be encoded in words, we propose a simplified cognitive approach to model how we perceive media. Representing song lyrics in a vector space of reduced dimensionality using LSA, we combine bottom-up defined term distances with affective adjectives, that top-down constrain the latent......, which we suggest might function as cognitive components for perceiving the underlying structure in lyrics....

  6. Interventional effects for mediation analysis with multiple mediators

    OpenAIRE

    Vansteelandt, Stijn; Daniel, Rhian M.

    2017-01-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

  7. Component-resolved diagnostics in vernal conjunctivitis.

    Science.gov (United States)

    Armentia, Alicia; Sanchís, Eugenia; Montero, Javier A

    2016-10-01

    Conventional diagnostic tests in allergy are insufficient to clarify the cause of vernal conjunctivitis. Component-resolved diagnostic (CRD) by microarray allergen assay may be useful in detecting allergens that might be involved in the inflammatory process. In a recent trial in patients suffered from eosinophilic esophagitis, after 2 years of the CRD-guided exclusion diet and specific immunotherapy, significant clinical improvement was observed, and 68% of patients were discharged (cure based on negative biopsy, no symptoms, and no medication intake). Our new objective was to evaluate IgE-mediated hypersensitivity by CRD in tears and serum from patients with vernal conjunctivitis and treat patients with identified triggering allergens by specific immunotherapy. Twenty-five patients with vernal conjunctivitis were evaluated. The identified triggering allergens were n Lol p 1 (11 cases), n Cyn d 1 (eight cases), group 4 and 6 grasses (six cases) and group 5 of grasses (five cases). Prick test and pollen IgE were positive in one case. Clinical improvement was observed in 13/25 vernal conjunctivitis patients after 1-year specific immunotherapy. CRD seems to be a more sensitive diagnostic tool compared with prick test and IgE detection. Specific CRD-led immunotherapy may achieve clinical improvements in vernal conjunctivitis patients.

  8. Frontopolar cortex mediates abstract integration in analogy.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Kraemer, David J M; Shamosh, Noah A; Dunbar, Kevin N

    2006-06-22

    Integration of abstractly similar relations during analogical reasoning was investigated using functional magnetic resonance imaging. Activation elicited by an analogical reasoning task that required both complex working memory and integration of abstractly similar relations was compared to activation elicited by a non-analogical task that required complex working memory in the absence of abstract relational integration. A left-sided region of the frontal pole of the brain (BA 9/10) was selectively active for the abstract relational integration component of analogical reasoning. Analogical reasoning also engaged a left-sided network of parieto-frontal regions. Activity in this network during analogical reasoning is hypothesized to reflect categorical alignment of individual component terms that make up analogies. This parieto-frontal network was also engaged by the complex control task, which involved explicit categorization, but not by a simpler control task, which did not involve categorization. We hypothesize that frontopolar cortex mediates abstract relational integration in complex reasoning while parieto-frontal regions mediate working memory processes, including manipulation of terms for the purpose of categorical alignment, that facilitate this integration.

  9. Interpreter-mediated dentistry.

    Science.gov (United States)

    Bridges, Susan; Drew, Paul; Zayts, Olga; McGrath, Colman; Yiu, Cynthia K Y; Wong, H M; Au, T K F

    2015-05-01

    The global movements of healthcare professionals and patient populations have increased the complexities of medical interactions at the point of service. This study examines interpreter mediated talk in cross-cultural general dentistry in Hong Kong where assisting para-professionals, in this case bilingual or multilingual Dental Surgery Assistants (DSAs), perform the dual capabilities of clinical assistant and interpreter. An initial language use survey was conducted with Polyclinic DSAs (n = 41) using a logbook approach to provide self-report data on language use in clinics. Frequencies of mean scores using a 10-point visual analogue scale (VAS) indicated that the majority of DSAs spoke mainly Cantonese in clinics and interpreted for postgraduates and professors. Conversation Analysis (CA) examined recipient design across a corpus (n = 23) of video-recorded review consultations between non-Cantonese speaking expatriate dentists and their Cantonese L1 patients. Three patterns of mediated interpreting indicated were: dentist designated expansions; dentist initiated interpretations; and assistant initiated interpretations to both the dentist and patient. The third, rather than being perceived as negative, was found to be framed either in response to patient difficulties or within the specific task routines of general dentistry. The findings illustrate trends in dentistry towards personalized care and patient empowerment as a reaction to product delivery approaches to patient management. Implications are indicated for both treatment adherence and the education of dental professionals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan

    2009-01-01

    Autophagy has been implicated as a prosurvival mechanism to restrict programmed cell death (PCD) associated with the pathogen-triggered hypersensitive response (HR) during plant innate immunity. This model is based on the observation that HR lesions spread in plants with reduced autophagy gene...... expression. Here, we examined receptor-mediated HR PCD responses in autophagy-deficient Arabidopsis knockout mutants (atg), and show that infection-induced lesions are contained in atg mutants. We also provide evidence that HR cell death initiated via Toll/Interleukin-1 (TIR)-type immune receptors through...... the defense regulator EDS1 is suppressed in atg mutants. Furthermore, we demonstrate that PCD triggered by coiled-coil (CC)-type immune receptors via NDR1 is either autophagy-independent or engages autophagic components with cathepsins and other unidentified cell death mediators. Thus, autophagic cell death...

  11. Environmental Forces - Some Esthetic Components.

    Science.gov (United States)

    Severino, D. Alexander

    Although our system of mass culture has raised our civilization to an extremely high level of material success and affluence, the fact remains that this system has the inherent flaw of not fully recognizing the esthetic needs of man. To overcome this weakness we need to re-introduce into the system a sizable component of first-hand experience…

  12. Components in the interstellar medium

    International Nuclear Information System (INIS)

    Martin, E.R.

    1981-01-01

    An analysis is made of the lines of sight toward 32 stars with a procedure that gives velocity components for various interstellar ions. The column densities found for species expected to be relatively undepleted are used to estimate the column density of neutral hydrogen in each component. Whenever possible, the molecular hydrogen excitation temperature, abundances (relative to S II), electron density, and hydrogen volume density are calculated for each component. The results for each star are combined to give total HI column density as a function of (LSR) velocity. The derived velocities correspond well with those found in optical studies. The mean electron density is found to be approximately constant with velocity, but the mean hydrogen volume density is found to vary. The data presented here are consistent with the assumption that some of the velocity components are due to circumstellar material. The total HI column density toward a given star is generally in agreement with Lyman alpha measurements, but ionization and abundance effects are important toward some stars. The total HI column density is found to vary exponentially with velocity (for N(HI)> 10 17 cm -2 ), with an indication that the velocity dispersion at low column densities (N(HI) 17 cm -2 ) is approximately constant. An estimate is made of the kinetic energy density due to cloud motion which depends only on the total HI column density as a function of velocity. The value of 9 x 10 42 erg/pc 3 is in good agreement with a theoretical prediction

  13. Embedded 100 Gbps Photonic Components:

    Energy Technology Data Exchange (ETDEWEB)

    Kuznia, Charlie

    2018-04-26

    This innovation to fiber optic component technology increases the performance, reduces the size and reduces the power consumption of optical communications within dense network systems, such as advanced distributed computing systems and data centers. VCSEL technology is enabling short-reach (< 100 m) and >100 Gbps optical interconnections over multi-mode fiber in commercial applications.

  14. Inspection of disposal canisters components

    International Nuclear Information System (INIS)

    Pitkaenen, J.

    2013-12-01

    This report presents the inspection techniques of disposal canister components. Manufacturing methods and a description of the defects related to different manufacturing methods are described briefly. The defect types form a basis for the design of non-destructive testing because the defect types, which occur in the inspected components, affect to choice of inspection methods. The canister components are to nodular cast iron insert, steel lid, lid screw, metal gasket, copper tube with integrated or separate bottom, and copper lid. The inspection of copper material is challenging due to the anisotropic properties of the material and local changes in the grain size of the copper material. The cast iron insert has some acoustical material property variation (attenuation, velocity changes, scattering properties), which make the ultrasonic inspection demanding from calibration point of view. Mainly three different methods are used for inspection. Ultrasonic testing technique is used for inspection of volume, eddy current technique, for copper components only, and visual testing technique are used for inspection of the surface and near surface area

  15. Component effects in mixture experiments

    International Nuclear Information System (INIS)

    Piepel, G.F.

    1980-01-01

    In a mixture experiment, the response to a mixture of q components is a function of the proportions x 1 , x 2 , ..., x/sub q/ of components in the mixture. Experimental regions for mixture experiments are often defined by constraints on the proportions of the components forming the mixture. The usual (orthogonal direction) definition of a factor effect does not apply because of the dependence imposed by the mixture restriction, /sup q/Σ/sub i=1/ x/sub i/ = 1. A direction within the experimental region in which to compute a mixture component effect is presented and compared to previously suggested directions. This new direction has none of the inadequacies or errors of previous suggestions while having a more meaningful interpretation. The distinction between partial and total effects is made. The uses of partial and total effects (computed using the new direction) in modification and interpretation of mixture response prediction equations are considered. The suggestions of the paper are illustrated in an example from a glass development study in a waste vitrification program. 5 figures, 3 tables

  16. Modelling Livestock Component in FSSIM

    NARCIS (Netherlands)

    Thorne, P.J.; Hengsdijk, H.; Janssen, S.J.C.; Louhichi, K.; Keulen, van H.; Thornton, P.K.

    2009-01-01

    This document summarises the development of a ruminant livestock component for the Farm System Simulator (FSSIM). This includes treatments of energy and protein transactions in ruminant livestock that have been used as a basis for the biophysical simulations that will generate the input production

  17. A forgotten component of biodiversity

    Indian Academy of Sciences (India)

    2011-07-08

    Jul 8, 2011 ... Home; Journals; Journal of Biosciences; Volume 36; Issue 4. Clipboard: Helminth richness in Arunachal Pradesh fishes: A forgotten component of biodiversity. Amit Tripathi. Volume 36 Issue 4 September 2011 pp 559-561. Fulltext. Click here to view fulltext PDF. Permanent link:

  18. Detecting decay in wood components

    Science.gov (United States)

    R.J. Ross; X. Wang; B.K. Brashaw

    2005-01-01

    This chapter presents a summary of the Wood and Timber Condition Assessment Manual. It focuses on current inspection techniques for decay detection and provides guidelines on the use of various non-destructive evaluation (NDE) methods in locating and defining areas of deterioration in timber bridge components and other civil structures.

  19. Mediation Analysis: A Practitioner's Guide.

    Science.gov (United States)

    VanderWeele, Tyler J

    2016-01-01

    This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

  20. Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells

    DEFF Research Database (Denmark)

    Spåhr, H; Samuelsen, C O; Baraznenok, V

    2001-01-01

    . cerevisiae share an essential protein module, which associates with nonessential speciesspecific subunits. In support of this view, sequence analysis of the conserved yeast Mediator components Med4 and Med8 reveals sequence homology to the metazoan Mediator components Trap36 and Arc32. Therefore, 8 of 10...... essential genes conserved between S. pombe and S. cerevisiae also have a metazoan homolog, indicating that an evolutionary conserved Mediator core is present in all eukaryotic cells. Our data suggest a closer functional relationship between yeast and metazoan Mediator than previously anticipated....

