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Sample records for combined cxcl10 cxcl8

  1. A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.

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    Alexandre Hainard

    2009-06-01

    Full Text Available Human African trypanosomiasis (HAT, also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS. As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.Cerebrospinal fluid (CSF originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and 5 WBC/microL patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10 were determined by bead suspension arrays.CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.

  2. Effects of peritoneal fluid from endometriosis patients on interferon-gamma-induced protein-10 (CXCL10) and interleukin-8 (CXCL8) released by neutrophils and CD4+ T cells.

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    Kim, Ji-Yeon; Lee, Dong-Hyung; Joo, Jong-Kil; Jin, Jun-O; Wang, Ji-Won; Hong, Young-Seoub; Kwak, Jong-Young; Lee, Kyu-Sup

    2009-09-01

    Intraperitoneal immuno-inflammatory changes may be associated with the pathogenesis of endometriosis. We evaluated the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the release of interferon-gamma-induced protein-10 (IP-10/CXCL10) and interleukin-8 (IL-8/CXCL8) by neutrophils, CD4(+) T cells, and monocytes. Neutrophils, CD4(+) T cells, and monocytes were cultured with ePF and the chemokine levels in the supernatants were then measured using enzyme-linked immunosorbent assay. The addition of ePF to cultures of CD4(+) T cells led to a significant increase in the release of IP-10 when compared with control PF without endometriosis (cPF). There was a positive correlation between the levels of IL-8 and IP-10 in ePF (R = 0.89, P = 0.041), but not between the levels of IP-10 and IL-8 released by neutrophils, CD4(+) T cells, and monocytes. The levels of IP-10 in ePF were positively correlated with the release of IP-10 by ePF-treated neutrophils (R = 0.89, P ePF significantly enhanced the interferon-gamma-induced release of IP-10 by nuetrophils and CD4(+) T cells. These findings suggest that neutrophils and T cells release differential levels of IP-10 and IL-8 in response to stimulation with ePF, and that these cells are a major source of IP-10 in the PF of endometriosis patients.

  3. Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement

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    Alrashdan, Yazan A.; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J.; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E.; Burgess, Janette K.; Armour, Carol L.; Ammit, Alaina J.

    2012-01-01

    CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma. PMID:22387292

  4. Programming of neurotoxic cofactor CXCL-10 in HIV-1-associated dementia: abrogation of CXCL-10-induced neuro-glial toxicity in vitro by PKC activator

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    Mehla Rajeev

    2012-10-01

    Full Text Available Abstract Background More than 50% of patients undergoing lifelong suppressive antiviral treatment for HIV-1 infection develop minor HIV-1-associated neurocognitive disorders. Neurological complications during HIV-1 infection are the result of direct neuronal damage by proinflammatory products released from HIV-1-infected or -uninfected activated lymphocytes, monocytes, macrophages, microglia and astrocytes. The specific pro-inflammatory products and their roles in neurotoxicity are far from clear. We investigated proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF of HIV-demented (HIV-D and HIV-nondemented (HIV-ND patients and studied their affect on neuroglial toxicity. Methods and results Bioplex array showed elevated levels of signatory chemokines or cytokines (IL-6, IFN-γ, CXCL10, MCP-1 and PDGF in the CSF of HIV-D patients (n = 7 but not in that of HIV-ND patients (n = 7. Among the signatory cytokines and chemokines, CXCL10 was distinctly upregulated in-vitro in HIV-1 (NLENG1-activated human fetal astrocytes, HIV-1 (Ba-L-infected macrophages, and HIV-1 (NLENG1-infected lymphocytes. Virus-infected macrophages also had increased levels of TNF-α. Consistently, human fetal astrocytes treated with HIV-1 and TNF-α induced the signatory molecules. CXCL10 in combination with HIV-1 synergistically enhanced neuronal toxicity and showed chemotactic activity (~ 40 fold for activated peripheral blood mononuclear cells (PBMC, suggesting the intersection of signaling events imparted by HIV-1 and CXCL10 after binding to their respective surface receptors, CXCR4 and CXCR3, on neurons. Blocking CXCR3 and its downstream MAP kinase (MAPK signaling pathway suppressed combined CXCL10 and HIV-1-induced neurotoxicity. Bryostatin, a PKC modulator and suppressor of CXCR4, conferred neuroprotection against combined insult with HIV-1 and CXCL10. Bryostatin also suppressed HIV-1 and CXCL10-induced PBMC chemotaxis. Although, therapeutic targeting

  5. Chemokines CXCL10 and CCL2

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    Sørensen, Torben Lykke; Sellebjerg, F; Jensen, C V

    2001-01-01

    leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9...... patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials....... Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls...

  6. The Multifaceted Functions of CXCL10 in Cardiovascular Disease

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    Pleunie van den Borne

    2014-01-01

    Full Text Available C-X-C motif ligand 10 (CXCL10, or interferon-inducible protein-10, is a small chemokine belonging to the CXC chemokine family. Its members are responsible for leukocyte trafficking and act on tissue cells, like endothelial and vascular smooth muscle cells. CXCL10 is secreted by leukocytes and tissue cells and functions as a chemoattractant, mainly for lymphocytes. After binding to its receptor CXCR3, CXCL10 evokes a range of inflammatory responses: key features in cardiovascular disease (CVD. The role of CXCL10 in CVD has been extensively described, for example for atherosclerosis, aneurysm formation, and myocardial infarction. However, there seems to be a discrepancy between experimental and clinical settings. This discrepancy occurs from differences in biological actions between species (e.g. mice and human, which is dependent on CXCL10 signaling via different CXCR3 isoforms or CXCR3-independent signaling. This makes translation from experimental to clinical settings challenging. Furthermore, the overall consensus on the actions of CXCL10 in specific CVD models is not yet reached. The purpose of this review is to describe the functions of CXCL10 in different CVDs in both experimental and clinical settings and to highlight and discuss the possible discrepancies and translational difficulties. Furthermore, CXCL10 as a possible biomarker in CVD will be discussed.

  7. The Chemokine CXCL-10 Is a Marker of Infection Stage in Individuals With DNAemia Due to Parvovirus B19.

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    Weseslindtner, Lukas; Aberle, Judith H; Hedman, Lea; Hedman, Klaus

    2017-01-15

    Accurate diagnosis of parvovirus B19 (B19V) infection requires the differentiation between acute and past infection, which is especially important when DNAemia due to B19V (hereafter, "B19V DNAemia") is detected in pregnancy. Here, we explored whether the level of the chemokine CXCL-10, in combination with findings of molecular and serological assays, can discriminate between acute and past B19V infection. B19V DNA-positive serum samples from 222 immunocompetent individuals were analyzed for (1) viral DNA loads, (2) anti-B19V immunoglobulin M (IgM) and immunoglobulin G (IgG), (3) anti-VP1 IgG avidity, (4) anti-VP-2 epitope type specificity (ETS), and (5) CXCL-10 serum levels. Anti-B19V IgM and IgG, avidity, and ETS assays were used to categorize individuals with B19V DNAemia as having acute or past B19V infection. Acute B19V infection caused a significant increase in the serum concentration of CXCL-10, compared with the concentration at baseline, before infection. Higher CXCL-10 serum levels were furthermore detected in acute B19V infection as compared to past infection. As a marker, CXCL-10 serum levels could discriminate between acute and past B19V infection, with an excellent discriminatory capacity when CXCL-10 and B19V DNA levels were used as combined parameters. Acute B19V infection is associated with increased CXCL-10 production, and measurement of CXCL-10 serum levels thus allows for the staging of B19V infection in individuals with B19V DNAemia. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. Astrocytes produce interferon-alpha and CXCL10, but not IL-6 or CXCL8, in Aicardi-Goutières syndrome

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    van Heteren, Jane T.; Rozenberg, Flore; Aronica, Eleonora; Troost, Dirk; Lebon, Pierre; Kuijpers, Taco W.

    2008-01-01

    Aicardi-Goutières syndrome (AGS) presents as a severe autosomal recessively inherited neurological brain disease. Clinical and neurological manifestations closely resemble those of congenital viral infection and are generally attributed to a perturbation of innate immunity including a long lasting

  9. Lethal Nipah virus infection induces rapid overexpression of CXCL10.

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    Cyrille Mathieu

    Full Text Available Nipah virus (NiV is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10, an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.

  10. Cxcl8b and Cxcr2 Regulate Neutrophil Migration through Bloodstream in Zebrafish

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    Constanza Zuñiga-Traslaviña

    2017-01-01

    Full Text Available Neutrophils play an essential role during an inflammatory response, which is dependent on their rapid recruitment from the bone marrow to the vasculature. However, there is no information about the molecular signals that regulate neutrophil entry to circulation during an inflammatory process in humans. This is mainly due to the lack of a suitable model of study that contains similar set of molecules and that allows in vivo analyses. In this study, we used the zebrafish to assess the role of Cxcl8a, Cxcl8b, and Cxcr2 in neutrophil migration to blood circulation after injury. Using Tg(BACmpx:GFPi114 transgenic embryos and two damage models (severe and mild, we developed in vivo lack of function assays. We found that the transcription levels of cxcl8a, cxcl8b, and cxcr2 were upregulated in the severe damage model. In contrast, only cxcr2 and cxcl8a mRNA levels were increased during mild damage. After knocking down Cxcl8a, neutrophil quantity decreased at the injury site, while Cxcl8b decreased neutrophils in circulation. When inhibiting Cxcr2, we observed a decrease in neutrophil entry to the bloodstream. In conclusion, we identified different functions for both Cxcl8 paralogues, being the Cxcl8b/Cxcr2 axis that regulates neutrophil entry to the bloodstream, while Cxcl8a/Cxcr2 regulates the migration to the affected area.

  11. Furin is a chemokine-modifying enzyme: in vitro and in vivo processing of CXCL10 generates a C-terminally truncated chemokine retaining full activity.

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    Hensbergen, Paul J; Verzijl, Dennis; Balog, Crina I A; Dijkman, Remco; van der Schors, Roel C; van der Raaij-Helmer, Elizabeth M H; van der Plas, Mariena J A; Leurs, Rob; Deelder, André M; Smit, Martine J; Tensen, Cornelis P

    2004-04-02

    Chemokines comprise a class of structurally related proteins that are involved in many aspects of leukocyte migration under basal and inflammatory conditions. In addition to the large number of genes, limited processing of these proteins by a variety of enzymes enhances the complexity of the total spectrum of chemokine variants. We have recently shown that the native chemokine CXCL10 is processed at the C terminus, thereby shedding the last four amino acids. The present study was performed to elucidate the mechanism in vivo and in vitro and to study the biological activity of this novel isoform of CXCL10. Using a combination of protein purification and mass spectrometric techniques, we show that the production of C-terminally truncated CXCL10 by primary keratinocytes is inhibited in vivo by a specific inhibitor of pro-protein convertases (e.g. furin) but not by inhibition of matrix metalloproteinases. Moreover, CXCL10 is processed by furin in vitro, which is abrogated by a mutation in the furin recognition site. Using GTPgammaS binding, Ca(2+) mobilization, and chemotaxis assays, we demonstrate that the C-terminally truncated CXCL10 variant is a potent ligand for CXCR3. Moreover, the inverse agonist activity on the virally encoded receptor ORF74 and the direct antibacterial activity of CXCL10 are fully retained. Hence, we have identified furin as a novel chemokine-modifying enzyme in vitro and most probably also in vivo, generating a C-terminally truncated CXCL10, which fully retains its (inverse) agonistic properties.

  12. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

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    Song, Yao; Baba, Tomohisa; Li, Ying-Yi; Furukawa, Kaoru; Tanabe, Yamato; Matsugo, Seiichi; Sasaki, Soichiro; Mukaida, Naofumi

    2015-01-01

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization

  13. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

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    Song, Yao; Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Li, Ying-Yi [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Furukawa, Kaoru; Tanabe, Yamato [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Matsugo, Seiichi [School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Sasaki, Soichiro [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Mukaida, Naofumi, E-mail: mukaida@staff.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan)

    2015-03-06

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

  14. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

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    Poghosyan, Anna, E-mail: pannagos@yahoo.com; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J., E-mail: alan.knox@nottingham.ac.uk

    2016-08-05

    Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

  15. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

    International Nuclear Information System (INIS)

    Poghosyan, Anna; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J.

    2016-01-01

    Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

  16. In silico analysis reveals sequential interactions and protein conformational changes during the binding of chemokine CXCL-8 to its receptor CXCR1.

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    Je-Wen Liou

    Full Text Available Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR family. The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling. Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it. The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD simulations. A multi-steps binding mode is proposed: (i the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1. Mutation of CXCR1 abrogates this mode of binding. The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.

  17. Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8 induction in lung epithelial cells

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    Refsnes M

    2014-12-01

    indispensable for CXCL8 induction. The early response, magnitude, and persistency of MAPK and NF-κB signaling seemed to be critical determinants for the potential to induce CXCL8. These findings underscore that a strong, rapid, and relatively transient activation of ERK1/2 in combination with NF-kB may be sufficient for a strong induction of CXCL8, which may exceed the effects of a more moderate ERK1/2 activation in combination with activation of p38, JNK1/2, and NF-κB. Keywords: TPA, sodium fluoride, CXCL8, MAPK, NF-κB, A549 cells

  18. H-2g, a glucose analog of blood group H antigen, mediates monocyte recruitment in vitro and in vivo via IL-8/CXCL8

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    Rabquer BJ

    2012-09-01

    Full Text Available Bradley J Rabquer,1,2 Yong Hou,1 Jeffrey H Ruth,1 Wei Luo,1 Daniel T Eitzman,1 Alisa E Koch,3,1 Mohammad A Amin11University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, MI, USA; 2Albion College, Biology Department, Albion, MI, USA; 3VA Medical Service, Department of Veterans Affairs, Ann Arbor, MI, USAObjective: Monocyte (MN recruitment is an essential inflammatory component of many autoimmune diseases, including rheumatoid arthritis (RA. In this study we investigated the ability of 2-fucosyllactose (H-2g, a glucose analog of blood group H antigen to induce MN migration in vivo and determined if H-2g-induced interleukin-8 (IL-8/CXCL8 plays a role in MN ingress in RA.Methods: Sponge granuloma and intravital microscopy assays were performed to examine H-2g-induced in vivo MN migration and rolling, respectively. MNs were stimulated with H-2g, and the production of IL-8/CXCL8 was assessed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Lastly, in vitro MN migration assays and an in vivo RA synovial tissue severe combined immunodeficiency mouse model were used to determine the role of IL-8/CXCL8 in H-2g-induced MN migration.Results: In vivo, H-2g induced significantly greater MN migration compared to phosphate buffered saline. Intravital microscopy revealed that H-2g mediates MN migration in vivo by inducing MN rolling. In addition, H-2g induced MN production of IL-8/CXCL8, a process that was dependent on Src kinase. Moreover, we found that H-2g mediated MN migration in vitro, and in vivo migration was inhibited by a neutralizing anti-IL-8/CXCL8 antibody.Conclusion: These findings suggest that H-2g mediates MN recruitment in vitro and in vivo (in part via IL-8/CXCL8.Keywords: inflammation, rheumatoid arthritis, chemokine, migration

  19. Role of CXCL10 in pathogenesis of hepatitis C and antiviral therapy

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    LI Mi

    2015-11-01

    Full Text Available Hepatitis C virus (HCV infection represents an important public health problem worldwide. Eradicating HCV can finally delay or prevent the progression of HCV infection to end-stage liver diseases such as liver cirrhosis and liver cancer. Chemokine (C-X-C motif ligand 10 (CXCL10 is a chemokine belonging to the CXC chemokine family, and it exerts its function through binding to chemokine (C-X-C motif receptor 3 (CXCR3, playing a critical role in eradication of HCV. This article reviews the relationship of CXCL10 with the pathogenesis of HCV and the effectiveness of antiviral treatment, as well as the CXCL10 measurements. Meanwhile, this article introduces the clinical value of CXCL10 in assessing the risk of liver fibrosis and liver cancer. Further studies are needed to investigate the association between CXCL10 and liver diseases, and CXCL10 may provide a new therapeutic strategy for HCV infection.

  20. CXCL-8 Regulates Head and Neck Carcinoma Progression through NOD Signalling Pathway

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    Chan Leong-Perng

    2017-01-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth among the most common cancers in the world. Interlukin-8 (CXCL-8, a major role in inflammatory response and tumor microenvironment, correlates with tumor progression, metastasis and invasion. We explored CXCL-8 promotes tumor progression in different differentiation HNSCC cells. This project would apply to development on biomarker and target in HNSCC as well as provide a basis of early diagnosis and treatment for clinical. CXCL-8, NOD1 (nucleotide-binding oligomerization domain-containing protein 1 and receptor-interacting protein kinase (RIPK2 levels were detected statistically higher in patient tissue with HNSCC than in non-cancerous matched tissue (NCMT in the microarray and qRT-PCR study, whereas NOD2 was weakly expressed. Similar results were obtained for CXCL-8, NOD1, NOD2 and RIP2 from RT-PCR and western blotting. High CXCL-8, NOD1 and RIP2 expressions were found on HNSCC patient tissue than that of NCMT, whereas NOD2 was weakly expressed. The analytical results indicate that CXCL-8 is required in NOD 1-mediated signalling pathways in HNSCC.

  1. CXCL10 can inhibit endothelial cell proliferation independently of CXCR3.

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    Gabriele S V Campanella

    2010-09-01

    Full Text Available CXCL10 (or Interferon-inducible protein of 10 kDa, IP-10 is an interferon-inducible chemokine with potent chemotactic activity on activated effector T cells and other leukocytes expressing its high affinity G protein-coupled receptor CXCR3. CXCL10 is also active on other cell types, including endothelial cells and fibroblasts. The mechanisms through which CXCL10 mediates its effects on non-leukocytes is not fully understood. In this study, we focus on the anti-proliferative effect of CXCL10 on endothelial cells, and demonstrate that CXCL10 can inhibit endothelial cell proliferation in vitro independently of CXCR3. Four main findings support this conclusion. First, primary mouse endothelial cells isolated from CXCR3-deficient mice were inhibited by CXCL10 as efficiently as wildtype endothelial cells. We also note that the proposed alternative splice form CXCR3-B, which is thought to mediate CXCL10's angiostatic activity, does not exist in mice based on published mouse CXCR3 genomic sequences as an in-frame stop codon would terminate the proposed CXCR3-B splice variant in mice. Second, we demonstrate that human umbilical vein endothelial cells and human lung microvascular endothelial cells that were inhibited by CXL10 did not express CXCR3 by FACS analysis. Third, two different neutralizing CXCR3 antibodies did not inhibit the anti-proliferative effect of CXCL10. Finally, fourth, utilizing a panel of CXCL10 mutants, we show that the ability to inhibit endothelial cell proliferation correlates with CXCL10's glycosaminoglycan binding affinity and not with its CXCR3 binding and signaling. Thus, using a very defined system, we show that CXCL10 can inhibit endothelial cell proliferation through a CXCR3-independent mechanism.

  2. Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality

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    Lehmann, Jennifer M; Claus, Karina; Jansen, Christian

    2018-01-01

    BACKGROUND & AIMS: CXCR% ligands play an important role in hepatic injury, inflammation and fibrosis. While CXCL9 and CXCL11 are associated with survival in patients receiving transjugular intrahepatic portosystemic shunt (TIPS), the role of CXCL10 in severe portal hypertension remains unknown...... inflammation and it is correlated with acute decompensation, ACLF and complications in patients with severe portal hypertension receiving TIPS. CXCL10 predicts survival in these patients and a decrease in CXCL10 after TIPS may be considered a good prognostic factor........ METHODS: A total of 89 cirrhotic patients were analysed. CXCL10 protein levels were measured in portal and hepatic blood at TIPS insertion and 2 weeks later in 24 patients. CXCL10 and IL8 levels were assessed in portal, hepatic, cubital vein and right atrium blood in a further 25 patients at TIPS...

  3. MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells.

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    Skye Storrie

    Full Text Available Waddlia chondrophila (W. chondrophila is an emerging agent of respiratory and reproductive disease in humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial agents, such as Chlamydia abortus (C. abortus. The current study investigated the growth characteristics and innate immune responses of human and ruminant epithelial cells in response to infection with W. chondrophila.Human epithelial cells (HEp2 were infected with W. chondrophila for 24h. CXCL8 release was significantly elevated in each of the cell lines by active-infection with live W. chondrophila, but not by exposure to UV-killed organisms. Inhibition of either p38 or p42/44 MAPK significantly inhibited the stimulation of CXCL8 release in each of the cell lines. To determine the pattern recognition receptor through which CXCL8 release was stimulated, wild-type HEK293 cells which express no TLR2, TLR4, NOD2 and only negligible NOD1 were infected with live organisms. A significant increase in CXCL8 was observed.W. chondrophila actively infects and replicates within both human and ruminant epithelial cells stimulating CXCL8 release. Release of CXCL8 is significantly inhibited by inhibition of either p38 or p42/44 MAPK indicating a role for this pathway in the innate immune response to W. chondrophila infection. W. chondrophila stimulation of CXCL8 secretion in HEK293 cells indicates that TLR2, TLR4, NOD2 and NOD1 receptors are not essential to the innate immune response to infection.

  4. Independent, parallel pathways to CXCL10 induction in HCV-infected hepatocytes.

    Science.gov (United States)

    Brownell, Jessica; Wagoner, Jessica; Lovelace, Erica S; Thirstrup, Derek; Mohar, Isaac; Smith, Wesley; Giugliano, Silvia; Li, Kui; Crispe, I Nicholas; Rosen, Hugo R; Polyak, Stephen J

    2013-10-01

    The pro-inflammatory chemokine CXCL10 is induced by HCV infection in vitro and in vivo, and is associated with outcome of IFN (interferon)-based therapy. We studied how hepatocyte sensing of early HCV infection via TLR3 (Toll-like receptor 3) and RIG-I (retinoic acid inducible gene I) led to expression of CXCL10. CXCL10, type I IFN, and type III IFN mRNAs and proteins were measured in PHH (primary human hepatocytes) and hepatocyte lines harboring functional or non-functional TLR3 and RIG-I pathways following HCV infection or exposure to receptor-specific stimuli. HuH7 human hepatoma cells expressing both TLR3 and RIG-I produced maximal CXCL10 during early HCV infection. Neutralization of type I and type III IFNs had no impact on virus-induced CXCL10 expression in TLR3+/RIG-I+ HuH7 cells, but reduced CXCL10 expression in PHH. PHH cultures were positive for monocyte, macrophage, and dendritic cell mRNAs. Immunodepletion of non-parenchymal cells (NPCs) eliminated marker expression in PHH cultures, which then showed no IFN requirement for CXCL10 induction during HCV infection. Immunofluorescence studies also revealed a positive correlation between intracellular HCV Core and CXCL10 protein expression (r(2) = 0.88, p ≤ 0.001). While CXCL10 induction in hepatocytes during the initial phase of HCV infection is independent of hepatocyte-derived type I and type III IFNs, NPC-derived IFNs contribute to CXCL10 induction during HCV infection in PHH cultures. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  5. An IP-10 (CXCL10)-Derived Peptide Inhibits Angiogenesis

    Science.gov (United States)

    Yates-Binder, Cecelia C.; Rodgers, Margaret; Jaynes, Jesse; Wells, Alan; Bodnar, Richard J.; Turner, Timothy

    2012-01-01

    Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the α-helical domain residues 77–98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was able to block the inhibitory effects of the IP-10p, demonstrating specificity of the peptide. Inhibition of endothelial function by IP-10p was similar to that described for IP-10, secondary to CXCR3-mediated increase in cAMP production, activation of PKA inhibiting cell migration, and inhibition of VEGF-mediated m-calpain activation. IP-10p provides a novel therapeutic agent that inhibits endothelial cell function thus, allowing for the modulation of angiogenesis. PMID:22815829

  6. Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels.

    Science.gov (United States)

    Alkhouri, H; Cha, V; Tong, K; Moir, L M; Armour, C L; Hughes, J M

    2014-01-01

    In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3(+) mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1 β , TNF- α , and/or IFN γ and treated with histamine (1-100  μ M) ± chlorpheniramine (H1R antagonist; 1  μ M) or ranitidine (H2R antagonist; 50  μ M) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50  μ M), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1 β /TNF- α -induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF- α and amplified IFN γ -induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.

  7. IL-29 Enhances CXCL10 Production in TNF-α-stimulated Human Oral Epithelial Cells.

    Science.gov (United States)

    Hosokawa, Yoshitaka; Hosokawa, Ikuko; Shindo, Satoru; Ozaki, Kazumi; Matsuo, Takashi

    2017-08-01

    Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay. We used a Western blot analysis to detect IL-29 receptor expression and the phosphorylation levels of signal transduction molecules, including p38 mitogen-activated protein kinases (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor (NF)- κB p65, in the TR146 cells. The TR146 cells expressed the IL-29 receptor. IL-29 induced CXCL10 production in the TR146 cells. IL-29 significantly enhanced CXCL10 production in tumor necrosis factor (TNF)-α-stimulated TR146 cells. The p38 MAPK, STAT3, and NF-κB pathways were found to be related to the IL-29-induced enhancement of CXCL10 production in TNF-α-stimulated TR146 cells. IL-29 promotes T helper 1-cell accumulation in periodontal lesions by inducing CXCL10 production in oral epithelial cells.

  8. Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans

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    Dolf Segers

    2011-01-01

    Full Text Available Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In ApoE-/- mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% (P=0.002, smooth muscle cell content increased 2-fold (P=0.03, while macrophage MHC class II expression decreased by 50% (P=0.005. Also, the size of necrotic cores decreased by 41% (P=0.01. In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, P=0.003, with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy.

  9. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo

    Science.gov (United States)

    Rashighi, Mehdi; Agarwal, Priti; Richmond, Jillian M; Harris, Tajie H; Dresser, Karen; Su, Mingwan; Zhou, Youwen; Deng, April; Hunter, Chris A; Luster, Andrew D; Harris, John E

    2014-01-01

    Vitiligo is an autoimmune disease of the skin that results in disfiguring white spots. There are no FDA-approved treatments for vitiligo, and most off-label treatments yield unsatisfactory results. Vitiligo patients have increased numbers of autoreactive, melanocyte-specific CD8+ T cells in the skin and blood, which are directly responsible for melanocyte destruction. Here we report that gene expression in lesional skin from vitiligo patients reveals an IFN-γ-specific signature, including the chemokine CXCL10. CXCL10 is elevated in both vitiligo patient skin and serum and CXCR3, its receptor, is expressed on pathogenic T cells. To address the function of CXCL10 in vitiligo, we employed a mouse model of disease that also exhibits an IFN-γ-specific gene signature, expression of CXCL10 in the skin, and upregulation of CXCR3 on antigen-specific T cells. Mice that receive Cxcr3−/− T cells develop minimal depigmentation, as do mice lacking Cxcl10 or treated with CXCL10 neutralizing antibody. CXCL9 promotes autoreactive T cell global recruitment to the skin but not effector function while, in contrast, CXCL10 is required for effector function and localization within the skin. Surprisingly, CXCL10 neutralization in mice with established, widespread depigmentation induces reversal of disease, evidenced by repigmentation. These data identify a critical role for CXCL10 in both the progression and maintenance of vitiligo, and thereby support inhibiting CXCL10 as a targeted treatment strategy. PMID:24523323

  10. Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity.

    Science.gov (United States)

    Karin, Nathan; Razon, Hila

    2018-09-01

    Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Protection mediated by chemokine CXCL10 in BALB/c mice infected by Leishmania infantum

    Science.gov (United States)

    Figueiredo, Webertty Mayk Eufrásio; Viana, Sayonara de Melo; Alves, Dorotheia Teixeira; Guerra, Priscila Valera; Coêlho, Zirlane Castelo Branco; Barbosa, Helene Santos; Teixeira, Maria Jania

    2017-01-01

    BACKGROUND Visceral leishmaniasis (VL) caused by Leishmania infantum is characterised by the loss of the ability of the host to generate an effective immune response. Chemokines have a direct involvement in the pathogenesis of leishmaniasis, causing a rapid change in the expression of these molecules during infection by Leishmania. OBJECTIVES Herein, it was investigated the role of CXCL10 in controlling infection by L. infantum. METHODS RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10 production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice were infected and treated or not with CXCL10 (5 μg/kg) at one, three and seven days of infection. Parasite load, IFN-g, IL-4, TGF-β and IL-10 were evaluated one, seven and 23 days post treatment. FINDINGS In vitro, CXCL10 reduced parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four weeks after infection, representing a higher decrease in the number of parasites in these organs, also induced IFN-γ at day 23 after treatment, correlating with the decrease in parasite load, and reduced IL-10 and TGF-β. MAIN CONCLUSIONS This study suggests a partial protective role of CXCL10 against L. infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10 and TGF-β. These data may provide information for the development of new approaches for future therapeutic interventions for VL. PMID:28767981

  12. 27-Oxygenated cholesterol induces expression of CXCL8 in macrophages via NF-κB and CD88

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    Kim, Sun-Mi, E-mail: lala1647@hanmail.net [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Chung Won, E-mail: vasculardoctorlee@gmail.com [Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Pusan 602-739 (Korea, Republic of); Kim, Bo-Young, E-mail: kimboyoung@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Jung, Young-Suk, E-mail: youngjung@pusan.ac.kr [College of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Eo, Seong-Kug, E-mail: vetvirus@chonbuk.ac.kr [College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan, Jeonbuk 570-752 (Korea, Republic of); Park, Young Chul, E-mail: ycpark@pusan.ac.kr [Department of Microbiology & Immunology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Kim, Koanhoi, E-mail: koanhoi@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of)

    2015-08-07

    We attempted to determine the effects of a milieu rich in cholesterol molecules on expression of chemokine CXCL8. A high-cholesterol diet led to an increased transcription of the IL-8 gene in the arteries and elevated levels of CXCL8 in sera of ApoE{sup −/−} mice, compared with those of wild-type C57BL/6 mice. Treatment of THP-1 monocyte/macrophage cells with 27-hydroxycholesterol (27OHChol) resulted in transcription of the IL-8 gene and increased secretion of its corresponding gene product whereas cholesterol did not induce expression of CXCL8 in THP-1 cells. 27OHChol-induced transcription of the IL-8 gene was blocked by cycloheximide, but not by polymyxin B. Treatment of THP-1 cells with 27OHChol caused translocation of p65 NF-κB subunit into the nucleus and up-regulation of CD88. Inhibition of NF-κB and CD88 using SN50 and W-54011, respectively, resulted in reduced transcription of the IL-8 gene and attenuated secretion of CXCL8 induced by 27OHChol. We propose that oxidatively modified cholesterol like 27OHChol, rather than cholesterol, is responsible for sustained expression of CXCL8 in monocytes/macrophages in atherosclerotic arteries. - Highlights: • Consumption of a high-cholesterol diet leads to increased CXCL8 expression in ApoE{sup −/−} mice. • 27OHChol, but not cholesterol, up-regulates expression of CXCL8 in macrophages. • 27OHChol enhances nuclear translocation of NF-κB and expression of CD88 in macrophages. • Inhibition of NF-κB or CD88 results in decreased CXCL8 expression induced by 27OHChol. • 27OHChol up-regulates CXCL8 expression via NF-κB and CD88 in macrophages.

  13. CXCL10/IP10 is a novel potential in vitro marker of TB infection

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    Ilaria Sauzullo

    2009-06-01

    Full Text Available Introduction IFN-γ is a pivotal cytokine in the immune response to Myc. tuberculosis, infact this is the key cytokine produced in response to antigens specific following tuberculosis exposure causing either active or latent tuberculosis (TB and this observation forms the basis of interferon gamma release assay (IGRA, but there are alternative or additional cytokines and chemokines that could be used to improve detection of Myc. tuberculosis infection.The aim of this study was to evaluate the diagnostic utility of chemokine CXCL10/IP-10 as biomarker of active TB and to compare the results with classical QuantiFERON-Gold assay . Methods CXCL10/IP-10 and IFN-γ responses to stimulation with ESAT-6 and CFP-10 were evaluated in 21 patients with active tuberculosis and in 6 healthy unexposed subjects with no history of TB or TB contact were used as controls healthy controls. QuantiFERON-TB Gold (QFT-G, Cellestis was used for the measurement of IFN-γ levels; CXCL10/IP-10 was detected by ELISA (R&D Systems . Results Of the 21 TB patients included, 11 had a QFT-G positive and 10 had negative QFT-G results.All QFT-G positive patients had increased levels of CXCL10/IP-10 (median, pg/ml in both ESAT-6 and CFP-10 stimulated samples patients compared to healthy controls (1807 and 1111 vs 251 and 188 of controls, respectively (p<0.001 for both. The patients with active TB and QFT-G negative exhibited higher concentrations of CXCL10/IP-10 following antigen stimulation (837 pg/ml for ESAT-6;1674 pg/ml for CFP-10 (p<0.001. Conclusion Our study showed that in all patients with active TB, the CXCL10/IP-10 is expressed in higher amounts than IFN-γ following Myc. tuberculosis antigen-specific stimulation, and CXCL10/IP-10 appeared to be even more sensitive than QuantiFERON TB-Gold in TB patients with negative IFN-γ response. The measurement of chemokine CXCL10/IP-10, although not specific for tuberculosis, may have potential as an alternative or additional marker

  14. Targeting the chemokine receptor CXCR3 and its ligand CXCL10 in the central nervous system

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke

    2004-01-01

    focuses on the present data regarding CXCL10 (previously known as IP-10) and CXRC3 in multiple sclerosis, since consistent data has suggested that this chemokine/chemokine receptor pair has a pivotal role in leukocyte recruitment into the central nervous system (CNS) in multiple sclerosis....

  15. Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson’s Disease

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    Natália Pessoa Rocha

    2014-01-01

    Full Text Available Cognitive impairment and depressive symptoms are of great interest in Parkinson’s disease (PD, since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD.

  16. Expression and migratory analysis of 5 human uveal melanoma cell lines for CXCL12, CXCL8, CXCL1, and HGF

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    Di Cesare Sebastian

    2007-01-01

    Full Text Available Abstract Background The aim of this study was to characterize the presence and roles of CXCL12, CXCL8, CXCL1, and HGF in five human uveal melanoma cell lines, using different methods, in order to ascertain their significance in this disease. Methods Five human uveal melanoma cell lines (92.1, SP6.5, MKT-BR, OCM-1, and UW-1 of known proliferative, invasive, and metastatic potential were used in this experiment. A migration assay was used in order to assess the responsiveness of each cell line towards the four chosen chemotactic factors. Immunohistochemistry was then performed for all five cell lines (cytospins using antibodies directed toward CXCL1, CXCL8 and their receptors CXCR2 and CXCR1 respectively. Quantitative real-time PCR was then performed on all five cell lines in order to establish the presence of these four chemotactic factors. Results All five human uveal melanoma cell lines migrated towards the four chosen chemotactic factors at a level greater than that of the negative control. Chemokines CXCL1 and CXCL8 resulted in the greatest number of migrating cells in all five of our cell lines. Immunohistochemistry confirmed the expression of CXCL1, CXCL8, and their receptors CXCR2 and CXCR1 in all five of the cell lines. Quantitative real-time PCR results established expression of CXCL8, CXCL1, and HGF in all 5 cell lines tested. CXCL1 and CXCL8 are highly expressed in SP6.5 and UW-1. None of the five cell lines expressed any detectable levels of CXCL12. Conclusion The migratory ability of the 5 human uveal melanoma cell lines was positively influenced by the four chemotactic factors tested, namely CXCL12, CXCL8, CXCL1, and HGF. Self-expression of chemotactic factors CXCL8, CXCL1, and HGF may indicate an autocrine system, which perhaps contributes to the cells' metastatic ability in vivo.

  17. The severity of experimental autoimmune cystitis can be ameliorated by anti-CXCL10 Ab treatment.

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    Udai P Singh

    Full Text Available Interstitial cystitis (IC, more recently called painful bladder syndrome (PBS is a complex disease associated with chronic bladder inflammation that primarily affects women. Its symptoms include frequent urinary urgency accompanied by discomfort or pain in the bladder and lower abdomen. In the United States, eight million people, mostly women, have IC/PBS. New evidence that autoimmune mechanisms are important in the pathogenesis of IC/PBS triggered interest.SWXJ mice immunized with a homogenate of similar mice's urinary bladders develop an autoimmune phenotype comparable to clinical IC with functional and histological alterations confined to the urinary bladder. Using the murine model of experimental autoimmune cystitis (EAC, we found that serum levels of CXCR3 ligand and local T helper type 1 (Th1 cytokine are elevated. Also, IFN-γ-inducible protein10 (CXCL10 blockade attenuated overall cystitis severity scores; reversed the development of IC; decreased local production of CXCR3 and its ligands, IFN-γ, and tumor necrosis factor-α (TNF-α; and lowered systemic levels of CXCR3 ligands. Urinary bladder CD4(+ T cells, mast cells, and neutrophils infiltrates were reduced following anti-CXCL10 antibody (Ab treatment of mice. Anti-CXCL10 Ab treatment also reversed the upregulated level of CXCR3 ligand mRNA at urinary bladder sites. The decreased number and percentage of systemic CD4(+ T cells in EAC mice returned to normal after anti-CXCL10 Ab treatment.Taken together, our findings provide important new information about the mechanisms underlying EAC pathogenesis, which has symptoms similar to those of IC/PBS. CXCL10 has the potential for use in developing new therapy for IC/PBS.

  18. submitter CXCL$_{10}$ Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study

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    Altara, Raffaele; Hessel, Marleen H; Gu, Yumei; van Vark, Laura C; Akkerhuis, K Martijn; Staessen, Jan A; Struijker-Boudier, Harry A J; Booz, George W; Blankesteijn, W Matthijs

    2016-01-01

    Chemokines are involved in the remodeling of the heart; however, their significance as biomarkers in heart failure is unknown. We observed that circulating CXCR3 receptor chemokines CXCL9 and CXCL10 in a rat model of heart failure were increased 1 week after myocardial infarction. CXCL10 was also increased in both remote and infarcted regions of the heart and remained elevated at 16 weeks; CXCL9 was elevated in the remote area at 1 week. In humans, hierarchical clustering and principal component analysis revealed that circulating CXCL10, MIP-1α, and CD40 ligand were the best indicators for differentiating healthy and heart failure subjects. Serum CXCL10 levels were increased in patients with symptomatic heart failure as indexed by NYHA classification II through IV. The presence of CXCL10, MIP-1α, and CD40 ligand appears to be dominant in patients with advanced heart failure. These findings identify a distinct profile of inflammatory mediators in heart failure patients

  19. Antigen-specific secretion of IFNγ and CXCL10 in whole blood assay detects Mycobacterium leprae infection but does not discriminate asymptomatic infection from symptomatic leprosy.

    Science.gov (United States)

    Hungria, Emerith Mayra; Freitas, Aline Araújo; Pontes, Maria Araci Andrade; Gonçalves, Heitor Sá; Sousa, Ana Lúcia Osório Maroccolo; Costa, Maurício Barcelos; Castilho, Mirian Lane Oliveira Rodrigues; Duthie, Malcolm S; Stefani, Mariane Martins Araújo

    2017-04-01

    To advance toward a whole blood assay (WBA)-based test capable of facilitating the diagnosis of paucibacillary (PB) leprosy, we evaluated a prototype in-tube WBA using combinations of Mycobacterium leprae antigens. Blood was collected from newly diagnosed untreated PB (n=38), multibacillary (MB) (n=30), healthy household contacts (HHC) of MB (n=27), and endemic controls (n=61) residing in Goiânia and Fortaleza, Brazil. Blood was incubated with M. leprae cell sonicate, recombinant proteins (46f+LID-1; ML0276+LID-1), or controls (phosphate-buffered saline, phytohemagglutinin, M. tuberculosis purified protein derivative). Antigen-specific IFNγ production was observed in 71-84% and 55% of PB and HHC, respectively. Antigen-specific CXCL10 levels were similarly assessed to determine if, unlike IFNγ, CXCL10 could differentiate PB from HHC with repeated exposure/asymptomatic M. leprae infection. The CXCL10 levels induced in response to M. leprae antigens could not, however, differentiate PB from HHC. Despite these limitations, the WBAs reported here still represent important tools for assessing M. leprae infection rates and evaluating the impact of control measures. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

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    Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

    2014-01-01

    Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture. PMID:24732949

  1. Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage

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    Felipe Gomes Naveca

    2018-05-01

    Full Text Available BACKGROUND Infection with Zika virus (ZIKV manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.

  2. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

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    Seidel Petra

    2012-10-01

    Full Text Available Abstract Background Activated mast cells are present within airway smooth muscle (ASM bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide, long-acting β2-agonists (salmeterol, formoterol and thiazolidinediones (ciglitazone, rosiglitazone on CXCL10 production by ASM cells (ASMC from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix. The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  3. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies.

    Science.gov (United States)

    Seidel, Petra; Alkhouri, Hatem; Lalor, Daniel J; Burgess, Janette K; Armour, Carol L; Hughes, J Margaret

    2012-10-04

    Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher's post-hoc test. Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1 nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  4. CXCL10/CXCR3 Signaling in Glia Cells Differentially Affects NMDA-Induced Cell Death in CA and DG Neurons of the Mouse Hippocampus

    NARCIS (Netherlands)

    van Weering, Hilmar R. J.; Boddeke, Hendrikus W. G. M.; Vinet, Jonathan; Brouwer, Nieske; de Haas, Alexander H.; van Rooijen, Nico; Thomsen, Allan R.; Biber, Knut P. H.

    2011-01-01

    The chemokine CXCL10 and its receptor CXCR3 are implicated in various CNS pathologies since interference with CXCL10/CXCR3 signaling alters the onset and progression in various CNS disease models. However, the mechanism and cell-types involved in CXCL10/CXCR3 signaling under pathological conditions

  5. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

    OpenAIRE

    Seidel Petra; Alkhouri Hatem; Lalor Daniel J; Burgess Janette K; Armour Carol L; Hughes J

    2012-01-01

    Abstract Background Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived ce...

  6. Developmental changes in circulating IL-8/CXCL8 isoforms in neonates.

    Science.gov (United States)

    Maheshwari, Akhil; Voitenok, Nikolai N; Akalovich, Svetlana; Shaik, Sadiq S; Randolph, David A; Sims, Brian; Patel, Rakesh P; Killingsworth, Cheryl R; Fallon, Michael B; Ohls, Robin K

    2009-04-01

    Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived [ala-IL-8](77) isoform and another, more potent [ser-IL-8](72) secreted by most other cells; [ala-IL-8](77) can be converted into [ser-IL-8](72) by proteolytic removal of an N-terminal pentapeptide from [ala-IL-8](77). In this study, we show [ala-IL-8](77) is the predominant circulating isoform of IL-8 in premature neonates but not in term neonates/adults, who have [ser-IL-8](72) as the major isoform. This isoform switch from the less potent [ala-IL-8](77) to [ser-IL-8](72) correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8](72) as the major isoform is likely due to increased plasma [ala-IL-8](77)-convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

  7. Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.

    Science.gov (United States)

    Suzukawa, Maho; Matsumoto, Hisako; Ohshima, Nobuharu; Tashimo, Hiroyuki; Asari, Isao; Tajiri, Tomoko; Niimi, Akio; Nagase, Hiroyuki; Matsui, Hirotoshi; Kobayashi, Nobuyuki; Shoji, Shunsuke; Ohta, Ken

    2018-01-01

    Omalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients. This study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab. Thirty-one patients with severe, persistent asthma were enrolled in this study and administered omalizumab for at least 1 year. Response to omalizumab was assessed based on the physician's global evaluation of treatment effectiveness (GETE) at 48 weeks of treatment. Blood samples were collected at baseline and 16 and 32 weeks after starting omalizumab and measured for 30 cytokines by Luminex 200 and ELISA. Exhaled nitric oxide (FeNO) levels, peripheral blood eosinophil counts, pre-bronchodilator pulmonary functions and Asthma Quality of Life Questionnaire scores were determined at baseline and 16, 32 and 48 weeks after starting omalizumab. The numbers of clinically significant asthma exacerbations in the previous year and during 48 weeks of treatment with omalizumab were assessed. GETE assessment showed 19 responders (61.3%) and 12 non-responders (38.7%). Responders showed significantly higher levels of CXCL10 and IL-12 at baseline compared to non-responders (CXCL10: responders, 1530.0 ± 315.2 pg/ml vs. non-responders, 1066.0 ± 396.8 pg/ml, P = 0.001; IL-12: responders, 60.2 ± 39.2 pg/ml vs. non-responders, 32.2 ± 26.3 pg/ml, P = 0.04). ROC curves to distinguish responders from non-responders using the baseline serum CXCL10 level showed a good AUC of 0.83. At 32 weeks of omalizumab therapy, serum CXCL10 tended to be increased (1350 ± 412.3 pg/ml at baseline vs. 1529 ± 637.6 pg/ml at 32 weeks, P = 0.16) and serum IL-12 tended to be decreased (49.4 ± 37.0 pg/ml at baseline vs. 43.9 ± 30.9 pg/ml at 32 weeks, P = 0.05). On the other hand, serum IL-5 and PDGF were significantly decreased (IL-5: 54.2 ± 13.8 pg/ml at baseline vs. 49

  8. Interplay between EZH2 and G9a Regulates CXCL10 Gene Repression in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Coward, William R; Brand, Oliver J; Pasini, Alice; Jenkins, Gisli; Knox, Alan J; Pang, Linhua

    2018-04-01

    Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodeling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 repression. In this study, we explored the role of H3K27 methylation and the interplay between the two histone lysine methyltransferases enhancer of zest homolog 2 (EZH2) and G9a in CXCL10 repression in IPF. By applying chromatin immunoprecipitation, Re-ChIP, and proximity ligation assays, we demonstrated that, like G9a-mediated H3K9 methylation, EZH2-mediated histone H3 lysine 27 trimethylation (H3K27me3) was significantly enriched at the CXCL10 promoter in fibroblasts from IPF lungs (F-IPF) compared with fibroblasts from nonfibrotic lungs, and we also found that EZH2 and G9a physically interacted with each other. EZH2 knockdown reduced not only EZH2 and H3K27me3 but also G9a and H3K9me3, and G9a knockdown reduced not only G9 and H3K9me3 but also EZH2 and H3K27me3. Depletion and inhibition of EZH2 and G9a also reversed histone deacetylation and restored CXCL10 expression in F-IPF. Furthermore, treatment of fibroblasts from nonfibrotic lungs with the profibrotic cytokine transforming growth factor-β1 increased EZH2, G9a, H3K27me3, H3K9me3, and histone deacetylation at the CXCL10 promoter, similar to that observed in F-IPF, which was correlated with CXCL10 repression and was prevented by EZH2 and G9a knockdown. These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other antifibrotic genes in IPF.

  9. Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, T.L.; Sellebjerg, F; Jensen, C.V.

    2001-01-01

    leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9...... patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials....... Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls...

  10. Assessment of CCL2 and CXCL8 chemokines in serum, bronchoalveolar lavage fluid and lung tissue samples from dogs affected with canine idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Roels, Elodie; Krafft, Emilie; Farnir, Frederic; Holopainen, Saila; Laurila, Henna P; Rajamäki, Minna M; Day, Michael J; Antoine, Nadine; Pirottin, Dimitri; Clercx, Cecile

    2015-10-01

    Canine idiopathic pulmonary fibrosis (CIPF) is a progressive disease of the lung parenchyma that is more prevalent in dogs of the West Highland white terrier (WHWT) breed. Since the chemokines (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 8 (CXCL8) have been implicated in pulmonary fibrosis in humans, the aim of the present study was to investigate whether these same chemokines are involved in the pathogenesis of CIPF. CCL2 and CXCL8 concentrations were measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) from healthy dogs and WHWTs affected with CIPF. Expression of the genes encoding CCL2 and CXCL8 and their respective receptors, namely (C-C motif) receptor 2 (CCR2) and (C-X-C motif) receptor 2 (CXCR2), was compared in unaffected lung tissue and biopsies from dogs affected with CIPF by quantitative PCR and localisation of CCL2 and CXCL8 proteins were determined by immunohistochemistry. Significantly greater CCL2 and CXCL8 concentrations were found in the BALF from WHWTs affected with CIPF, compared with healthy dogs. Significantly greater serum concentrations of CCL2, but not CXCL8, were found in CIPF-affected dogs compared with healthy WHWTs. No differences in relative gene expression for CCL2, CXCL8, CCR2 or CXCR2 were observed when comparing lung biopsies from control dogs and those affected with CIPF. In affected lung tissues, immunolabelling for CCL2 and CXCL8 was observed in bronchial airway epithelial cells in dogs affected with CIPF. The study findings suggest that both CCL2 and CXCL8 are involved in the pathogenesis of CIPF. Further studies are required to determine whether these chemokines might have a clinical use as biomarkers of fibrosis or as targets for therapeutic intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Vitamin D Receptor Agonists Target CXCL10: New Therapeutic Tools for Resolution of Inflammation

    Directory of Open Access Journals (Sweden)

    Sabino Scolletta

    2013-01-01

    Full Text Available Understanding the many biological extraskeletal actions of vitamin D has increased in the past decades. Indeed, vitamin D and analogue molecules, besides the classical actions on bone metabolism, exert several beneficial effects on metabolic homeostasis, heart-cardiovascular, brain, and muscle physiological functions, throughout the interaction with the specific vitamin D receptor (VDR. In particular, VDR agonists powerfully control innate and adaptive immune system with favorable effects on human health. VDR ligands act as immunomodulators that are potent enough to retain anti-inflammatory effects, even though the mechanism underlying those effects is not yet fully elucidated. VDR agonists exert a significant suppression of inflammatory processes switching the immune response from T helper 1 (Th1 to T helper 2 (Th2 dominance and counteracting the self-enhancing inflammatory loop between immune and resident cells, especially by cytokine release impairment. Those molecules are able, indeed, to reduce the release of the interferon (IFN-induced 10 kDa protein IP-10/CXCL10, a powerful chemokine driving Th1-mediated inflammation. Based on their features, VDR ligands show the potentiality to be included in immunosuppressive regimens, aimed to control auto- and alloimmune Th1-driven overreactivity, occurring, for example, in autoimmune disease or graft rejection.

  12. Elevated Plasma Soluble CD14 and Skewed CD16+ Monocyte Distribution Persist despite Normalisation of Soluble CD163 and CXCL10 by Effective HIV Therapy: A Changing Paradigm for Routine HIV Laboratory Monitoring?

    Science.gov (United States)

    Castley, Alison; Berry, Cassandra; French, Martyn; Fernandez, Sonia; Krueger, Romano; Nolan, David

    2014-01-01

    Objective We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice. Design Cross-sectional evaluation of concurrent plasma and whole blood samples. Methods A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14), soluble CD163 (sCD163) and CXCL10 were measured by ELISA. Results HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001). Conclusions Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune activation in HIV

  13. Elevated plasma soluble CD14 and skewed CD16+ monocyte distribution persist despite normalisation of soluble CD163 and CXCL10 by effective HIV therapy: a changing paradigm for routine HIV laboratory monitoring?

    Directory of Open Access Journals (Sweden)

    Alison Castley

    Full Text Available OBJECTIVE: We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice. DESIGN: Cross-sectional evaluation of concurrent plasma and whole blood samples. METHODS: A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14, soluble CD163 (sCD163 and CXCL10 were measured by ELISA. RESULTS: HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001. CONCLUSIONS: Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune

  14. Late production of CXCL8 in ruminant oro-nasal turbinate cells in response to Chlamydia abortus infection.

    Science.gov (United States)

    Doull, L; Wattegedera, S R; Longbottom, D; Mwangi, D; Nath, M; Glass, E J; Entrican, G

    2015-11-15

    Chlamydia abortus is an obligate intracellular bacterium that is an important cause of ovine abortion worldwide. There are reports of abortions in cattle, but these are very rare compared to the reported incidence in sheep. The bacterium is transmitted oro-nasally and can establish a sub-clinical infection until pregnancy, when it can invade the placenta and induce an inflammatory cascade leading to placentitis and abortion. Early host-pathogen interactions could explain differential pathogenesis and subsequent disease outcome in ruminant species. In this study, we assessed the ability of sheep and cattle oro-nasal turbinate cells to sense and respond to C. abortus infection. The cells expressed toll like receptor (TLR) 2, TLR4, nucleotide oligomerization domain (NOD) 1 and NOD-like receptor pyrin domain containing 3 (NLRP3) mRNA. In response to C. abortus infection, both ovine and bovine turbinate cells produce CXCL8 mRNA and protein late in the bacterial developmental cycle, but do not produce IL-1β or TNF-α. The UV-inactivated bacteria did not elicit a CXCL8 response, suggesting that intracellular multiplication of the bacteria is important for activating the signalling pathways. The production of innate immune cytokines from cattle and sheep turbinate cells in response to C. abortus infection was found to be largely similar. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. High Levels of CXCL10 Are Produced by Intestinal Epithelial Cells in AIDS Patients with Active Cryptosporidiosis but Not after Reconstitution of Immunity▿

    Science.gov (United States)

    Wang, Heuy-Ching; Dann, Sara M.; Okhuysen, Pablo C.; Lewis, Dorothy E.; Chappell, Cynthia L.; Adler, Douglas G.; White, A. Clinton

    2007-01-01

    Chemokines play key roles in attracting immune cells to sites of infections. However, few data on chemokine expression in the gut during human infections are available. We examined expression of chemokines in intestinal tissues of AIDS patients during active Cryptosporidium infection and during resolution of such an infection. The chemokines and cytokines in cell lysates from jejunal biopsy tissues were assayed by a 22-multiplex bead immunoassay. CXCL10 (IP-10) and its receptor, CXCR3, in sections were studied by immunohistochemistry. In biopsies from AIDS patients with active cryptosporidiosis, four chemokines (CXCL10, CCL11 [eotaxin], CCL5 [RANTES], and CCL2 [monocyte chemoattractant protein 1]) and three cytokines (interleukin-1α [IL-1α], IL-10, and granulocyte colony-stimulating factor) were detected. The level of CXCL10 was significantly increased in AIDS patients with cryptosporidiosis compared to the level in AIDS patients without cryptosporidiosis or in normal volunteers (median in AIDS patients with cryptosporidiosis, 508 pg/mg protein, compared to 111 pg/mg and 72 pg/mg protein in AIDS patients without cryptosporidiosis and in normal volunteers, respectively [P < 0.05 and P < 0.005, respectively, as determined by a Mann-Whitney test]). The level of CXCL10 correlated with the parasite burden (as measured by the number of Cryptosporidium oocysts in the stools) and also with the IL-1α concentration (Pearson correlation values, 0.961 [P < 0.01] and 0.737 [P < 0.05]). As determined by immunohistochemistry, CXCL10 localized to epithelial cells at the site of infection. Following effective antiparasite and antiretroviral therapy, Cryptosporidium infections resolved, and the levels of CXCL10 decreased to normal levels. We hypothesized that CXCL10 plays an important role in the resolution of cryptosporidiosis by attracting immune effector cells to the site of infection. By contrast, in AIDS patients lacking effector cells, CXCL10 may contribute to the

  16. Vectorial secretion of interleukin-8 (IL-8 or CXCL8) mediates homeostatic effects on the intestinal epithelium via apically located CXCR1

    NARCIS (Netherlands)

    Baarlen, van Peter; Rossi, Oriana; Wells, Jerry

    2014-01-01

    CXCL8 is produced by many cell types including epithelial, endothelial, fibroblasts and macrophages in response to TLR recognition of microbe-associated molecular patterns (MAMPs) or inflammatory cytokines and recruits phagocytes from the vasculature to sites of infection via interaction with its

  17. Skeletal muscle cell contraction reduces a novel myokine, chemokine (C-X-C motif) ligand 10 (CXCL10): potential roles in exercise-regulated angiogenesis.

    Science.gov (United States)

    Ishiuchi, Yuri; Sato, Hitoshi; Tsujimura, Kazuki; Kawaguchi, Hideo; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi; Nedachi, Taku

    2018-01-01

    Accumulating evidence indicates that skeletal muscle secrets proteins referred to as myokines and that exercise contributes to their regulation. In this study, we propose that chemokine (C-X-C motif) ligand 10 (CXCL10) functions as a novel myokine. Initially, we stimulated differentiated C2C12 myotubes with or without electrical pulse stimulation (EPS) to identify novel myokines. Cytokine array analysis revealed that CXCL10 secretion was significantly reduced by EPS, which was further confirmed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction analysis. Treadmill experiments in mice identified significant reduction of Cxcl10 gene expression in the soleus muscle. Additionally, contraction-dependent p38 MAPK activation appeared to be involved in this reduction. Furthermore, C2C12 conditioned medium obtained after applying EPS could induce survival of MSS31, a vascular endothelial cell model, which was partially attenuated by the addition of recombinant CXCL10. Overall, our findings suggest CXCL10 as a novel exercise-reducible myokine, to control endothelial cell viability.

  18. Heme-Mediated Induction of CXCL10 and Depletion of CD34+ Progenitor Cells Is Toll-Like Receptor 4 Dependent.

    Directory of Open Access Journals (Sweden)

    Carmen M Dickinson-Copeland

    Full Text Available Plasmodium falciparum infection can cause microvascular dysfunction, cerebral encephalopathy and death if untreated. We have previously shown that high concentrations of free heme, and C-X-C motif chemokine 10 (CXCL10 in sera of malaria patients induce apoptosis in microvascular endothelial and neuronal cells contributing to vascular dysfunction, blood-brain barrier (BBB damage and mortality. Endothelial progenitor cells (EPC are microvascular endothelial cell precursors partly responsible for repair and regeneration of damaged BBB endothelium. Studies have shown that EPC's are depleted in severe malaria patients, but the mechanisms mediating this phenomenon are unknown. Toll-like receptors recognize a wide variety of pathogen-associated molecular patterns generated by pathogens such as bacteria and parasites. We tested the hypothesis that EPC depletion during malaria pathogenesis is a function of heme-induced apoptosis mediated by CXCL10 induction and toll-like receptor (TLR activation. Heme and CXCL10 concentrations in plasma obtained from malaria patients were elevated compared with non-malaria subjects. EPC numbers were significantly decreased in malaria patients (P < 0.02 and TLR4 expression was significantly elevated in vivo. These findings were confirmed in EPC precursors in vitro; where it was determined that heme-induced apoptosis and CXCL10 expression was TLR4-mediated. We conclude that increased serum heme mediates depletion of EPC during malaria pathogenesis.

  19. CXCL10/CXCR3 signaling in glia cells differentially affects NMDA-induced cell death in CA and DG neurons of the mouse hippocampus

    DEFF Research Database (Denmark)

    van Weering, Hilmar R J; Boddeke, Hendrikus W G M; Vinet, Jonathan

    2011-01-01

    are far from understood. Here, we investigated the potential role for CXCL10/CXCR3 signaling in neuronal cell death and glia activation in response to N-methyl-D-aspartic acid (NMDA)-induced excitotoxicity in mouse organotypic hippocampal slice cultures (OHSCs). Our findings demonstrate that astrocytes...

  20. Relationship between single nucleotide polymorphism of chemokine CXCL10 G-210A and the chronicity and severity of HBV infection

    Directory of Open Access Journals (Sweden)

    Li-ming LIU

    2011-01-01

    Full Text Available Objective To investigate the single nucleotide polymorphism(SNP in the promoter of chemokine CXCL10 G-201A,and explore the relationship between the SNP and the chronicity and severity of hepatitis B virus(HBV infection.Methods Blood samples were collected from 792 patients with HBV infection,including 200 with acute hepatitis B(AHB,200 with mild/moderate chronic hepatitis B(CHB-M,192 with severe chronic hepatitis B(CHB-S and 200 with acute liver failure of chronic hepatitis(ACLF,and 300 healthy people were enrolled as normal control(NC.DNA were extracted and subjected to PCR amplification of fragment containing C-1596 site that links with G-201 variation,followed by restriction fragment length polymerase(RFLP analysis.Simultaneously,400 samples were randomly extracted from various groups for direct sequencing of G-201 variation.The consistency of SNP typing results of the two methods was analyzed.Results Variation rates of G-201A were 17.77% for AHB group,25.26% for CHB-M group,26.59% for CHB-S group,21.28% for ACLF group,and 13.82% for NC group.The overall P value obtained from the general χ2 test among the 5 groups was 0.0037.The correlation test(P=0.0015 demonstrated that the variation rate was related to different disease status,and the linear trend test(P=0.0029,Z=-2.9748 indicated an increasing trend of variation rate with the disease progression.Paired comparison showed that the differences in variation rate between CHB-M and NC(P=0.0024,CHB-S and NC(P=0.0007,ACLF and NC(P=0.0428,as well as CHB-S and CHB(P=0.0488 were statistically significant.Direct PCR sequencing showed 98.68% identity with the results from PCR-RFLP.Kappa test(U=58.425,P < 0.05 indicated that the consistency of the two assays met the statistical requirements.Conclusion The G-201A variation in CXCL10 promoter is related to chronicity of HBV infection,and the relations between the variation and the severity of HBV infection remains to be further clarified.

  1. Expression of chemokine CXCL10 in dendritic-cell-like S100β-positive cells in rat anterior pituitary gland.

    Science.gov (United States)

    Horiguchi, Kotaro; Fujiwara, Ken; Higuchi, Masashi; Yoshida, Saishu; Tsukada, Takehiro; Ueharu, Hiroki; Chen, Mo; Hasegawa, Rumi; Takigami, Shu; Ohsako, Shunji; Yashiro, Takashi; Kato, Takako; Kato, Yukio

    2014-09-01

    Chemokines are mostly small secreted polypeptides whose signals are mediated by seven trans-membrane G-protein-coupled receptors. Their functions include the control of leukocytes and the intercellular mediation of cell migration, proliferation, and adhesion in several tissues. We have previously revealed that the CXC chemokine ligand 12 (CXCL12) and its receptor 4 (CXCR4) are expressed in the anterior pituitary gland, and that the CXCL12/CXCR4 axis evokes the migration and interconnection of S100β-protein-positive cells (S100β-positive cells), which do not produce classical anterior pituitary hormones. However, little is known of the cells producing the other CXCLs and CXCRs or of their characteristics in the anterior pituitary. We therefore examined whether CXCLs and CXCRs occurred in the rat anterior pituitary lobe. We used reverse transcription plus the polymerase chain reaction to analyze the expression of Cxcl and Cxcr and identified the cells that expressed Cxcl by in situ hybridization. Transcripts of Cxcl10 and its receptor (Cxcr3 and toll-like receptor 4, Tlr4) were clearly detected: cells expressing Cxcl10 and Tlr4 were identified amongst S100β-positive cells and those expressing Cxcr3 amongst adrenocorticotropic hormone (ACTH)-producing cells. We also investigated Cxcl10 expression in subpopulations of S100β-positive cells. We separated cultured S100β-positive cells into the round-type (dendritic-cell-like) and process-type (astrocyte- or epithelial-cell-like) by their adherent activity to laminin, a component of the extracellular matrix; CXCL10 was expressed only in round-type S100β-positive cells. Thus, CXCL10 produced by a subpopulation of S100β-positive cells probably exerts an autocrine/paracrine effect on S100β-positive cells and ACTH-producing cells in the anterior lobe.

  2. CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2013-12-01

    Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

  3. Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation.

    Science.gov (United States)

    Yoshimatsu, Gumpei; Kunnathodi, Faisal; Saravanan, Prathab Balaji; Shahbazov, Rauf; Chang, Charles; Darden, Carly M; Zurawski, Sandra; Boyuk, Gulbahar; Kanak, Mazhar A; Levy, Marlon F; Naziruddin, Bashoo; Lawrence, Michael C

    2017-11-01

    Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these "isletokines" in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours of infusion. The proinflammatory cytokine interferon-γ-induced protein 10 (IP-10/CXCL10) was among the highest released, and high levels correlated with poor islet transplant outcomes. Transgenic mouse studies confirmed that donor islet-specific expression of IP-10 contributed to islet inflammation and loss of β-cell function in islet grafts. The effects of islet-derived IP-10 could be blocked by treatment of donor islets and recipient mice with anti-IP-10 neutralizing monoclonal antibody. In vitro studies showed induction of the IP-10 gene was mediated by calcineurin-dependent NFAT signaling in pancreatic β-cells in response to oxidative or inflammatory stress. Sustained association of NFAT and p300 histone acetyltransferase with the IP-10 gene required p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) activity, which differentially regulated IP-10 expression and subsequent protein release. Overall, these findings elucidate an NFAT-MAPK signaling paradigm for induction of isletokine expression in β-cells and reveal IP-10 as a primary therapeutic target to prevent β-cell-induced inflammatory loss of graft function after islet cell transplantation. © 2017 by the American Diabetes Association.