  1. A higher form (of) mediation

    International Nuclear Information System (INIS)

    Verlinde, Herman; Wang, L-T; Yavin, Itay; Wijnholt, Martijn

    2008-01-01

    We exhibit a simple and robust mechanism for bulk mediation of supersymmetry breaking between hidden and visible sectors localized on geometrically separated D-branes in type II string theory. The mediation proceeds via RR p-forms that couple via linear Chern-Simons terms to the abelian vector bosons on the branes. From a 4-d low energy perspective, the mechanism reduces to U(1) mediation

  2. Cold component flow in a two-component mirror machine

    International Nuclear Information System (INIS)

    Rognlien, T.D.

    1975-12-01

    Steady-state solutions are given for the flow characteristics along the magnetic field of the cold plasma component in a two-component mirror machine. The hot plasma component is represented by a fixed density profile. The fluid equations are used to describe the cold plasma, which is assumed to be generated in a localized region at one end of the machine. The ion flow speed, v/sub i/, is required to satisfy the Bohm sheath condition at the end walls, i.e., v/sub i/ greater than or equal to c/sub s/, where c/sub s/ is the ion-acoustic speed. For the case when the cold plasma density, n/sub c/, is much less than the hot plasma density, n/sub h/, the cold plasma is stagnant and does not penetrate through the machine in the zero temperature case. The effect of a finite temperature is to allow for the penetration of a small amount of cold plasma through the machine. For the density range n/sub c/ approximately n/sub h/, the flow solutions are asymmetric about the midplane and have v/sub i/ = c/sub s/ near the midplane. Finally, for n/sub c/ much greater than n/sub h/, the solutions become symmetric about the midplane and approach the Lee--McNamara type solutions with v/sub i/ = c/sub s/ near the mirror throats

  3. Mediating Trust in Terrorism Coverage

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    crisis. While the framework is presented in the context of television coverage of a terror-related crisis situation, it can equally be used in connection with all other forms of mediated trust. Key words: National crisis, risk communication, crisis management, television coverage, mediated trust.......Mass mediated risk communication can contribute to perceptions of threats and fear of “others” and/or to perceptions of trust in fellow citizens and society to overcome problems. This paper outlines a cross-disciplinary holistic framework for research in mediated trust building during an acute...

  4. Substrate mediated enzyme prodrug therapy

    DEFF Research Database (Denmark)

    Fejerskov, Betina; Jarlstad Olesen, Morten T; Zelikin, Alexander N

    2017-01-01

    Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug administra......Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug...

  5. The Strategic Mediator

    DEFF Research Database (Denmark)

    Rossignoli, Cecilia; Carugati, Andrea; Mola, Lapo

    2009-01-01

    process. Through the study of services evolving over time we show that, as marketplaces support increasingly complex business processes, the market participants begin to privilege the well connected small number to the convenience of the openness to the entire market. The participants see the marketplace......The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter......-organizational relationships. The interest of this paper is to investigate the shift in the role and evolution of services proposed by e-marketplaces in response to the demands of the market participants. We carried out a longitudinal qualitative field study of an e-marketplace providing the outsourcing of the procurement...

  6. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    Action movies participate in the administration of fear [Virilio, P., 2012. The administration of fear. Translated by Ames Hodges. Los Angeles, CA: Semiotext(e)], and the networked affects of contemporary warfare [Anderson, B., 2013. Targeting affective life from above: morale and airpower. In: P......’ [Shaviro, S., 2010. Post-cinematic affect. Winchester: Zero Books]. These intensity effects mediate between the age of terror's ecology of fear [Massumi, Brian, 2002. Parables for the virtual: movement, affect, sensation. Durham: Duke University Press] and our bodies. Rather than producing fear, action...... movies work to dispel fear by producing potency and bolstering resolve. We can thus understand action movies as participating in the biopolitical effects of contemporary warfare. Affect is globalized and intensified through action movies’ aesthetics, with the aim of producing a kind of drone subject...

  7. Den sundhedsfremmende mediator

    DEFF Research Database (Denmark)

    Læssøe, Jeppe

    2009-01-01

      Mediatorer er en relativ ny aktør-type og job-funktion, som passer godt ind i det dynamiske videns- og netværkssamfund. I sundhedsfremmende arbejde med vægt på borgernes deltagelse kan mediatorer spille en nøglerolle. Det er derfor vigtigt begrebsmæssigt at kunne skelne mellem forskellige typer...... mediering samt mellem forskellige mediator-roller og tilhørsforhold. Det er også vigtigt at være bevidst om de centrale kvaliteter, risici og dilemmaer, som mediering indebærer i forhold til involvering af borgerne. Denne artikel rummer et bud på en sådan nuanceret begrebsliggørelse og refleksion, relateret...

  8. Soluble lymphocytic mediators

    Science.gov (United States)

    Pick, E.

    1974-01-01

    The effect of a number of drugs on the production of macrophage migration inhibitory factor (MIF) by antigen-stimulated sensitized guinea-pig lymph node cells was studied. The drugs were present during the entire culture period and eliminated from supernatants by dialysis. It was found that MIF secretion is inhibited by exogenous dibutyryl cyclic AMP and by theophylline and chlorphenesin, two agents raising the endogenous level of cyclic AMP. On the other hand, isoproterenol, which stimulates cyclic AMP generation in several tissues, did not block MIF production. The formation of the mediator was also suppressed by the microfilament-affecting drug, cytochalasin B. The microtubular disruptive agents, colchicine and vinblastine sulphate, did not influence MIF production. It is concluded that: (a) endogenous cyclic AMP may act as a regulator of MIF production; (b) the activity of contractile microfilaments is probably required for MIF formation; and (c) microtubules are not involved in the secretory process. PMID:4369184

  9. Mediating environmental disputes

    Energy Technology Data Exchange (ETDEWEB)

    Lake, L.M.

    1977-09-01

    Environmental disputes and lawsuits are examined. Site-specific disputes focus on visible physical phenomena, such as a power plant or local river, and have an immediacy and intensity about them that make it politically hazardous for public officials to assume responsibility for resolving them. As new precedents in environmental case law become less frequent and the number of disputes increases, alternative processes for environmental conflict resolution, such as third-party intervention, become appropriate. Third-party intervention techniques of fact finding, conflict avoidance, conciliation and mediation have been applied to international, labor, prison, school, racial, and hospital disputes. Underlying concepts are described. Two case studies, the Snoqualmie Dam dispute in Washington and the West Side Highway dispute in New York City, illustrate the basic elements associated with third-party intervention. 1 map, 17 references.

  10. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    do not tend to get a media coverage that matches the EU’s considerable influence on European citizens’ daily lives. This study, which is based on in-depth interviews with European Parliament press officers, concludes that these professionals are indeed attuned to a “media logic......Social actors see exposure in the news media as attractive for publicity purposes and are under pressure to adapt their press work to a “media logic” to be attractive sources for journalists and editors. This article investigates the European Parliament’s press officers’ professional practices...... in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs...

  11. Cylinder components properties, applications, materials

    CERN Document Server

    2016-01-01

    Owing to the ever-increasing requirements to be met by gasoline and diesel engines in terms of CO2 reduction, emission behavior, weight, and service life, a comprehensive understanding of combustion engine components is essential today. It is no longer possible for professionals in automotive engineering to manage without the corresponding expertise, whether they work in the field of design, development, testing, or maintenance. This technical book provides in-depth answers to questions about design, production, and machining of cylinder components. In this second edition, every section has been revised and expanded to include the latest developments in the combustion engine. Content Piston rings Piston pins and piston pin circlips Bearings Connecting rods Crankcase and cylinder liners Target audience Engineers in the field of engine development and maintenanceLecturers and students in the areas of mechanical engineering, engine technology, and vehicle constructionAnyone interested in technology Publisher MAH...

  12. Tritium in fusion reactor components

    International Nuclear Information System (INIS)

    Watson, J.S.; Fisher, P.W.; Talbot, J.B.

    1980-01-01

    When tritium is used in a fusion energy experiment or reactor, several implications affect and usually restrict the design and operation of the system and involve questions of containment, inventory, and radiation damage. Containment is expected to be particularly important both for high-temperature components and for those components that are prone to require frequent maintenance. Inventory is currently of major significance in cases where safety and environmental considerations limit the experiments to very low levels of tritium. Fewer inventory restrictions are expected as fusion experiments are placed in more-remote locations and as the fusion community gains experience with the use of tritium. However, the advent of power-producing experiments with high-duty cycle will again lead to serious difficulties based principally on tritium availability; cyclic operations with significant regeneration times are the principal problems

  13. HG ion thruster component testing

    Science.gov (United States)

    Mantenieks, M. A.

    1979-01-01

    Cathodes, isolators, and vaporizers are critical components in determining the performance and lifetime of mercury ion thrusters. The results of life tests of several of these components are reported. A 30-cm thruster CIV test in a bell jar has successfully accumulated over 26,000 hours. The cathode has undergone 65 restarts during the life test without requiring any appreciable increases in starting power. Recently, all restarts have been achieved with only the 44 volt keeper supply with no change required in the starting power. Another ongoing 30-cm Hg thruster cathode test has successfully passed the 10,000 hour mark. A solid-insert, 8-cm thruster cathode has accumulated over 4,000 hours of thruster operation. All starts have been achieved without the use of a high voltage ignitor. The results of this test indicate that the solid impregnated insert is a viable neutralizer cathode for the 8-cm thruster.

  14. Component processes underlying future thinking.

    Science.gov (United States)

    D'Argembeau, Arnaud; Ortoleva, Claudia; Jumentier, Sabrina; Van der Linden, Martial

    2010-09-01

    This study sought to investigate the component processes underlying the ability to imagine future events, using an individual-differences approach. Participants completed several tasks assessing different aspects of future thinking (i.e., fluency, specificity, amount of episodic details, phenomenology) and were also assessed with tasks and questionnaires measuring various component processes that have been hypothesized to support future thinking (i.e., executive processes, visual-spatial processing, relational memory processing, self-consciousness, and time perspective). The main results showed that executive processes were correlated with various measures of future thinking, whereas visual-spatial processing abilities and time perspective were specifically related to the number of sensory descriptions reported when specific future events were imagined. Furthermore, individual differences in self-consciousness predicted the subjective feeling of experiencing the imagined future events. These results suggest that future thinking involves a collection of processes that are related to different facets of future-event representation.

  15. Nuclear power plant component protection

    International Nuclear Information System (INIS)

    Michel, E.; Ruf, R.; Dorner, H.

    1976-01-01

    Described is a nuclear power plant installation which includes a concrete biological shield forming a pit in which a reactor pressure vessel is positioned. A steam generator on the outside of the shield is connected with the pressure vessel via coolant pipe lines which extend through the shield, the coolant circulation being provided by a coolant pump which is also on the outside of the shield. To protect these components on the outside of the shield and which are of mainly or substantially cylindrical shape, semicylindrical concrete segments are interfitted around them to form complete outer cylinders which are retained against outward separation radially from the components, by rings of high tensile steel which may be interspaced so closely that they provide, in effect, an outer steel cylinder. The invention is particularly applicable to pressurized-water coolant reactor installations

  16. G-computation demonstration in causal mediation analysis

    International Nuclear Information System (INIS)

    Wang, Aolin; Arah, Onyebuchi A.

    2015-01-01

    Recent work has considerably advanced the definition, identification and estimation of controlled direct, and natural direct and indirect effects in causal mediation analysis. Despite the various estimation methods and statistical routines being developed, a unified approach for effect estimation under different effect decomposition scenarios is still needed for epidemiologic research. G-computation offers such unification and has been used for total effect and joint controlled direct effect estimation settings, involving different types of exposure and outcome variables. In this study, we demonstrate the utility of parametric g-computation in estimating various components of the total effect, including (1) natural direct and indirect effects, (2) standard and stochastic controlled direct effects, and (3) reference and mediated interaction effects, using Monte Carlo simulations in standard statistical software. For each study subject, we estimated their nested potential outcomes corresponding to the (mediated) effects of an intervention on the exposure wherein the mediator was allowed to attain the value it would have under a possible counterfactual exposure intervention, under a pre-specified distribution of the mediator independent of any causes, or under a fixed controlled value. A final regression of the potential outcome on the exposure intervention variable was used to compute point estimates and bootstrap was used to obtain confidence intervals. Through contrasting different potential outcomes, this analytical framework provides an intuitive way of estimating effects under the recently introduced 3- and 4-way effect decomposition. This framework can be extended to complex multivariable and longitudinal mediation settings

  17. Evolution of disorder in Mediator complex and its functional relevance.

    Science.gov (United States)

    Nagulapalli, Malini; Maji, Sourobh; Dwivedi, Nidhi; Dahiya, Pradeep; Thakur, Jitendra K

    2016-02-29

    Mediator, an important component of eukaryotic transcriptional machinery, is a huge multisubunit complex. Though the complex is known to be conserved across all the eukaryotic kingdoms, the evolutionary topology of its subunits has never been studied. In this study, we profiled disorder in the Mediator subunits of 146 eukaryotes belonging to three kingdoms viz., metazoans, plants and fungi, and attempted to find correlation between the evolution of Mediator complex and its disorder. Our analysis suggests that disorder in Mediator complex have played a crucial role in the evolutionary diversification of complexity of eukaryotic organisms. Conserved intrinsic disordered regions (IDRs) were identified in only six subunits in the three kingdoms whereas unique patterns of IDRs were identified in other Mediator subunits. Acquisition of novel molecular recognition features (MoRFs) through evolution of new subunits or through elongation of the existing subunits was evident in metazoans and plants. A new concept of 'junction-MoRF' has been introduced. Evolutionary link between CBP and Med15 has been provided which explain the evolution of extended-IDR in CBP from Med15 KIX-IDR junction-MoRF suggesting role of junction-MoRF in evolution and modulation of protein-protein interaction repertoire. This study can be informative and helpful in understanding the conserved and flexible nature of Mediator complex across eukaryotic kingdoms. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Therapeutic potential of Mediator complex subunits in metabolic diseases.

    Science.gov (United States)

    Ranjan, Amol; Ansari, Suraiya A

    2018-01-01

    The multisubunit Mediator is an evolutionary conserved transcriptional coregulatory complex in eukaryotes. It is needed for the transcriptional regulation of gene expression in general as well as in a gene specific manner. Mediator complex subunits interact with different transcription factors as well as components of RNA Pol II transcription initiation complex and in doing so act as a bridge between gene specific transcription factors and general Pol II transcription machinery. Specific interaction of various Mediator subunits with nuclear receptors (NRs) and other transcription factors involved in metabolism has been reported in different studies. Evidences indicate that ligand-activated NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These NRs have been explored as therapeutic targets in different metabolic diseases; however, they show side-effects as targets due to their overlapping involvement in different signaling pathways. Here we discuss the interaction of various Mediator subunits with transcription factors involved in metabolism and whether specific interaction of these transcription factors with Mediator subunits could be potentially utilized as therapeutic strategy in a variety of metabolic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  19. The Effects Radiation on Cellular Components of the Immune

    International Nuclear Information System (INIS)

    Zubaidah-Alatas

    2001-01-01

    The immune system describes the body's ability to defend itself against various foreign intruders named as antigens by calling on an immune mechanism. Antigens penetration into body activate the body's immune system that may be humoral response, cellular response, or both. The immune response is primarily mediated by two cell types, lymphocyte and macrophage. This paper will discuss the cellular component of immune system and the radiation effects on various cells involved in system. Moreover, the effects of radiation on humoral and cellular responses and the relation among immunity, cancer and radiotherapy are also described. (author)

  20. Open Component Portability Infrastructure (OPENCPI)

    Science.gov (United States)

    2013-03-01

    declaration of the authored worker that must be implemented . If there is existing legacy VHDL entity architecture, then it is wrapped or modified to...that the software implementations were written to. Since all of the original code was VHDL , the HDL Authoring Model for VHDL was enhanced to meet...engineering process. This application was completed for the execution of all the components, the software implementations , and the VHDL skeletons for the

  1. Behavior Protocols for Software Components

    Czech Academy of Sciences Publication Activity Database

    Plášil, František; Višňovský, Stanislav

    2002-01-01

    Roč. 28, č. 11 (2002), s. 1056-1076 ISSN 0098-5589 R&D Projects: GA AV ČR IAA2030902; GA ČR GA201/99/0244 Grant - others:Eureka(XE) Pepita project no.2033 Institutional research plan: AV0Z1030915 Keywords : behavior protocols * component-based programming * software architecture Subject RIV: JC - Computer Hardware ; Software Impact factor: 1.170, year: 2002

  2. Chemical decontamination of reactor components

    International Nuclear Information System (INIS)

    Riess, R.; Berthold, H.O.

    1977-08-01

    A solution for the decontamination of reactor components of the primary system was developed. This solution is a modification of the APAC- (Alkaline Permanganate Ammonium Citrate) system described in the literature. The most important advantage of the present solution over the APAC-method is that it does not induce any selective corrosion attack on materials like stainless steel (austenitic), Inconel 600 and Incoloy 800. (orig.) [de

  3. The risk components of liquidity

    OpenAIRE

    Chollete, Lorán; Næs, Randi; Skjeltorp, Johannes A.

    2008-01-01

    Does liquidity risk differ depending on our choice of liquidity proxy? Unlike literature that considers common liquidity variation, we focus on identifying different components of liquidity, statistically and economically, using more than a decade of US transaction data. We identify three main statistical liquidity factors which are utilized in a linear asset pricing framework. We motivate a correspondence of the statistical factors to traditional dimensions of liquidity as well as the notion...

  4. The mediation procedure in Romania

    Directory of Open Access Journals (Sweden)

    Alexandrina Zaharia

    2009-06-01

    Full Text Available The mediation activity as an alternative way of solving conflicts occupies an important place in modernsociety. Currently, the mediation reached its maturity worldwide being adopted without reservations.The future of solving conflicts is undoubtedly closely related to mediation. XXth century is the century of solvingconflicts amiably outside the court room. In Romania and the mediation profession were regulated by the Law no.192/2006, on the basis of the idea that mediation is one of the major themes of the reform strategy of the judicialsystem 2005-2007. By adopting the mentioned law it was followed the idea of reducing the volume of activitycourts, and therefore, relieve them of as many cases, with the direct effect on the quality of justice. Mediation is avoluntary process in which the parties with a neutral and impartial third party, without power of decision - themediator - who is qualified to assist the parties to negotiate, facilitating the communication between them andhelping them to reach a unanimous effective and sustainable agreement. The parties may resort to mediation beforeor after triggering a trial. Mediation can be applied, in principle, on any type of conflict. However, theRomanian legislator has established special stipulations on conflict mediation in criminal, civil and familylaw. Although not expressly provided, the stipulations regarding the civil conflicts and also apply to commercialconflicts. Therefore, the mediation is applicable to most types of lawsuits, except those relating to personalrights. As a "win- win" principle, the mediation does not convert any of the parties defeated or victorious; allthose involved have gained by applying this procedure.

  5. USP21 regulates Hippo pathway activity by mediating MARK protein turnover

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Kugler, Jan-Michael; Loya, Anand Chainsukh

    2017-01-01

    observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components...

  6. Reformulating Component Identification as Document Analysis Problem

    NARCIS (Netherlands)

    Gross, H.G.; Lormans, M.; Zhou, J.

    2007-01-01

    One of the first steps of component procurement is the identification of required component features in large repositories of existing components. On the highest level of abstraction, component requirements as well as component descriptions are usually written in natural language. Therefore, we can

  7. Coherent systems with multistate components

    International Nuclear Information System (INIS)

    Caldarola, L.

    1980-01-01

    The basic rules of the Boolean algebra with restrictions on variables are briefly recalled. This special type of Boolean algebra allows one to handle fault trees of systems made of multistate (two or more than two states) components. Coherent systems are defined in the case of multistate components. This definition is consistent with that originally suggested by Barlow in the case of binary (two states) components. The basic properties of coherence are described and discussed. Coherent Boolean functions are also defined. It is shown that these functions are irredundant, that is they have only one base which is at the same time complete and irredundant. However, irredundant functions are not necessarily coherent. Finally a simplified algorithm for the calculation of the base of a coherent function is described. In the case that the function is not coherent, the algorithm can be used to reduce the size of the normal disjunctive form of the function. This in turn eases the application of the Nelson algorithm to calculate the complete base of the function. The simplified algorithm has been built in the computer program MUSTAFA-1. In a sample case the use of this algorithm caused a reduction of the CPU time by a factor of about 20. (orig.)

  8. Radiation damage to electronic components

    International Nuclear Information System (INIS)

    Battisti, S.; Bossart, R.; Schoenbacher, H.; Van de Voorde, M.

    1975-01-01

    Characteristic properties are presented of some 40 different electronic components (resistors, capacitors, diodes, transistors, and integrated circuits) which were irradiated in a nuclear reactor up to 1015 n/cm 2 (E > 1 MeV). Complete circuits (e.g. RF amplifiers and detectors, mixers, differential amplifiers, voltage-to-frequency converters, oscillators, power supplies) were irradiated near the CERN Intersecting Storage Rings up to 106 rad(RPL) (dose measured with radiophotoluminescent dosimeters) under simulated operational conditions. Representative measured parameters, such as resistance, capacitance, forward voltage, reverse current, toggle frequencies, are given in graphs as a function of radiation dose. The results are discussed in detail and lead to the over-all conclusion that the operation of electronic components and circuits is seriously affected by radiation environments with doses in the order of 10 13 n/cm 2 or 10 4 rad(RPL); some components and circuits fail completely at doses of 10 14 n/cm 2 or 10 5 rad(RPL). (Author)

  9. Fusion-component lifetime analysis

    International Nuclear Information System (INIS)

    Mattas, R.F.

    1982-09-01

    A one-dimensional computer code has been developed to examine the lifetime of first-wall and impurity-control components. The code incorporates the operating and design parameters, the material characteristics, and the appropriate failure criteria for the individual components. The major emphasis of the modeling effort has been to calculate the temperature-stress-strain-radiation effects history of a component so that the synergystic effects between sputtering erosion, swelling, creep, fatigue, and crack growth can be examined. The general forms of the property equations are the same for all materials in order to provide the greatest flexibility for materials selection in the code. The individual coefficients within the equations are different for each material. The code is capable of determining the behavior of a plate, composed of either a single or dual material structure, that is either totally constrained or constrained from bending but not from expansion. The code has been utilized to analyze the first walls for FED/INTOR and DEMO and to analyze the limiter for FED/INTOR

  10. Radiation effects on eye components

    International Nuclear Information System (INIS)

    Durchschlag, H.; Fochler, C.; Abraham, K.; Kulawik, B.