  4. Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

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    Alison Castley

    Full Text Available We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p0.2. Associations between higher sCD163 and protease inhibitor therapy (p = 0.05 and lower sCD14 with integrase inhibitor therapy (p = 0.02 were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI, with a favourable influence of Framingham score <10% (p = 0.04. Soluble CD14 levels were higher among smokers (p = 0.002, with no effect of other CVD risk factors, except age (p = 0.045. Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation.

  5. Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

    Science.gov (United States)

    Castley, Alison; Williams, Leah; James, Ian; Guelfi, George; Berry, Cassandra; Nolan, David

    2016-01-01

    We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation. PMID:27355513

  6. CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; de Lemos, Carina; Moos, Torben

    2006-01-01

    /ligand pair is thought to play a central role in regulating T cell-mediated inflammation in this organ site. In this report, we investigated the role of CXCL10 in regulating CD8(+) T cell-mediated inflammation in the virus-infected brain. This was done through analysis of CXCL10-deficient mice infected...... indicate a central role for CXCL10 in regulating the accumulation of effector T cells at sites of CNS inflammation, with no apparent compensatory effect of other CXCR3 ligands....

  7. Higher expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 chemokines in the skin associated with parasite density in canine visceral leishmaniasis.

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    Daniel Menezes-Souza

    Full Text Available BACKGROUND: The immune response in the skin of dogs infected with Leishmania infantum is poorly understood, and limited studies have described the immunopathological profile with regard to distinct levels of tissue parasitism and the clinical progression of canine visceral leishmaniasis (CVL. METHODOLOGY/PRINCIPAL FINDINGS: A detailed analysis of inflammatory cells (neutrophils, eosinophils, mast cells, lymphocytes, and macrophages as well as the expression of chemokines (CCL2, CCL4, CCL5, CCL13, CCL17, CCL21, CCL24, and CXCL8 was carried out in dermis skin samples from 35 dogs that were naturally infected with L. infantum. The analysis was based on real-time polymerase chain reaction (PCR in the context of skin parasitism and the clinical status of CVL. We demonstrated increased inflammatory infiltrate composed mainly of mononuclear cells in the skin of animals with severe forms of CVL and high parasite density. Analysis of the inflammatory cell profile of the skin revealed an increase in the number of macrophages and reductions in lymphocytes, eosinophils, and mast cells that correlated with clinical progression of the disease. Additionally, enhanced parasite density was correlated with an increase in macrophages and decreases in eosinophils and mast cells. The chemokine mRNA expression demonstrated that enhanced parasite density was positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. CONCLUSIONS/SIGNIFICANCE: These findings represent an advance in the knowledge about skin inflammatory infiltrates in CVL and the systemic consequences. Additionally, the findings may contribute to the design of new and more efficient prophylactic tools and immunological therapies against CVL.

  8. Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis

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    Luzia Maria de-Oliveira-Pinto

    2012-02-01

    Full Text Available Dengue virus (DENV and parvovirus B19 (B19V infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL-1 receptor antagonist (Ra, CXCL10/inducible protein-10 (IP-10, CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1 were determined by multiplex immunoassay in serum samples obtained from B19V (37 and DENV-infected (36 patients and from healthy individuals (7. Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

  9. Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine.

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    Katri Koli

    Full Text Available Idiopathic pulmonary fibrosis (IPF is characterized by activation and injury of epithelial cells, the accumulation of connective tissue and changes in the inflammatory microenvironment. The bone morphogenetic protein (BMP inhibitor protein gremlin-1 is associated with the progression of fibrosis both in human and mouse lung. We generated a transgenic mouse model expressing gremlin-1 in type II lung epithelial cells using the surfactant protein C (SPC promoter and the Cre-LoxP system. Gremlin-1 protein expression was detected specifically in the lung after birth and did not result in any signs of respiratory insufficiency. Exposure to silicon dioxide resulted in reduced amounts of lymphocyte aggregates in transgenic lungs while no alteration in the fibrotic response was observed. Microarray gene expression profiling and analyses of bronchoalveolar lavage fluid cytokines indicated a reduced lymphocytic response and a downregulation of interferon-induced gene program. Consistent with reduced Th1 response, there was a downregulation of the mRNA and protein expression of the anti-fibrotic chemokine CXCL10, which has been linked to IPF. In human IPF patient samples we also established a strong negative correlation in the mRNA expression levels of gremlin-1 and CXCL10. Our results suggest that in addition to regulation of epithelial-mesenchymal crosstalk during tissue injury, gremlin-1 modulates inflammatory cell recruitment and anti-fibrotic chemokine production in the lung.

  10. Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine.

    Science.gov (United States)

    Koli, Katri; Sutinen, Eva; Rönty, Mikko; Rantakari, Pia; Fortino, Vittorio; Pulkkinen, Ville; Greco, Dario; Sipilä, Petra; Myllärniemi, Marjukka

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by activation and injury of epithelial cells, the accumulation of connective tissue and changes in the inflammatory microenvironment. The bone morphogenetic protein (BMP) inhibitor protein gremlin-1 is associated with the progression of fibrosis both in human and mouse lung. We generated a transgenic mouse model expressing gremlin-1 in type II lung epithelial cells using the surfactant protein C (SPC) promoter and the Cre-LoxP system. Gremlin-1 protein expression was detected specifically in the lung after birth and did not result in any signs of respiratory insufficiency. Exposure to silicon dioxide resulted in reduced amounts of lymphocyte aggregates in transgenic lungs while no alteration in the fibrotic response was observed. Microarray gene expression profiling and analyses of bronchoalveolar lavage fluid cytokines indicated a reduced lymphocytic response and a downregulation of interferon-induced gene program. Consistent with reduced Th1 response, there was a downregulation of the mRNA and protein expression of the anti-fibrotic chemokine CXCL10, which has been linked to IPF. In human IPF patient samples we also established a strong negative correlation in the mRNA expression levels of gremlin-1 and CXCL10. Our results suggest that in addition to regulation of epithelial-mesenchymal crosstalk during tissue injury, gremlin-1 modulates inflammatory cell recruitment and anti-fibrotic chemokine production in the lung.

  11. Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment – A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine

    Science.gov (United States)

    Koli, Katri; Sutinen, Eva; Rönty, Mikko; Rantakari, Pia; Fortino, Vittorio; Pulkkinen, Ville; Greco, Dario; Sipilä, Petra; Myllärniemi, Marjukka

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by activation and injury of epithelial cells, the accumulation of connective tissue and changes in the inflammatory microenvironment. The bone morphogenetic protein (BMP) inhibitor protein gremlin-1 is associated with the progression of fibrosis both in human and mouse lung. We generated a transgenic mouse model expressing gremlin-1 in type II lung epithelial cells using the surfactant protein C (SPC) promoter and the Cre-LoxP system. Gremlin-1 protein expression was detected specifically in the lung after birth and did not result in any signs of respiratory insufficiency. Exposure to silicon dioxide resulted in reduced amounts of lymphocyte aggregates in transgenic lungs while no alteration in the fibrotic response was observed. Microarray gene expression profiling and analyses of bronchoalveolar lavage fluid cytokines indicated a reduced lymphocytic response and a downregulation of interferon-induced gene program. Consistent with reduced Th1 response, there was a downregulation of the mRNA and protein expression of the anti-fibrotic chemokine CXCL10, which has been linked to IPF. In human IPF patient samples we also established a strong negative correlation in the mRNA expression levels of gremlin-1 and CXCL10. Our results suggest that in addition to regulation of epithelial-mesenchymal crosstalk during tissue injury, gremlin-1 modulates inflammatory cell recruitment and anti-fibrotic chemokine production in the lung. PMID:27428020

  12. 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine inhibit TNF-α and CXCL10 production from activated primary murine microglia via A2A receptors.

    Science.gov (United States)

    Newell, Elizabeth A; Exo, Jennifer L; Verrier, Jonathan D; Jackson, Travis C; Gillespie, Delbert G; Janesko-Feldman, Keri; Kochanek, Patrick M; Jackson, Edwin K

    2015-01-12

    Some cells, tissues and organs release 2',3'-cAMP (a positional isomer of 3',5'-cAMP) and convert extracellular 2',3'-cAMP to 2'-AMP plus 3'-AMP and convert these AMPs to adenosine (called the extracellular 2',3'-cAMP-adenosine pathway). Recent studies show that microglia have an extracellular 2',3'-cAMP-adenosine pathway. The goal of the present study was to investigate whether the extracellular 2',3'-cAMP-adenosine pathway could have functional consequences on the production of cytokines/chemokines by activated microglia. Experiments were conducted in cultures of primary murine microglia. In the first experiment, the effect of 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine on LPS-induced TNF-α and CXCL10 production was determined. In the next experiment, the first protocol was replicated but with the addition of 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) (0.1 μM; antagonist of adenosine receptors). The last experiment compared the ability of 2-chloro-N(6)-cyclopentyladenosine (CCPA) (10 μM; selective A1 agonist), 5'-N-ethylcarboxamide adenosine (NECA) (10 μM; agonist for all adenosine receptor subtypes) and CGS21680 (10 μM; selective A2A agonist) to inhibit LPS-induced TNF-α and CXCL10 production. (1) 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine similarly inhibited LPS-induced TNF-α and CXCL10 production; (2) DPSPX nearly eliminated the inhibitory effects of 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine on LPS-induced TNF-α and CXCL10 production; (3) CCPA did not affect LPS-induced TNF-α and CXCL10; (4) NECA and CGS21680 similarly inhibited LPS-induced TNF-α and CXCL10 production. 2',3'-cAMP and its metabolites (3'-AMP, 2'-AMP and adenosine) inhibit LPS-induced TNF-α and CXCL10 production via A2A-receptor activation. Adenosine and its precursors, via A2A receptors, likely suppress TNF-α and CXCL10 production by activated microglia in brain diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. 2’,3’-cAMP, 3’-AMP, 2’-AMP and Adenosine Inhibit TNF-α and CXCL10 Production From Activated Primary Murine Microglia via A2A Receptors

    Science.gov (United States)

    Newell, Elizabeth A.; Exo, Jennifer L.; Verrier, Jonathan D.; Jackson, Travis C.; Gillespie, Delbert G.; Janesko-Feldman, Keri; Kochanek, Patrick M.

    2014-01-01

    Background Some cells, tissues and organs release 2’,3’-cAMP (a positional isomer of 3’,5’-cAMP) and convert extracellular 2’,3’-cAMP to 2’-AMP plus 3’-AMP and convert these AMPs to adenosine (called the extracellular 2’,3’-cAMP-adenosine pathway). Recent studies show that microglia have an extracellular 2’,3’-cAMP-adenosine pathway. The goal of the present study was to investigate whether the extracellular 2’,3’-cAMP-adenosine pathway could have functional consequences on the production of cytokines/chemokines by activated microglia. Methods Experiments were conducted in cultures of primary murine microglia. In the first experiment, the effect of 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine on LPS-induced TNF-α and CXCL10 production was determined. In the next experiment, the first protocol was replicated but with the addition of 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) (0.1 µM; antagonist of adenosine receptors). The last experiment compared the ability of 2-chloro-N6-cyclopentyladenosine (CCPA) (10 µM; selective A1 agonist), 5’-N-ethylcarboxamide adenosine (NECA) (10 µM; agonist for all adenosine receptor subtypes) and CGS21680 (10 µM; selective A2A agonist) to inhibit LPS-induced TNF-α and CXCL10 production. Results 1) 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine similarly inhibited LPS-induced TNF-α and CXCL10 production; 2) DPSPX nearly eliminated the inhibitory effects of 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine on LPS-induced TNF-α and CXCL10 production; 3) CCPA did not affect LPS-induced TNF-α and CXCL10; 4) NECA and CGS21680 similarly inhibited LPS-induced TNF-α and CXCL10 production. Conclusions 2’,3’-cAMP and its metabolites (3’-AMP, 2’-AMP and adenosine) inhibit LPS-induced TNF-α and CXCL10 production via A2A-receptor activation. Adenosine and its precursors, via A2A receptors, likely suppress TNF-α and CXCL10 production by activated microglia in brain diseases. PMID:25451117

  14. CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8+ TEM and CD8+ TRM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease.

    Science.gov (United States)

    Srivastava, Ruchi; Khan, Arif A; Chilukuri, Sravya; Syed, Sabrina A; Tran, Tien T; Furness, Julie; Bahraoui, Elmostafa; BenMohamed, Lbachir

    2017-07-15

    Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8 + T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8 + T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8 + T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3 + CD8 + T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10 -/- or CXCR3 -/- deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10 -/- mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8 + T cells (T EM ) and tissue-resident memory CD8 + T cells (T RM ), but not of central memory CD8 + T cells (T CM ), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10 -/- deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8 + T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease. IMPORTANCE We determined how the CXCL10/CXCR3 pathway affects CD8 + T cell responses to recurrent ocular herpesvirus

  15. Systemic levels of CCL2, CCL3, CCL4 and CXCL8 differ according to age, time period and season among children newly diagnosed with type 1 diabetes and their healthy siblings

    DEFF Research Database (Denmark)

    Thorsen, S U; Eising, S; Mortensen, H B

    2014-01-01

    The mechanisms by which antigen-specific T cells migrate to the islets of Langerhans in type 1 diabetes (T1D) are largely unknown. Chemokines attract immune cells to sites of inflammation. The aim was to elucidate the role of inflammatory chemokines in T1D at time of diagnosis. From a population......-based registry of children diagnosed with T1D from 1997 to 2005, we studied five different inflammatory chemokines (CCL2, CCL3, CCL4, CCL5 and CXCL8). Four hundred and eighty-two cases and 479 sibling frequencies matched on age and sample year distribution were included. Patients showed lower levels of CCL4...... compared to siblings, but this result was not significant after correction for multiple testing. CCL2, CCL3, CCL4 and CXCL8 levels were highest in the most recent cohorts (P

  16. Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

    Science.gov (United States)

    Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A; Villinger, Francois; Mori, Kazuyasu

    2017-07-01

    Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4 + T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4 + T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3 + CCR5 + CD4 + T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3 + T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14 + CD16 + monocytes and MAC387 + macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387 + macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages. IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4 + T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3

  17. Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.

    Science.gov (United States)

    Andersen-Nissen, Erica; Chang, Joanne T; Thomas, Katherine K; Adams, Devin; Celum, Connie; Sanchez, Jorge; Coombs, Robert W; McElrath, M Juliana; Baeten, Jared M

    2016-12-01

    Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment. To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines. Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment. These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.

  18. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

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    Mickaël J Ploquin

    2016-08-01

    Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

  19. Acidic pH stimulates the production of the angiogenic CXC chemokine, CXCL8 (interleukin-8), in human adult mesenchymal stem cells via the extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and NF-kappaB pathways.

    Science.gov (United States)

    Bischoff, David S; Zhu, Jian-Hua; Makhijani, Nalini S; Yamaguchi, Dean T

    2008-07-01

    Blood vessel injury results in limited oxygen tension and diffusion leading to hypoxia, increased anaerobic metabolism, and elevated production of acidic metabolites that cannot be easily removed due to the reduced blood flow. Therefore, an acidic extracellular pH occurs in the local microenvironment of disrupted bone. The potential role of acidic pH and glu-leu-arg (ELR(+)) CXC chemokines in early events in bone repair was studied in human mesenchymal stem cells (hMSCs) treated with medium of decreasing pH (7.4, 7.0, 6.7, and 6.4). The cells showed a reciprocal increase in CXCL8 (interleukin-8, IL-8) mRNA levels as extracellular pH decreased. At pH 6.4, CXCL8 mRNA was induced >60x in comparison to levels at pH 7.4. hMSCs treated with osteogenic medium (OGM) also showed an increase in CXCL8 mRNA with decreasing pH; although, at a lower level than that seen in cells grown in non-OGM. CXCL8 protein was secreted into the medium at all pHs with maximal induction at pH 6.7. Inhibition of the G-protein-coupled receptor alpha, G(alphai), suppressed CXCL8 levels in response to acidic pH; whereas phospholipase C inhibition had no effect on CXCL8. The use of specific mitogen-activated protein kinase (MAPK) signal transduction inhibitors indicated that the pH-dependent increase in CXCL8 mRNA is due to activation of ERK and p38 pathways. The JNK pathway was not involved. NF-kappaB inhibition resulted in a decrease in CXCL8 levels in hMSCs grown in non-OGM. However, OGM-differentiated hMSCs showed an increase in CXCL8 levels when treated with the NF-kappaB inhibitor PDTC, a pyrrolidine derivative of dithiocarbamate. 2008 Wiley-Liss, Inc.

  20. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors

    DEFF Research Database (Denmark)

    Damgaard, C; Kantarci, A; Holmstrup, P

    2017-01-01

    BACKGROUND AND OBJECTIVES: Porphyromonas gingivalis is regarded as a significant contributor in the pathogenesis of periodontitis and certain systemic diseases, including atherosclerosis. P. gingivalis occasionally translocates from periodontal pockets into the circulation, where it adheres to red...... (ROS) in response to challenge with P. gingivalis. In addition, the impact of RBC interaction with P. gingivalis was investigated. The actions of resolvin E1 (RvE1), a known regulator of P. gingivalis induced neutrophil responses, on the cytokine and ROS responses elicited by P. gingivalis in cultures...... of neutrophils were investigated. RESULTS: Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant...

  1. Lipopolysaccharide, immune activation, and liver abnormalities in HIV/hepatitis B virus (HBV)-coinfected individuals receiving HBV-active combination antiretroviral therapy.

    Science.gov (United States)

    Crane, Megan; Avihingsanon, Anchalee; Rajasuriar, Reena; Velayudham, Pushparaj; Iser, David; Solomon, Ajantha; Sebolao, Baotuti; Tran, Andrew; Spelman, Tim; Matthews, Gail; Cameron, Paul; Tangkijvanich, Pisit; Dore, Gregory J; Ruxrungtham, Kiat; Lewin, Sharon R

    2014-09-01

    We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10. © The Author 2014. 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.

  2. Human Asymptomatic Epitope Peptide/CXCL10-Based Prime/Pull Vaccine Induces Herpes Simplex Virus-Specific Gamma Interferon-Positive CD107+ CD8+ T Cells That Infiltrate the Cornea and Trigeminal Ganglia of Humanized HLA Transgenic Rabbits and Protect against Ocular Herpes Challenge.

    Science.gov (United States)

    Khan, Arif A; Srivastava, Ruchi; Vahed, Hawa; Roy, Soumyabrata; Walia, Sager S; Kim, Grace J; Fouladi, Mona A; Yamada, Taikun; Ly, Vincent T; Lam, Cynthia; Lou, Anthony; Nguyen, Vivianna; Boldbaatar, Undariya; Geertsema, Roger; Fraser, Nigel W; BenMohamed, Lbachir

    2018-06-13

    Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull vaccine was tested in Human Leukocyte Antigen- (HLA-) transgenic rabbit model of ocular herpes (HLA Tg rabbit). Three asymptomatic (ASYMP) peptide epitopes were selected from the HSV-1 membrane glycoprotein C (UL44 400-408 ), the DNA replication binding helicase (UL9 196-204 ), and the tegument protein (UL25 572-580 ), all preferentially recognized by CD8 + T cells from "naturally protected" HSV-1-seropositive healthy ASYMP individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were immunized with a mixture of these three ASYMP CD8 + T cell peptide epitopes (UL44 400-408 , UL9 196-204 and UL25 572-580 ), delivered subcutaneously with CpG 2007 adjuvant (prime). Fifteen days later, half of the rabbits received a topical ocular treatment with a recombinant neurotropic AAV8 vector, expressing the T cell-attracting CXCL10 chemokine (pull). The frequency, function of HSV-specific CD8 + T cells induced by the prime/pull vaccine were assessed in peripheral blood, cornea, and trigeminal ganglia (TG). Compared to peptides alone, the peptides/CXCL10 prime/pull vaccine generated frequent polyfunctional gamma interferon-positive (IFN-γ + ) CD107 + CD8 + T cells that infiltrated both the cornea and TG. CD8 + T cells mobilization into cornea and TG of prime/pull- vaccinated rabbits was associated with a significant reduction in corneal herpes infection and disease following an ocular HSV-1 challenge (McKrae). These findings draw attention to the novel prime/pull vaccine strategy to mobilize anti-viral CD8 + T cells into tissues protecting them against herpes infection and disease. IMPORTANCE There is an urgent need for a vaccine against widespread herpes simplex virus infections. The present study demonstrates that immunization of HLA

  3. Anti-Inflammatory Benefits of Antibiotics: Tylvalosin Induces Apoptosis of Porcine Neutrophils and Macrophages, Promotes Efferocytosis, and Inhibits Pro-Inflammatory CXCL-8, IL1α, and LTB4 Production, While Inducing the Release of Pro-Resolving Lipoxin A4 and Resolvin D1.

    Science.gov (United States)

    Moges, Ruth; De Lamache, Dimitri Desmonts; Sajedy, Saman; Renaux, Bernard S; Hollenberg, Morley D; Muench, Gregory; Abbott, Elizabeth M; Buret, Andre G

    2018-01-01

    Excessive accumulation of neutrophils and their uncontrolled death by necrosis at the site of inflammation exacerbates inflammatory responses and leads to self-amplifying tissue injury and loss of organ function, as exemplified in a variety of respiratory diseases. In homeostasis, neutrophils are inactivated by apoptosis, and non phlogistically removed by neighboring macrophages in a process known as efferocytosis, which promotes the resolution of inflammation. The present study assessed the potential anti-inflammatory and pro-resolution benefits of tylvalosin, a recently developed broad-spectrum veterinary macrolide derived from tylosin. Recent findings indicate that tylvalosin may modulate inflammation by suppressing NF-κB activation. Neutrophils and monocyte-derived macrophages were isolated from fresh blood samples obtained from 12- to 22-week-old pigs. Leukocytes exposed to vehicle or to tylvalosin (0.1, 1.0, or 10 µg/mL; 0.096-9.6 µM) were assessed at various time points for apoptosis, necrosis, efferocytosis, and changes in the production of cytokines and lipid mediators. The findings indicate that tylvalosin increases porcine neutrophil and macrophage apoptosis in a concentration- and time-dependent manner, without altering levels of necrosis or reactive oxygen species production. Importantly, tylvalosin increased the release of pro-resolving Lipoxin A 4 (LXA 4 ) and Resolvin D1 (RvD 1 ) while inhibiting the production of pro-inflammatory Leukotriene B4 (LTB 4 ) in Ca 2+ ionophore-stimulated porcine neutrophils. Tylvalosin increased neutrophil phospholipase C activity, an enzyme involved in releasing arachidonic acid from membrane stores. Tylvalosin also inhibited pro-inflammatory chemokine (C-X-C motif) ligand 8 (CXCL-8, also known as Interleukin-8) and interleukin-1 alpha (IL-1α) protein secretion in bacterial lipopolysaccharide-stimulated macrophages. Together, these data illustrate that tylvalosin has potent immunomodulatory effects in porcine

  4. Anti-Inflammatory Benefits of Antibiotics: Tylvalosin Induces Apoptosis of Porcine Neutrophils and Macrophages, Promotes Efferocytosis, and Inhibits Pro-Inflammatory CXCL-8, IL1α, and LTB4 Production, While Inducing the Release of Pro-Resolving Lipoxin A4 and Resolvin D1

    Directory of Open Access Journals (Sweden)

    Ruth Moges

    2018-04-01

    Full Text Available Excessive accumulation of neutrophils and their uncontrolled death by necrosis at the site of inflammation exacerbates inflammatory responses and leads to self-amplifying tissue injury and loss of organ function, as exemplified in a variety of respiratory diseases. In homeostasis, neutrophils are inactivated by apoptosis, and non phlogistically removed by neighboring macrophages in a process known as efferocytosis, which promotes the resolution of inflammation. The present study assessed the potential anti-inflammatory and pro-resolution benefits of tylvalosin, a recently developed broad-spectrum veterinary macrolide derived from tylosin. Recent findings indicate that tylvalosin may modulate inflammation by suppressing NF-κB activation. Neutrophils and monocyte-derived macrophages were isolated from fresh blood samples obtained from 12- to 22-week-old pigs. Leukocytes exposed to vehicle or to tylvalosin (0.1, 1.0, or 10 µg/mL; 0.096–9.6 µM were assessed at various time points for apoptosis, necrosis, efferocytosis, and changes in the production of cytokines and lipid mediators. The findings indicate that tylvalosin increases porcine neutrophil and macrophage apoptosis in a concentration- and time-dependent manner, without altering levels of necrosis or reactive oxygen species production. Importantly, tylvalosin increased the release of pro-resolving Lipoxin A4 (LXA4 and Resolvin D1 (RvD1 while inhibiting the production of pro-inflammatory Leukotriene B4 (LTB4 in Ca2+ ionophore-stimulated porcine neutrophils. Tylvalosin increased neutrophil phospholipase C activity, an enzyme involved in releasing arachidonic acid from membrane stores. Tylvalosin also inhibited pro-inflammatory chemokine (C–X–C motif ligand 8 (CXCL-8, also known as Interleukin-8 and interleukin-1 alpha (IL-1α protein secretion in bacterial lipopolysaccharide-stimulated macrophages. Together, these data illustrate that tylvalosin has potent immunomodulatory effects

  5. Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Takuya Matsushita

    Full Text Available BACKGROUND: Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO, relapsing remitting multiple sclerosis (RRMS, and primary progressive MS (PPMS, and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis. METHODS/PRINCIPAL FINDINGS: We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND by multiplexed fluorescent bead-based immunoassay. Interleukin (IL-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients. CONCLUSIONS: Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell

  6. Human B cells produce chemokine CXCL10 in the presence of Mycobacterium tuberculosis specific T cells

    DEFF Research Database (Denmark)

    Hoff, Soren T; Salman, Ahmed M; Ruhwald, Morten

    2015-01-01

    BACKGROUND: The role of B cells in human host response to Mycobacterium tuberculosis (Mtb) infection is still controversial, but recent evidence suggest that B cell follicle like structures within the lung may influence host responses through regulation of the local cytokine environment. A candid......BACKGROUND: The role of B cells in human host response to Mycobacterium tuberculosis (Mtb) infection is still controversial, but recent evidence suggest that B cell follicle like structures within the lung may influence host responses through regulation of the local cytokine environment...

  7. Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

    Science.gov (United States)

    Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

    2015-12-01

    Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

  8. Characterization of an adaptive immune response in microsatellite-instable colorectal cancer

    Science.gov (United States)

    Boissière-Michot, Florence; Lazennec, Gwendal; Frugier, Hélène; Jarlier, Marta; Roca, Lise; Duffour, Jacqueline; Du Paty, Emilie; Laune, Daniel; Blanchard, France; Le Pessot, Florence; Sabourin, Jean-Christophe; Bibeau, Frédéric

    2014-01-01

    Sporadic or hereditary colorectal cancer (CRC) with microsatellite instability (MSI) is frequently characterized by inflammatory lymphocytic infiltration and tends to be associated with a better outcome than microsatellite stable (MSS) CRC, probably reflecting a more effective immune response. We investigated inflammatory mechanisms in 48 MSI CRCs and 62 MSS CRCs by analyzing: (1) the expression of 48 cytokines using Bio-Plex multiplex cytokine assays, and (2) the in situ immune response by immunohistochemical analysis with antibodies against CD3 (T lymphocytes), CD8 (cytotoxic T lymphocytes), CD45RO (memory T lymphocytes), T-bet (Th1 CD4 cells), and FoxP3 (regulatory T cells). MSI CRC exhibited significantly higher expression of CCL5 (RANTES), CXCL8 (IL-8), CXCL9 (MIG), IL-1β, CXCL10 (IP-10), IL-16, CXCL1 (GROα), and IL-1ra, and lower expression of MIF, compared with MSS CRC. Immunohistochemistry combined with image analysis indicated that the density of CD3+, CD8+, CD45RO+, and T-bet+ T lymphocytes was higher in MSI CRC than in MSS CRC, whereas the number of regulatory T cells (FoxP3+) was not statistically different between the groups. These results indicate that MSI CRC is associated with a specific cytokine expression profile that includes CCL5, CXCL10, and CXCL9, which are involved in the T helper type 1 (Th1) response and in the recruitment of memory CD45RO+ T cells. Our findings highlight the major role of adaptive immunity in MSI CRC and provide a possible explanation for the more favorable prognosis of this CRC subtype. PMID:25101223

  9. Urine chemokines indicate pathogenic association of obesity with BPH/LUTS.

    Science.gov (United States)

    Tyagi, Pradeep; Motley, Saundra S; Kashyap, Mahendra; Pore, Subrata; Gingrich, Jeffrey; Wang, Zhou; Yoshimura, Naoki; Fowke, Jay H

    2015-07-01

    High prevalence of lower urinary tract symptoms (LUTS) consistent with benign prostate hyperplasia (BPH) is associated with obesity and prostatic inflammation. Here, we investigated whether chemokines associated with obesity and prostatic inflammation can be measured in normally voided urine of BPH/LUTS patients to demonstrate the mechanistic association between obesity and BPH/LUTS. Frozen urine specimens of BPH/LUTS patients enrolled in the Nashville Men's Health Study were sent for blinded analysis to University of Pittsburgh. Thirty patients were blocked by their AUA-SI (>7 or ≤7) and prostatic enlargement (60 cc). Clinical parameters including age, prostate size, and medications were derived from chart review. CXC chemokines (CXCL-1, CXCL-8, and CXCL-10), CC chemokines (CCL2 and CCL3), and sIL-1ra were measured in thawed urine using Luminex™ xMAP(®) technology and ELISA for NGF. Urinary CCL2 levels were several fold higher compared with the other six proteins, of which CCL3 was detectable in less than one-fourth of patients. Urine levels of sIL-1ra and CXCL-8 were significantly associated with increasing BMI and waist circumference in BPH patients. CXCL-8 showed a marginal association with overall AUA-SI scores, as well as obstructive (p = 0.08) symptom subscores. Prostate volume was inversely and marginally associated with urinary CXCL-10 (p = 0.09). Urine levels of CXCL-8, CXCL-10, and sIL-1ra were associated with varying degrees with LUTS severity, prostate size, and obesity, respectively. These findings in urine are consistent with past studies of chemokine levels from expressed prostatic secretions and demonstrate the potential of noninvasively measured chemokine in urine to objectively classify BPH/LUTS patients.

  10. Combination of roflumilast with a beta-2 adrenergic receptor agonist inhibits proinflammatory and profibrotic mediator release from human lung fibroblasts

    Directory of Open Access Journals (Sweden)

    Tannheimer Stacey L

    2012-03-01

    Full Text Available Abstract Background Small airway narrowing is an important pathology which impacts lung function in chronic obstructive pulmonary disease (COPD. The accumulation of fibroblasts and myofibroblasts contribute to inflammation, remodeling and fibrosis by production and release of mediators such as cytokines, profibrotic factors and extracellular matrix proteins. This study investigated the effects of the phosphodiesterase 4 inhibitor roflumilast, combined with the long acting β2 adrenergic agonist indacaterol, both approved therapeutics for COPD, on fibroblast functions that contribute to inflammation and airway fibrosis. Methods The effects of roflumilast and indacaterol treatment were characterized on transforming growth factor β1 (TGFβ1-treated normal human lung fibroblasts (NHLF. NHLF were evaluated for expression of the profibrotic mediators endothelin-1 (ET-1 and connective tissue growth factor (CTGF, expression of the myofibroblast marker alpha smooth muscle actin, and fibronectin (FN secretion. Tumor necrosis factor-α (TNF-α was used to induce secretion of chemokine C-X-C motif ligand 10 (CXCL10, chemokine C-C motif ligand 5 (CCL5 and granulocyte macrophage colony-stimulating factor (GM-CSF from NHLF and drug inhibition was assessed. Results Evaluation of roflumilast (1-10 μM showed no significant inhibition alone on TGFβ1-induced ET-1 and CTGF mRNA transcripts, ET-1 and FN protein production, alpha smooth muscle expression, or TNF-α-induced secretion of CXCL10, CCL5 and GM-CSF. A concentration-dependent inhibition of ET-1 and CTGF was shown with indacaterol treatment, and a submaximal concentration was chosen for combination studies. When indacaterol (0.1 nM was added to roflumilast, significant inhibition was seen on all inflammatory and fibrotic mediators evaluated, which was superior to the inhibition seen with either drug alone. Roflumilast plus indacaterol combination treatment resulted in significantly elevated phosphorylation

  11. Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Trebst, Corinna; Kivisäkk, Pia

    2002-01-01

    T-cell accumulation in the central nervous system (CNS) is considered crucial to the pathogenesis of multiple sclerosis (MS). We found that the majority of T cells within the cerebrospinal fluid (CSF) compartment expressed the CXC chemokine receptor 3 (CXCR), independent of CNS inflammation...