    1998-01-01

    The radiation damage (X-ray, UV light) of the most important components of the vertebrate eye (crystallins and other proteins, hyaluronic acid, vitreous, aqueous humour, ascorbic acid) has been investigated by various methods of physical chemistry. UV absorption and fluorescence spectroscopy as well as circular dichroism unveiled changes of the chromophores/fluorophores of the constituent biopolymers and low-molecular components, together with alterations of helix content and the occurrence of aggregation. Size-exclusion chromatography, analytical ultracentrifugation, densimetry, viscometry and light scattering experiments monitored changes of the global structure of proteins and polysaccharides involved. Electrophoreses allowed conclusions on fragmentation, unfolding and crosslinking. Analytical methods provided information regarding the integrity of groups of special concern (SH, SS) and revealed the existence of stable noxious species (H 2 O 2 ). By means of various measures and additives, manifold modifications of the impact of both ionizing and nonionizing radiation may be achieved. Caused by differences in the primary reactions, eye polymers are protected efficaciously by typical OH radical scavengers against X-irradiation, whereas compounds which exhibit absorption behavior in the UV range turn out to act as potent protectives ('chemical filters') against UV light. A few substances, such as ascorbate, are able to provide protection against both sorts of radiation and are even able to exhibit a slight chemical repair of already damaged particles. The results obtained are of importance for understanding pathological alterations of the eye (loss of transparency, cataractogenesis) and for developing new strategies for protection and repair of eye components. (author)

  11. Anomaly mediation deformed by axion

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Kazunori, E-mail: kazunori@hep-th.phys.s.u-tokyo.ac.jp [Department of Physics, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan); Yanagida, Tsutomu T. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan)

    2013-05-13

    We show that in supersymmetric axion models the axion supermultiplet obtains a sizable F-term due to a non-supersymmetric dynamics and it generally gives the gaugino masses comparable to the anomaly mediation contribution. Thus the gaugino mass relation predicted by the anomaly mediation effect can be significantly modified in the presence of axion to solve the strong CP problem.

  12. Theorizing with/out "Mediators".

    Science.gov (United States)

    Roth, Wolff-Michael; Jornet, Alfredo

    2017-01-05

    Mediation is one of the most often cited concepts in current cultural-historical theory literature, in which cultural actions and artifacts are often characterized as mediators standing between situational stimuli and behavioral responses. Most often presented as a means to overcome Cartesian dualism between subject and object, and between individual and society, some scholars have nonetheless raised criticism suggesting that such mediators are problematic for a dialectical psychology that takes a unit analysis (monist) approach. In fact, Spinoza develops a monist theory of mind and body that goes without and even excludes every form of mediation. In this study, we follow up on the latter criticisms and explore what we consider to be problematic uses of the notion of mediation as an analytical construct in the literature. We elaborate an empirically grounded discussion on the ways the concept of mediation may lead to dualistic readings; and we offer an alternative account where the notion of mediator is not needed. We conclude discussing prospects for and implications of a cultural-historical theory where the notion of mediation no longer is invoked to account for human action and development.

  13. Comments on general gauge mediation

    International Nuclear Information System (INIS)

    Intriligator, Kenneth; Sudano, Matthew

    2008-01-01

    There has been interest in generalizing models of gauge mediation of supersymmetry breaking. As shown by Meade, Seiberg, and Shih (MSS), the soft masses of general gauge mediation can be expressed in terms of the current two-point functions of the susy-breaking sector. We here give a simple extension of their result which provides, for general gauge mediation, the full effective potential for squark pseudo-D-flat directions. The effective potential reduces to the sfermion soft masses near the origin, and the full potential, away from the origin, can be useful for cosmological applications. We also generalize the soft masses and effective potential to allow for general gauge mediation by Higgsed gauge groups. Finally, we discuss general gauge mediation in the limit of small F-terms, and how the results of MSS connect with the analytic continuation in superspace results, based on a spurion analysis.

  14. Practical Guide to Civil Mediation

    CERN Document Server

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of international organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreeme...

  15. Practical Guide to Civil Mediation

    CERN Multimedia

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of International Organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreem...

  16. Mediating mechanisms of a military Web-based alcohol intervention.

    Science.gov (United States)

    Williams, Jason; Herman-Stahl, Mindy; Calvin, Sara L; Pemberton, Michael; Bradshaw, Michael

    2009-03-01

    This study explored the mediating mechanisms of two Web-based alcohol interventions in a sample of active duty United States military personnel. Personnel were recruited from eight bases and received the Drinker's Check-Up (N=1483), Alcohol Savvy (N=688), or served as controls (N=919). The interventions drew on motivational interviewing and social learning theory and targeted multiple mediators including social norms, perceived risks and benefits, readiness to change, and coping strategies. Baseline data were collected prior to the intervention and follow-up data on alcohol consumption were gathered 1 month and 6 months after program completion. Two mediation models were examined: (1) a longitudinal two-wave model with outcomes and mediators assessed concurrently at the 1-month follow-up; and (2) a three-wave model in which the causal chain was fully lagged. Results indicated strong support for the role of perceived descriptive norms in transmitting the effects of the Drinker's Check-Up, with consistent mediation across the majority of alcohol outcome measures for both the concurrent and fully lagged mediation models. These results suggest that web-based interventions that are effective in lowering perceived norms about the frequency and quantity of drinking may be a viable strategy for reducing alcohol consumption in military populations. The results did not support program mediation by the other targeted variables, indicating the need for future research on the effective components of alcohol interventions. The mediation models also suggest reasons why program effects were not found for some outcomes or were different across programs.

  17. 29 CFR 35.32 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Mediation. 35.32 Section 35.32 Labor Office of the Secretary... Mediation. (a) Referral to mediation. CRC will promptly refer to the Federal Mediation and Conciliation Service or the mediation agency designated by the Secretary of Health and Human Services under 45 CFR part...

  18. 22 CFR 143.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 143.33 Section 143.33 Foreign... Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and... participate in the mediation process to the extent necessary to reach an agreement or make an informed...

  19. 29 CFR 1203.1 - Mediation services.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation services. 1203.1 Section 1203.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD APPLICATIONS FOR SERVICE § 1203.1 Mediation services. Applications for the mediation services of the National Mediation Board under section 5, First, of the Railway...

  20. 34 CFR 81.13 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 81.13 Section 81.13 Education Office of the... Mediation. (a) Voluntary mediation is available for proceedings that are pending before the OALJ. (b) A... mediation by filing a motion with the ALJ assigned to the case. The OALJ arranges for a mediator if the...

  1. 24 CFR 3288.35 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Mediation. 3288.35 Section 3288.35...-Administered States § 3288.35 Mediation. (a) Mediator. The dispute resolution provider will provide for the... identifies any other party that should be included in the mediation, the mediator will contact the other...

  2. 44 CFR 7.942 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Mediation. 7.942 Section 7..., Conciliation, and Enforcement Procedures § 7.942 Mediation. (a) FEMA will promptly refer to a mediation agency... participate in the mediation process to the extent necessary to reach an agreement or for the mediator to make...

  3. 32 CFR 776.38 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Mediation. 776.38 Section 776.38 National... Professional Conduct § 776.38 Mediation. (a) Mediation: (1) A covered attorney may act as a mediator between... mediation, including the advantages and risks involved, and the effect on the attorney-client...

  4. 29 CFR 1202.1 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation. 1202.1 Section 1202.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.1 Mediation. The mediation..., or where conferences are refused. The National Mediation Board may proffer its services in case any...

  5. Microbially mediated mineral carbonation

    Science.gov (United States)

    Power, I. M.; Wilson, S. A.; Dipple, G. M.; Southam, G.

    2010-12-01

    Mineral carbonation involves silicate dissolution and carbonate precipitation, which are both natural processes that microorganisms are able to mediate in near surface environments (Ferris et al., 1994; Eq. 1). (Ca,Mg)SiO3 + 2H2CO3 + H2O → (Ca,Mg)CO3 + H2O + H4SiO4 + O2 (1) Cyanobacteria are photoautotrophs with cell surface characteristics and metabolic processes involving inorganic carbon that can induce carbonate precipitation. This occurs partly by concentrating cations within their net-negative cell envelope and through the alkalinization of their microenvironment (Thompson & Ferris, 1990). Regions with mafic and ultramafic bedrock, such as near Atlin, British Columbia, Canada, represent the best potential sources of feedstocks for mineral carbonation. The hydromagnesite playas near Atlin are a natural biogeochemical model for the carbonation of magnesium silicate minerals (Power et al., 2009). Field-based studies at Atlin and corroborating laboratory experiments demonstrate the ability of a microbial consortium dominated by filamentous cyanobacteria to induce the precipitation of carbonate minerals. Phototrophic microbes, such as cyanobacteria, have been proposed as a means for producing biodiesel and other value added products because of their efficiency as solar collectors and low requirement for valuable, cultivable land in comparison to crops (Dismukes et al., 2008). Carbonate precipitation and biomass production could be facilitated using specifically designed ponds to collect waters rich in dissolved cations (e.g., Mg2+ and Ca2+), which would allow for evapoconcentration and provide an appropriate environment for growth of cyanobacteria. Microbially mediated carbonate precipitation does not require large quantities of energy or chemicals needed for industrial systems that have been proposed for rapid carbon capture and storage via mineral carbonation (e.g., Lackner et al., 1995). Therefore, this biogeochemical approach may represent a readily

  6. Nanoparticle mediated micromotor motion

    Science.gov (United States)

    Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.

    2015-03-01

    In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric field. Both strategies lead to dramatically increased moving velocities, with the highest value reaching ~200 μm s-1. By decreasing the nanoparticles' surface wettability and increasing their catalytic activity, a maximum of a ~10-fold increase in the moving speed of the nanoparticle based micromotor can be achieved. Our results demonstrate the advantages of using nanoparticles in micromotor systems.In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric

  7. Web components and the semantic web

    OpenAIRE

    Casey, Maire; Pahl, Claus

    2003-01-01

    Component-based software engineering on the Web differs from traditional component and software engineering. We investigate Web component engineering activites that are crucial for the development,com position, and deployment of components on the Web. The current Web Services and Semantic Web initiatives strongly influence our work. Focussing on Web component composition we develop description and reasoning techniques that support a component developer in the composition activities,fo cussing...

  8. Component Control System for a Vehicle

    Science.gov (United States)

    Fraser-Chanpong, Nathan (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Bluethmann, William J. (Inventor); Lee, Chunhao J. (Inventor); Vitale, Robert L. (Inventor); Guo, Raymond (Inventor); Waligora, Thomas M. (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Reed, Ryan M. (Inventor)

    2016-01-01

    A vehicle includes a chassis, a modular component, and a central operating system. The modular component is supported by the chassis. The central operating system includes a component control system, a primary master controller, and a secondary master controller. The component control system is configured for controlling the modular component. The primary and secondary master controllers are in operative communication with the component control system. The primary and secondary master controllers are configured to simultaneously transmit commands to the component control system. The component control system is configured to accept commands from the secondary master controller only when a fault occurs in the primary master controller.

  9. Experimental qualification of nuclear components

    Energy Technology Data Exchange (ETDEWEB)

    Alliot, P; Fronte, T; Genty, F [FRAMATOME - Cedex 16, Paris la Defense (France)

    1988-07-01

    In the process of showing the adequacy of the seismic design of French PWR reactor, Fermat has repeatedly used dynamic testing on actual nuclear reactor components both on site and in manufacturing shops. The objective and results of a few representative examples of this on-site experimental verification are presented in this paper: the experimental dynamic analysis of a manipulator crane; the investigation of the seismic behaviour of fuel storage racks equipped with aseismic bearing devices. Difficulties to select satisfactory testing methods are also discussed for the particular case of the electrical cabinets. (author)

  10. Lifetime of superheated steam components

    International Nuclear Information System (INIS)

    Stoklossa, K.H.; Oude-Hengel, H.H.; Kraechter, H.J.

    1974-01-01

    The current evaluation schemes in use for judging the lifetime expectations of superheated steam components are compared with each other. The influence of pressure and temperature fluctuations, the differences in the strength of the wall, and the spread band of constant-strainrates are critically investigated. The distribution of these contributory effects are demonstrated in the hight of numerous measuring results. As an important supplement to these evaluation schemes a newly developed technique is introduced which is designed to calculate failure probabilities. (orig./RW) [de

  11. Cooling concepts for HTS components

    International Nuclear Information System (INIS)

    Binneberg, A.; Buschmann, H.; Neubert, J.

    1993-01-01

    HTS components require that low-cost, reliable cooling systems be used. There are no general solutions to such systems. Any cooling concept has to be tailored to the specific requirements of a system. The following has to he taken into consideration when designing cooling concepts: - cooling temperature - constancy and controllability of the cooling temperature - cooling load and refrigerating capacity - continuous or discontinuous mode - degree of automation - full serviceability or availability before evacuation -malfunctions caused by microphonic, thermal or electromagnetic effects -stationary or mobile application - investment and operating costs (orig.)

  12. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    . In particular, 3-15% of very low birth weight preterm infants suffer from the most servere form of intestinal inflammation, known as necrotizing enterocolitis (NEC). This disease is incurable with a high mortality rate of 15-30%. Mother’s breast milk consists of different bioactive constituents...... of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  13. Experimental qualification of nuclear components

    International Nuclear Information System (INIS)

    Alliot, P.; Fronte, T.; Genty, F.

    1988-01-01

    In the process of showing the adequacy of the seismic design of French PWR reactor, Fermat has repeatedly used dynamic testing on actual nuclear reactor components both on site and in manufacturing shops. The objective and results of a few representative examples of this on-site experimental verification are presented in this paper: the experimental dynamic analysis of a manipulator crane; the investigation of the seismic behaviour of fuel storage racks equipped with aseismic bearing devices. Difficulties to select satisfactory testing methods are also discussed for the particular case of the electrical cabinets. (author)

  14. Failures on stainless steel components

    International Nuclear Information System (INIS)

    Haenninen, H.

    1994-01-01

    Economic losses due to failure mainly by corrosion in process and nuclear industries are considered. In these industries the characteristics of different forms of corrosion and their economic effects are fairly well known and, especially, in nuclear industry the assessment of corrosion related costs has been comprehensive. In both industries the economic losses resulting from environmentally enhanced cracking of stainless steel components and the accompanying failures and outages have been considerable, owing as much to the frequency as the unpredictability of such occurrences. (orig.)

  15. Anthropological Component of Descartes’ Ontology

    Directory of Open Access Journals (Sweden)

    Anatolii M. Malivskyi

    2014-06-01

    Full Text Available The purpose of the article is to outline and comprehend the Descartes’ theory about anthropological component of ontology as the most important part of his philosophy. The accomplishment of this purpose covers the successive solution of the following tasks: 1 review of the research literature concerning the problem of human’s presence and the individual nature of truth; 2 emphasize the ambivalence of the basic intention of his legacy; 3 justify the thesis about constitutivity of human’s presence and comprehend passions as the form of disclosure of ontology’s anthropological component. Methodology. The use of the euristic potential of phenomenology, postpositivism and postmodernism makes it possible to emphasize the multiple-layer and multiple-meaning classical philosophy works, to comprehend the limitation and scarcity of the naïve-enlightening vision of human nature and to look for a new reception of European classics that provides the overcoming of established nihilism and pessimism concerning the interpretation of human nature. Scientific novelty. It is the first time that anthropological component of Descartes’ ontology became an object of particular attention. It previously lacked attention because of following main reasons: 1 traditional underestimating of the fact of Descartes’ legacy incompleteness as an unrealized anthropological project and 2 lack of proper attention to the individual nature of truth. The premise for its constructive overcoming is the attention to ambivalence of the basic intention and the significance of ethics in the philosopher’s legacy. His texts and research literature allow confirming the constitutive nature of human’s presence and passions as the key form of disclosure of the ontology anthropological component. Conclusions. The established tradition of interpretation the Descartes’ philosophizing nature as the filiation process of impersonal knowledge loses its cogency these days. The

  16. ANTHROPOLOGICAL COMPONENT OF DESCARTES’ ONTOLOGY

    Directory of Open Access Journals (Sweden)

    Anatolii M. Malivskyi

    2014-06-01

    Full Text Available The purpose of the article is to outline and comprehend the Descartes’ theory about anthropological component of ontology as the most important part of his philosophy. The accomplishment of this purpose covers the successive solution of the following tasks: 1 review of the research literature concerning the problem of human’s presence and the individual nature of truth; 2 emphasize the ambivalence of the basic intention of his legacy; 3 justify the thesis about constitutivity of human’s presence and comprehend passions as the form of disclosure of ontology’s anthropological component. Methodology. The use of the euristic potential of phenomenology, postpositivism and postmodernism makes it possible to emphasize the multiple-layer and multiple-meaning classical philosophy works, to comprehend the limitation and scarcity of the naïve-enlightening vision of human nature and to look for a new reception of European classics that provides the overcoming of established nihilism and pessimism concerning the interpretation of human nature. Scientific novelty. It is the first time that anthropological component of Descartes’ ontology became an object of particular attention. It previously lacked attention because of following main reasons: 1 traditional underestimating of the fact of Descartes’ legacy incompleteness as an unrealized anthropological project and 2 lack of proper attention to the individual nature of truth. The premise for its constructive overcoming is the attention to ambivalence of the basic intention and the significance of ethics in the philosopher’s legacy. His texts and research literature allow confirming the constitutive nature of human’s presence and passions as the key form of disclosure of the ontology anthropological component. Conclusions. The established tradition of interpretation the Descartes’ philosophizing nature as the filiation process of impersonal knowledge loses its cogency these days. The

  17. An UPF3-based nonsense-mediated decay in Paramecium.

    Science.gov (United States)

    Contreras, Julia; Begley, Victoria; Macias, Sandra; Villalobo, Eduardo

    2014-12-01

    Nonsense-mediated decay recognises mRNAs containing premature termination codons. One of its components, UPF3, is a molecular link bridging through its binding to the exon junction complex nonsense-mediated decay and splicing. In protists UPF3 has not been identified yet. We report that Paramecium tetraurelia bears an UPF3 gene and that it has a role in nonsense-mediated decay. Interestingly, the identified UPF3 has not conserved the essential amino acids required to bind the exon junction complex. Though, our data indicates that this ciliate bears genes coding for core proteins of the exon junction complex. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  18. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    OpenAIRE

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets ...

  19. Working Memory Components and Problem-Solving Accuracy: Are There Multiple Pathways?

    Science.gov (United States)

    Swanson, H. Lee; Fung, Wenson

    2016-01-01

    This study determined the working memory (WM) components (executive, phonological short-term memory [STM], and visual-spatial sketchpad) that best predicted mathematical word problem-solving accuracy in elementary schoolchildren (N = 392). The battery of tests administered to assess mediators between WM and problem-solving included measures of…

  20. The essential YycFG two-component system controls cell wall metabolism in Bacillus subtilis

    DEFF Research Database (Denmark)

    Bisicchia, Paola; Noone, David; Lioliou, Efthimia

    2007-01-01

    Adaptation of bacteria to the prevailing environmental and nutritional conditions is often mediated by two-component signal transduction systems (TCS). The Bacillus subtilis YycFG TCS has attracted special attention as it is essential for viability and its regulon is poorly defined. Here we show...

  1. Modular Three-Component Synthesis of 4-Aminoquinolines via an Imidoylative Sonogashira/Cyclization Cascade

    NARCIS (Netherlands)

    Collet, Jurriën W.; Ackermans, Kelly; Lambregts, Jeffrey; Maes, Bert U.W.; Orru, Romano V.A.; Ruijter, Eelco

    2018-01-01

    We developed a one-pot, two-stage synthetic route to substituted 4-aminoquinolines involving an imidoylative Sonogashira coupling followed by acid-mediated cyclization. This three-component reaction affords pharmaceutically valuable 4-aminoquinolines in a one-pot procedure from readily available

  2. Bioactive Components in Fish Venoms

    Science.gov (United States)

    Ziegman, Rebekah; Alewood, Paul

    2015-01-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  3. Safety engineering with COTS components

    International Nuclear Information System (INIS)

    O'Halloran, Mark; Hall, Jon G.; Rapanotti, Lucia

    2017-01-01

    Safety-critical systems are becoming more widespread, complex and reliant on software. Increasingly they are engineered through (COTS) (Commercial Off The Shelf) components to alleviate the spiralling costs and development time, often in the context of complex supply chains. A parallel increased concern for safety has resulted in a variety of safety standards, with a growing consensus that a safety life cycle is needed which is fully integrated with the design and development life cycle, to ensure that safety has appropriate influence on the design decisions as system development progresses. In this article we explore the application of an integrated approach to safety engineering in which assurance drives the engineering process. The paper reports on the outcome of a case study on a live industrial project with a view to evaluate: its suitability for application in a real-world safety engineering setting; its benefits and limitations in counteracting some of the difficulties of safety engineering with (COTS) components across supply chains; and, its effectiveness in generating evidence which can contribute directly to the construction of safety cases. - Highlights: • Assurance as effective driver for COTS-based safety-critical system development. • Engages stakeholders, captures requirements and provides rich traceability. • Shares appropriate safety requirements across the supply chain.

  4. Tipping device for large components

    International Nuclear Information System (INIS)

    Guigon, J.P.; Beraudier, D.

    1984-01-01

    For large components machining as components of a pressurized water reactor, it is necessary to have means allowing to present them in a position determined with regard to the machine tool used. The aim of the invention is a tipping device which consists of a base resting on the ground, a support-table mounted on this base, moving in rotation with the aid of at least a pivot joint of which axis is horizontal and parallel to the table and a gear pivot allowing to get a very good precision for the orientation of the piece and a very good stability whatever the orientation may be. The output shaft pinion of the base meshes with a gear wheel segment fixed to the table structure. Safety straps fasten the table structure to the base, as they are secured by horizontal pins. The toe pins run in straight slot holes incorporated in base jaws. The table rotation may be controlled by a spring-loaded braking mechanism which acts on the pivot axis and can be released by a hydraulic jack. The hydraulic pressure is used to prevent motor operation, unless the brakes have been released [fr

  5. Food components with anticaries activity.

    Science.gov (United States)

    Gazzani, Gabriella; Daglia, Maria; Papetti, Adele

    2012-04-01

    Caries is the most common oral infectious disease in the world. Its development is influenced also by diet components that interfere with pathogen mutans group Streptococci (MGS) activity. A very active research to identify functional foods and their components that are generally recognised as safe has been ongoing, with the aim of developing alternative approaches, to the use of synthetic chlorhexidine, and at the reduction or prevention of caries. Until now convincing evidence exists only for green tea as a functional food for oral health, partly owing to its high content of catechins, especially epigallocatechin-gallate. A number of other foods showed potential anticaries activity. Some other foods able to act against MGS growth and/or their virulence factors in in vitro tests are: apple, red grape seeds, red wine (proanthocyanidins), nutmeg (macelignan), ajowan caraway (nafthalen-derivative), coffee (trigonelline, nicotinic and chlorogenic acids, melanoidins), barley coffee (melanoidins), chicory and mushroom (quinic acid). In vivo anticaries activity has been shown by cranberry (procyanidins), glycyrrhiza root (glycyrrhizol-A), myrtus ethanolic extract, garlic aqueous extract, cocoa extracts (procyanidins), and propolis (apigenin, tt-farnesol). Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Interpretable functional principal component analysis.