  12. Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes

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    Gi Soo Youn

    2017-08-01

    Full Text Available Histone deacetylase 6 (HDAC6 likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat activates NADPH oxidase resulting in generation of reactive oxygen species (ROS, leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation. Keywords: HIV-1 Tat, HDAC6, NADPH oxidase, ROS, Inflammation, Astrocytes

  13. Peroxisome proliferator-activated receptor α agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    International Nuclear Information System (INIS)

    Antonelli, Alessandro; Ferrari, Silvia Martina; Frascerra, Silvia; Corrado, Alda; Pupilli, Cinzia; Bernini, Giampaolo; Benvenga, Salvatore; Ferrannini, Ele; Fallahi, Poupak

    2011-01-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR)α activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPARα and PPARγ activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN)γ and tumor necrosis factor (TNF)α. IFNγ stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNFα alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFNγ and TNFα had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPARα activators inhibited the secretion of both chemokines (stimulated with IFNγ and TNFα) at a level higher (for CXCL10, about 60-72%) than PPARγ agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFNγ and TNFα in GD and normal thyrocytes. Furthermore we first show that PPARα activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPARα may be involved in the modulation of the immune response in the thyroid.

  14. Induction of cytokine (interleukin-1alpha and tumor necrosis factor-alpha) and chemokine (CCL20, CCL27, and CXCL8) alarm signals after allergen and irritant exposure

    NARCIS (Netherlands)

    Spiekstra, S.W.; Toebak, M.J.; Sampat-Sardjoepersad, S.; van Beek, P.J; Boorsma, D.M.; Stoof, T.J.; von Blomberg, B.M.; Scheper, R.J.; Bruynzeel, D.P.; Rustemeyer, T.; Gibbs, S.

    2005-01-01

    The immune system is called into action by alarm signals generate from injured tissues. We examined the nature of these alarm signals after exposure of skin residential cells to contact allergens (nickel sulfate and potassium dichromate) and a contact irritant [sodium dodecyl sulfate (SDS)]. Nickel

  15. Early serum biomarker networks in infants with distinct retinochoroidal lesion status of congenital toxoplasmosis.

    Science.gov (United States)

    de Araújo, Thádia Evelyn; Coelho-Dos-Reis, Jordana Grazziela; Béla, Samantha Ribeiro; Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Cardoso, Ludmila Melo; Ribeiro, Ágata Lopes; Dias, Michelle Hallais França; Queiroz Andrade, Gláucia Manzan; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Ferro, Eloisa Amália Vieira; Martins-Filho, Olindo Assis

    2017-07-01

    The present study characterized the early changes in the serum chemokines/cytokine signatures and networks in infants with congenital-toxoplasmosis/(TOXO) as compared to non-infected-controls/(NI). TOXO were subgrouped according to the retinochoroidal lesion status as no-lesion/(NL), active-lesion/(ARL), active/cicatricial-lesion/(ACRL) and cicatricial-lesion/(CRL). The results showed that TOXO display prominent chemokine production mediated by IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and RANTES/CCL5. Additionally, TOXO is accompanied by mixed proinflammatory/regulatory cytokine pattern mediated by IL-6, IFN-γ, IL-4, IL-5 and IL-10. While TNF appears as a putative biomarker for NL and IFN-γ/IL-5 as immunological features for ARL, IL-10 emerges as a relevant mediator in ACRL/CRL. IL-8/CXCL8 and IP-10/CXCL10 are broad-spectrum indicators of ocular disease, whereas TNF is a NL biomarker, IFN-γ and MIG/CXCL9 point out to ARL; and IL-10 is highlighted as a genuine serum biomarker of ACRL/CRL. The network analysis demonstrated a broad chemokine/cytokine crosstalk with divergences in the molecular signatures in patients with different ocular lesions during congenital toxoplasmosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Forecast Combinations

    OpenAIRE

    Timmermann, Allan G

    2005-01-01

    Forecast combinations have frequently been found in empirical studies to produce better forecasts on average than methods based on the ex-ante best individual forecasting model. Moreover, simple combinations that ignore correlations between forecast errors often dominate more refined combination schemes aimed at estimating the theoretically optimal combination weights. In this paper we analyse theoretically the factors that determine the advantages from combining forecasts (for example, the d...

  17. Inhibition by salmeterol and cilomilast of fluticasone-enhanced IP-10 release in airway epithelial cells.

    Science.gov (United States)

    Reddy, P J; Aksoy, Mark O; Yang, Yi; Li, Xiu Xia; Ji, Rong; Kelsen, Steven G

    2008-02-01

    The CXC chemokines, IP-10/CXCL10 and IL-8/CXCL8, play a role in obstructive lung disease by attracting Th1/Tc1 lymphocytes and neutrophils, respectively. Inhaled corticosteroids (ICS) and long acting beta 2-agonists (LABA) are widely used. However, their effect(s) on the release of IP-10 and IL-8 by airway epithelial cells are poorly understood. This study examined the effects of fluticasone, salmeterol, and agents which raise intracellular cAMP (cilomilast and db-cAMP) on the expression of IP-10 and IL-8 protein and mRNA. Studies were performed in cultured human airway epithelial cells during cytokine-stimulated IP-10 and IL-8 release. Cytokine treatment (TNF-alpha, IL-1beta and IFN-gamma) increased IP-10 and IL-8 protein and mRNA levels. Fluticasone (0.1 nM to 1 microM) increased IP-10 but reduced IL-8 protein release without changing IP-10 mRNA levels assessed by real time RT-PCR. The combination of salmeterol (1 micro M) and cilomilast (1-10 mu M) reduced IP-10 but had no effect on IL-8 protein. Salmeterol alone (1 micro M) and db-cAMP alone (1 mM) antagonised the effects of fluticasone on IP-10 but not IL-8 protein. In human airway epithelial cells, inhibition by salmeterol of fluticasone-enhanced IP-10 release may be an important therapeutic effect of the LABA/ICS combination not present when the two drugs are used separately.

  18. Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination.

    Directory of Open Access Journals (Sweden)

    Chad W MacPherson

    Full Text Available Genome-wide transcriptional analysis in intestinal epithelial cells (IEC can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052, Bifidobacterium longum subsp. infantis R0033 (Bl-R0033 and Bifidobacterium bifidum R0071 (Bb-R0071 individually and in combination, and of a surface-layer protein (SLP purified from Lh-R0052, on HT-29 cells' transcriptional profile to poly(I:C-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10, indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic.

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

    Science.gov (United States)

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

    2018-04-01

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

  20. Chemokines and chemokine receptors expression in the lesions of patients with American cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Nilka Luisa Diaz

    2013-06-01

    Full Text Available American cutaneous leishmaniasis (ACL presents distinct active clinical forms with different grades of severity, known as localised (LCL, intermediate (ICL and diffuse (DCL cutaneous leishmaniasis. LCL and DCL are associated with a polarised T-helper (Th1 and Th2 immune response, respectively, whereas ICL, or chronic cutaneous leishmaniasis, is associated with an exacerbated immune response and a mixed cytokine expression profile. Chemokines and chemokine receptors are involved in cellular migration and are critical in the inflammatory response. Therefore, we evaluated the expression of the chemokines CXCL10, CCL4, CCL8, CCL11 and CXCL8 and the chemokine receptors CCR3, CXCR3, CCR5 and CCR7 in the lesions of patients with different clinical forms of ACL using immunohistochemistry. LCL patients exhibited a high density of CXCL10+, CCL4+ and CCL8+ cells, indicating an important role for these chemokines in the local Th1 immune response and the migration of CXCR3+ cells. LCL patients showed a higher density of CCR7+ cells than ICL or DCL patients, suggesting major dendritic cell (DC migration to lymph nodes. Furthermore, DCL was associated with low expression levels of Th1-associated chemokines and CCL11+ epidermal DCs, which contribute to the recruitment of CCR3+ cells. Our findings also suggest an important role for epidermal cells in the induction of skin immune responses through the production of chemokines, such as CXCL10, by keratinocytes.

  1. Semaphorin4D Drives CD8+ T-Cell Lesional Trafficking in Oral Lichen Planus via CXCL9/CXCL10 Upregulations in Oral Keratinocytes.

    Science.gov (United States)

    Ke, Yao; Dang, Erle; Shen, Shengxian; Zhang, Tongmei; Qiao, Hongjiang; Chang, Yuqian; Liu, Qing; Wang, Gang

    2017-11-01

    Chemokine-mediated CD8 + T-cell recruitment is an essential but not well-established event for the persistence of oral lichen planus (OLP). Semaphorin 4D (Sema4D)/CD100 is implicated in immune dysfunction, chemokine modulation, and cell migration, which are critical aspects for OLP progression, but its implication in OLP pathogenesis has not been determined. In this study, we sought to explicate the effect of Sema4D on human oral keratinocytes and its capacity to drive CD8 + T-cell lesional trafficking via chemokine modulation. We found that upregulations of sSema4D in OLP tissues and blood were positively correlated with disease severity and activity. In vitro observation revealed that Sema4D induced C-X-C motif chemokine ligand 9/C-X-C motif chemokine ligand 10 production by binding to plexin-B1 via protein kinase B-NF-κB cascade in human oral keratinocytes, which elicited OLP CD8 + T-cell migration. We also confirmed using clinical samples that elevated C-X-C motif chemokine ligand 9/C-X-C motif chemokine ligand 10 levels were positively correlated with sSema4D levels in OLP lesions and serum. Notably, we determined matrix metalloproteinase-9 as a new proteolytic enzyme for the cleavage of sSema4D from the T-cell surface, which may contribute to the high levels of sSema4D in OLP lesions and serum. Our findings conclusively revealed an amplification feedback loop involving T cells, chemokines, and Sema4D-dependent signal that promotes OLP progression. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. combination Dictionary

    African Journals Online (AJOL)

    rbr

    of the idiomatic expression as a whole" (Crystal 2003: 225-226). Idiomatic .... nations and idioms.11 Nonetheless, free combinations of words have not been .... those who thronged Emmett place last night wanted to see the film, and they.

  3. Winning Combinations

    DEFF Research Database (Denmark)

    Criscuolo, Paola; Laursen, Keld; Reichstein, Toke

    2018-01-01

    examine the effectiveness of different combinations of knowledge sources for achieving innovative performance. We suggest that combinations involving integrative search strategies – combining internal and external knowledge – are the most likely to generate product and process innovation. In this context......, we present the idea that cognitively distant knowledge sources are helpful for innovation only when used in conjunction with knowledge sources that are closer to the focal firm. We also find important differences between product and process innovation, with the former associated with broader searches......Searching for the most rewarding sources of innovative ideas remains a key challenge in management of technological innovation. Yet, little is known about which combinations of internal and external knowledge sources are triggers for innovation. Extending theories about searching for innovation, we...

  4. Peroxisome proliferator-activated receptor {alpha} agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro, E-mail: a.antonelli@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Ferrari, Silvia Martina, E-mail: sm.ferrari@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Frascerra, Silvia, E-mail: lafrasce@gmail.com [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Corrado, Alda, E-mail: dala_res@hotmail.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Pupilli, Cinzia, E-mail: c.pupilli@dfc.unifi.it [Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy); Bernini, Giampaolo, E-mail: g.bernini@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Benvenga, Salvatore, E-mail: s.benvenga@me.nettuno.it [Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy); Ferrannini, Ele, E-mail: eferrannini@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Fallahi, Poupak, E-mail: poupak@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)

    2011-07-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR){alpha} activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPAR{alpha} and PPAR{gamma} activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN){gamma} and tumor necrosis factor (TNF){alpha}. IFN{gamma} stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNF{alpha} alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFN{gamma} and TNF{alpha} had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPAR{alpha} activators inhibited the secretion of both chemokines (stimulated with IFN{gamma} and TNF{alpha}) at a level higher (for CXCL10, about 60-72%) than PPAR{gamma} agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFN{gamma} and TNF{alpha} in GD and normal thyrocytes. Furthermore we first show that PPAR{alpha} activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPAR{alpha} may be involved in the modulation of the immune response in the thyroid.

  5. Forecast combinations

    OpenAIRE

    Aiolfi, Marco; Capistrán, Carlos; Timmermann, Allan

    2010-01-01

    We consider combinations of subjective survey forecasts and model-based forecasts from linear and non-linear univariate specifications as well as multivariate factor-augmented models. Empirical results suggest that a simple equal-weighted average of survey forecasts outperform the best model-based forecasts for a majority of macroeconomic variables and forecast horizons. Additional improvements can in some cases be gained by using a simple equal-weighted average of survey and model-based fore...

  6. Combined homicide

    Directory of Open Access Journals (Sweden)

    Slović Živana

    2017-01-01

    Full Text Available Introduction: Combined homicide is a combination of two or more different modes of killing. These homicides occur when multiple perpetrators have different mode of killing, to hide the true manner of death, or when an initially unsuccessful attack with one weapon is abandoned and changed by another mode which is more successful, or due to availability of weapons at the scene of homicide, or unexpected appearance of possible eyewitness, or else. Case report: This case report is about 65-year old woman who was found in her residence on the floor next to the bed lying on her back with two kitchen knives in her neck. Autopsy revealed an abrasion on the frontal part of the neck and a bruise of the soft tissues of the neck with a double fracture of both greater horns of the hyoid bone and a fracture of both superior horns of the thyroid cartilage. The cause of death was exsanguination into right half of the thoracic cavity from the left subclavian artery which was cut, on the spot of stab wound in the neck. Conclusion: Hemorrhage in the soft tissue near broken hyoid bone and thyroid cartilage indicate that the victim was first strangulated and then stabbed with kitchen knives. Combined homicides are caused by one or more killers in order to accelerate the killing, or to be sure to provide the fatal outcome. This case is also interesting because the killer left weapon in the victim's neck.

  7. Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

    Science.gov (United States)

    Zielińska, Karolina A.; de Cauwer, Lode; Knoops, Sofie; Van der Molen, Kristof; Sneyers, Alexander; Thommis, Jonathan; De Souza, J. Brian; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

    2017-01-01

    Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs) have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ) and Plasmodium berghei NK65 (PbNK65). Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES) by 90% and both CCL2 (MCP-1) and CXCL10 (IP-10) by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1) unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK), JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs. PMID:29033931

  8. Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

    Directory of Open Access Journals (Sweden)

    Karolina A. Zielińska

    2017-09-01

    Full Text Available Malaria-associated acute respiratory distress syndrome (MA-ARDS is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ and Plasmodium berghei NK65 (PbNK65. Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES by 90% and both CCL2 (MCP-1 and CXCL10 (IP-10 by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1 unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK, JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs.

  9. Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study

    Directory of Open Access Journals (Sweden)

    Malmvall Bo-Eric

    2011-04-01

    Full Text Available Abstract Background Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB is associated with a strong T helper (Th 1-type cytokine response in the cerebrospinal fluid (CSF followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown. Methods To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker, CCL22 (Th2 marker, IL-17 (Th17 marker and CXCL8 (general inflammation marker, in serum and in CSF from untreated patients with confirmed NB (n = 133, and non-NB patients (n = 96, and related the findings to clinical data. Samples from patients with possible early NB (n = 15 and possible late NB (n = 19 were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17, where CSF was obtained at spinal anaesthesia. Results The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p Borrelia-antibodies. Conclusion Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.

  10. MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Mythili Dileepan

    Full Text Available Airway smooth muscle (ASM cells play a critical role in the pathophysiology of asthma due to their hypercontractility and their ability to proliferate and secrete inflammatory mediators. microRNAs (miRNAs are gene regulators that control many signaling pathways and thus serve as potential therapeutic alternatives for many diseases. We have previously shown that miR-708 and miR-140-3p regulate the MAPK and PI3K signaling pathways in human ASM (HASM cells following TNF-α exposure. In this study, we investigated the regulatory effect of these miRNAs on other asthma-related genes. Microarray analysis using the Illumina platform was performed with total RNA extracted from miR-708 (or control miR-transfected HASM cells. Inhibition of candidate inflammation-associated gene expression was further validated by qPCR and ELISA. The most significant biologic functions for the differentially expressed gene set included decreased inflammatory response, cytokine expression and signaling. qPCR revealed inhibition of expression of CCL11, CXCL10, CCL2 and CXCL8, while the release of CCL11 was inhibited in miR-708-transfected cells. Transfection of cells with miR-140-3p resulted in inhibition of expression of CCL11, CXCL12, CXCL10, CCL5 and CXCL8 and of TNF-α-induced CXCL12 release. In addition, expression of RARRES2, CD44 and ADAM33, genes known to contribute to the pathophysiology of asthma, were found to be inhibited in miR-708-transfected cells. These results demonstrate that miR-708 and miR-140-3p exert distinct effects on inflammation-associated gene expression and biological function of ASM cells. Targeting these miRNA networks may provide a novel therapeutic mechanism to down-regulate airway inflammation and ASM proliferation in asthma.

  11. Urinary Levels of IL-1β and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Rafael Coelho Magalhães

    2017-01-01

    Full Text Available Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1β, IL-6, IL-10, TNF, and IL-12p70, chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG, and neurotrophic factors (BDNF and GDNF were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood (T0, at 48 (T1, at 72 hours (T2, and at 3 weeks after birth (T3. Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1β and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

  12. Elevated CXC chemokines in urine noninvasively discriminate OAB from UTI.

    Science.gov (United States)

    Tyagi, Pradeep; Tyagi, Vikas; Qu, Xianggui; Chuang, Yao Chi; Kuo, Hann-Chorng; Chancellor, Michael

    2016-09-01

    Overlapping symptoms of overactive bladder (OAB) and urinary tract infection (UTI) often complicate the diagnosis and contribute to overprescription of antibiotics. Inflammatory response is a shared characteristic of both UTI and OAB and here we hypothesized that molecular differences in inflammatory response seen in urine can help discriminate OAB from UTI. Subjects in the age range of (20-88 yr) of either sex were recruited for this urine analysis study. Urine specimens were available from 62 UTI patients with positive dipstick test before antibiotic treatment. Six of these patients also provided urine after completion of antibiotic treatment. Subjects in cohorts of OAB (n = 59) and asymptomatic controls (n = 26) were negative for dipstick test. Urinary chemokines were measured by MILLIPLEX MAP Human Cytokine/Chemokine Immunoassay and their association with UTI and OAB was determined by univariate and multivariate statistics. Significant elevation of CXCL-1, CXCL-8 (IL-8), and CXCL-10 together with reduced levels for a receptor antagonist of IL-1A (sIL-1RA) were seen in UTI relative to OAB and asymptomatic controls. Elevated CXCL-1 urine levels predicted UTI with odds ratio of 1.018 and showed a specificity of 80.77% and sensitivity of 59.68%. Postantibiotic treatment, reduction was seen in all CXC chemokines with a significant reduction for CXCL-10. Strong association of CXCL-1 and CXCL-10 for UTI over OAB indicates mechanistic differences in signaling pathways driving inflammation secondary of infection in UTI compared with a lack of infection in OAB. Urinary chemokines highlight molecular differences in the paracrine signaling driving the overlapping symptoms of UTI and OAB. Copyright © 2016 the American Physiological Society.

  13. Effect of pregnancy on anti-HEV antibody titres, plasma cytokines and the corresponding gene expression levels in the PBMCs of patients presenting with self-recovering clinical and subclinical hepatitis E.

    Directory of Open Access Journals (Sweden)

    Ashwini Y Ramdasi

    Full Text Available High mortality in pregnant women (PR is a characteristic of hepatitis E in developing countries. To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients and subclinical-HEV-infections in pregnant women in the first (SC-PR-1 and later (2nd and 3rd, SC-PR-2+3 trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p<0.05-0.0001. IFNγ/IL4ratios indicated Th2/Th1 bias in non-PR and PR-patients respectively. Raised levels of 10/20 plasma cytokines in the non-PR-patients reflect predominant inflammatory response, unaltered- IFNγ/reduced-IFNα responses and a robust chemokine secretion. On contrary, the acute-PR-patients exhibited drastic reduction in majority of the cytokines relative to in the non-PR-patients. Importantly, diminished or unaltered response was noted in the acute-PR-group when compared to the corresponding controls. The only exception was sIL2RA, increasing in both patient categories. Of the 14 genes evaluated, the expression of IFNγ/IL10/IL1A/IL7/CCL2/CCL3/CXCL8/CXCL10 was higher in the non-PR patients. Of these, the expression of IFNγ/IL10/IL1A/CCL2/CCL3/CXCL8 and, additionally, IL2/IL6/TNF genes was higher in the clinical-PRs. Almost identical pattern was noted in the control-PR-2+3 category indicating no influence of HEV infection. Comparison of patient-categories identified significant elevation of IFNγ(P<0.001, CCL2(p<0.01, CXCL8(P<0.05, IL1B(p<0.05 and IL10(P<0.0001 and decrease in CXCL10(<0.05 in the PR-patients. The results suggest antibody-dependent disease severity and impaired immune response in the PR patients. Higher expression of cytokine-genes in the PBMCs did not correlate with the plasma-cytokine levels in the PR-patients.

  14. Anti-Inflammatory benefits of antibiotic-induced neutrophil apoptosis: tulathromycin induces caspase-3-dependent neutrophil programmed cell death and inhibits NF-kappaB signaling and CXCL8 transcription.

    Science.gov (United States)

    Fischer, Carrie D; Beatty, Jennifer K; Zvaigzne, Cheryl G; Morck, Douglas W; Lucas, Merlyn J; Buret, A G

    2011-01-01

    Clearance of apoptotic neutrophils is a central feature of the resolution of inflammation. Findings indicate that immuno-modulation and induction of neutrophil apoptosis by macrolide antibiotics generate anti-inflammatory benefits via mechanisms that remain obscure. Tulathromycin (TUL), a new antimicrobial agent for bovine respiratory disease, offers superior clinical efficacy for reasons not fully understood. The aim of this study was to identify the immuno-modulating effects of tulathromycin and, in this process, to establish tulathromycin as a new model for characterizing the novel anti-inflammatory properties of antibiotics. Bronchoalveolar lavage specimens were collected from Holstein calves 3 and 24 h postinfection, challenged intratracheally with live Mannheimia haemolytica (2 × 10(7) CFU), and treated with vehicle or tulathromycin (2.5 mg/kg body weight). Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) revealed that tulathromycin treatment significantly increased leukocyte apoptosis and reduced levels of proinflammatory leukotriene B(4) in M. haemolytica-challenged calves. In vitro, tulathromycin concentration dependently induced apoptosis in freshly isolated bovine neutrophils from healthy steers in a capase-3-dependent manner but failed to induce apoptosis in bovine fibroblasts, epithelial cells, and endothelial cells, as well as freshly isolated bovine blood monocytes and monocyte-derived macrophages. The proapoptotic effects of TUL were also, in part, drug specific; equimolar concentrations of penicillin G, oxytetracycline, and ceftiofur failed to cause apoptosis in bovine neutrophils. In addition, tulathromycin significantly reduced levels of phosphorylated IκBα, nuclear translocation of NF-κB p65, and mRNA levels of proinflammatory interleukin-8 in lipopolysaccharide (LPS)-stimulated bovine neutrophils. The findings illustrate novel mechanisms through which tulathromycin confers anti-inflammatory benefits.

  15. Immunological and cardiometabolic risk factors in the prediction of type 2 diabetes and coronary events: MONICA/KORA Augsburg case-cohort study.

    Directory of Open Access Journals (Sweden)

    Christian Herder

    Full Text Available BACKGROUND: This study compares inflammation-related biomarkers with established cardiometabolic risk factors in the prediction of incident type 2 diabetes and incident coronary events in a prospective case-cohort study within the population-based MONICA/KORA Augsburg cohort. METHODS AND FINDINGS: Analyses for type 2 diabetes are based on 436 individuals with and 1410 individuals without incident diabetes. Analyses for coronary events are based on 314 individuals with and 1659 individuals without incident coronary events. Mean follow-up times were almost 11 years. Areas under the receiver-operating characteristic curve (AUC, changes in Akaike's information criterion (ΔAIC, integrated discrimination improvement (IDI and net reclassification index (NRI were calculated for different models. A basic model consisting of age, sex and survey predicted type 2 diabetes with an AUC of 0.690. Addition of 13 inflammation-related biomarkers (CRP, IL-6, IL-18, MIF, MCP-1/CCL2, IL-8/CXCL8, IP-10/CXCL10, adiponectin, leptin, RANTES/CCL5, TGF-β1, sE-selectin, sICAM-1; all measured in nonfasting serum increased the AUC to 0.801, whereas addition of cardiometabolic risk factors (BMI, systolic blood pressure, ratio total/HDL-cholesterol, smoking, alcohol, physical activity, parental diabetes increased the AUC to 0.803 (ΔAUC [95% CI] 0.111 [0.092-0.149] and 0.113 [0.093-0.149], respectively, compared to the basic model. The combination of all inflammation-related biomarkers and cardiometabolic risk factors yielded a further increase in AUC to 0.847 (ΔAUC [95% CI] 0.044 [0.028-0.066] compared to the cardiometabolic risk model. Corresponding AUCs for incident coronary events were 0.807, 0.825 (ΔAUC [95% CI] 0.018 [0.013-0.038] compared to the basic model, 0.845 (ΔAUC [95% CI] 0.038 [0.028-0.059] compared to the basic model and 0.851 (ΔAUC [95% CI] 0.006 [0.003-0.021] compared to the cardiometabolic risk model, respectively. CONCLUSIONS: Inclusion of multiple

  16. Birth control pills - combination

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000655.htm Birth control pills - combination To use the sharing features on ... both progestin and estrogen. What Are Combination Birth Control Pills? Birth control pills help keep you from ...

  17. Modifiable Combining Functions

    OpenAIRE

    Cohen, Paul; Shafer, Glenn; Shenoy, Prakash P.

    2013-01-01

    Modifiable combining functions are a synthesis of two common approaches to combining evidence. They offer many of the advantages of these approaches and avoid some disadvantages. Because they facilitate the acquisition, representation, explanation, and modification of knowledge about combinations of evidence, they are proposed as a tool for knowledge engineers who build systems that reason under uncertainty, not as a normative theory of evidence.

  18. Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease

    DEFF Research Database (Denmark)

    Nicoletti, F; Conget, I; Di Mauro, M

    2002-01-01

    Chemokines are chemotactic cytokines controlling the recruitment of leukocytes from the blood by regulating integrin adhesiveness. It has been shown that the migration of CD4+Th1 and CD4+Th2 cells is governed by specific chemokines. Increasing evidence suggests that the CD4+Th1 cheomoattractant...

  19. Practical, general parser combinators

    NARCIS (Netherlands)

    A. Izmaylova (Anastasia); A. Afroozeh (Ali); T. van der Storm (Tijs)

    2016-01-01

    textabstractParser combinators are a popular approach to parsing where contextfree grammars are represented as executable code. However, conventional parser combinators do not support left recursion, and can have worst-case exponential runtime. These limitations hinder the expressivity and

  20. Trendwatch combining expert opinion

    NARCIS (Netherlands)

    Hendrix, E.M.T.; Kornelis, M.; Pegge, S.M.; Galen, van M.A.

    2006-01-01

    In this study, focus is on a systematic way to detect future changes in trends that may effect the dynamics in the agro-food sector, and on the combination of opinions of experts. For the combination of expert opinions, the usefulness of multilevel models is investigated. Bayesian data analysis is

  1. Effective Nutritional Supplement Combinations

    Science.gov (United States)

    Cooke, Matt; Cribb, Paul J.

    Few supplement combinations that are marketed to athletes are supported by scientific evidence of their effectiveness. Quite often, under the rigor of scientific investigation, the patented combination fails to provide any greater benefit than a group given the active (generic) ingredient. The focus of this chapter is supplement combinations and dosing strategies that are effective at promoting an acute physiological response that may improve/enhance exercise performance or influence chronic adaptations desired from training. In recent years, there has been a particular focus on two nutritional ergogenic aids—creatine monohydrate and protein/amino acids—in combination with specific nutrients in an effort to augment or add to their already established independent ergogenic effects. These combinations and others are discussed in this chapter.

  2. Secondary combined suicide pact.

    Science.gov (United States)

    Jayanth, S H; Girish Chandra, Y P; Hugar, Basappa S; Kainoor, Sunilkumar

    2014-03-01

    This article reports a combined suicide pact, where in a young couple; a 26 year old male and a 20 year old female committed suicide by using two methods. The couple had resorted to hanging and self-immolation to prevent failure of single method alone. In secondary combined suicides, several other methods of suicide are tried after the first method chosen has failed. It is primary combined suicide only when two or more methods are used simultaneously. Both types of combined suicide by one individual is well reported in the literature whereas the same by two persons together is rare. In this report, the deceased were disappointed lovers, poor and the family members were against their marriage. The investigation of scene, methods employed to commit suicide, autopsy findings and the interview with their relatives altogether suggested that it was a secondary combined suicide pact. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  3. PUVA combination therapy.

    Science.gov (United States)

    Morison, W L

    1985-08-01

    Various adjunctive treatments are now frequently used in combination with PUVA therapy with the aims of limiting adverse effects, improving efficacy and decreasing the cost of treatment. In the management of psoriasis, PUVA plus retinoids, PUVA plus methotrexate and PUVA plus UVB phototherapy are the most frequently used combinations. PUVA plus topical corticosteroids and PUVA plus anthralin are also efficacious but adverse effects and poor acceptance by patients are limiting factors. Combinations of PUVA plus nitrogen mustard and ionizing radiation are used in mycosis fungoides to treat tumors and residual disease in secluded sites. In the management of photodermatoses with PUVA therapy, prednisone is often required to prevent exacerbation of disease. A combination of prednisone and PUVA therapy can also be useful in lichen planus and atopic eczema. The selection of a suitable combination treatment, will depend upon the preferences of the clinician, the disease being treated, and the characteristics of the patient.

  4. Optical Communications Channel Combiner

    Science.gov (United States)

    Quirk, Kevin J.; Quirk, Kevin J.; Nguyen, Danh H.; Nguyen, Huy

    2012-01-01

    NASA has identified deep-space optical communications links as an integral part of a unified space communication network in order to provide data rates in excess of 100 Mb/s. The distances and limited power inherent in a deep-space optical downlink necessitate the use of photon-counting detectors and a power-efficient modulation such as pulse position modulation (PPM). For the output of each photodetector, whether from a separate telescope or a portion of the detection area, a communication receiver estimates a log-likelihood ratio for each PPM slot. To realize the full effective aperture of these receivers, their outputs must be combined prior to information decoding. A channel combiner was developed to synchronize the log-likelihood ratio (LLR) sequences of multiple receivers, and then combines these into a single LLR sequence for information decoding. The channel combiner synchronizes the LLR sequences of up to three receivers and then combines these into a single LLR sequence for output. The channel combiner has three channel inputs, each of which takes as input a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The cross-correlation between the channels LLR time series are calculated and used to synchronize the sequences prior to combining. The output of the channel combiner is a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The unit is controlled through a 1 Gb/s Ethernet UDP/IP interface. A deep-space optical communication link has not yet been demonstrated. This ground-station channel combiner was developed to demonstrate this capability and is unique in its ability to process such a signal.