    Science.gov (United States)

    Lin, Zhenhua; Wang, Liangliang; Cao, Jiguo

    2016-09-01

    Functional principal component analysis (FPCA) is a popular approach to explore major sources of variation in a sample of random curves. These major sources of variation are represented by functional principal components (FPCs). The intervals where the values of FPCs are significant are interpreted as where sample curves have major variations. However, these intervals are often hard for naïve users to identify, because of the vague definition of "significant values". In this article, we develop a novel penalty-based method to derive FPCs that are only nonzero precisely in the intervals where the values of FPCs are significant, whence the derived FPCs possess better interpretability than the FPCs derived from existing methods. To compute the proposed FPCs, we devise an efficient algorithm based on projection deflation techniques. We show that the proposed interpretable FPCs are strongly consistent and asymptotically normal under mild conditions. Simulation studies confirm that with a competitive performance in explaining variations of sample curves, the proposed FPCs are more interpretable than the traditional counterparts. This advantage is demonstrated by analyzing two real datasets, namely, electroencephalography data and Canadian weather data. © 2015, The International Biometric Society.

  7. Ionic liquid-mediated three-component synthesis of fluorinated spiro ...

    Indian Academy of Sciences (India)

    ... and DEEPTI SAINI. Department of Chemistry, University of Rajasthan, Jaipur 302 004, India ... muscarinic serotonin receptors,23 antitumour activity against human brain ... the combination of two privileged structures in one molecule leads to ...

  8. A Component of Retinal Light Adaptation Mediated by the Thyroid Hormone Cascade

    OpenAIRE

    Bedolla, Diana E.; Torre, Vincent

    2011-01-01

    Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2-3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4-...

  9. The hypocretins (orexins mediate the “phasic” components of REM sleep: A new hypothesis

    Directory of Open Access Journals (Sweden)

    Pablo Torterolo

    2014-03-01

    The hypocretinergic neurons are active during wakefulness in conjunction with the presence of motor activity that occurs during survival-related behaviors. These neurons decrease their firing rate during non-REM sleep; however there is still controversy upon the activity and role of these neurons during REM sleep. Hence, in the present report we conducted a critical review of the literature of the hypocretinergic system during REM sleep, and hypothesize a possible role of this system in the generation of REM sleep.

  10. Expression of Aeromonas caviae ST pyruvate dehydrogenase complex components mediate tellurite resistance in Escherichia coli

    International Nuclear Information System (INIS)

    Castro, Miguel E.; Molina, Roberto C.; Diaz, Waldo A.; Pradenas, Gonzalo A.; Vasquez, Claudio C.

    2009-01-01

    Potassium tellurite (K 2 TeO 3 ) is harmful to most organisms and specific mechanisms explaining its toxicity are not well known to date. We previously reported that the lpdA gene product of the tellurite-resistant environmental isolate Aeromonas caviae ST is involved in the reduction of tellurite to elemental tellurium. In this work, we show that expression of A. caviae ST aceE, aceF, and lpdA genes, encoding pyruvate dehydrogenase, dihydrolipoamide transacetylase, and dihydrolipoamide dehydrogenase, respectively, results in tellurite resistance and decreased levels of tellurite-induced superoxide in Escherichia coli. In addition to oxidative damage resulting from tellurite exposure, a metabolic disorder would be simultaneously established in which the pyruvate dehydrogenase complex would represent an intracellular tellurite target. These results allow us to widen our vision regarding the molecular mechanisms involved in bacterial tellurite resistance by correlating tellurite toxicity and key enzymes of aerobic metabolism.

  11. NMDA Signaling in CA1 Mediates Selectively the Spatial Component of Episodic Memory

    Science.gov (United States)

    Place, Ryan; Lykken, Christy; Beer, Zachery; Suh, Junghyup; McHugh, Thomas J.; Tonegawa, Susumu; Eichenbaum, Howard; Sauvage, Magdalena M.

    2012-01-01

    Recent studies focusing on the memory for temporal order have reported that CA1 plays a critical role in the memory for the sequences of events, in addition to its well-described role in spatial navigation. In contrast, CA3 was found to principally contribute to the memory for the association of items with spatial or contextual information in…

  12. Corticosterone mediates the condition-dependent component of melanin-based coloration

    Czech Academy of Sciences Publication Activity Database

    Roulin, A.; Almasi, B.; Rossi-Pedruzzi, A.; Ducrest, A.-L.; Wakamatsu, K.; Mikšík, Ivan; Blount, J.D.; Jenni-Eiermann, S.; Jenni, L.

    2008-01-01

    Roč. 75, č. 4 (2008), s. 1351-1358 ISSN 0003-3472 Institutional research plan: CEZ:AV0Z50110509 Keywords : coricosterone * barn owl * melanin Subject RIV: CE - Biochemistry Impact factor: 2.828, year: 2008

  13. Characterization of sur-2, a Novel Ras-Mediated Signal Transduction Component in C. elegans

    National Research Council Canada - National Science Library

    DesJardins, Edward

    1998-01-01

    ... (oncogenes). A subset of proto-oncogenes comprise the RAS signal transduction pathway. Vulval development in the nematode worm Caenorhabditis elegans is controlled by a RAS signal transduction pathway...

  14. Characterization of sur-2, a Novel Ras-Mediated Signal Transduction Component in C. elegans

    National Research Council Canada - National Science Library

    DesJardins, Edward

    1999-01-01

    ... (oncogenes). A subset of proto-oncogenes comprise the RAS signal transduction pathway. Vulval development in the nematode worm Caenorhabditis elegans is controlled by a RAS signal transduction pathway. C...

  15. GMES Space Component: Programme overview

    Science.gov (United States)

    Aschbacher, J.; Milagro-Perez, M. P.

    2012-04-01

    The European Union (EU) and the European Space Agency (ESA) have developed the Global Monitoring for Environment and Security (GMES) programme as Europe's answer to the vital need for joined-up data about our climate, environment and security. Through a unique combination of satellite, atmospheric and Earth-based monitoring systems, the initiative will provide new insight into the state of the land, sea and air, providing policymakers, scientists, businesses and the public with accurate and timely information. GMES capabilities include monitoring and forecasting of climatic change, flood risks, soil and coastal erosion, crop and fish resources, air pollution, greenhouse gases, iceberg distribution and snow cover, among others. To accomplish this, GMES has been divided into three main components: Space, In-situ and Services. The Space Component, led by ESA, comprises five types of new satellites called Sentinels that are being developed by ESA specifically to meet the needs of GMES, the first of which to be launched in 2013. These missions carry a range of technologies, such as radar and multi-spectral imaging instruments for land, ocean and atmospheric monitoring. In addition, access to data from the so-called Contributing Missions guarantees that European space infrastructure is fully used for GMES. An integrated Ground Segment ensures access to Sentinels and Contributing Missions data. The in-situ component, under the coordination of the European Environment Agency (EEA), is composed of atmospheric and Earth based monitoring systems, and based on established networks and programmes at European and international levels. The European Commission is in charge of implementing the services component of GMES and of leading GMES overall. GMES services, fed with data from the Space and In-situ components, will provide essential information in five main domains, atmosphere, ocean and land monitoring as well as emergency response and security. Climate change has been added

  16. Mediation of information and educational mediation: conceptual discussions

    Directory of Open Access Journals (Sweden)

    Helena Célia de Souza Sacerdote

    2016-04-01

    Full Text Available Introduction: This is systematization of theoretical and methodological contributions related to the concepts of mediation information and pedagogical mediation in the literature. Objective: To understand possible intersection of information science and Online Education with regard to these concepts to check that both can be considered as analogous in its essence and practice. Methodology: Literature review based on literature by consulting the scientific productions selected in search of SciELO.ORG databases and EBSCO Host, the portal of CAPES / MEC and Google Scholar. Results: The most cited concepts in information science and education were de Almeida Junior (2009 and Masetto (2013, respectively. Conclusion: It is observed that the concept of mediation can move interchangeably between both areas. This is because the evidence found in the productions of the last five years indicate that the concept of information of mediation seems to have found its bases in education (educational psychology.

  17. A component analysis of positive behaviour support plans.

    Science.gov (United States)

    McClean, Brian; Grey, Ian

    2012-09-01

    Positive behaviour support (PBS) emphasises multi-component interventions by natural intervention agents to help people overcome challenging behaviours. This paper investigates which components are most effective and which factors might mediate effectiveness. Sixty-one staff working with individuals with intellectual disability and challenging behaviours completed longitudinal competency-based training in PBS. Each staff participant conducted a functional assessment and developed and implemented a PBS plan for one prioritised individual. A total of 1,272 interventions were available for analysis. Measures of challenging behaviour were taken at baseline, after 6 months, and at an average of 26 months follow-up. There was a significant reduction in the frequency, management difficulty, and episodic severity of challenging behaviour over the duration of the study. Escape was identified by staff as the most common function, accounting for 77% of challenging behaviours. The most commonly implemented components of intervention were setting event changes and quality-of-life-based interventions. Only treatment acceptability was found to be related to decreases in behavioural frequency. No single intervention component was found to have a greater association with reductions in challenging behaviour.

  18. X-ray-mediated cross linking of protein and DNA

    International Nuclear Information System (INIS)

    Minsky, B.D.; Braun, A.

    1977-01-01

    Using a simple filter assay for the binding of BSA or lysozyme to DNA, two mechanisms of x-ray-mediated cross linking are shown to occur. One, a fast reaction, appears to involve a radical intermediate, is inhibited by high pH and salt, and seems to be enhanced by deoxygenation. The second mechanism, a slow time-dependent component, differs from the fast reaction in its stimulation by histidine, its inhibition by catalase, and the lack of an oxygen effect. Separate irradiation of DNA or water does not lead to cross linking. However, separate irradiation of protein leads to cross linking which proceeds with slow-component kinetics

  19. The mediatization of ethical consumption

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2013-01-01

    Over the years, mediatization studies have investigated the influence of media in numerous sections of contemporary society. One area that has received limited attention is the mediatization of consumption, particularly issues concerning ethical consumption. This article presents a study of how...... mediatization is transforming modern consumption and contributing to the mainstreaming of ethical consumption. Based on a study of a Danish online eco-store, the article argues that modern ethical consumption increasingly depends on new media practices to present sustainable consumption as practical...

  20. Assay of mast cell mediators

    DEFF Research Database (Denmark)

    Rådinger, Madeleine; Jensen, Bettina M; Swindle, Emily

    2015-01-01

    Mediator release from activated mast cells is a major initiator of the symptomology associated with allergic disorders such as anaphylaxis and asthma. Thus, methods to monitor the generation and release of such mediators have widespread applicability in studies designed to understand the processes...... regulating mast cell activation and for the identification of therapeutic approaches to block mast cell-driven disease. In this chapter, we discuss approaches used for the determination of mast cell degranulation, lipid-derived inflammatory mediator production, and cytokine/chemokine gene expression as well...