  5. Wood-plastic combination

    International Nuclear Information System (INIS)

    Schaudy, R.

    1978-02-01

    A review on wood-plastic combinations is given including the production (wood and plastic component, radiation hardening, curing), the obtained properties, present applications and prospects for the future of these materials. (author)

  6. Resonant High Power Combiners

    CERN Document Server

    Langlois, Michel; Peillex-Delphe, Guy

    2005-01-01

    Particle accelerators need radio frequency sources. Above 300 MHz, the amplifiers mostly used high power klystrons developed for this sole purpose. As for military equipment, users are drawn to buy "off the shelf" components rather than dedicated devices. IOTs have replaced most klystrons in TV transmitters and find their way in particle accelerators. They are less bulky, easier to replace, more efficient at reduced power. They are also far less powerful. What is the benefit of very compact sources if huge 3 dB couplers are needed to combine the power? To alleviate this drawback, we investigated a resonant combiner, operating in TM010 mode, able to combine 3 to 5 IOTs. Our IOTs being able to deliver 80 kW C.W. apiece, combined power would reach 400 kW minus the minor insertion loss. Values for matching and insertion loss are given. The behavior of the system in case of IOT failure is analyzed.

  7. Combining in Theory Building

    Directory of Open Access Journals (Sweden)

    Uolevi Lehtinen

    2013-07-01

    Full Text Available The objectives of this article strive to describe the idea and rationale of combining i.e. why, when and how to develop theoretically new combined approaches. Then business administration, especially marketing is used as a theoretical and empirical illustrative area. Methodology is inductive and deductive logic and in the empirical examples surveys, case analysis and utilization of secondary data. This article introduce a new promising way, in the long run, to develop new comprehensive approaches and even paradigms for different disciplines, subdisciplines and branches of subdiciplines. Therefore, the ultimate message of the article is to challenge the researchers to put the idea and rationale for combing to the test in their own research field and to build new combined and comprehensive approaches if possible in the field. This message is rather multidisciplinary concerning for example economics, social sciences and political sciences in addition to business administration.

  8. Combinators for Paraconsistent Attitudes

    DEFF Research Database (Denmark)

    Villadsen, Jørgen

    2001-01-01

    In order to analyse the semantics of natural language sentences a translation into a partial type logic using lexical and logical combinators is presented. The sentences cover a fragment of English with propositional attitudes like knowledge, belief and assertion. A combinator is a closed term...... used for embedded sentences expressing propositional attitudes, thereby allowing for inconsistency without explosion (also called paraconsistency), and is based on a few key equalities for the connectives giving four truth values (truth, falsehood, and undefinedness with negative and positive polarity...

  9. Combined PET/MRI

    DEFF Research Database (Denmark)

    Bailey, D. L.; Pichler, B. J.; Gückel, B.

    2015-01-01

    This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from...

  10. Combine Harvester Simulator

    DEFF Research Database (Denmark)

    Vilmann, Ole; Sørlie, James Arnold

    1999-01-01

    A simulator for training pilots in the operation of a modern high-tech combine harvester is presented. The new simulator application is based on DMI´s well-known DMS maritime simulator architecture. Two major challenges have been encountered in the development of the simulator: 1) interfacing the...

  11. ILSE combiner study

    International Nuclear Information System (INIS)

    Hahn, K.

    1994-03-01

    In a heavy ion inertial fusion (HIF) driver, the beam energy and current are increased several orders of magnitude from the injector to the final focus system. At low and high energy stages of the driver, electrostatic and magnetic focusing transport channels, respectively, can be used. At the electric-to-magnetic transition point, the beams may be combined to reduce the transverse dimensions of the system, which could have significant impact on the driver cost. In a presently envisioned combiner, four beams are brought together transversely into a single transport channel. A matching section follows the combiner in order to provide a smooth transition to the subsequent magnetic transport channel. This report summarizes a conceptual design study of possible combiner configurations for the proposed Introduction Linac Systems Experiment (ILSE). The conceptual design study includes subjects such as the expected technical difficulties, predicted emittance growth, particle loss, effect of geometric and chromatic aberrations, and the sensitivity of emittance growth on the initial beam position and angle errors

  12. Combined-cycle plants

    International Nuclear Information System (INIS)

    Valenti, M.

    1991-01-01

    This paper reports that as tougher emissions standards take hold throughout the industrialized world, manufacturers such as GE, Siemens, Foster Wheeler, and Asea Brown Boveri are designing advanced combined-cycle equipment that offers improved environmental performance without sacrificing power efficiency

  13. Propagating Class and Method Combination

    DEFF Research Database (Denmark)

    Ernst, Erik

    1999-01-01

    number of implicit combinations. For example, it is possible to specify separate aspects of a family of classes, and then combine several aspects into a full-fledged class family. The combination expressions would explicitly combine whole-family aspects, and by propagation implicitly combine the aspects...

  14. Combined radiotherapy-chemotherapy

    International Nuclear Information System (INIS)

    Steel, G.G.

    1989-01-01

    This paper presents the clinically confirmed benefits of combined chemotherapy-radiotherapy. They have been found in a small group of diseases that respond to chemotherapy alone. According to the author, only when a drug or drug combination has the ability to eradicate occult disease or substantially to reduce the size of objectively measurable disease is there likely to be an demonstrable benefit from its use in conjunction with radiotherapy. It is the author's belief that the immediate future lies in selecting drugs and patients in which a good chemotherapeutic response can be expected, avoiding drugs that seriously enhance radiation damage to normal tissues and keeping drug and radiation treatments far enough apart in time to minimize interactions

  15. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  16. Combined XRD and XAS

    International Nuclear Information System (INIS)

    Ehrlich, S.N.; Hanson, J.C.; Lopez Camara, A.; Barrio, L.; Estrella, M.; Zhou, G.; Si, R.; Khalid, S.; Wang, Q.

    2011-01-01

    X-ray diffraction (XRD) and X-ray absorption fine structure (XAFS) are complementary techniques for investigating the structure of materials. XRD probes long range order and XAFS probes short range order. We have combined the two techniques at one synchrotron beamline, X18A at the NSLS, allowing samples to be studied in a single experiment. This beamline will allow for coordinated measurements of local and long range structural changes in chemical transformations and phase transitions using both techniques.

  17. Transfer function combinations

    KAUST Repository

    Zhou, Liang; Schott, Mathias; Hansen, Charles

    2012-01-01

    Direct volume rendering has been an active area of research for over two decades. Transfer function design remains a difficult task since current methods, such as traditional 1D and 2D transfer functions, are not always effective for all data sets. Various 1D or 2D transfer function spaces have been proposed to improve classification exploiting different aspects, such as using the gradient magnitude for boundary location and statistical, occlusion, or size metrics. In this paper, we present a novel transfer function method which can provide more specificity for data classification by combining different transfer function spaces. In this work, a 2D transfer function can be combined with 1D transfer functions which improve the classification. Specifically, we use the traditional 2D scalar/gradient magnitude, 2D statistical, and 2D occlusion spectrum transfer functions and combine these with occlusion and/or size-based transfer functions to provide better specificity. We demonstrate the usefulness of the new method by comparing to the following previous techniques: 2D gradient magnitude, 2D occlusion spectrum, 2D statistical transfer functions and 2D size based transfer functions. © 2012 Elsevier Ltd.

  18. Transfer function combinations

    KAUST Repository

    Zhou, Liang

    2012-10-01

    Direct volume rendering has been an active area of research for over two decades. Transfer function design remains a difficult task since current methods, such as traditional 1D and 2D transfer functions, are not always effective for all data sets. Various 1D or 2D transfer function spaces have been proposed to improve classification exploiting different aspects, such as using the gradient magnitude for boundary location and statistical, occlusion, or size metrics. In this paper, we present a novel transfer function method which can provide more specificity for data classification by combining different transfer function spaces. In this work, a 2D transfer function can be combined with 1D transfer functions which improve the classification. Specifically, we use the traditional 2D scalar/gradient magnitude, 2D statistical, and 2D occlusion spectrum transfer functions and combine these with occlusion and/or size-based transfer functions to provide better specificity. We demonstrate the usefulness of the new method by comparing to the following previous techniques: 2D gradient magnitude, 2D occlusion spectrum, 2D statistical transfer functions and 2D size based transfer functions. © 2012 Elsevier Ltd.

  19. A coal combine

    Energy Technology Data Exchange (ETDEWEB)

    Wlachovsky, I; Bartos, J

    1980-02-15

    A design is presented for a coal combine, equipped with two drum operational units, on whose both ends of the upper surface of the body, two coal saws are mounted with the help of a lever system. These saws, found in an operational position, form a gap in the block of the coal block, which is not embraced by the drum operational unit. The coal block, found between the gap and the support, falls down onto the longwall scraper conveyor. The lever system of each coal saw is controlled by two hydraulic jacks. One of the jacks is mounted vertically on the facial wall of the body of the combine and is used for the hoisting for the required height of the horizontal arm of the lever, reinforced by one end in the hinge on the body of the combine. On the ''free'' end of that lever, a coal saw is mounted in a hinge-like fashion and which is connected by the hydraulic jack to the horizontal arm of the lever system. This hydraulic jack is used for the clamping of the coal saw to the face.

  20. VEGF-A is increased in exogenous endophthalmitis.

    Science.gov (United States)

    Seamone, Mark E; Lewis, Darrell R; Haidl, Ian D; Gupta, R Rishi; O' Brien, Daniel M; Dickinson, John; Samad, Arif; Marshall, Jean S; Cruess, Alan F

    2017-06-01

    Exogenous endophthalmitis is an ophthalmologic emergency defined by panocular inflammation. Vascular endothelial growth factor A (VEGF-A) contributes to inflammation by promoting chemotaxis of monocytes and granulocytes and by increasing vascular permeability. The purpose of this article is to determine if VEGF-A is elevated in the vitreous samples obtained from individuals with exogenous endophthalmitis. Vitreous samples from individuals with exogenous endophthalmitis (n = 18) were analyzed via Luminex assay and enzyme-linked immunosorbent assay for the cytokines VEGF-A, tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8 (chemokine [CXCL]-8), IL-1β, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-β, chemokine ligand (CCL)-3, IL-2, IL-5, IL-15, CXCL-10, CCL-2, IL-1Ra, CCL-5, IL-17, and CCL-11. Vitreous samples obtained at the time of macular hole surgery served as controls (n = 8). Concentrations of VEGF-A were significantly elevated in vitreous samples from individuals with exogenous endophthalmitis compared with macular hole (p exogenous endophthalmitis after cataract surgery (p = 0.001), vitrectomy (p = 0.024), and intravitreal injection (p = 0.012). VEGF-A concentrations were similar in both culture-positive and culture-negative populations (p > 0.05). In a linear regression model, levels of VEGF-A correlated significantly with the chemokine CXCL-8 (p = 0.028). We demonstrate that VEGF-A is potently upregulated in exogenous endophthalmitis. This observation provides a foundation for future studies of targeted VEGF-A blockade in the management of endophthalmitis. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  1. Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.

    Directory of Open Access Journals (Sweden)

    Sarah A Hamilton

    Full Text Available Current therapies for preterm labour (PTL focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface. Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL and term labour (TL, thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL, idiopathic PTL and PTL with infection (PTLI. Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid

  2. Belladonna Alkaloid Combinations and Phenobarbital

    Science.gov (United States)

    Donnatal® Elixir (as a combination product containing Atropine, Hyoscyamine, Phenobarbital, Scopolamine) ... PB Hyos® Elixir (as a combination product containing Atropine, Hyoscyamine, Phenobarbital, Scopolamine)

  3. Coherent laser beam combining

    CERN Document Server

    Brignon, Arnaud

    2013-01-01

    Recently, the improvement of diode pumping in solid state lasers and the development of double clad fiber lasers have allowed to maintain excellent laser beam quality with single mode fibers. However, the fiber output power if often limited below a power damage threshold. Coherent laser beam combining (CLBC) brings a solution to these limitations by identifying the most efficient architectures and allowing for excellent spectral and spatial quality. This knowledge will become critical for the design of the next generation high-power lasers and is of major interest to many industrial, environme

  4. Combined radiochemotherapy. Review

    Energy Technology Data Exchange (ETDEWEB)

    Konecny, M; Mechl, Z [Onkologicky Ustav, Brno (Czechoslovakia). Betatronove Pracoviste

    1978-09-01

    Physical, chemical, biochemical and biological modifications are described of the radiation reaction. The biochemical modification with antimetabolites has so far been the one most frequently used in clinical oncology. It has not yet been clarified whether treatment should begin with irradiation or chemotherapy. Conclusions are presented of the study of simultaneous chemotherapy and radiotherapy applications, ie., the attempt at synchronization of the tumor population. The present-time existence of a great number of combined treatment plans is more a consequence of empirical data which have not yet been clinically confirmed.

  5. Structural load combinations

    International Nuclear Information System (INIS)

    Hwang, H.; Reich, M.; Ellingwood, B.; Shinozuka, M.

    1985-01-01

    This paper presents the latest results of the program entitled, ''Probability Based Load Combinations For Design of Category I Structures''. In FY 85, a probability-based reliability analysis method has been developed to evaluate safety of shear wall structures. The shear walls are analyzed using stick models with beam elements and may be subjected to dead load, live load and in-plane eqrthquake. Both shear and flexure limit states are defined analytically. The limit state probabilities can be evaluated on the basis of these limit states. Utilizing the reliability analysis method mentioned above, load combinations for the design of shear wall structures have been established. The proposed design criteria are in the load and resistance factor design (LRFD) format. In this study, the resistance factors for shear and flexure and load factors for dead and live loads are preassigned, while the load factor for SSE is determined for a specified target limit state probability of 1.0 x 10 -6 or 1.0 x 10 -5 during a lifetime of 40 years. 23 refs., 9 tabs

  6. Combining Boosted Global

    Directory of Open Access Journals (Sweden)

    Szidónia Lefkovits

    2011-06-01

    Full Text Available The domain of object detection presents a wide range of interest due to its numerous application possibilities especially real time applications. All of them require high detection rate correlated with short processing time. One of the most efficient systems, working with visual information, were presented in the publication of Viola et al. [1], [2].This detection system uses classifiers based on Haar-like separating features combined with the AdaBoost learning algorithm. The most important bottleneck of the system is the big number of false detections at high hit rate. In this paper we propose to overcome this disadvantage by using specialized parts classifiers. This aim comes from the observation that the target object does not resemble the false detections at all.The reason of this fact is the coding manner of Haar-like features which attend to handle image patches and neglect the edges and contours. In order to obtain a more robust classifier, a global aspect method is combined with a part-based method, having the goal to improve the performance of the detector without significant increase of the detection time.

  7. Structural load combinations

    International Nuclear Information System (INIS)

    Hwang, H.; Reich, M.; Ellingwood, B.; Shinozuka, M.

    1986-01-01

    This paper presents the latest results of the program entitled, ''Probability Based Load Combinations For Design of Category I Structures''. In FY 85, a probability-based reliability analysis method has been developed to evaluate safety of shear wall structures. The shear walls are analyzed using stick models with beam elements and may be subjected to dead load, live load and in-plane earthquake. Both shear and flexure limit states are defined analytically. The limit state probabilities can be evaluated on the basis of these limit states. Utilizing the reliability analysis method mentioned above, load combinations for the design of shear wall structures have been established. The proposed design criteria are in the load and resistance factor design (LRFD) format. In this study, the resistance factors for shear and flexure and load factors for dead and live loads are preassigned, while the load factor for SSE is determined for a specified target limit state probability of 1.0 x 10 -6 or 1.0 x 10 -5 during a lifetime of 40 years

  8. IL-6 amplifies TLR mediated cytokine and chemokine production: implications for the pathogenesis of rheumatic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Ivan Caiello

    Full Text Available The role of Interleukin(IL-6 in the pathogenesis of joint and systemic inflammation in rheumatoid arthritis (RA and systemic juvenile idiopathic arthritis (s-JIA has been clearly demonstrated. However, the mechanisms by which IL-6 contributes to the pathogenesis are not completely understood. This study investigates whether IL-6 affects, alone or upon toll like receptor (TLR ligand stimulation, the production of inflammatory cytokines and chemokines in human peripheral blood mononuclear cells (PBMCs, synovial fluid mononuclear cells from JIA patients (SFMCs and fibroblast-like synoviocytes from rheumatoid arthritis patients (RA synoviocytes and signalling pathways involved. PBMCs were pre-treated with IL-6 and soluble IL-6 Receptor (sIL-6R. SFMCs and RA synoviocytes were pre-treated with IL-6/sIL-6R or sIL-6R, alone or in combination with Tocilizumab (TCZ. Cells were stimulated with LPS, S100A8-9, poly(I-C, CpG, Pam2CSK4, MDP, IL-1β. Treatment of PBMCs with IL-6 induced production of TNF-α, CXCL8, and CCL2, but not IL-1β. Addition of IL-6 to the same cells after stimulation with poly(I-C, CpG, Pam2CSK4, and MDP induced a significant increase in IL-1β and CXCL8, but not TNF-α production compared with TLR ligands alone. This enhanced production of IL-1β and CXCL8 paralleled increased p65 NF-κB activation. In contrast, addition of IL-6 to PBMCs stimulated with LPS or S100A8-9 (TLR-4 ligands led to reduction of IL-1β, TNF-α and CXCL8 with reduced p65 NF-κB activation. IL-6/IL-1β co-stimulation increased CXCL8, CCL2 and IL-6 production. Addition of IL-6 to SFMCs stimulated with LPS or S100A8 increased CXCL8, CCL2 and IL-1β production. Treatment of RA synoviocytes with sIL-6R increased IL-6, CXCL8 and CCL2 production, with increased STAT3 and p65 NF-κB phosphorylation. Our results suggest that IL-6 amplifies TLR-induced inflammatory response. This effect may be relevant in the presence of high IL-6 and sIL-6R levels, such as in arthritic

  9. Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

    International Nuclear Information System (INIS)

    Crescioli, Clara; Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

    2008-01-01

    CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFNγ and TNFαα; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNFα-induced up-regulation of IFNγR. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor γ agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFNγ-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants

  10. Combined Heat and Power

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    At their 2007 Summit in Heiligendamm, G8 leaders called on countries to 'adopt instruments and measures to significantly increase the share of combined heat and power (CHP) in the generation of electricity.' As a result, energy, economic, environmental and utility regulators are looking for tools and information to understand the potential of CHP and to identify appropriate policies for their national circumstances. This report forms the first part of the response. It includes answers to policy makers' questions about the potential economic, energy and environmental benefits of an increased policy commitment to CHP. It also includes for the first time integrated IEA data on global CHP installations, and analyses the benefits of increased CHP investment in the G8+5 countries. A companion report will be produced later in 2008 to document best practice policy approaches that have been used to expand the use of CHP in a variety of countries.

  11. Biomass Gasification Combined Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Judith A. Kieffer

    2000-07-01

    Gasification combined cycle continues to represent an important defining technology area for the forest products industry. The ''Forest Products Gasification Initiative'', organized under the Industry's Agenda 2020 technology vision and supported by the DOE ''Industries of the Future'' program, is well positioned to guide these technologies to commercial success within a five-to ten-year timeframe given supportive federal budgets and public policy. Commercial success will result in significant environmental and renewable energy goals that are shared by the Industry and the Nation. The Battelle/FERCO LIVG technology, which is the technology of choice for the application reported here, remains of high interest due to characteristics that make it well suited for integration with the infrastructure of a pulp production facility. The capital cost, operating economics and long-term demonstration of this technology area key input to future economically sustainable projects and must be verified by the 200 BDT/day demonstration facility currently operating in Burlington, Vermont. The New Bern application that was the initial objective of this project is not currently economically viable and will not be implemented at this time due to several changes at and around the mill which have occurred since the inception of the project in 1995. The analysis shows that for this technology, and likely other gasification technologies as well, the first few installations will require unique circumstances, or supportive public policies, or both to attract host sites and investors.

  12. Combined approach for gynecomastia

    Directory of Open Access Journals (Sweden)

    El-Sabbagh, Ahmed Hassan

    2016-02-01

    Full Text Available Background: Gynecomastia is a deformity of male chest. Treatment of gynecomastia varied from direct surgical excision to other techniques (mainly liposuction to a combination of both. Skin excision is done according to the grade. In this study, experience of using liposuction adjuvant to surgical excision was described. Patients and methods: Between September 2012 and April 2015, a total of 14 patients were treated with liposuction and surgical excision through a periareolar incision. Preoperative evaluation was done in all cases to exclude any underlying cause of gynecomastia. Results: All fourteen patients were treated bilaterally (28 breast tissues. Their ages ranged between 13 and 33 years. Two patients were classified as grade I, and four as grade IIa, IIb or III, respectively. The first showed seroma. Partial superficial epidermolysis of areola occurred in 2 cases. Superficial infection of incision occurred in one case and was treated conservatively. Conclusion: All grades of gynecomastia were managed by the same approach. Skin excision was added to a patient that had severe skin excess with limited activity and bad skin complexion. No cases required another setting or asked for 2 opinion.

  13. Combined approach for gynecomastia.

    Science.gov (United States)

    El-Sabbagh, Ahmed Hassan

    2016-01-01

    Gynecomastia is a deformity of male chest. Treatment of gynecomastia varied from direct surgical excision to other techniques (mainly liposuction) to a combination of both. Skin excision is done according to the grade. In this study, experience of using liposuction adjuvant to surgical excision was described. Between September 2012 and April 2015, a total of 14 patients were treated with liposuction and surgical excision through a periareolar incision. Preoperative evaluation was done in all cases to exclude any underlying cause of gynecomastia. All fourteen patients were treated bilaterally (28 breast tissues). Their ages ranged between 13 and 33 years. Two patients were classified as grade I, and four as grade IIa, IIb or III, respectively. The first 3 patients showed seroma. Partial superficial epidermolysis of areola occurred in 2 cases. Superficial infection of incision occurred in one case and was treated conservatively. All grades of gynecomastia were managed by the same approach. Skin excision was added to a patient that had severe skin excess with limited activity and bad skin complexion. No cases required another setting or asked for 2(nd) opinion.

  14. Challenges of Combining Perspectives.

    Science.gov (United States)

    Sundvall, Maria; Titelman, David; Bäärnhielm, Sofie

    2018-02-23

    Asylum seekers have increased risk of suicide and suicidal behavior, with differences related to origin, gender, and age. There are barriers to communication in clinical encounters between asylum seekers and clinicians. There is insufficient knowledge about how communication in the clinical encounter affects the suicide risk in female asylum seekers. To explore the documented communication between female asylum-seeking suicide attempters and clinicians and how it affects treatment. The medical records of 18 asylum-seeking women who had attempted suicide were analyzed with content analysis. Communication between patients and clinicians was affected by: the unbearable realities of the women; difficulties for clinicians in decoding languages of distress, and understanding trauma and subjective meanings of suicide; challenges of combining patients' and clinicians' perspectives; and a sense of shared powerlessness. The medical records did not give direct access to the patient's experience, only to the patient as documented by the clinician. The results suggest that clinicians working with asylum seekers who have attempted suicide need to develop an understanding of social and cultural factors and of trauma issues. A question for further study is how an enhanced integration of context and subjectivity in psychiatric practice would equip clinicians for the specific challenges encountered.

  15. LIDAR COMBINED SCANNING UNIT

    Directory of Open Access Journals (Sweden)

    V. V. Elizarov

    2016-11-01

    Full Text Available Subject of Research. The results of lidar combined scanning unit development for locating leaks of hydrocarbons are presented The unit enables to perform high-speed scanning of the investigated space in wide and narrow angle fields. Method. Scanning in a wide angular field is produced by one-line scanning path by means of the movable aluminum mirror with a frequency of 20Hz and amplitude of 20 degrees of swing. Narrowband scanning is performed along a spiral path by the deflector. The deflection of the beam is done by rotation of the optical wedges forming part of the deflector at an angle of ±50. The control function of the scanning node is performed by a specialized software product written in C# programming language. Main Results. This scanning unit allows scanning the investigated area at a distance of 50-100 m with spatial resolution at the level of 3 cm. The positioning accuracy of the laser beam in space is 15'. The developed scanning unit gives the possibility to browse the entire investigated area for the time not more than 1 ms at a rotation frequency of each wedge from 50 to 200 Hz. The problem of unambiguous definition of the beam geographical coordinates in space is solved at the software level according to the rotation angles of the mirrors and optical wedges. Lidar system coordinates are determined by means of GPS. Practical Relevance. Development results open the possibility for increasing the spatial resolution of scanning systems of a wide range of lidars and can provide high positioning accuracy of the laser beam in space.

  16. Combined dyslipidemia in childhood.

    Science.gov (United States)

    Kavey, Rae-Ellen W

    2015-01-01

    Combined dyslipidemia (CD) is now the predominant dyslipidemic pattern in childhood, characterized by moderate-to-severe elevation in triglycerides and non-high-density lipoprotein cholesterol (non-HDL-C), minimal elevation in low-density lipoprotein cholesterol (LDL-C), and reduced HDL-C. Nuclear magnetic resonance spectroscopy shows that the CD pattern is represented at the lipid subpopulation level as an increase in small, dense LDL and in overall LDL particle number plus a reduction in total HDL-C and large HDL particles, a highly atherogenic pattern. In youth, CD occurs almost exclusively with obesity and is highly prevalent, seen in more than 40% of obese adolescents. CD in childhood predicts pathologic evidence of atherosclerosis and vascular dysfunction in adolescence and young adulthood, and early clinical cardiovascular events in adult life. There is a tight connection between CD, visceral adiposity, insulin resistance, nonalcoholic fatty liver disease, and the metabolic syndrome, suggesting an integrated pathophysiological response to excessive weight gain. Weight loss, changes in dietary composition, and increases in physical activity have all been shown to improve CD significantly in children and adolescents in short-term studies. Most importantly, even small amounts of weight loss are associated with significant decreases in triglyceride levels and increases in HDL-C levels with improvement in lipid subpopulations. Diet change focused on limitation of simple carbohydrate intake with specific elimination of all sugar-sweetened beverages is very effective. Evidence-based recommendations for initiating diet and activity change are provided. Rarely, drug therapy is needed, and the evidence for drug treatment of CD in childhood is reviewed. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  17. Glycosaminoglycans Regulate CXCR3 Ligands at Distinct Levels: Protection against Processing by Dipeptidyl Peptidase IV/CD26 and Interference with Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Mieke Metzemaekers

    2017-07-01

    Full Text Available CXC chemokine ligand (CXCL9, CXCL10 and CXCL11 direct chemotaxis of mainly T cells and NK cells through activation of their common CXC chemokine receptor (CXCR3. They are inactivated upon NH2-terminal cleavage by dipeptidyl peptidase IV/CD26. In the present study, we found that different glycosaminoglycans (GAGs protect the CXCR3 ligands against proteolytic processing by CD26 without directly affecting the enzymatic activity of CD26. In addition, GAGs were shown to interfere with chemokine-induced CXCR3 signaling. The observation that heparan sulfate did not, and heparin only moderately, altered CXCL10-induced T cell chemotaxis in vitro may be explained by a combination of protection against proteolytic inactivation and altered receptor interaction as observed in calcium assays. No effect of CD26 inhibition was found on CXCL10-induced chemotaxis in vitro. However, treatment of mice with the CD26 inhibitor sitagliptin resulted in an enhanced CXCL10-induced lymphocyte influx into the joint. This study reveals a dual role for GAGs in modulating the biological activity of CXCR3 ligands. GAGs protect the chemokines from proteolytic cleavage but also directly interfere with chemokine–CXCR3 signaling. These data support the hypothesis that both GAGs and CD26 affect the in vivo chemokine function.

  18. Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients.

    Science.gov (United States)

    Tyagi, Pradeep; Motley, Saundra S; Koyama, Tatsuki; Kashyap, Mahendra; Gingrich, Jeffrey; Yoshimura, Naoki; Fowke, Jay H

    2018-01-01

    Benign prostatic hyperplasia (BPH) is strongly associated with obesity and prostatic tissue inflammation, but the molecular underpinning of this relationship is not known. Here, we examined the association between urine levels of chemokines/adipokines with histological markers of prostate inflammation, obesity, and lower urinary tract symptoms LUTS in BPH patients. Frozen urine specimens from 207 BPH/LUTS patients enrolled in Nashville Men's Health Study were sent for blinded analysis of 11 analytes, namely sIL-1RA, CXC chemokines (CXCL-1, CXCL-8, CXCL-10), CC chemokines (CCL2, CCL3, CCL5), PDGF-BB, interleukins IL-6, IL-17, and sCD40L using Luminex™ xMAP® technology. After adjusting for age and medication use, the urine levels of analytes were correlated with the scales of obesity, prostate inflammation grade, extent, and markers of lymphocytic infiltration (CD3 and CD20) using linear regression. sIL-1RA levels were significantly raised with higher BMI, waist circumference and waist-hip ratio in BPH patients after correction for multiple testing (P = 0.02). Men with greater overall extent of inflammatory infiltrates and maximal CD3 infiltration were marginally associated with CXCL-10 (P = 0.054) and CCL5 (P = 0.054), respectively. CCL3 in 15 patients with moderate to severe grade inflammation was marginally associated with maximal CD20 infiltration (P = 0.09), whereas CCL3 was undetectable in men with mild prostate tissue inflammation. There was marginal association of sCD40L with AUA-SI scores (P = 0.07). Strong association of sIL-1RA in urine with greater body size supports it as a major molecular correlate of obesity in the urine of BPH patients. Increased urine levels of CXCL-10, CCL5, and CCL3 were marginally associated with the scores for prostate tissue inflammation and lymphocytic infiltration. Overall, elevated urinary chemokines support that BPH is a metabolic disorder and suggest a molecular link between BPH/LUTS and prostatic

  19. Conceptual Combination During Sentence Comprehension

    Science.gov (United States)

    Swinney, David; Love, Tracy; Walenski, Matthew; Smith, Edward E.

    2008-01-01

    This experiment examined the time course of integration of modifier-noun (conceptual) combinations during auditory sentence comprehension using cross-modal lexical priming. The study revealed that during ongoing comprehension, there is initial activation of features of the noun prior to activation of (emergent) features of the entire conceptual combination. These results support compositionality in conceptual combination; that is, they indicate that features of the individual words constituting a conceptual combination are activated prior to combination of the words into a new concept. PMID:17576278

  20. Generator of combined logical signals

    International Nuclear Information System (INIS)

    Laviron, Andre; Berard, Claude.

    1982-01-01

    The invention concerns a generator of combined logical signals to form combinations of two outputs at logical level 1 and N-2 outputs at logical level 0, among N generator outputs. This generator is characterized in that it includes a set of N means for storing combinations. Means enable the N storage means to be loaded with the logical levels corresponding to a pre-set starting combination, to control the operations for shifting the contents of the storage means and to control, by transfer facilities, the transfers of contents between these storage means. Controls enable the storage means to be actuated in order to obtain combinations of logical levels 1 and 0. The generation of combinations can be stopped after another pre-set combination. Application is for testing of safety circuits for nuclear power stations [fr

  1. CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II

    Directory of Open Access Journals (Sweden)

    Prasse Antje

    2005-07-01

    Full Text Available Abstract The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2 and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11 in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II. AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.

  2. Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

    Science.gov (United States)

    Laperchia, Claudia; Tesoriero, Chiara; Seke-Etet, Paul F; La Verde, Valentina; Colavito, Valeria; Grassi-Zucconi, Gigliola; Rodgers, Jean; Montague, Paul; Kennedy, Peter G E; Bentivoglio, Marina

    2017-08-01

    Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis.

  3. Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    2017-08-01

    Full Text Available Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease.The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi, but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness.The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African

  4. Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

    Directory of Open Access Journals (Sweden)

    Jordana Grazziela Alves Coelho-dos-Reis

    Full Text Available In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+HLA-DR(+, CD8(+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

  5. Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls.

    Directory of Open Access Journals (Sweden)

    Pierre de Flon

    Full Text Available To investigate changes in the cerebrospinal fluid (CSF immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS, and to compare the profile in MS patients with healthy controls (HC.Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10, IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8 decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

  6. Tumor-Promoting Circuits That Regulate a Cancer-Related Chemokine Cluster: Dominance of Inflammatory Mediators Over Oncogenic Alterations

    International Nuclear Information System (INIS)

    Leibovich-Rivkin, Tal; Buganim, Yosef; Solomon, Hilla; Meshel, Tsipi; Rotter, Varda; Ben-Baruch, Adit

    2012-01-01

    Here, we investigated the relative contribution of genetic/signaling components versus microenvironmental factors to the malignancy phenotype. In this system, we took advantage of non-transformed fibroblasts that carried defined oncogenic modifications in Ras and/or p53. These cells were exposed to microenvironmental pressures, and the expression of a cancer-related chemokine cluster was used as readout for the malignancy potential (CCL2, CCL5, CXCL8, CXCL10). In cells kept in-culture, synergism between Ras hyper-activation and p53 dysfunction was required to up-regulate the expression of the chemokine cluster. The in vivo passage of Ras High /p53 Low -modified cells has led to tumor formation, accompanied by potentiation of chemokine release, implicating a powerful role for the tumor microenvironment in up-regulating the chemokine cluster. Indeed, we found that inflammatory mediators which are prevalent in tumor sites, such as TNFα and IL-1β, had a predominant impact on the release of the chemokines, which was substantially higher than that obtained by the oncogenic modifications alone, possibly acting through the transcription factors AP-1 and NF-κB. Together, our results propose that in the unbiased model system that we were using, inflammatory mediators of the tumor milieu have dominating roles over oncogenic modifications in dictating the expression of a pro-malignancy chemokine readout

  7. The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea

    Directory of Open Access Journals (Sweden)

    Francesco Drago

    2015-01-01

    Full Text Available Introduction. Pityriasis rosea (PR is an exanthematous disease related to human herpesvirus- (HHV- 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied. Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis. Materials and Methods. Interleukin- (IL- 1, IL-6, IL-17, interferon- (IFN- γ, tumor necrosis factor- (TNF- α, vascular endothelial growth factor (VEGF, granulocyte colony stimulating factor (G-CSF, and chemokines, CXCL8 (IL-8 and CXCL10 (IP-10, were measured simultaneously by a multiplex assay in early acute PR patients’ sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days. Results and discussion. Serum levels of IL-17, IFN-γ, VEGF, and IP-10 resulted to be upregulated in PR patients compared to controls. IL-17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN-γ has a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP-10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis. Conclusions. Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.

  8. Packet reversed packet combining scheme

    International Nuclear Information System (INIS)

    Bhunia, C.T.

    2006-07-01

    The packet combining scheme is a well defined simple error correction scheme with erroneous copies at the receiver. It offers higher throughput combined with ARQ protocols in networks than that of basic ARQ protocols. But packet combining scheme fails to correct errors when the errors occur in the same bit locations of two erroneous copies. In the present work, we propose a scheme that will correct error if the errors occur at the same bit location of the erroneous copies. The proposed scheme when combined with ARQ protocol will offer higher throughput. (author)

  9. Combined Environment Acoustic Chamber (CEAC)

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The CEAC imposes combined acoustic, thermal and mechanical loads on aerospace structures. The CEAC is employed to measure structural response and determine...

  10. Symbol Stream Combining Versus Baseband Combining for Telemetry Arraying

    Science.gov (United States)

    Divsalar, D.

    1983-01-01

    The objectives of this article are to investigate and analyze the problem of combining symbol streams from many Deep Space Network stations to enhance bit signal-to-noise ratio and to compare the performance of this combining technique with baseband combining. Symbol stream combining (SSC) has some advantages and some disadvantages over baseband combining (BBC). The SSC suffers almost no loss in combining the digital data and no loss due to the transmission of the digital data by microwave links between the stations. The BBC suffers 0.2 dB loss due to alignment and combining the IF signals and 0.2 dB loss due to transmission of signals by microwave links. On the other hand, the losses in the subcarrier demodulation assembly (SDA) and in the symbol synchronization assembly (SSA) for SSC are more than the losses in the SDA and SSA for BBC. It is shown that SSC outperforms BBC by about 0.35 dB (in terms of the required bit energy-to-noise spectral density for a bit error rate of 1,000) for an array of three DSN antennas, namely 64 m, 34m(T/R) and 34m(R).

  11. Revised Accounting for Business Combinations

    Science.gov (United States)

    Wilson, Arlette C.; Key, Kimberly

    2008-01-01

    The Financial Accounting Standards Board (FASB) has recently issued Statement of Financial Accounting Standards No. 141 (Revised 2007) Business Combinations. The object of this Statement is to improve the relevance, representational faithfulness, and comparability of reported information about a business combination and its effects. This Statement…

  12. Modified Aggressive Packet Combining Scheme

    International Nuclear Information System (INIS)

    Bhunia, C.T.

    2010-06-01

    In this letter, a few schemes are presented to improve the performance of aggressive packet combining scheme (APC). To combat error in computer/data communication networks, ARQ (Automatic Repeat Request) techniques are used. Several modifications to improve the performance of ARQ are suggested by recent research and are found in literature. The important modifications are majority packet combining scheme (MjPC proposed by Wicker), packet combining scheme (PC proposed by Chakraborty), modified packet combining scheme (MPC proposed by Bhunia), and packet reversed packet combining (PRPC proposed by Bhunia) scheme. These modifications are appropriate for improving throughput of conventional ARQ protocols. Leung proposed an idea of APC for error control in wireless networks with the basic objective of error control in uplink wireless data network. We suggest a few modifications of APC to improve its performance in terms of higher throughput, lower delay and higher error correction capability. (author)

  13. Uniportal anatomic combined unusual segmentectomies.

    Science.gov (United States)

    González-Rivas, Diego; Lirio, Francisco; Sesma, Julio

    2017-01-01

    Nowadays, sublobar anatomic resections are gaining momentum as a valid alternative for early stage lung cancer. Despite being technically demanding, anatomic segmentectomies can be performed by uniportal video-assisted thoracic surgery (VATS) approach to combine the benefits of minimally invasiveness with the maximum lung sparing. This procedure can be even more complex if a combined resection of multiple segments from different lobes has to be done. Here we report five cases of combined and unusual segmentectomies done by the same experienced surgeon in high volume institutions to show uniportal VATS is a feasible approach for these complex resections and to share an excellent educational resource.

  14. Combination contraceptives: effects on weight.

    Science.gov (United States)

    Gallo, Maria F; Lopez, Laureen M; Grimes, David A; Carayon, Florence; Schulz, Kenneth F; Helmerhorst, Frans M

    2014-01-29

    Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length. All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post-treatment measurements using a fixed-effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated. We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find

  15. Mode Combinations and International Operations

    DEFF Research Database (Denmark)

    Benito, Gabriel R. G.; Petersen, Bent; Welch, Lawrence S.

    2011-01-01

    reveals that companies tend to combine modes of operation; thereby producing unique foreign operation mode “packages” for given activities and/or countries, and that the packages are liable to be modified over time – providing a potentially important optional path for international expansion. Our data...... key markets (China, UK and USA) as the basis for an exploration of the extent to which, and how and why, companies combine clearly different foreign operation modes. We examine their use of foreign operation mode combinations within given value activities as well as within given countries. The study...

  16. Mode Combinations and International Operations

    DEFF Research Database (Denmark)

    Benito, Gabriel R. G.; Petersen, Bent; Welch, Lawrence S.

    2011-01-01

    reveals that companies tend to combine modes of operation; thereby producing unique foreign operation mode “packages” for given activities and/or countries, and that the packages are liable to be modified over time—providing a potentially important optional path for international expansion. The data show...... markets (China, UK and USA) is used as the basis for an exploration of the extent to which, and how and why, companies combine clearly different foreign operation modes. We examine their use of foreign operation mode combinations within given value activities as well as within given countries. The study...

  17. Combined keratoplasty and cataract extraction.

    Science.gov (United States)

    Demeler, U; Hinzpeter, E N

    1977-04-01

    A short film showing our technique of combined penetrating keratoplasty and intracapsular cataract extraction was shown, and the postoperative results in 72 eyes after an average of 3 years were reported.

  18. Atypical combinations and scientific impact.

    Science.gov (United States)

    Uzzi, Brian; Mukherjee, Satyam; Stringer, Michael; Jones, Ben

    2013-10-25

    Novelty is an essential feature of creative ideas, yet the building blocks of new ideas are often embodied in existing knowledge. From this perspective, balancing atypical knowledge with conventional knowledge may be critical to the link between innovativeness and impact. Our analysis of 17.9 million papers spanning all scientific fields suggests that science follows a nearly universal pattern: The highest-impact science is primarily grounded in exceptionally conventional combinations of prior work yet simultaneously features an intrusion of unusual combinations. Papers of this type were twice as likely to be highly cited works. Novel combinations of prior work are rare, yet teams are 37.7% more likely than solo authors to insert novel combinations into familiar knowledge domains.

  19. Autonomous grain combine control system

    Science.gov (United States)

    Hoskinson, Reed L.; Kenney, Kevin L.; Lucas, James R.; Prickel, Marvin A.

    2013-06-25

    A system for controlling a grain combine having a rotor/cylinder, a sieve, a fan, a concave, a feeder, a header, an engine, and a control system. The feeder of the grain combine is engaged and the header is lowered. A separator loss target, engine load target, and a sieve loss target are selected. Grain is harvested with the lowered header passing the grain through the engaged feeder. Separator loss, sieve loss, engine load and ground speed of the grain combine are continuously monitored during the harvesting. If the monitored separator loss exceeds the selected separator loss target, the speed of the rotor/cylinder, the concave setting, the engine load target, or a combination thereof is adjusted. If the monitored sieve loss exceeds the selected sieve loss target, the speed of the fan, the size of the sieve openings, or the engine load target is adjusted.

  20. Combining supramolecular chemistry with biology

    NARCIS (Netherlands)

    Uhlenheuer, D.A.; Petkau - Milroy, K.; Brunsveld, L.

    2010-01-01

    Supramolecular chemistry has primarily found its inspiration in biological molecules, such as proteins and lipids, and their interactions. Currently the supramolecular assembly of designed compounds can be controlled to great extent. This provides the opportunity to combine these synthetic

  1. Tariff Model for Combined Transport

    Directory of Open Access Journals (Sweden)

    Velimir Kolar

    2002-11-01

    Full Text Available By analysing the cwTen.t situation on the Croatian transportationmarket, and considering all parameters needed forthe development of combined transport, measures are suggestedin order to improve and stimulate its development. Oneof the first measures is the standardisation and introduction ofunique tariffs for combined transport, and then government incentivefor the organisation and development of combinedtransport means and equipment. A significant role in thisshould be set on adequately defined transport policy.

  2. Combining norms to prove termination

    DEFF Research Database (Denmark)

    Genaim, S.; Codish, M.; Gallagher, John Patrick

    2002-01-01

    Automatic termination analysers typically measure the size of terms applying norms which are mappings from terms to the natural numbers. This paper illustrates howt o enable the use of size functions defined as tuples of these simpler norm functions. This approach enables us to simplify the probl...... of the recursive data-types in the program, is often a suitable choice. We first demonstrate the power of combining norm functions and then the adequacy of combining norms based on regular types....

  3. Combined radar and telemetry system

    Energy Technology Data Exchange (ETDEWEB)

    Rodenbeck, Christopher T.; Young, Derek; Chou, Tina; Hsieh, Lung-Hwa; Conover, Kurt; Heintzleman, Richard

    2017-08-01

    A combined radar and telemetry system is described. The combined radar and telemetry system includes a processing unit that executes instructions, where the instructions define a radar waveform and a telemetry waveform. The processor outputs a digital baseband signal based upon the instructions, where the digital baseband signal is based upon the radar waveform and the telemetry waveform. A radar and telemetry circuit transmits, simultaneously, a radar signal and telemetry signal based upon the digital baseband signal.

  4. Food irradiation and combination processes

    International Nuclear Information System (INIS)

    Campbell-Platt, G.; Grandison, A.S.

    1990-01-01

    International approval of food irradiation is being given for the use of low and medium doses. Uses are being permitted for different categories of foods with maximum levels being set between 1 and 10 kGy. To maximize the effectiveness of these mild irradiation treatments while minimizing any organoleptic quality changes, combination processes of other technologies with irradiation will be useful. Combinations most likely to be exploited in optimal food processing include the use of heat, low temperature, and modified-atmosphere packaging. Because irradiation does not have a residual effect, the food packaging itself becomes an important component of a successful process. These combination processes provide promising alternatives to the use of chemical preservatives or harsher processing techniques. (author)

  5. Combined oral contraceptives: venous thrombosis.

    Science.gov (United States)

    de Bastos, Marcos; Stegeman, Bernardine H; Rosendaal, Frits R; Van Hylckama Vlieg, Astrid; Helmerhorst, Frans M; Stijnen, Theo; Dekkers, Olaf M

    2014-03-03

    Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. We selected studies including healthy women taking COC with VT as outcome. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene

  6. Planned combined radiotherapy and surgery

    International Nuclear Information System (INIS)

    Silverman, C.L.; Marks, J.E.

    1987-01-01

    Though the planned combined use of surgery and radiation has been shown to be beneficial for other tumors, the authors feel that the present evidence is far from persuasive in demonstrating a definite superiority of combined therapy over surgery or radiation alone for advanced laryngeal tumors. The actuarial or disease-free survival rates for patients treated with combined therapy have not been significantly increased over those obtained with a single modality in any randomized, well-controlled study, although the trend is toward improved local regional control. Many of the retrospective studies are probably flawed by selection bias; the patients selected for combined treatment generally have more advanced cancers and represent a worse prognostic group. It is clear from this review that the positive value of irradiation for advanced transglottic and supraglottic tumors needs to be documented by a controlled study that compares surgery alone with salvage radiation at time of recurrence to surgery plus adjuvant radiation. The authors feel that such a study is needed to put to rest the present controversy before they can advocate a course of treatment that is expensive, time-consuming, and difficult for the patients to tolerate owing to severe acute side effects and potentially morbid late effects (xerostomia, necrosis) that can greatly lessen the quality of life for these patients

  7. SUPPLEMENTARY INFORMATION A combined Electrochemical ...

    Indian Academy of Sciences (India)

    DELL

    A combined Electrochemical and Theoretical study of pyridine-based Schiff bases as novel corrosion inhibitors for mild steel in hydrochloric acid medium. PARUL DOHAREa, M A QURAISHIb* and I B OBOTb. aDepartment of Chemistry, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar. Pradesh 221 ...

  8. Combination Chemoprevention with Grape Antioxidants

    OpenAIRE

    Singh, Chandra K.; Siddiqui, Imtiaz A.; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

    2016-01-01

    Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resver...

  9. Combining Paraconsistent Logic with Argumentation

    NARCIS (Netherlands)

    Grooters, Diana; Prakken, Hendrik

    2014-01-01

    One tradition in the logical study of argumentation is to allow for arguments that combine strict and defeasible inference rules, and to derive the strict inference rules from a logic at least as strong as classical logic. An unsolved problem in this tradition is how the trivialising effect of the

  10. Combination treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Holbech, Jakob Vormstrup; Jung, Anne; Jonsson, Torsten

    2017-01-01

    BACKGROUND: Current Danish treatment algorithms for pharmacological treatment of neuropathic pain (NeP) are tricyclic antidepressants (TCA), gabapentin and pregabalin as first-line treatment for the most common NeP conditions. Many patients have insufficient pain relief on monotherapy, but combin...

  11. Methodology for combining dynamic responses

    International Nuclear Information System (INIS)

    Cudlin, R.; Hosford, S.; Mattu, R.; Wichman, K.

    1978-09-01

    The NRC has historically required that the structural/mechanical responses due to various accident loads and loads caused by natural phenomena, (such as earthquakes) be combined when analyzing structures, systems, and components important to safety. Several approaches to account for the potential interaction of loads resulting from accidents and natural phenomena have been used. One approach, the so-called absolute or linear summation (ABS) method, linearly adds the peak structural responses due to the individual dynamic loads. In general, the ABS method has also reflected the staff's conservative preference for the combination of dynamic load responses. A second approach, referred to as SRSS, yields a combined response equal to the square root of the sum of the squares of the peak responses due to the individual dynamic loads. The lack of a physical relationship between some of the loads has raised questions as to the proper methodology to be used in the design of nuclear power plants. An NRR Working Group was constituted to examine load combination methodologies and to develop a recommendation concerning criteria or conditions for their application. Evaluations of and recommendations on the use of the ABS and SRSS methods are provided in the report

  12. Combined enteral and parenteral nutrition.

    Science.gov (United States)

    Wernerman, Jan

    2012-03-01

    To review and discuss the evidence and arguments to combine enteral nutrition and parenteral nutrition in the ICU, in particular with reference to the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study. The EPaNIC study shows an advantage in terms of discharges alive from the ICU when parenteral nutrition is delayed to day 8 as compared with combining enteral nutrition and parenteral nutrition from day 3 of ICU stay. The difference between the guidelines from the European Society of Enteral and Parenteral Nutrition in Europe and American Society for Parenteral and Enteral Nutrition/Society of Critical Care Medicine in North America concerning the combination of enteral nutrition and parenteral nutrition during the initial week of ICU stay was reviewed. The EPaNIC study clearly demonstrates that early parenteral nutrition in the ICU is not in the best interests of most patients. Exactly at what time point the combination of enteral nutrition and parenteral nutrition should be considered is still an open question.

  13. Airbreathing combined cycle engine systems

    Science.gov (United States)

    Rohde, John

    1992-01-01

    The Air Force and NASA share a common interest in developing advanced propulsion systems for commercial and military aerospace vehicles which require efficient acceleration and cruise operation in the Mach 4 to 6 flight regime. The principle engine of interest is the turboramjet; however, other combined cycles such as the turboscramjet, air turborocket, supercharged ejector ramjet, ejector ramjet, and air liquefaction based propulsion are also of interest. Over the past months careful planning and program implementation have resulted in a number of development efforts that will lead to a broad technology base for those combined cycle propulsion systems. Individual development programs are underway in thermal management, controls materials, endothermic hydrocarbon fuels, air intake systems, nozzle exhaust systems, gas turbines and ramjet ramburners.

  14. Combined Surgical Treatment of Gynecomastia

    Directory of Open Access Journals (Sweden)

    Yordanov Y.

    2015-05-01

    Full Text Available Surgical treatment of gynecomastia could present unique challenges for the plastic surgeon. Achieving a good balance between effectiveness of the selected approach and the satisfactory aesthetic outcome often is a difficult endeavor. Optimal surgical treatment involves a combination of liposuction and direct excision. In the present study the charts of 11 patients treated with suction-assisted liposuction and direct surgical excision were retrospectively reviewed; a special emphasis is placed on the surgical technique. The mean follow-up period of the patients was 11.6 months. No infection, hematoma, nipple-areola complex necrosis and nipple retraction was encountered in this series. The combined surgical treatment of gynecomastia has shown to be a reliable technique in both small and moderate breast enlargement including those with skin excess.

  15. Anti-Inflammatory Benefits of Antibiotics: Tylvalosin Induces Apoptosis of Porcine Neutrophils and Macrophages, Promotes Efferocytosis, and Inhibits Pro-Inflammatory CXCL-8, IL1α, and LTB4 Production, While Inducing the Release of Pro-Resolving Lipoxin A4 and Resolvin D1

    OpenAIRE

    Ruth Moges; Ruth Moges; Dimitri Desmonts De Lamache; Dimitri Desmonts De Lamache; Saman Sajedy; Bernard S. Renaux; Bernard S. Renaux; Morley D. Hollenberg; Morley D. Hollenberg; Gregory Muench; Elizabeth M. Abbott; Andre G. Buret; Andre G. Buret

    2018-01-01

    Excessive accumulation of neutrophils and their uncontrolled death by necrosis at the site of inflammation exacerbates inflammatory responses and leads to self-amplifying tissue injury and loss of organ function, as exemplified in a variety of respiratory diseases. In homeostasis, neutrophils are inactivated by apoptosis, and non phlogistically removed by neighboring macrophages in a process known as efferocytosis, which promotes the resolution of inflammation. The present study assessed the ...

  16. Chemical and natural stressors combined:

    DEFF Research Database (Denmark)

    Gergs, André; Zenker, Armin; Grimm, Volker

    2013-01-01

    In addition to natural stressors, populations are increasingly exposed to chemical pollutants released into the environment. We experimentally demonstrate the loss of resilience for Daphnia magna populations that are exposed to a combination of natural and chemical stressors even though effects...... demonstrates that population size can be a poor endpoint for risk assessments of chemicals and that ignoring disturbance interactions can lead to severe underestimation of extinction risk...

  17. Combination chemoprevention with grape antioxidants.

    Science.gov (United States)

    Singh, Chandra K; Siddiqui, Imtiaz A; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

    2016-06-01

    Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape ingredients alone or together with other agents could impart 'additive synergism' against cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Imagining a Stata / Python Combination

    Science.gov (United States)

    Fiedler, James

    2012-01-01

    There are occasions when a task is difficult in Stata, but fairly easy in a more general programming language. Python is a popular language for a range of uses. It is easy to use, has many high ]quality packages, and programs can be written relatively quickly. Is there any advantage in combining Stata and Python within a single interface? Stata already offers support for user-written programs, which allow extensive control over calculations, but somewhat less control over graphics. Also, except for specifying output, the user has minimal programmatic control over the user interface. Python can be used in a way that allows more control over the interface and graphics, and in so doing provide a roundabout method for satisfying some user requests (e.g., transparency levels in graphics and the ability to clear the results window). My talk will explore these ideas, present a possible method for combining Stata and Python, and give examples to demonstrate how this combination might be useful.

  19. Effect of Sodium Alginate Addition to Resveratrol on Acute Gouty Arthritis

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2015-04-01

    Full Text Available Objective: Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. Methods: Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU solution (25g/mL into ankle joint cavity. IL-1β, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. Results: The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1β, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1β, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. Conclusion: The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

  20. Combinations of complex dynamical systems

    CERN Document Server

    Pilgrim, Kevin M

    2003-01-01

    This work is a research-level monograph whose goal is to develop a general combination, decomposition, and structure theory for branched coverings of the two-sphere to itself, regarded as the combinatorial and topological objects which arise in the classification of certain holomorphic dynamical systems on the Riemann sphere. It is intended for researchers interested in the classification of those complex one-dimensional dynamical systems which are in some loose sense tame. The program is motivated by the dictionary between the theories of iterated rational maps and Kleinian groups.

  1. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  2. Radiation, chemicals and combined effects

    International Nuclear Information System (INIS)

    Sinclair, W.K.

    1991-01-01

    A brief background has been provided on current carcinogenic risks from ionizing radiation and their magnitude in background circumstances. The magnitude of the risks from possibly carcinogenic chemicals at background levels in air, water and food are surprisingly similar. The exception is, perhaps, for the single source of radon which, while variable, on the average stands out above all other sources. Some basic principles concerning the interaction of combined radiation and chemicals and some practical examples where the two interact synergistically to enhance radiation effects has also been provided. Areas for human research in the future are discussed. (Author)

  3. [Combination chemotherapy of experimental leukemia].

    Science.gov (United States)

    Emanuel', N M; Konovalova, N P; D'iachkovskaia, R F

    1977-01-01

    In the present work an attempt was made to gain greater therapeutic effect of diazane coupled with adriamycin and sarcolysin. Leucemias L-1210 and La served as a model. In leucosis La diazane was injected once in 5 days. Either an additional injection of adriamycin two days prior to diazane injection or sarcolysin injected simultaneously with diazane enabled the authors to obtain a distinct synergestic effect. In leucemia L-1210 a simultaneous administration of diazane and sarcolysin also contributes to considerably longer survival of leucemic animals. Such combinations are likely to be promising in their clinical use.

  4. Malignant peritoneal pseudomyxona: Combined treatment

    International Nuclear Information System (INIS)

    Martin, A.; Alvarado, E.; Marcos, A.; Palacios, E.; Gomez, A.

    1993-01-01

    We describe a special treatment for the malignant peritoneal pseudomyxoma as suggested by Sugarbaker. Shortly, it is a combination of surgical cytoreduction with a curative aim, completed with inmediate postoperative intraperitoneal chemotherapy. Having in mind the lack of metastasic danger of these tumours, as well as its lack of infiltrative character, by this surgical technique which consists in five different ''peritonectomies'', one may be able to free the patient of macroscopic tumour. The additional intraperitoneal chemotherapy might contribute to increase the survival of these patients and, perhaps, even to cure them. (Author) 12 refs

  5. Strategies for combinational cancer therapies

    International Nuclear Information System (INIS)

    Khleif, Samir

    2014-01-01

    The countless pre-clinical studies and many clinical trials that have applied tumor antigen-based therapies for the cancer treatment, and although the necessary tumor-specific immune response may be elicited in tumor-bearing hosts, this was not sufficient for the positive therapeutic outcome since there are multiple mechanisms that tumors develop to escape immune surveillance. The tumor-mediated inhibitory mechanisms involve co-inhibitory receptor-ligand interactions, such as PD-1/ PD-L1, secretion of inhibitory molecules, such as TGFb, and recruitment of suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), etc. Therefore, we hypothesized that successful cancer immunotherapy requires not only induction and enhancement of effector immune response but also simultaneous targeting of suppressor arm of immune system, thus in addition to enhancing antigen-specific immunity using vaccines or radiation therapy, one should also target tumor-mediated immune suppression to improve the overall efficacy of therapy. We developed multiple strategies to target various tumor-mediated immune inhibitory mechanisms that can enhance anti-tumor immunity and restructure tumor microenvironment to allow effector cells generated due to vaccination or radiation therapy to function potently. We evaluated the immune and therapeutic efficacy of multiple combinational therapies, including blocking and agonist antibodies to co-inhibitory/co-stimulatory molecules, such as PD-1, PD-L1, OX40, CTLA-4, GITR, inhibitors and neutralizing antibodies to inhibitory cytokines/molecules, such as IL-10, TGFb, IDO, and small molecules for selective inhibition of Tregs. In addition to evaluation of anti-tumor efficacy we are also investigated cellular and molecular mechanisms of action for these agents when combined with vaccine or radiation therapy and exploring the interactions between compounds within combinational therapies in animal tumor models. We are

  6. Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Caro

    Full Text Available Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients.Circulating levels of the inflammatory cytokines IL-1, IL-6, IL-10, TNFalpha, CCL2, CXCL8, VEGF and the acute phase protein Pentraxin-3 were measured by ELISA in preoperative serum samples prospectively collected from a cohort of sixty-nine patients undergoing surgical resection for stage 0-IV CRC and associated with post-operative disease recurrence.Cox multivariate analysis showed that combined high levels (≥ROC cut off-value of CXCL8, VEGF and Pentraxin3 were associated with increased risk of disease recurrence [HR: 14.28; 95%CI: (3.13-65.1] independently of TNM staging. Kaplan-Meier analysis showed that CXCL8, VEGF and Pentraxin3 levels were significantly associated with worse survival (P<0.001.Circulating inflammatory mediators efficiently predicted postoperative recurrence after CRC surgery. Therefore, this study suggest that their validation in large-scale clinical trials may help in tailoring CRC post-surgical management.

  7. Radiation tolerant combinational logic cell

    Science.gov (United States)

    Maki, Gary R. (Inventor); Gambles, Jody W. (Inventor); Whitaker, Sterling (Inventor)

    2009-01-01

    A system has a reduced sensitivity to Single Event Upset and/or Single Event Transient(s) compared to traditional logic devices. In a particular embodiment, the system includes an input, a logic block, a bias stage, a state machine, and an output. The logic block is coupled to the input. The logic block is for implementing a logic function, receiving a data set via the input, and generating a result f by applying the data set to the logic function. The bias stage is coupled to the logic block. The bias stage is for receiving the result from the logic block and presenting it to the state machine. The state machine is coupled to the bias stage. The state machine is for receiving, via the bias stage, the result generated by the logic block. The state machine is configured to retain a state value for the system. The state value is typically based on the result generated by the logic block. The output is coupled to the state machine. The output is for providing the value stored by the state machine. Some embodiments of the invention produce dual rail outputs Q and Q'. The logic block typically contains combinational logic and is similar, in size and transistor configuration, to a conventional CMOS combinational logic design. However, only a very small portion of the circuits of these embodiments, is sensitive to Single Event Upset and/or Single Event Transients.

  8. [Familial combined hyperlipidemia: consensus document].

    Science.gov (United States)

    Mata, Pedro; Alonso, Rodrigo; Ruíz-Garcia, Antonio; Díaz-Díaz, Jose L; González, Noemí; Gijón-Conde, Teresa; Martínez-Faedo, Ceferino; Morón, Ignacio; Arranz, Ezequiel; Aguado, Rocío; Argueso, Rosa; Perez de Isla, Leopoldo

    2014-10-01

    Familial combined hyperlipidemia (FCH) is a frequent disorder associated with premature coronary artery disease. It is transmitted in an autosomal dominant manner, although there is not a unique gene involved. The diagnosis is performed using clinical criteria, and variability in lipid phenotype and family history of hyperlipidemia are necessaries. Frequently, the disorder is associated with type2 diabetes mellitus, arterial hypertension and central obesity. Patients with FCH are considered as high cardiovascular risk and the lipid target is an LDL-cholesterol <100mg/dL, and <70mg/dL if cardiovascular disease or type 2 diabetes are present. Patients with FCH require lipid lowering treatment using potent statins and sometimes, combined lipid-lowering treatment. Identification and management of other cardiovascular risk factors as type 2 diabetes and hypertension are fundamental to reduce cardiovascular disease burden. This document gives recommendations for the diagnosis and global treatment of patients with FCH directed to specialists and general practitioners. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  9. Combined trauma in peaceful time

    Directory of Open Access Journals (Sweden)

    Chaika V.A.

    2014-06-01

    Full Text Available In the article epidemiological features of combined trauma (CT, characteristic for the industrial region were summarized. 486 cases of CT were analyzed for the period from 2010 to 2012. Male patients dominated. 267 (54.9% patients were the age from 25 to 44 years. Most often the damage occurred in 2 anatomic regions (AR - 224 (46.1%, 3 AR - 177 (36.4% and 4 or more - 85 (17.5%. Trau¬matic brain injury - 94.2%, skeletal trauma - 70.6%, the trauma of the chest and abdomen - 68.4% and 35.7%, respectively prevailed. Injury of the abdominal cavity as a dominant one - 148 (30.5% occupied the first place. In 17 (3.5% cases it was impossible to establish the dominant damage. Mortality rate was directly dependent on the type of the trauma and patient's age. Maximum values were found in the combined brain injury and that of abdominal organs - 28.6%, as well as in the group of patients older than 60 years - 35.1%. From 2010 to 2012 the overall mortality decreased by 3.5%.

  10. Combining Renewable Energy With Coal

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-09-01

    There are various possibilities for incorporating biomass into coal-fuelled processes and a number of these are already being deployed commercially. Others are the focus of ongoing research and development. Biomass materials can vary widely, although the present report concentrates mainly on the use of woody biomass in the form of forest residues. Potentially, large amounts are available in some parts of the world. However, not all forested regions are very productive, and the degree of commercial exploitation varies considerably between individual countries. The level of wastage associated with timber production and associated downstream processing is frequently high and considerable quantities of potentially useful materials are often discarded. Overall, forest residues are a largely underexploited resource. Combining the use of biomass with coal can be beneficial, particularly from an environmental standpoint, although any such process may have its limitations or drawbacks. Each coal type and biomass feedstock has different characteristics although by combining the two, it may be possible to capitalise on the advantages of each, and minimise their individual disadvantages. An effective way is via cogasification, and useful operating experience has been achieved in a number of large-scale coal-fuelled gasification and IGCC plants. Cogasification can be the starting point for producing a range of products that include synthetic natural gas, chemicals, fertilisers and liquid transport fuels. It also has the potential to form the basis of systems that combine coal and biomass use with other renewable energy technologies to create clean, efficient energy-production systems. Thus, various hybrid energy concepts, some based on coal/biomass cogasification, have been proposed or are in the process of being developed or trialled. Some propose to add yet another element of renewable energy to the system, generally by incorporating electricity generated by intermittent

  11. Combined Shape and Topology Optimization

    DEFF Research Database (Denmark)

    Christiansen, Asger Nyman

    Shape and topology optimization seeks to compute the optimal shape and topology of a structure such that one or more properties, for example stiffness, balance or volume, are improved. The goal of the thesis is to develop a method for shape and topology optimization which uses the Deformable...... Simplicial Complex (DSC) method. Consequently, we present a novel method which combines current shape and topology optimization methods. This method represents the surface of the structure explicitly and discretizes the structure into non-overlapping elements, i.e. a simplicial complex. An explicit surface...... representation usually limits the optimization to minor shape changes. However, the DSC method uses a single explicit representation and still allows for large shape and topology changes. It does so by constantly applying a set of mesh operations during deformations of the structure. Using an explicit instead...