  1. Doing statistical mediation and moderation

    CERN Document Server

    Jose, Paul E

    2013-01-01

    Written in a friendly, conversational style, this book offers a hands-on approach to statistical mediation and moderation for both beginning researchers and those familiar with modeling. Starting with a gentle review of regression-based analysis, Paul Jose covers basic mediation and moderation techniques before moving on to advanced topics in multilevel modeling, structural equation modeling, and hybrid combinations, such as moderated mediation. User-friendly features include numerous graphs and carefully worked-through examples; ""Helpful Suggestions"" about procedures and pitfalls; ""Knowled

  2. Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

    Science.gov (United States)

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

    2013-10-30

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Science.gov (United States)

    Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

  4. Mediation analysis with multiple versions of the mediator

    OpenAIRE

    VanderWeele, Tyler J.

    2012-01-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well defined hypothetical interventions on the mediator. In many settings there may be multiple ways to fix the mediator to a particular value and these different hypothetical interventions may have very different implications for the outcome of interest. In this paper we cons...

  5. Pathogen reduction of blood components.

    Science.gov (United States)

    Solheim, Bjarte G

    2008-08-01

    Thanks to many blood safety interventions introduced in developed countries the risk of transfusion transmitted infections has become exceedingly small in these countries. However, emerging pathogens still represent a serious challenge, as demonstrated by West Nile virus in the US and more recently by Chikungunya virus in the Indian Ocean. In addition bacterial contamination, particularly in platelets, and protozoa transmitted by blood components still represent sizeable risks in developed countries. In developing countries the risk of all transfusion transmitted infections is still high due to insufficient funding and organisation of the health service. Pathogen reduction of pooled plasma products has virtually eliminated the risk of transfusion transmitted infections, without compromising the quality of the products significantly. Pathogen reduction of blood components has been much more challenging. Solvent detergent treatment which has been so successfully applied for plasma products dissolves cell membranes, and can, therefore, only be applied for plasma and not for cellular blood components. Targeting of nucleic acids has been another method for pathogen inactivation of plasma and the only approach possible for cellular blood products. As documented in more than 15 year's track record, solvent detergent treatment of pooled plasma can yield high quality plasma. The increased risk for contamination by unknown viruses due to pooling is out weighed by elimination of TRALI, significant reduction in allergic reactions and standardisation of the product. Recently, a promising method for solvent detergent treatment of single donor plasma units has been published. Methylene blue light treatment of single donor plasma units has a similar long track record as pooled solvent detergent treated plasma; but the method is less well documented and affects coagulation factor activity more. Psoralen light treated plasma has only recently been introduced (CE marked in Europe

  6. Rac1 mediates cytokine-stimulated hemocyte spreading via prostaglandin biosynthesis in the beet armyworm, Spodoptera exigua

    Science.gov (United States)

    Cell spreading is an integral component of insect hemocytic immune reactions to infections and invasions. Cell spreading is accomplished by cytoskeleton rearrangement, which is activated by three major immune mediators, biogenic monoamines, plasmatocyte-spreading peptide (PSP), and eicosanoids, part...

  7. Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

    Science.gov (United States)

    Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

    2015-10-30

    Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Components of Co-creation

    DEFF Research Database (Denmark)

    Tanev, Stoyan

    2009-01-01

    , such an approach misses the advantages of an empirically driven quantitative approach that benefits from larger size samples and is more appropriate for theory building through the development and testing of hypotheses. It is important, therefore, to seek the development of a research methodology that combines...... the benefits of both qualitative and quantitative research approaches for studying the nature of value co-creation. The article provides a first attempt to identify the main research steps of such a methodology. It provides some preliminary results on the key components of value co-creation between firms...... the inner logic of the value co-creation phenomenon as well as the nature of the results reported in this article. The specific nature of the results was found to be suitable for the application of small-N techniques such as the Qualitative Comparative Analysis (QCA) technique which combines the advantages...

  9. The magnet components database system

    International Nuclear Information System (INIS)

    Baggett, M.J.; Leedy, R.; Saltmarsh, C.; Tompkins, J.C.

    1990-01-01

    The philosophy, structure, and usage MagCom, the SSC magnet components database, are described. The database has been implemented in Sybase (a powerful relational database management system) on a UNIX-based workstation at the Superconducting Super Collider Laboratory (SSCL); magnet project collaborators can access the database via network connections. The database was designed to contain the specifications and measured values of important properties for major materials, plus configuration information (specifying which individual items were used in each cable, coil, and magnet) and the test results on completed magnets. These data will facilitate the tracking and control of the production process as well as the correlation of magnet performance with the properties of its constituents. 3 refs., 10 figs

  10. RCM and component evaluation logic

    International Nuclear Information System (INIS)

    Davis, B.; Anderson, J.

    1991-01-01

    This paper reports on the prevention maintenance program at Palo Verde Nuclear Generating Station (PVNGS), initially developed based on recommendations found in vendor technical manuals and accepted industry standards. The method was used until there was sufficient operating history to justify changes. The Reliability Centered Maintenance (RCM) project was started to provide another approach to the implementation of preventive maintenance. RCM evaluations were performed on nine systems. RCM was then suspended since it was found during implementation that additional documentation was necessary. RCM was selected as a preventive maintenance development process because it provides a documented analytical approach to establishing a preventive maintenance program. It is also being developed throughout the industry as a standard approach to preventive maintenance. PVNGS became interested in performing RCM analyses primarily to ensure that system and component reliability is maintained at the highest level possible and that hidden or rare failures are addressed by appropriate and effective maintenance. A secondary reason was to save maintenance expenditures

  11. Lubrication of nuclear reactor components

    International Nuclear Information System (INIS)

    Wild, E.; Mack, K.J.

    1978-01-01

    Safe operation of liquid metal cooled nuclear reactors requires a knowledge of the tribological behaviour of contacting components at high temperatures with slow relative movement at high frictional loads in a chemically aggressive environment. Experiments have been performed on various material combinations in liquid sodium and argon. Because of the small sliding movements, hydrodynamic lubrication is not expected and thus surface finish is an important factor. Tests have been performed on brushed, ground and lapped surfaces. Among the material combinations tested a CrC-coating on a 1.4961 stainless steel substrate performed well. Friction coefficients of 0.35-0.5 in argon and 0.1-1.2 in liquid sodium were recorded. (author)

  12. On Bayesian Principal Component Analysis

    Czech Academy of Sciences Publication Activity Database

    Šmídl, Václav; Quinn, A.

    2007-01-01

    Roč. 51, č. 9 (2007), s. 4101-4123 ISSN 0167-9473 R&D Projects: GA MŠk(CZ) 1M0572 Institutional research plan: CEZ:AV0Z10750506 Keywords : Principal component analysis ( PCA ) * Variational bayes (VB) * von-Mises–Fisher distribution Subject RIV: BC - Control Systems Theory Impact factor: 1.029, year: 2007 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6V8V-4MYD60N-6&_user=10&_coverDate=05%2F15%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=b8ea629d48df926fe18f9e5724c9003a

  13. Functional Generalized Structured Component Analysis.

    Science.gov (United States)

    Suk, Hye Won; Hwang, Heungsun

    2016-12-01

    An extension of Generalized Structured Component Analysis (GSCA), called Functional GSCA, is proposed to analyze functional data that are considered to arise from an underlying smooth curve varying over time or other continua. GSCA has been geared for the analysis of multivariate data. Accordingly, it cannot deal with functional data that often involve different measurement occasions across participants and a large number of measurement occasions that exceed the number of participants. Functional GSCA addresses these issues by integrating GSCA with spline basis function expansions that represent infinite-dimensional curves onto a finite-dimensional space. For parameter estimation, functional GSCA minimizes a penalized least squares criterion by using an alternating penalized least squares estimation algorithm. The usefulness of functional GSCA is illustrated with gait data.

  14. Component codification and identification systems

    International Nuclear Information System (INIS)

    Pannenbaecker, K.

    1977-01-01

    The lecture covers the codification in power stations during the erection phase and commercial operation phase. A diagram gives a survey. There are three basic-codifications for application; 1) Kraftwerk-Kennzeichen-System (KKS) for marking each component in orientated systems, for marking electrical orientated positions in cubicals, switch gears etc. and for marking rooms in buildings; 2) Ordnungssystem (OS) for cost calculation and ordering; 3) Unterlagenarten-Schluessel (UAS) for letters, reports etc. and for documentation. The OS is developed on the principle of cost account number and is therefore close to the organization of each supplier and his special form of design and constrution. KKS has only to mark hardware. Therefore all German owners, consultants, authorities and suppliers develop KKS together and conform to it in DIN 407119. (ORU) [de

  15. The magnet components database system

    International Nuclear Information System (INIS)

    Baggett, M.J.; Leedy, R.; Saltmarsh, C.; Tompkins, J.C.

    1990-01-01

    The philosophy, structure, and usage of MagCom, the SSC magnet components database, are described. The database has been implemented in Sybase (a powerful relational database management system) on a UNIX-based workstation at the Superconducting Super Collider Laboratory (SSCL); magnet project collaborators can access the database via network connections. The database was designed to contain the specifications and measured values of important properties for major materials, plus configuration information (specifying which individual items were used in each cable, coil, and magnet) and the test results on completed magnets. The data will facilitate the tracking and control of the production process as well as the correlation of magnet performance with the properties of its constituents. 3 refs., 9 figs

  16. The genetic component of preeclampsia

    DEFF Research Database (Denmark)

    Hansen, Anette Tarp; Bernth Jensen, Jens Magnus; Hvas, Anne-Mette

    2018-01-01

    Preeclampsia is a major cause of maternal and perinatal deaths. The aetiology of preeclampsia is largely unknown but a polygenetic component is assumed. To explore this hypothesis, we performed an in-depth whole-exome sequencing study in women with (cases, N = 50) and without (controls, N = 50......) preeclampsia. The women were identified in an unselected cohort of 2,545 pregnant women based on data from the Danish National Patient Registry and the Medical Birth Registry. Matching DNA was obtained from a biobank containing excess blood from routine antenatal care visits. Novogene performed the whole......-exome sequencing blinded to preeclampsia status. Variants for comparison between cases and controls were filtered in the Ingenuity Variant Analysis software. We applied two different strategies; a disease association panel approach, which included variants in single genes associated with established clinical risk...

  17. Kinanthropometry - Components of body constitution

    Directory of Open Access Journals (Sweden)

    Maria Tereza Silveira Böhme

    2000-12-01

    Full Text Available The objective of this study is to present the conceptual and historical background to Kinanthropometry and to characterize this area of research. The components of body constitution relating to dimensions, proportions, shape and body composition that should be considered in Physical Education and Sports programs are also described. ARESUMO Este trabalho tem por objetivo apresentar os aspectos conceituais referentes à Cineantropometria, assim como os aspectos históricos e caracterização desta área de estudos. São também descritos os componentes de constituição corporal referentes à dimensões, proporções, forma e composição corporal que devem ser considerados em programas de Educação Física e Esporte.

  18. Structural analysis of nuclear components

    International Nuclear Information System (INIS)

    Ikonen, K.; Hyppoenen, P.; Mikkola, T.; Noro, H.; Raiko, H.; Salminen, P.; Talja, H.