  12. How rats combine temporal cues.

    Science.gov (United States)

    Guilhardi, Paulo; Keen, Richard; MacInnis, Mika L M; Church, Russell M

    2005-05-31

    The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

  13. Factorized combinations of Virasoro characters

    International Nuclear Information System (INIS)

    Bytsko, A.G.; Fring, A.

    2000-01-01

    We investigate linear combinations of characters for minimal Virasoro models which are representable as a product of several basic blocks. Our analysis is based on consideration of asymptotic behaviour of the characters in the quasi-classical limit. In particular, we introduce a notion of the secondary effective central charge. We find all possible cases for which factorization occurs on the base of the Gauss-Jacobi or the Watson identities. Exploiting these results, we establish various types of identities between different characters. In particular, we present several identities generalizing the Rogers-Ramanujan identities. Applications to quasi-particle representations, modular invariant partition functions, super-conformal theories and conformal models with boundaries are briefly discussed. (orig.)

  14. Combining Narrative and Numerical Simulation

    DEFF Research Database (Denmark)

    Hansen, Mette Sanne; Ladeby, Klaes Rohde; Rasmussen, Lauge Baungaard

    2011-01-01

    for decision makers to systematically test several different outputs of possible solutions in order to prepare for future consequences. The CSA can be a way to evaluate risks and address possible unforeseen problems in a more methodical way than either guessing or forecasting. This paper contributes...... to the decision making in operations and production management by providing new insights into modelling and simulation based on the combined narrative and numerical simulation approach as a tool for strategy making. The research question asks, “How can the CSA be applied in a practical context to support strategy...... making?” The paper uses a case study where interviews and observations were carried out in a Danish corporation. The CSA is a new way to address decision making and has both practical value and further expands the use of strategic simulation as a management tool....

  15. Severe combined immune deficiency syndrome

    International Nuclear Information System (INIS)

    Saleem, A.F.; Khawaja, R.D.A.; Shaikh, A.S.; Ali, S.A.; Zaidi, A.K.M.

    2013-01-01

    To determine the clinico-demographic features and laboratory parameters of children with severe combined immunodeficiency (SCID). Study Design: Case series. Place and Duration of Study: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, from July 2006 to July 2011. Methodology: Thirteen infants who were discharged with a diagnosis of SCID were inducted in the study. Their clinicodemographic features and laboratory parameters were determined. Descriptive statistics has been used for computing frequency and percentage. Results: The median age at diagnosis was five months; 5 infants presented within 3 months of life. Three-fourth (77%) were males. Most of the infants were severely malnourished (85%) at the time of presentation. More than two-thirds (69%) were products of consanguineous marriages. All subjects had severe lymphopenia (absolute lymphocyte count (ALC) ranging between 170 – 2280) and low T and B lymphocyte counts. Conclusion: SCID should be considered in infants presenting with severe and recurrent infections. Low ALC (< 2500/mm3), is a reliable diagnostic feature of SCID. These infants should be promptly referred to a facility where stem cell transplant can be done. (author)

  16. Efficient Web Services Policy Combination

    Science.gov (United States)

    Vatan, Farrokh; Harman, Joseph G.

    2010-01-01

    Large-scale Web security systems usually involve cooperation between domains with non-identical policies. The network management and Web communication software used by the different organizations presents a stumbling block. Many of the tools used by the various divisions do not have the ability to communicate network management data with each other. At best, this means that manual human intervention into the communication protocols used at various network routers and endpoints is required. Developing practical, sound, and automated ways to compose policies to bridge these differences is a long-standing problem. One of the key subtleties is the need to deal with inconsistencies and defaults where one organization proposes a rule on a particular feature, and another has a different rule or expresses no rule. A general approach is to assign priorities to rules and observe the rules with the highest priorities when there are conflicts. The present methods have inherent inefficiency, which heavily restrict their practical applications. A new, efficient algorithm combines policies utilized for Web services. The method is based on an algorithm that allows an automatic and scalable composition of security policies between multiple organizations. It is based on defeasible policy composition, a promising approach for finding conflicts and resolving priorities between rules. In the general case, policy negotiation is an intractable problem. A promising method, suggested in the literature, is when policies are represented in defeasible logic, and composition is based on rules for non-monotonic inference. In this system, policy writers construct metapolicies describing both the policy that they wish to enforce and annotations describing their composition preferences. These annotations can indicate whether certain policy assertions are required by the policy writer or, if not, under what circumstances the policy writer is willing to compromise and allow other assertions to take

  17. Combined modalities: chemotherapy/radiotherapy. Meeting summary

    International Nuclear Information System (INIS)

    Phillips, T.L.

    1979-01-01

    The effects of combined modalities, the standardization of terminology, the mechanisms of chemotherapeutic interactions with radiation and responses of normal and tumor systems are summarized from information presented at the Conference on Combined Modalities

  18. 27 CFR 6.93 - Combination packaging.

    Science.gov (United States)

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Exceptions § 6.93 Combination packaging. The act by an industry member of packaging and distributing distilled spirits, wine, or malt beverages in combination...

  19. Combining multiple classifiers for age classification

    CSIR Research Space (South Africa)

    Van Heerden, C

    2009-11-01

    Full Text Available The authors compare several different classifier combination methods on a single task, namely speaker age classification. This task is well suited to combination strategies, since significantly different feature classes are employed. Support vector...

  20. Systemic combination treatment for psoriasis: a review

    DEFF Research Database (Denmark)

    Jensen, Peter; Skov, Lone; Zachariae, Claus

    2010-01-01

    exist for the use of systemic combination therapy. Therefore, our aim was to review the current literature on systemic anti-psoriatic combination regimens. We searched PubMed and identified 98 papers describing 116 studies (23 randomized) reporting on the effect of various systemic combination...

  1. Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults.

    Directory of Open Access Journals (Sweden)

    Nelson Lee

    Full Text Available BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1 influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation. Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years, and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%, although severe pneumonia with hypoxemia (54.0% vs 28.3% and ICU admissions (25.4% vs 1.9% were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01. This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10unit increase; P = 0.002, and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01 in influenza infections. PBMCs in seasonal influenza patients were activated and

  2. Binocular Combination of Second-Order Stimuli

    Science.gov (United States)

    Zhou, Jiawei; Liu, Rong; Zhou, Yifeng; Hess, Robert F.

    2014-01-01

    Phase information is a fundamental aspect of visual stimuli. However, the nature of the binocular combination of stimuli defined by modulations in contrast, so-called second-order stimuli, is presently not clear. To address this issue, we measured binocular combination for first- (luminance modulated) and second-order (contrast modulated) stimuli using a binocular phase combination paradigm in seven normal adults. We found that the binocular perceived phase of second-order gratings depends on the interocular signal ratio as has been previously shown for their first order counterparts; the interocular signal ratios when the two eyes were balanced was close to 1 in both first- and second-order phase combinations. However, second-order combination is more linear than previously found for first-order combination. Furthermore, binocular combination of second-order stimuli was similar regardless of whether the carriers in the two eyes were correlated, anti-correlated, or uncorrelated. This suggests that, in normal adults, the binocular phase combination of second-order stimuli occurs after the monocular extracting of the second-order modulations. The sensory balance associated with this second-order combination can be obtained from binocular phase combination measurements. PMID:24404180

  3. Combined eye-atmosphere visibility model

    Science.gov (United States)

    Kaufman, Y. J.

    1981-01-01

    Existing models of the optical characteristics of the eye are combined with a recent model of optical characteristics of the atmosphere given by its modulation transfer function. This combination results in the combined eye-atmosphere performance given by the product of their modulation transfer functions. An application for the calculation of visibility thresholds in the case of a two-halves field is given.

  4. GLONASS orbit/clock combination in VNIIFTRI

    Science.gov (United States)

    Bezmenov, I.; Pasynok, S.

    2015-08-01

    An algorithm and a program for GLONASS satellites orbit/clock combination based on daily precise orbits submitted by several Analytic Centers were developed. Some theoretical estimates for combine orbit positions RMS were derived. It was shown that under condition that RMS of satellite orbits provided by the Analytic Centers during a long time interval are commensurable the RMS of combine orbit positions is no greater than RMS of other satellite positions estimated by any of the Analytic Centers.

  5. Systemic combination treatment for psoriasis: a review

    DEFF Research Database (Denmark)

    Jensen, Peter; Skov, Lone; Zachariae, Claus

    2010-01-01

    Psoriasis is a chronic inflammatory skin disease, which affects approximately 2.6% of the population in Northern Europe and Scandinavia. In order to achieve disease control, combinations of systemic treatments are sometimes needed for variable time periods. However, no evidence-based guidelines...... exist for the use of systemic combination therapy. Therefore, our aim was to review the current literature on systemic anti-psoriatic combination regimens. We searched PubMed and identified 98 papers describing 116 studies (23 randomized) reporting on the effect of various systemic combination...

  6. Radiation and combined heat transfer in channels

    International Nuclear Information System (INIS)

    Tamonis, M.

    1986-01-01

    This book presents numerical methods of calculation of radiative and combined heat transfer in channel flows of radiating as well as nonradiating media. Results obtained in calculations for flow conditions of combustion products from organic fuel products are given and methods used in determining the spectral optical properties of molecular gases are analyzed. The book presents applications of heat transfer in solving problems. Topic covered are as follows: optical properties of molecular gases; transfer equations for combined heat transfer; experimental technique; convective heat transfer in heated gas flows; radiative heat transfer in gaseous media; combined heat transfer; and radiative and combined heat transfer in applied problems

  7. 12 CFR 5.33 - Business combinations.

    Science.gov (United States)

    2010-01-01

    ... with safe and sound banking practices. (iii) Money laundering. The OCC considers the effectiveness of any insured depository institution involved in the business combination in combating money laundering...

  8. Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, A.F. Tibúrcio; Nobre, V.; Neuenschwander, L.C. [Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, A.L. [Laboratório de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Xavier, S.G.; Paula, F.D.F. [Departamento de Propedêutica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, M.M. [Laboratório de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, J.C.A.; Bittencourt, H. [Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2013-02-01

    Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α), soluble TNF-α I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1α (MIP-1α or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

  9. Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia

    Directory of Open Access Journals (Sweden)

    A.F. Tiburcio Ribeiro

    2013-02-01

    Full Text Available Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α, soluble TNF-α I and II receptors (sTNFRI and sTNFRII, monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif ligand 2 (CCL2], macrophage inflammatory protein-1α (MIP-1α or CCL3, eotaxin (CCL11, interleukin-8 (IL-8 or CXCL8, and interferon-inducible protein-10 (IP-10 or CXCL10 in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15 before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02. Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

  10. αMβ2-integrin-intercellular adhesion molecule-1 interactions drive the flow-dependent trafficking of Guillain-Barré syndrome patient derived mononuclear leukocytes at the blood-nerve barrier in vitro

    Science.gov (United States)

    Yosef, Nejla; Ubogu, Eroboghene E.

    2012-01-01

    The mechanisms of hematogenous leukocyte trafficking at the human blood-nerve barrier (BNB) are largely unknown. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the pathogenesis of Guillain-Barré syndrome (GBS). We developed a cytokine-activated human in vitro BNB model using primary endoneurial endothelial cells. Endothelial treatment with 10 U/mL tissue necrosis factor-α and 20 U/mL interferon-γ resulted in de novo expression of proinflammatory chemokines CCL2, CXCL9, CXCL11 and CCL20, with increased expression of CXCL2-3, CXCL8 and CXCL10 relative to basal levels. Cytokine treatment induced/ enhanced ICAM-1, E- and P-selectin, vascular cell adhesion molecule-1 and the alternatively spliced pro-adhesive fibronectin variant, fibronectin connecting segment-1 expression in a time-dependent manner, without alterations in junctional adhesion molecule-A expression. Lymphocytes and monocytes from untreated GBS patients express ICAM-1 counterligands, αM- and αL-integrin, with differential regulation of αM-integrin expression compared to healthy controls. Under flow conditions that mimic capillary hemodynamics in vivo, there was a >3-fold increase in total GBS patient and healthy control mononuclear leukocyte adhesion/ migration at the BNB following cytokine treatment relative to the untreated state. Function neutralizing monoclonal antibodies against human αM-integrin (CD11b) and ICAM-1 reduced untreated GBS patient mononuclear leukocyte trafficking at the BNB by 59% and 64.2% respectively. Monoclonal antibodies against αL-integrin (CD11a) and human intravenous immunoglobulin reduced total leukocyte adhesion/migration by 22.8% and 17.6% respectively. This study demonstrates differential regulation of αM-integrin on circulating mononuclear cells in GBS, as well as an important role for αM-integrin-ICAM-1 interactions in pathogenic GBS patient leukocyte trafficking at the human BNB in vitro. PMID:22552879

  11. CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis.

    Science.gov (United States)

    Lind, Liza; Studahl, Marie; Persson Berg, Linn; Eriksson, Kristina

    2017-07-10

    The closely related herpes simplex viruses 1 and 2 can cause inflammations of the central nervous system (CNS), where type 1 most often manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated with severe neurological complications, while HSM is benign in adults. We proposed that studying the chemokine and cytokine production in cerebrospinal fluid (CSF) and serum could indicate why two closely related viruses exhibit different severity of their accompanied CNS inflammation. Secretion patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and compared to control subjects without viral central nervous system infections and to levels in serum. Most measured chemokines and cytokines increased in CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF of HSM patients compared to HSE patients. However, only five chemokines reached levels in the CSF that exceeded those in serum facilitating a positive CSF-serum chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone. Several chemokines were also elevated in serum of HSE patients but only one in HSM patients. No chemokine in- or efflux between CSF and serum was indicated as the levels of chemokines in CSF and serum did not correlate. We show that HSM is associated with a stronger and more diverse inflammatory response in the CNS compared to HSE in the initial stage of disease. The chemokine patterns were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was associated with systemic inflammation.

  12. Cytokine and chemokine levels in tears from healthy subjects.

    Science.gov (United States)

    Carreño, Ester; Enríquez-de-Salamanca, Amalia; Tesón, Marisa; García-Vázquez, Carmen; Stern, Michael E; Whitcup, Scott M; Calonge, Margarita

    2010-11-01

    There is growing evidence for the existence of an 'immune tone' in normal tears. The aim of this study was to determine the levels of a large panel of cytokines and chemokines in tears obtained from healthy subjects. These levels can then serve as baseline values for comparison with patients suffering from ocular surface diseases. Nine healthy subjects participated in this study, and normal ocular surface health was documented by the results of a dry eye questionnaire, Schirmer strip wetting, and vital staining of the cornea. Four microliters of tears were collected from each eye and analysed separately with multiplex bead-based assays for the concentration of 30 cytokines and chemokines. Twenty-five cytokines/chemokines were detected. CCL11/Eotaxin1, GM-CSF, G-CSF, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-10, IL-13, IL-12p70, IL-15, CX3CL1/Fractalkine, TNF-α, epidermal growth factor, and CCL4/MIP-1β were present at 5-100 pg/ml. IL-1β, IL-6, IL-7A, CXCL8/IL-8, and CCL2/MCP-1 were present at 100-400 pg/ml. IL-1Ra, CXCL10/IP-10 and vascular endothelial growth factor were present at more than 1000 pg/ml. Multiplex bead-based assays are convenient for cytokine/chemokine detection in tears. Fracktalkine has been detected in human healthy tears for the first time. The knowledge of cytokine/chemokine concentrations in tears from normal subjects is an important reference for further comparison with patients suffering from ocular surface diseases. Variability in their levels can reflect a phenomenon of potential importance for the understanding of the ocular surface cytokine pattern. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

  13. High rhinovirus burden in lower airways of children with cystic fibrosis.

    Science.gov (United States)

    Kieninger, Elisabeth; Singer, Florian; Tapparel, Caroline; Alves, Marco P; Latzin, Philipp; Tan, Hui-Leng; Bossley, Cara; Casaulta, Carmen; Bush, Andrew; Davies, Jane C; Kaiser, Laurent; Regamey, Nicolas

    2013-03-01

    Rhinovirus (RV)-induced pulmonary exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium in vitro. Here, we assess in vivo the association of RV prevalence and load with antiviral defense mechanisms, airway inflammation, and lung function parameters in children with CF compared with a control group and children with other chronic respiratory diseases. RV presence and load were measured by real-time reverse transcription-polymerase chain reaction in BAL samples and were related to antiviral and inflammatory mediators measured in BAL and to clinical parameters. BAL samples were obtained from children with CF (n = 195), non-CF bronchiectasis (n = 40), or asthma (n = 29) and from a control group (n = 35) at a median (interquartile range [IQR]) age of 8.2 (4.0-11.7) years. RV was detected in 73 samples (24.4%). RV prevalence was similar among groups. RV load (median [IQR] x 10(3) copies/mL) was higher in children with CF (143.0 [13.1-1530.0]), especially during pulmonary exacerbations, compared with children with asthma (3.0 [1.3-25.8], P = .006) and the control group (0.5 [0.3-0.5], P < .001), but similar to patients with non-CF bronchiectasis (122.1 [2.7-4423.5], P = not significant). In children with CF, RV load was negatively associated with interferon (IFN)- b and IFN- l , IL-1ra levels, and FEV 1 , and positively with levels of the cytokines CXCL8 and CXCL10. RV load in CF BAL is high, especially during exacerbated lung disease. Impaired production of antiviral mediators may lead to the high RV burden in the lower airways of children with CF. Whether high RV load is a cause or a consequence of inflammation needs further investigation in longitudinal studies.

  14. Age-related changes in expression and function of Toll-like receptors in human skin

    Science.gov (United States)

    Iram, Nousheen; Mildner, Michael; Prior, Marion; Petzelbauer, Peter; Fiala, Christian; Hacker, Stefan; Schöppl, Alice; Tschachler, Erwin; Elbe-Bürger, Adelheid

    2012-01-01

    Toll-like receptors (TLRs) initiate innate immune responses and direct subsequent adaptive immunity. They play a major role in cutaneous host defense against micro-organisms and in the pathophysiology of several inflammatory skin diseases. To understand the role of TLRs in the acquisition of immunological competence, we conducted a comprehensive study to evaluate TLR expression and function in the developing human skin before and after birth and compared it with adults. We found that prenatal skin already expresses the same spectrum of TLRs as adult skin. Strikingly, many TLRs were significantly higher expressed in prenatal (TLRs 1-5) and infant and child (TLRs 1 and 3) skin than in adult skin. Surprisingly, neither dendritic cell precursors in prenatal skin nor epidermal Langerhans cells and dermal dendritic cells in adult skin expressed TLRs 3 and 6, whereas the staining pattern and intensity of both TLRs in fetal basal keratinocytes was almost comparable to those of adults. Stimulation of primary human keratinocytes from fetal, neonatal and adult donors with selected TLR agonists revealed that the synthetic TLR3 ligand poly (I:C) specifically, mimicking viral double-stranded RNA, induced a significantly enhanced secretion of CXCL8/IL8, CXCL10/IP-10 and TNFα in fetal and neonatal keratinocytes compared with adult keratinocytes. This study demonstrates quantitative age-specific modifications in TLR expression and innate skin immune reactivity in response to TLR activation. Thus, antiviral innate immunity already in prenatal skin may contribute to protect the developing human body from viral infections in utero in a scenario where the adaptive immune system is not yet fully functional. PMID:23034637

  15. 15-Lipoxygenases regulate the production of chemokines in human lung macrophages.

    Science.gov (United States)

    Abrial, C; Grassin-Delyle, S; Salvator, H; Brollo, M; Naline, E; Devillier, P

    2015-09-01

    15-Lipoxygenase (15-LOX) activity is associated with inflammation and immune regulation. The objectives of the present study were to investigate the expression of 15-LOX-1 and 15-LOX-2 and evaluate the enzymes' roles in the polarization of human lung macrophages (LMs) in response to LPS and Th2 cytokines (IL-4/-13). LMs were isolated from patients undergoing surgery for carcinoma. The cells were cultured with a 15-LOX inhibitor (PD146176 or ML351), a COX inhibitor (indomethacin), a 5-LOX inhibitor (MK886) or vehicle and then stimulated with LPS (10 ng · mL(-1)), IL-4 (10 ng · mL(-1)) or IL-13 (50 ng · mL(-1)) for 24 h. Levels of ALOX15 (15-LOX-1) and ALOX15B (15-LOX-2) transcripts were determined by real-time quantitative PCR. Immunoassays were used to measure levels of LPS-induced cytokines (TNF-α, CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL10) and Th2 cytokine-induced chemokines (CCL13, CCL18 and CCL22) in the culture supernatant. Stimulation of LMs with LPS was associated with increased expression of ALOX15B, whereas stimulation with IL-4/IL-13 induced the expression of ALOX15. PD146176 and ML351 (10 μM) reduced the release of the chemokines induced by LPS and Th2 cytokines. The effects of these 15-LOX inhibitors were maintained in the presence of indomethacin and MK886. Furthermore, indomethacin revealed the inhibitory effect of PD146176 on TNF-α release. Inhibition of the 15-LOX pathways is involved in the down-regulation of the in vitro production of chemokines in LMs. Our results suggest that the 15-LOX pathways have a role in the pathogenesis of inflammatory lung disorders and may thus constitute a potential drug target. © 2015 The British Pharmacological Society.

  16. CXCL1 is a negative regulator of mast cell chemotaxis to airway smooth muscle cell products in vitro.

    Science.gov (United States)

    Alkhouri, H; Moir, L M; Armour, C L; Hughes, J M

    2014-03-01

    Activated mast cells (MC) numbers on airway smooth muscle (ASM) are increased in eosinophilic asthma. In vitro, asthmatic cytokine-stimulated ASM cell-conditioned medium (CM) induces more MC chemotaxis than CM from nonasthmatic ASM cells. Intriguingly the nonasthmatic ASM CM inhibits MC chemotaxis to the asthmatic ASM CM. However, the inhibitory factor(s) in the nonasthmatic ASM CM is still to be identified. To identify the factor(s) released by nonasthmatic ASM cells that inhibits MC chemotaxis. Confluent, serum-starved ASM cells from donors with and without asthma were stimulated with IL-1β and T-helper (Th)1 (TNFα and IFNγ) or Th2 (IL-4, IL-13) cytokines, or left unstimulated. CM samples were collected after 24 h, and a potential inhibitory factor identified using cytokine protein arrays. Its production was assessed using ELISA and RT-PCR and inhibitory role investigated in MC chemotaxis and Ca(2+) mobilization assays. Only CXCL1 was produced in greater amounts by nonasthmatic than asthmatic ASM cells following Th1 and Th2 cytokine stimulation. CXCL1 mRNA expression was also increased. Exogenous rh-CXCL1 significantly inhibited MC intracellular Ca(2+) mobilization and chemotaxis to either CXCL10, CXCL8 or CM collected from asthmatic ASM cells following Th1 or Th2 cytokine stimulation. Neutralizing CXCL1 in nonasthmatic ASM CM or blocking its receptor significantly promoted MC chemotaxis. CXCL1 was a major factor regulating MC chemotaxis in vitro. Its differential release by ASM cells may explain the differences observed in MC localization to the ASM of people with and without asthma. CXCL1 inhibition of MC recruitment to the ASM may lead to new targets to limit asthma pathophysiology. © 2013 John Wiley & Sons Ltd.

  17. Human astrocytes: secretome profiles of cytokines and chemokines.

    Directory of Open Access Journals (Sweden)

    Sung S Choi

    Full Text Available Astrocytes play a key role in maintenance of neuronal functions in the central nervous system by producing various cytokines, chemokines, and growth factors, which act as a molecular coordinator of neuron-glia communication. At the site of neuroinflammation, astrocyte-derived cytokines and chemokines play both neuroprotective and neurotoxic roles in brain lesions of human neurological diseases. At present, the comprehensive profile of human astrocyte-derived cytokines and chemokines during inflammation remains to be fully characterized. We investigated the cytokine secretome profile of highly purified human astrocytes by using a protein microarray. Non-stimulated human astrocytes in culture expressed eight cytokines, including G-CSF, GM-CSF, GROα (CXCL1, IL-6, IL-8 (CXCL8, MCP-1 (CCL2, MIF and Serpin E1. Following stimulation with IL-1β and TNF-α, activated astrocytes newly produced IL-1β, IL-1ra, TNF-α, IP-10 (CXCL10, MIP-1α (CCL3 and RANTES (CCL5, in addition to the induction of sICAM-1 and complement component 5. Database search indicated that most of cytokines and chemokines produced by non-stimulated and activated astrocytes are direct targets of the transcription factor NF-kB. These results indicated that cultured human astrocytes express a distinct set of NF-kB-target cytokines and chemokines in resting and activated conditions, suggesting that the NF-kB signaling pathway differentially regulates gene expression of cytokines and chemokines in human astrocytes under physiological and inflammatory conditions.

  18. Combined strategies for the improvement of heterologous ...

    African Journals Online (AJOL)

    use

    2011-12-14

    Dec 14, 2011 ... Full Length Research Paper. Combined ... Three different cultivation strategies had been compared for the production of .... biorector using combined fermentation strategies, and the ... shaking flask was chosen as a host for the transformation of SalI- linearized ... sterile filtered after bioreactor sterilization.

  19. 7 CFR 51.304 - Combination grades.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... Standards for Grades of Apples Grades § 51.304 Combination grades. (a) Combinations of the above grades may...

  20. IPTV program recommendation based on combination strategies

    Directory of Open Access Journals (Sweden)

    Li Hao

    2018-01-01

    Full Text Available As a new interactive service technology, IPTV has been extensively studying in the field of TV pro-gram recommendation, but the sparse of the user-program rating matrix and the cold-start problem is a bottleneck that the program recommended accurately. In this paper, a flexible combination of two recommendation strategies proposed, which explored the sparse and cold-start problem as well as the issue of user interest change over time. This paper achieved content-based filtering section and collaborative filtering section according to the two combination strategies, which effectively solved the cold-start program and over the sparse problem and the problem of users interest change over time. The experimental results showed that this combinational recommendation system in optimal parameters compared by using any one of two combination strategies or not using any combination strategy at all, and the reducing range of MAE is [2.7%,3%].The increasing range of precision and recall is [13.8%95.5%] and [0,97.8%], respectively. The experiment showed better results when using combinational recommendation system in optimal parameters than using each combination strategies individually or not using any combination strategy.

  1. A linear combination of modified Bessel functions

    Science.gov (United States)

    Shitzer, A.; Chato, J. C.

    1971-01-01

    A linear combination of modified Bessel functions is defined, discussed briefly, and tabulated. This combination was found to recur in the analysis of various heat transfer problems and in the analysis of the thermal behavior of living tissue when modeled by cylindrical shells.

  2. Using sentence combining in technical writing classes

    Science.gov (United States)

    Rosner, M.; Paul, T.

    1981-01-01

    Sentence combining exercises are advanced as a way to teach technical writing style without reliance upon abstractions, from which students do not learn. Such exercises: (1) give students regular writing practice; (2) teach the logic of sentence structure, sentence editing, and punctuation; (3) paragraph development and organization; and (4) rhetorical stance. Typical sentence, paragraph, and discourse level sentence combining exercises are described.

  3. 7 CFR 29.1008 - Combination symbols.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Combination symbols. 29.1008 Section 29.1008..., 13, 14 and Foreign Type 92) § 29.1008 Combination symbols. A color or group symbol used with another symbol to form the third factor of a grademark to denote a particular side or characteristic of the...

  4. COMBINED-SEWER OVERFLOW CONTROL AND TREATMENT

    Science.gov (United States)

    Combined-sewer overflow (CSO), along with sanitary-sewer overflow and stormwater are significant contributors of contamination to surface waters. During a rain event, the flow in a combined sewer system may exceed the capacity of the intercepting sewer leading to the wastewater t...

  5. Combine material against electromagnetic pulse disturbance

    International Nuclear Information System (INIS)

    Liu Yan

    2004-01-01

    A novel combined material is introduced, which is hard against electromagnetic pulse disturbance, The attenuation characteristics and the penetration probability of the combine material is discussed in detail. The penetration probability of electromagnetic wave is calculated approximately and the characteristic curve is measured for this material. (authors)

  6. Economic and Accounting Issues Regarding Business Combination

    OpenAIRE

    Asalos Nicoleta; Georgescu Cristina Elena

    2011-01-01

    Some businesses units do not survives the competition and finally close the business. Hence the excessive competition became a very powerful cause of business combination. Elimination of competition means creating monopoly in the market. Adopting IFRS 3 was to improve the relevance, reliability and comparability of the information that a reporting entity provides in its financial statements about a business combination and its effects.

  7. On combining algorithms for deformable image registration

    NARCIS (Netherlands)

    Muenzing, S.E.A.; Ginneken, van B.; Pluim, J.P.W.; Dawant, B.M.

    2012-01-01

    We propose a meta-algorithm for registration improvement by combining deformable image registrations (MetaReg). It is inspired by a well-established method from machine learning, the combination of classifiers. MetaReg consists of two main components: (1) A strategy for composing an improved

  8. Multimedia: How to Combine Language and Visuals

    Directory of Open Access Journals (Sweden)

    Holger Horz

    2008-08-01

    Full Text Available In the last decade, advanced computer technology has allowed for development of information systems and learning environments that combine language with other forms of human communication in innovative ways. Language in the form of written texts, for example, can be combined not only with static pictures or graphs as in printed material, but also with animation or video.

  9. Investigations on combined injuries. Pt. 24

    International Nuclear Information System (INIS)

    Sedlmeier, H.; Lehner, K.; Werdan, K.; Messerschmidt, O.

    1979-01-01

    Combined injuries were inflicted upon NMRI-mice, hurting each with an open skin wound subsequent to sublethal exposition to X-rays. Lethality among animals with combined injuries was between 40 and 60%, while animals only irradiated and those with only a skin wound had lethalities between 10 and 20% and 0%, respectively. Blood circulation and respiration of animals injured with combined lesions were studied in an attempt to understand the cause of the high lethality in this group. The blood volume and the oxygen transport capacity were drastically reduced in animals with combined injuries as compared to those in animals only irradiated, although plasma volume, vascular permeability and distribution of the blood volume remained similar in both groups. Analyses of gases and acid/base composition of blood revealed neither respiratory nor metabolic acidosis. These findings indicate that combined injuries hardly impair blood circulation and respiratory function. (orig.) [de

  10. Data combinations accounting for LISA spacecraft motion

    International Nuclear Information System (INIS)

    Shaddock, Daniel A.; Tinto, Massimo; Estabrook, Frank B.; Armstrong, J.W.

    2003-01-01

    The laser interferometer space antenna is an array of three spacecraft in an approximately equilateral triangle configuration which will be used as a low-frequency gravitational wave detector. We present here new generalizations of the Michelson- and Sagnac-type time-delay interferometry data combinations. These combinations cancel laser phase noise in the presence of different up and down propagation delays in each arm of the array, and slowly varying systematic motion of the spacecraft. The gravitational wave sensitivities of these generalized combinations are the same as previously computed for the stationary cases, although the combinations are now more complicated. We introduce a diagrammatic representation to illustrate that these combinations are actually synthesized equal-arm interferometers

  11. Combination of the LEP II ffbar Results

    CERN Document Server

    Geweniger, C; Elsing, M; Goy, C; Holt, J; Liebig, W; Minard, M N; Renton, P B; Riemann, S; Sachs, K; Ward, P; Wynhoff, S

    2002-01-01

    Preliminary combinations of measurements of the 4 LEP collaborations of the process e+e-->ffbar at LEP-II are presented, using data from the full LEP-II data set where available. Cross-sections and forward-backward asymmetry measurements are combined for the full LEP-II data set. Combined differential cross-sections $\\frac{{\\rm d}\\sigma}{{\\rm d}\\cos\\theta}$ for electron-pairs, muon pair and tau-pair final states are presented. Measurements of the production of heavy flavours are combined. The combined results are interpreted in terms of contact interactions and the exchange Z' bosons and leptoquarks, and within models of low scale gravity in large extra dimensions.