    1983-05-01

    THe report describes the activities accomplished in the project 'Structural Analysis Project of Nuclear Power Plant Components' during the years 1974-1982 in the Nuclear Engineering Laboratory at the Technical Research Centre of Finland. The objective of the project has been to develop Finnish expertise in structural mechanics related to nuclear engineering. The report describes the starting point of the research work, the organization of the project and the research activities on various subareas. Further the work done with computer codes is described and also the problems which the developed expertise has been applied to. Finally, the diploma works, publications and work reports, which are mainly in Finnish, are listed to give a view of the content of the project. (author)

  19. A Mediation Analysis of a Tobacco Prevention Program for Adolescents in India: How Did Project MYTRI Work?

    Science.gov (United States)

    Stigler, Melissa Harrell; Perry, Cheryl L.; Smolenski, Derek; Arora, Monika; Reddy, K. Srinath

    2011-01-01

    This article presents the results of a mediation analysis of Project MYTRI (Mobilizing Youth for Tobacco Related Initiatives in India), a randomized, controlled trial of a multiple-component, school-based tobacco prevention program for sixth- to ninth-graders (n = 14,085) in Delhi and Chennai, India. A mediation analysis identifies "how"…

  20. Model reduction by weighted Component Cost Analysis

    Science.gov (United States)

    Kim, Jae H.; Skelton, Robert E.

    1990-01-01

    Component Cost Analysis considers any given system driven by a white noise process as an interconnection of different components, and assigns a metric called 'component cost' to each component. These component costs measure the contribution of each component to a predefined quadratic cost function. A reduced-order model of the given system may be obtained by deleting those components that have the smallest component costs. The theory of Component Cost Analysis is extended to include finite-bandwidth colored noises. The results also apply when actuators have dynamics of their own. Closed-form analytical expressions of component costs are also derived for a mechanical system described by its modal data. This is very useful to compute the modal costs of very high order systems. A numerical example for MINIMAST system is presented.

  1. Library thermohydraulic components for training simulators

    International Nuclear Information System (INIS)

    Castelao Caruana, M. J.; Di Benedetto, A.; Pierini, J.P.

    2013-01-01

    The thermohydraulic components Library was modeled in MatLab/Simulink®. This library owns Pipe type components (pump, control valve and / or heaters), storage tanks (Open, Closed and Equilibrium Water Vapor-Air) and Heat Exchangers (Co-Current, Counter-Current and U-tubes). Each component can be attached to other components through the component library Header, in order to create a more complex thermal-hydraulic system which in turn can interact with other thermal-hydraulic systems. (author)

  2. Dimensional reduction in anomaly mediation

    International Nuclear Information System (INIS)

    Boyda, Ed; Murayama, Hitoshi; Pierce, Aaron

    2002-01-01

    We offer a guide to dimensional reduction in theories with anomaly-mediated supersymmetry breaking. Evanescent operators proportional to ε arise in the bare Lagrangian when it is reduced from d=4 to d=4-2ε dimensions. In the course of a detailed diagrammatic calculation, we show that inclusion of these operators is crucial. The evanescent operators conspire to drive the supersymmetry-breaking parameters along anomaly-mediation trajectories across heavy particle thresholds, guaranteeing the ultraviolet insensitivity

  3. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H

    1985-01-01

    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...... of the cellular localization, expression and structure of the C3 receptors, especially the C3b (CR1) receptor, has been considerably extended in the last few years, whereas our understanding of the physiological role of these receptors is still fragmentary. However, it is becoming increasingly evident...

  4. How do different types of community commitment influence brand commitment? The mediation of brand attachment.

    Science.gov (United States)

    Zhang, Ning; Zhou, Zhi-min; Su, Chen-ting; Zhou, Nan

    2013-11-01

    Although previous research indicates that participation in a brand community may foster consumer loyalty to the brand in question, research has seldom examined the mediating effect of community commitment on brand commitment. Drawing from the typologies of organizational commitment, we divide community commitment into three components: continuance community commitment (continuance CC), affective community commitment (affective CC), and normative community commitment (normative CC). We then assess the mediating role of brand attachment in the relationship between these three components and brand commitment. We test the hypotheses using a sample of online mobile phone brand communities in China. The empirical results reveal that brand attachment exerts an indirect (but not mediated) effect on the relationship between continuance CC and brand commitment and on the relationship between normative CC and brand commitment. We also find that it exerts a partial mediating effect on the relationship between affective CC and brand commitment. The findings contribute to the branding literature and have important implications for brand community management.

  5. Precision fiducialization of transport components

    International Nuclear Information System (INIS)

    Fischer, G.E.; Bressler, V.E.; Cobb, J.K.; Jensen, D.R.; Ruland, R.E.; Walz, H.V.; Williams, S.H.

    1992-03-01

    The Final Focus Test Beam (FFTB) is a transport line designed to test both concept and advanced technology for application to future linear colliders. It is currently under construction at SLAC in the central beam line. Most of the quadrupoles of the FFTB have ab initio alignment tolerances of less than 30 microns, if the planned for beam based alignment tuning procedure is to converge. For such placement tolerances to have any meaning requires that the coordinates of the effective centers, seen by the beam particles, be tansferred to tooling (that can be reached by mechanical or optical alignment methods) located on the outside of the components to comparable or better values. We have constructed an apparatus that simultaneously locates to micron tolerances, the effective magnetic center of fussing lenses, as well as the electrical center of beam position monitors (BPM) imbedded therein, and once located, for transferring these coordinates to specially mounted tooling frames that supported the external retroreflectors used in a laser tracker based alignment of the beam line. Details of construction as well as experimental results from the method are presented

  6. Teaching Principal Components Using Correlations.

    Science.gov (United States)

    Westfall, Peter H; Arias, Andrea L; Fulton, Lawrence V

    2017-01-01

    Introducing principal components (PCs) to students is difficult. First, the matrix algebra and mathematical maximization lemmas are daunting, especially for students in the social and behavioral sciences. Second, the standard motivation involving variance maximization subject to unit length constraint does not directly connect to the "variance explained" interpretation. Third, the unit length and uncorrelatedness constraints of the standard motivation do not allow re-scaling or oblique rotations, which are common in practice. Instead, we propose to motivate the subject in terms of optimizing (weighted) average proportions of variance explained in the original variables; this approach may be more intuitive, and hence easier to understand because it links directly to the familiar "R-squared" statistic. It also removes the need for unit length and uncorrelatedness constraints, provides a direct interpretation of "variance explained," and provides a direct answer to the question of whether to use covariance-based or correlation-based PCs. Furthermore, the presentation can be made without matrix algebra or optimization proofs. Modern tools from data science, including heat maps and text mining, provide further help in the interpretation and application of PCs; examples are given. Together, these techniques may be used to revise currently used methods for teaching and learning PCs in the behavioral sciences.

  7. Molecular Components of Catalytic Selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Somorjai, Gabor A.; Park, Jeong Y.

    2008-07-02

    Selectivity, that is, to produce one molecule out of many other thermodynamically feasible product molecules, is the key concept to develop 'clean manufacturing' processes that do not produce byproducts (green chemistry). Small differences in potential energy barriers for elementary reaction steps control which reaction channel is more likely to yield the desired product molecule (selectivity), instead of the overall activation energy for the reaction that controls turnover rates (activity). Recent studies have demonstrated the atomic- or molecular-level tailoring of parameters such as the surface structures of active sites that give rise to nanoparticle size and shape dependence of turnover rates and reaction selectivities. Here, we highlight seven molecular components that influence reaction selectivities. These include: surface structure, adsorbate-induced restructuring, adsorbate mobility, reaction intermediates, surface composition, charge transport, and oxidation states for model metal single crystal and colloid nanoparticle catalysts. We show examples of their functioning and describe in-situ instruments that permit us to investigate their roles in surface reactions.

  8. MICROFLUIDIC COMPONENT CAPABLE OF SELF-SEALING

    DEFF Research Database (Denmark)

    2009-01-01

    A microfluidic component (100) for building a microfluidic system is provided. The microfluidic component (100) can be mounted on a microf luidic breadboard (202) in a manner that allows it to be connected to other microfluidic components (204, 206) without the requirement of additional devices....... The microfluidic component (100) comprises at least one flexible tube piece (102) for transporting a fluid. The microfluidic component (100) also comprises means for applying and maintaining pressure (104) between the flexible tube piece (102) and a tube piece (208, 210) housed in another microfluidic component...

  9. Stochastic Modeling Of Wind Turbine Drivetrain Components

    DEFF Research Database (Denmark)

    Rafsanjani, Hesam Mirzaei; Sørensen, John Dalsgaard

    2014-01-01

    reliable components are needed for wind turbine. In this paper focus is on reliability of critical components in drivetrain such as bearings and shafts. High failure rates of these components imply a need for more reliable components. To estimate the reliability of these components, stochastic models...... are needed for initial defects and damage accumulation. In this paper, stochastic models are formulated considering some of the failure modes observed in these components. The models are based on theoretical considerations, manufacturing uncertainties, size effects of different scales. It is illustrated how...

  10. 22 CFR 218.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 218.33 Section 218.33 Foreign... § 218.33 Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and Conciliation Service all complaints that: (1) fall within the jurisdiction of these...

  11. 15 CFR 923.54 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Mediation. 923.54 Section 923.54... Mediation. (a) Section 307(h) of the Act provides for mediation of serious disagreement between any Federal... cases, mediation by the Secretary, with the assistance of the Executive Office of the President, may be...

  12. 10 CFR 4.333 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Mediation. 4.333 Section 4.333 Energy NUCLEAR REGULATORY... Investigation, Conciliation, and Enforcement Procedures § 4.333 Mediation. (a) Referral of complaints for mediation. NRC will refer to a mediation agency designated by the Secretary of the Department of Health and...

  13. 45 CFR 1156.16 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Mediation. 1156.16 Section 1156.16 Public Welfare... Procedures § 1156.16 Mediation. (a) Referral of complaints for mediation. The Endowment will promptly refer all complaints to the agency designated by the Secretary of HHS to manage the mediation process that...

  14. 15 CFR 930.111 - OCRM mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false OCRM mediation. 930.111 Section 930... FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.111 OCRM mediation. The availability of mediation does not preclude use by the parties of alternative means for...

  15. 14 CFR 1252.402 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Mediation. 1252.402 Section 1252.402... Procedures § 1252.402 Mediation. (a) Referral of complaints for mediation. NASA will refer to the Federal Mediation and Conciliation Service all complaints that: (1) Fall within the jurisdiction of the Act and...

  16. 10 CFR 1040.89-6 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Mediation. 1040.89-6 Section 1040.89-6 Energy DEPARTMENT... Enforcement Procedures § 1040.89-6 Mediation. (a) Referral of complaints for mediation. DOE will refer to the Federal Mediation and Conciliation Service, in accordance with 45 CFR 90.43(c)(3), all complaints that: (1...

  17. 34 CFR 110.32 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 110.32 Section 110.32 Education Regulations..., Conciliation, and Enforcement Procedures § 110.32 Mediation. (a) ED promptly refers to the Federal Mediation and Conciliation Service or to the mediation agency designated by the Secretary of Health and Human...

  18. 7 CFR 780.9 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Mediation. 780.9 Section 780.9 Agriculture Regulations... PROGRAMS APPEAL REGULATIONS § 780.9 Mediation. (a) Any request for mediation must be submitted after... once: (1) If resolution of an adverse decision is not achieved in mediation, a participant may exercise...

  19. 24 CFR 146.35 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Mediation. 146.35 Section 146.35... ASSISTANCE Investigation, Settlement, and Enforcement Procedures § 146.35 Mediation. (a) HUD shall refer to the Federal Mediation and Conciliation Service, a mediation agency designated by the Secretary of...

  20. 7 CFR 614.11 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mediation. 614.11 Section 614.11 Agriculture... AGRICULTURE CONSERVATION OPERATIONS NRCS APPEAL PROCEDURES § 614.11 Mediation. (a) A participant who wishes to pursue mediation must file request for mediation under this part with the NRCS official designated in the...