  12. Combining Ideas in Crowdsourced Idea Generation

    Directory of Open Access Journals (Sweden)

    Wang Kai

    2017-02-01

    Full Text Available Collecting ideas through crowdsourcing has become a common practice for companies to benefit from external ideas and innovate. It is desirable that crowd members build on each other's ideas to achieve synergy. This study proposes and verifies a new method for idea combination which can result in combined ideas that are both novel and useful. The domain-specific knowledge of crowd members does not influence the effectiveness of such idea combination. The new method can be used for collecting highly creative ideas from the crowd. The implications for future research are discussed.

  13. Combined algorithms in nonlinear problems of magnetostatics

    International Nuclear Information System (INIS)

    Gregus, M.; Khoromskij, B.N.; Mazurkevich, G.E.; Zhidkov, E.P.

    1988-01-01

    To solve boundary problems of magnetostatics in unbounded two- and three-dimensional regions, we construct combined algorithms based on a combination of the method of boundary integral equations with the grid methods. We study the question of substantiation of the combined method of nonlinear magnetostatic problem without the preliminary discretization of equations and give some results on the convergence of iterative processes that arise in non-linear cases. We also discuss economical iterative processes and algorithms that solve boundary integral equations on certain surfaces. Finally, examples of numerical solutions of magnetostatic problems that arose when modelling the fields of electrophysical installations are given too. 14 refs.; 2 figs.; 1 tab

  14. Studies of a Combined-Cycle Engine

    OpenAIRE

    苅田, 丈士; KANDA, Takeshi

    2003-01-01

    For a Single-Stage-to-Orbit (SSTO) aerospace plane (Fig.1), several engines will be necessary to reach orbit. The combined-cycle engine incorporates several operational modes in a single engine. Study of the combined cycle engine has a long history, and several kinds of such engines have been proposed and studied. When several engines are mounted on a vehicle, each engine of the system will show a performance higher than that of the combined cycle engine. However, during the operation of one ...

  15. Combination solar photovoltaic heat engine energy converter

    Science.gov (United States)

    Chubb, Donald L.

    1987-01-01

    A combination solar photovoltaic heat engine converter is proposed. Such a system is suitable for either terrestrial or space power applications. The combination system has a higher efficiency than either the photovoltaic array or the heat engine alone can attain. Advantages in concentrator and radiator area and receiver mass of the photovoltaic heat engine system over a heat-engine-only system are estimated. A mass and area comparison between the proposed space station organic Rankine power system and a combination PV-heat engine system is made. The critical problem for the proposed converter is the necessity for high temperature photovoltaic array operation. Estimates of the required photovoltaic temperature are presented.

  16. Memristive Perceptron for Combinational Logic Classification

    Directory of Open Access Journals (Sweden)

    Lidan Wang

    2013-01-01

    Full Text Available The resistance of the memristor depends upon the past history of the input current or voltage; so it can function as synapse in neural networks. In this paper, a novel perceptron combined with the memristor is proposed to implement the combinational logic classification. The relationship between the memristive conductance change and the synapse weight update is deduced, and the memristive perceptron model and its synaptic weight update rule are explored. The feasibility of the novel memristive perceptron for implementing the combinational logic classification (NAND, NOR, XOR, and NXOR is confirmed by MATLAB simulation.

  17. Combined Sparsifying Transforms for Compressive Image Fusion

    Directory of Open Access Journals (Sweden)

    ZHAO, L.

    2013-11-01

    Full Text Available In this paper, we present a new compressive image fusion method based on combined sparsifying transforms. First, the framework of compressive image fusion is introduced briefly. Then, combined sparsifying transforms are presented to enhance the sparsity of images. Finally, a reconstruction algorithm based on the nonlinear conjugate gradient is presented to get the fused image. The simulations demonstrate that by using the combined sparsifying transforms better results can be achieved in terms of both the subjective visual effect and the objective evaluation indexes than using only a single sparsifying transform for compressive image fusion.

  18. Cost Comparison of Conventional Gray Combined Sewer Overflow Control Infrastructure versus a Green/Gray Combination

    Science.gov (United States)

    This paper outlines a life-cycle cost analysis comparing a green (rain gardens) and gray (tunnels) infrastructure combination to a gray-only option to control combined sewer overflow in the Turkey Creek Combined Sewer Overflow Basin, in Kansas City, MO. The plan area of this Bas...

  19. Combining nonthermal technologies to control foodborne microorganisms.

    Science.gov (United States)

    Ross, Alexander I V; Griffiths, Mansel W; Mittal, Gauri S; Deeth, Hilton C

    2003-12-31

    Novel nonthermal processes, such as high hydrostatic pressure (HHP), pulsed electric fields (PEFs), ionizing radiation and ultrasonication, are able to inactivate microorganisms at ambient or sublethal temperatures. Many of these processes require very high treatment intensities, however, to achieve adequate microbial destruction in low-acid foods. Combining nonthermal processes with conventional preservation methods enhances their antimicrobial effect so that lower process intensities can be used. Combining two or more nonthermal processes can also enhance microbial inactivation and allow the use of lower individual treatment intensities. For conventional preservation treatments, optimal microbial control is achieved through the hurdle concept, with synergistic effects resulting from different components of the microbial cell being targeted simultaneously. The mechanisms of inactivation by nonthermal processes are still unclear; thus, the bases of synergistic combinations remain speculative. This paper reviews literature on the antimicrobial efficiencies of nonthermal processes combined with conventional and novel nonthermal technologies. Where possible, the proposed mechanisms of synergy is mentioned.

  20. Combined assessment (aspiration cytology and mammography) of ...

    African Journals Online (AJOL)

    Combined assessment (aspiration cytology and mammography) of clinically suspicious breast masses. W.F. van Wyk, D Dent, E Anne Hacking, Genevieve Learmonth, R.E. Kottler, C Anne Gudgeon, A Tiltman ...

  1. Advances in combination therapy of lung cancer

    DEFF Research Database (Denmark)

    Wu, Lan; Leng, Donglei; Cun, Dongmei

    2017-01-01

    Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy......, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....

  2. Combining Teacher Assessment Scores with External Examination ...

    African Journals Online (AJOL)

    Combining Teacher Assessment Scores with External Examination Scores for Certification: Comparative Study of Four Statistical Models. ... University entrance examination scores in mathematics were obtained for a subsample of 115 ...

  3. Investigations on combined injuries. Pt. 25

    International Nuclear Information System (INIS)

    Lehner, K.; Werdan, K.; Sedlmeier, H.; Zimmer, P.; Messerschmidt, O.

    1979-01-01

    In NMRI-mice injured with combined lesions (whole-body irradiation with 500 R and, two or seven days later, an open skin wound), lethality increased from 10 to 20% following sole irradiation up to 60%. Investigations of urinary excretion and serum levels in animals with combined injuries did not show undue elevations of the levels of electrolytes, creatinine, urea, uric acid and acid or alkaline equivalents. Analysis of lactate, pyruvate, ATP and ADP in liver tissue and blood serum indicated no significant changes in the energy metabolism in animals with combined injuries in comparison with mice irradiated only. These findings and those of our last communication (24. Mitteilung) seem to be incompatible wit the presence of a shock state as cause of the high lethality of mice with combined injuries. (orig.) 891 MG/orig. 892 RKD [de

  4. Predictors of combined cognitive and physical decline

    NARCIS (Netherlands)

    Atkinson, H.H.; Cesari, M.; Kritchevsky, S.B.; Penninx, B.W.J.H.; Fried, L.P.; Guralnik, J.M.; Williamson, J.D.

    2005-01-01

    OBJECTIVES: To determine the incidence and correlates of combined declines in cognitive and physical performance. DESIGN: Cohort study of community-dwelling older women with moderate to severe disability. SETTING: The community surrounding Baltimore, Maryland. PARTICIPANTS: Participants in the

  5. Immunotherapy Combination Approved for Advanced Kidney Cancer

    Science.gov (United States)

    FDA has approved the combination of the immunotherapy drugs nivolumab (Opdivo) and ipilimumab (Yervoy) as an initial treatment for some patients with advanced kidney cancer. The approval is expected to immediately affect patient care, as this Cancer Currents post explains.

  6. Learning about Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    ... immunodeficiency From The Journal of Allergy and Clinical Immunology Learning About Severe Combined Immunodeficiency (SCID) What is ... immunodeficiency From The Journal of Allergy and Clinical Immunology Get Email Updates Privacy Copyright Contact Accessibility Plug- ...

  7. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Science.gov (United States)

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  8. Optimizing sales areas of combined transport chains

    Directory of Open Access Journals (Sweden)

    Philip Michalk

    2013-12-01

    Full Text Available Background: Combined transport chains (such as intermodal transport, have certain advantages. The main advantage from customer points of view is the possibility to bundle freight and thereby decrease transport costs. On the other hand, a combined transport chain can cause longer transport times, due to the necessary transshipment processes. Methods: The area around a terminal, in which a combined service has favourable properties to a customer in comparison to a direct transport, can be understood as a sales-area, in which a combined transport product is marketable. The aim of this paper was to find a method to determine the best shape and size of this area. Results and conclusions: The paper at hand lined out a method in order to calculate such a sales area and determine which geographical points around a terminal have an advantage in comparison to a direct transport service.

  9. Unrewarded Object Combinations in Captive Parrots

    Directory of Open Access Journals (Sweden)

    Alice Marie Isabel Auersperg

    2014-11-01

    Full Text Available In primates, complex object combinations during play are often regarded as precursors of functional behavior. Here we investigate combinatory behaviors during unrewarded object manipulation in seven parrot species, including kea, African grey parrots and Goffin cockatoos, three species previously used as model species for technical problem solving. We further examine a habitually tool using species, the black palm cockatoo. Moreover, we incorporate three neotropical species, the yellow- and the black-billed Amazon and the burrowing parakeet. Paralleling previous studies on primates and corvids, free object-object combinations and complex object-substrate combinations such as inserting objects into tubes/holes or stacking rings onto poles prevailed in the species previously linked to advanced physical cognition and tool use. In addition, free object-object combinations were intrinsically structured in Goffin cockatoos and in kea.

  10. COMBINED ALUMINIUM SULFATE/HYDROXIDE PROCESS FOR ...

    African Journals Online (AJOL)

    sulfate, and used for fluoride removal from water by combining with Nalgonda Technique. ... effects on human health and could result in fluorosis. ... [23], nanoscale aluminium oxide hydroxide (AlOOH) [24] and natural zeolite [25], were among.

  11. Pulse wave velocity in familial combined hyperlipidemia.

    NARCIS (Netherlands)

    Avest, E. ter; Holewijn, S.; Bredie, S.J.H.; Tits, L.J.H. van; Stalenhoef, A.F.H.; Graaf, J. de

    2007-01-01

    BACKGROUND: In the present cross-sectional study we investigated whether familial combined hyperlipidemia (FCH) is associated with an increased arterial wall stiffness, and whether measures of arterial wall stiffness in FCH family members could contribute to cardiovascular risk stratification.

  12. Methodology for combining dynamic responses. Technical report

    International Nuclear Information System (INIS)

    Mattu, R.K.

    1980-05-01

    Procedures in accordance with Appendix A of 10 CFR 50, GDC 2, call for an appropriate combination of the effects of the accident loads and loads caused by natural phenomena (such as earthquakes) to be reflected in the design bases of safety equipment. This requirement of interaction of loads has been implemented in various ways both within the NRC and the Nuclear Industry. An NRR Working Group constituted to examine load combination methodologies developed recommendations which were published in September 1978 as NUREG-0484, (PB-287 432). Revision 1 of NUREG-0484 extends the conclusions of the original NUREG-0484 on the use of SRSS methodology for the combination of SSE and LOCA responses beyond RCPB to any other ASME Section III, Class 1, 2, or 3 affected system, component or support, and provides criteria for the combination of dynamic responses other than SSE and LOCA

  13. Coherent combining pulse bursts in time domain

    Science.gov (United States)

    Galvanauskas, Almantas

    2018-01-09

    A beam combining and pulse stacking technique is provided that enhances laser pulse energy by coherent stacking pulse bursts (i.e. non-periodic pulsed signals) in time domain. This energy enhancement is achieved by using various configurations of Fabry-Perot, Gires-Tournois and other types of resonant cavities, so that a multiple-pulse burst incident at either a single input or multiple inputs of the system produces an output with a solitary pulse, which contains the summed energy of the incident multiple pulses from all beams. This disclosure provides a substantial improvement over conventional coherent-combining methods in that it achieves very high pulse energies using a relatively small number of combined laser systems, thus providing with orders of magnitude reduction in system size, complexity, and cost compared to current combining approaches.

  14. On Combining Language Models: Oracle Approach

    National Research Council Canada - National Science Library

    Hacioglu, Kadri; Ward, Wayne

    2001-01-01

    In this paper, we address the of combining several language models (LMs). We find that simple interpolation methods, like log-linear and linear interpolation, improve the performance but fall short of the performance of an oracle...

  15. Combination Classes and "Hora de comunicacion."

    Science.gov (United States)

    Eldredge, Dee L.

    1989-01-01

    Ways to combine small classes of higher education students studying Spanish at various levels are described, including judicious use of language laboratories, staggering of the different level groups, and rotation of activities geared toward students' individual proficiency levels. (CB)

  16. Ameliorative Effects of Herbal Combinations in Hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Nishant P. Visavadiya

    2011-01-01

    Full Text Available The roots of Glycyrrhiza glabra, Withania somnifera, Asparagus racemosus, and Chlorophytum borivilianum and seeds of Sesamum indicum are ayurvedic medicinal plants used in India to treat several ailments. Our previous studies indicated that these plants possess hypolipidemic and antioxidant potential. The present study was aimed at investigating the composite effects of these plants on hypercholesterolemic rats. Three different combinations (5 gm%, given for four weeks used in this study effectively reduced plasma and hepatic lipid profiles and increased fecal excretion of cholesterol, neutral sterol, and bile acid along with increasing the hepatic HMG-CoA reductase activity and bile acid content in hypercholesterolemic rats. Further, all three combinations also improved the hepatic antioxidant status (catalase, SOD, and ascorbic acid levels and plasma total antioxidant capacity with reduced hepatic lipid peroxidation. Overall, combination I had the maximum effect on hypercholesterolemic rats followed by combinations II and III due to varying concentrations of the different classes of phytocomponents.

  17. A Combined Preconditioning Strategy for Nonsymmetric Systems

    KAUST Repository

    Ayuso Dios, Blanca; Barker, A. T.; Vassilevski, P. S.

    2014-01-01

    of the additive Schwarz method applied to nonsymmetric but definite matrices is presented for which the abstract assumptions are verified. A variable preconditioner, combining the original nonsymmetric one and a weighted least-squares version of it, is shown

  18. Comparison of accounting methods for business combinations

    Directory of Open Access Journals (Sweden)

    Jaroslav Sedláček

    2012-01-01

    Full Text Available The revised accounting rules applicable to business combinations in force on July1st 2009, are the result of several years efforts the convergence of U.S. and International Committee of the Financial Accounting Standards. Following the harmonization of global accounting procedures are revised and implemented also Czech accounting regulations. In our research we wanted to see how changes can affect the strategy and timing of business combinations. Comparative analysis is mainly focused on the differences between U.S. and international accounting policies and Czech accounting regulations. Key areas of analysis and synthesis are the identification of business combination, accounting methods for business combinations and goodwill recognition. The result is to assess the impact of the identified differences in the reported financial position and profit or loss of company.

  19. Combined surface and volumetric occlusion shading

    KAUST Repository

    Schott, Matthias O.; Martin, Tobias; Grosset, A. V Pascal; Brownlee, Carson; Hollt, Thomas; Brown, Benjamin P.; Smith, Sean T.; Hansen, Charles D.

    2012-01-01

    In this paper, a method for interactive direct volume rendering is proposed that computes ambient occlusion effects for visualizations that combine both volumetric and geometric primitives, specifically tube shaped geometric objects representing streamlines, magnetic field lines or DTI fiber tracts. The proposed algorithm extends the recently proposed Directional Occlusion Shading model to allow the rendering of those geometric shapes in combination with a context providing 3D volume, considering mutual occlusion between structures represented by a volume or geometry. © 2012 IEEE.

  20. Object attributes combine additively in visual search

    OpenAIRE

    Pramod, R. T.; Arun, S. P.

    2016-01-01

    We perceive objects as containing a variety of attributes: local features, relations between features, internal details, and global properties. But we know little about how they combine. Here, we report a remarkably simple additive rule that governs how these diverse object attributes combine in vision. The perceived dissimilarity between two objects was accurately explained as a sum of (a) spatially tuned local contour-matching processes modulated by part decomposition; (b) differences in in...

  1. Simulation of a combined-cycle engine

    Science.gov (United States)

    Vangerpen, Jon

    1991-01-01

    A FORTRAN computer program was developed to simulate the performance of combined-cycle engines. These engines combine features of both gas turbines and reciprocating engines. The computer program can simulate both design point and off-design operation. Widely varying engine configurations can be evaluated for their power, performance, and efficiency as well as the influence of altitude and air speed. Although the program was developed to simulate aircraft engines, it can be used with equal success for stationary and automative applications.

  2. Osteogenesis imperfecta in combination with Graves disease

    Directory of Open Access Journals (Sweden)

    Marina S. Sheremeta

    2017-12-01

    Full Text Available Osteogenesis imperfecta (OI – is a group of genetically disorders, which are charaterized by a disturbed bone formation. In turn, the excess of thyroid hormones in Graves' disease (GD also posses a negative effect on bone tissue, thereby aggravating OI. That requires from the endocrinologist the most careful management of patients with the combination of these pathologies. In this article, we present a unique clinical case of a combination of GD and OI.

  3. Combining Stocks and Flows of Knowledge

    DEFF Research Database (Denmark)

    Ambos, Tina C.; Nell, Phillip Christopher; Pedersen, Torben

    2013-01-01

    While previous research has mostly focused on either knowledge stocks or knowledge flows, our study is among the first to integrate these perspectives in order to shed light on the complementarity effects of different types of knowledge stocks and flows in the multinational corporation (MNC...... of complementarity create benefits for these units, but that the effects from intra-functional combinations of knowledge stocks and flows are significantly stronger than from cross-functional combinations....

  4. Combined surface and volumetric occlusion shading

    KAUST Repository

    Schott, Matthias O.

    2012-02-01

    In this paper, a method for interactive direct volume rendering is proposed that computes ambient occlusion effects for visualizations that combine both volumetric and geometric primitives, specifically tube shaped geometric objects representing streamlines, magnetic field lines or DTI fiber tracts. The proposed algorithm extends the recently proposed Directional Occlusion Shading model to allow the rendering of those geometric shapes in combination with a context providing 3D volume, considering mutual occlusion between structures represented by a volume or geometry. © 2012 IEEE.

  5. [Using combined magnetotherapy in patients with acne].

    Science.gov (United States)

    Kul'chitskaia, D B; Orekhova, E M; Vasil'eva, E S

    2004-01-01

    Laser Doppler flowmetry discovered microcirculatory disorders in acne patients. Affected are arterioles as well as capillaries and venules. Combination of magnetotherapy with medication improves microcirculation in acne patients. More marked positive changes occurred in the microcirculatory system due to combined treatment compared to medication therapy only. Thus, laser Doppler flowmetry is a new, noninvasive method of assessing microcirculation in acne patients and can serve an objective criterion of treatment efficacy.

  6. Spectral coherent combination of ultrashort pulses

    International Nuclear Information System (INIS)

    Ursescu, D.; Banici, R.; Ionel, L.; Rusen, L.; Sandel, S.; Blanaru, C.

    2010-01-01

    Complete text of publication follows. The coherent beam combination was chosen in several laser systems, including ELI, as a solution to increase the final attainable intensity. However, the coherent beam combination it is also a difficult technique while it has to combine coherently in space and in time several beams amplified in different laser chains. That means in particular that the beams should be in phase in every point of the amplified beam so the spatial beam profiling techniques have to be mastered with high accuracy for all the combined beams. Here it is proposed an alternative coherent beam combination than the use of identical ultrashort pulses. The idea is to spectrally combine laser pulses with complementary spectra. Collinear and non-collinear approaches have been modelled. Ongoing experimental development, including the demonstration of the rephasing for two spectrally complementary ultrashort pulses will be presented. Acknowledgements. The research leading to these results has received funding from the EC's Seventh Framework Programme (LASERLAB-EUROPE, grant agreement no. 228334).

  7. Forecast Combination under Heavy-Tailed Errors

    Directory of Open Access Journals (Sweden)

    Gang Cheng

    2015-11-01

    Full Text Available Forecast combination has been proven to be a very important technique to obtain accurate predictions for various applications in economics, finance, marketing and many other areas. In many applications, forecast errors exhibit heavy-tailed behaviors for various reasons. Unfortunately, to our knowledge, little has been done to obtain reliable forecast combinations for such situations. The familiar forecast combination methods, such as simple average, least squares regression or those based on the variance-covariance of the forecasts, may perform very poorly due to the fact that outliers tend to occur, and they make these methods have unstable weights, leading to un-robust forecasts. To address this problem, in this paper, we propose two nonparametric forecast combination methods. One is specially proposed for the situations in which the forecast errors are strongly believed to have heavy tails that can be modeled by a scaled Student’s t-distribution; the other is designed for relatively more general situations when there is a lack of strong or consistent evidence on the tail behaviors of the forecast errors due to a shortage of data and/or an evolving data-generating process. Adaptive risk bounds of both methods are developed. They show that the resulting combined forecasts yield near optimal mean forecast errors relative to the candidate forecasts. Simulations and a real example demonstrate their superior performance in that they indeed tend to have significantly smaller prediction errors than the previous combination methods in the presence of forecast outliers.

  8. Exact analysis of Packet Reversed Packet Combining Scheme and Modified Packet Combining Scheme; and a combined scheme

    International Nuclear Information System (INIS)

    Bhunia, C.T.

    2007-07-01

    Packet combining scheme is a well defined simple error correction scheme for the detection and correction of errors at the receiver. Although it permits a higher throughput when compared to other basic ARQ protocols, packet combining (PC) scheme fails to correct errors when errors occur in the same bit locations of copies. In a previous work, a scheme known as Packet Reversed Packet Combining (PRPC) Scheme that will correct errors which occur at the same bit location of erroneous copies, was studied however PRPC does not handle a situation where a packet has more than 1 error bit. The Modified Packet Combining (MPC) Scheme that can correct double or higher bit errors was studied elsewhere. Both PRPC and MPC schemes are believed to offer higher throughput in previous studies, however neither adequate investigation nor exact analysis was done to substantiate this claim of higher throughput. In this work, an exact analysis of both PRPC and MPC is carried out and the results reported. A combined protocol (PRPC and MPC) is proposed and the analysis shows that it is capable of offering even higher throughput and better error correction capability at high bit error rate (BER) and larger packet size. (author)

  9. Combined precut in difficult biliary cannulation

    Directory of Open Access Journals (Sweden)

    Jesús Espinel-Díez

    2013-06-01

    Full Text Available Aim: precut sphincterotomy refers to a variety of endoscopic techniques that are used in order to access the bile duct when conventional methods of cannulation have failed. There are not significant data (such as efficacy, safety about the use of different techniques of precutting at the same session. We have described our experience with combined precut sphincterotomy (CPS and we have compared our results to the use of an isolated precut. Patients and methods: we have performed 247 precuts of a total of 2.390 ERCPs. Patients were distributed according to the type of precut practiced: Needle-knife, transpancreatic and combined precut sphincterotomies. "Combined precut" consisted in performing first a transpancreatic sphincterotomy and, if the access was not achieved, then performing a needle-knife sphincterotomy in the same session. The data about safety and efficacy were prospectively collected. The complications were defined according to the consensus criteria. Results: we performed precutting techniques in 247 patients. Needle-knife, transpancreatic, and combined precuts were performed in 125 (6.9%, 74 (4.1% and 48 (2.6% patients, respectively. Bile duct cannulation was successful in 48 patients (100% in the group of combined precut, 121 patients (96.8% in the transpancreatic group, and 67 patients (90.5% in the needle-knife group (p = 0.03. There were not differences in complications rates between the three groups. There was no pancreatitis in the combined precut group. The complications were successfully managed with conservative treatment. Conclusions: combined precut sphincterotomy seems to be a safe and successful technique in those cases of difficult bile duct cannulation.

  10. [Combination drug therapy in patients with BPH].

    Science.gov (United States)

    Kuzmenko, A V; Kuzmenko, V V; Gyaurgiev, T A

    2018-03-01

    Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself

  11. The danger of fixed drug combinations.

    Science.gov (United States)

    Herxheimer, H

    1975-07-01

    After the second world war a number of pharmaceutical firms which were not able to create new therapeutic substances by their own research, put a great number of fixed drug combinations on the market. Their number quickly increased, as the efficiency of these compounds required no legal proof and as, with appropriate propaganda, large profits could be earned. The number of firms doing this sort of production also increased, and in West Germany, for instance, more than 3/4 of all drugs on the official list are now fixed combinations. Our task is, therefore, to ask for regulations which limit fixed combinations to such preparation the efficiency of which has been shown and whose advantages more than outweigh their disadvantages. The advantages of these preparations are convenience to the patient, avoidance of potential mistakes made possible by too many drugs given on the same day and, perhaps, lower prices. The disadvantages are: 1. The individual optimum dose for a patient cannot be achieved, because in case of a change of dosis all components are changed. 2. Different components may have different duration of action. 3. Different components may have a different bioavailability. 4. Different components may interact. 5. Some components may create tolerance, others not. In many cases fixed combinations have been used to make drugs with poor efficiency financially viable by combining them with very efficient drugs. The existence of thousands of fixed combinations makes the drug market indiscernible and useless. They obscure the relatively few essential drugs and make it difficult for the doctor to find his way amongst the mass of offered medicaments. Few fixed combinations are justifiable. These are well known and they should be permitted as before. All others should be banned until it has been shown that their advantages are greater than their disadvantages.

  12. Estimation of structural reliability under combined loads

    International Nuclear Information System (INIS)

    Shinozuka, M.; Kako, T.; Hwang, H.; Brown, P.; Reich, M.

    1983-01-01

    For the overall safety evaluation of seismic category I structures subjected to various load combinations, a quantitative measure of the structural reliability in terms of a limit state probability can be conveniently used. For this purpose, the reliability analysis method for dynamic loads, which has recently been developed by the authors, was combined with the existing standard reliability analysis procedure for static and quasi-static loads. The significant parameters that enter into the analysis are: the rate at which each load (dead load, accidental internal pressure, earthquake, etc.) will occur, its duration and intensity. All these parameters are basically random variables for most of the loads to be considered. For dynamic loads, the overall intensity is usually characterized not only by their dynamic components but also by their static components. The structure considered in the present paper is a reinforced concrete containment structure subjected to various static and dynamic loads such as dead loads, accidental pressure, earthquake acceleration, etc. Computations are performed to evaluate the limit state probabilities under each load combination separately and also under all possible combinations of such loads. Indeed, depending on the limit state condition to be specified, these limit state probabilities can indicate which particular load combination provides the dominant contribution to the overall limit state probability. On the other hand, some of the load combinations contribute very little to the overall limit state probability. These observations provide insight into the complex problem of which load combinations must be considered for design, for which limit states and at what level of limit state probabilities. (orig.)

  13. Energy Analysis in Combined Reforming of Propane

    Directory of Open Access Journals (Sweden)

    K. Moon

    2013-01-01

    Full Text Available Combined (steam and CO2 reforming is one of the methods to produce syngas for different applications. An energy requirement analysis of steam reforming to dry reforming with intermediate steps of steam reduction and equivalent CO2 addition to the feed fuel for syngas generation has been done to identify condition for optimum process operation. Thermodynamic equilibrium data for combined reforming was generated for temperature range of 400–1000°C at 1 bar pressure and combined oxidant (CO2 + H2O stream to propane (fuel ratio of 3, 6, and 9 by employing the Gibbs free energy minimization algorithm of HSC Chemistry software 5.1. Total energy requirement including preheating and reaction enthalpy calculations were done using the equilibrium product composition. Carbon and methane formation was significantly reduced in combined reforming than pure dry reforming, while the energy requirements were lower than pure steam reforming. Temperatures of minimum energy requirement were found in the data analysis of combined reforming which were optimum for the process.

  14. Combined Medical Treatment Of Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Umnova Larisa

    2015-04-01

    Full Text Available The aim of the study was to determine the most effective medical treatment of patients with chronic pancreatitis, by using either pancreatin alone or in combination with proton pump inhibitor (PPI or PPI and non-steroidal anti-inflammatory drug (NSAID. Patients with chronic pancreatitis, who did not require a surgical treatment, received medical treatment for a one–month period: 20 patients received pancreatin monotherapy; 48 patients were given a combination of pancreatin and PPI; 38 patients were treated with a combination of pancreatin, PPI and NSAID (PNP therapy group. In comparison with other groups, patients in the PNP therapy group showed improvement in body mass index, abdominal pain, bowel movements, chronic pancreatitis severity, as well as their quality of life assessment (p < 0.05. The combination of pancreatin, PPI and NSAID was the most effective among those applied in chronic pancreatitis patient treatment. A one–month long course of this therapy was safe and did not cause any significant adverse effects. The combination of pancreatin, PPI and NSAID for treatment of chronic pancreatitis can be recommended, as it is based on pathogenesis of the disease, effective, safe and economically advantageous.

  15. OT-Combiners Via Secure Computation

    DEFF Research Database (Denmark)

    Harnik, Danny; Ishai, Yuval; Kushilevitz, Eyal

    2008-01-01

    of faulty candidates (t = Ω(n)). Previous OT-combiners required either ω(n) or poly(k) calls to the n candidates, where k is a security parameter, and produced only a single secure OT. We demonstrate the usefulness of the latter result by presenting several applications that are of independent interest......An OT-combiner implements a secure oblivious transfer (OT) protocol using oracle access to n OT-candidates of which at most t may be faulty. We introduce a new general approach for combining OTs by making a simple and modular use of protocols for secure computation. Specifically, we obtain an OT......, strengthen the security, and improve the efficiency of previous OT-combiners. In particular, we obtain the first constant-rate OT-combiners in which the number of secure OTs being produced is a constant fraction of the total number of calls to the OT-candidates, while still tolerating a constant fraction...

  16. Bifuel coal-gas combined cycles

    International Nuclear Information System (INIS)

    Chmielniak, Tadeusz; Kotowicz, Janusz; Lyczko, Jacek

    1997-01-01

    This paper describes basic ways of realization of bi fuel cool-gas combined cycles. The criterion of classification of the systems specification is a joint of the gas pail with the steam part: a) The gas turbine flue gases are introduced into the steam boiler combustion chamber (the serial, hot wind box). b) Bypass of the beat exchangers at the steam turbine unit and/or the steam boiler, by use the waste heat exchangers, or waste boiler at the gas turbine unit (the parallel-coupled). c) The mixed, it's a combination of the two upper. The analysis of the parallel system has been specially presented. In derived formulas for the total efficiency of the bi fuel parallel combined cycle balance equations have been used. This formulas can be used for planning new combined cycle power plants and for modernization existing steam power plants. It was made a discussion about influence of the ratio the gas and the steam turbine electric power on the cycle efficiency in care of the full and the part load of the bi fuel combined cycle power plant. The various systems of the joint of the gas part with the steam part have been examined. The selected results of the calculations have been attached. The models and the numerical simulations have been based on data from the existing steam power plants and real gas turbine units. (Author)

  17. Coherent combination of ultrafast fiber amplifiers

    International Nuclear Information System (INIS)

    Hanna, Marc; Guichard, Florent; Druon, Frédéric; Georges, Patrick; Zaouter, Yoann; Papadopoulos, Dimitris N

    2016-01-01

    We review recent progress in coherent combining of femtosecond pulses amplified in optical fibers as a way to scale the peak and average power of ultrafast sources. Different methods of achieving coherent pulse addition in space (beam combining) and time (divided pulse amplification) domains are described. These architectures can be widely classified into active methods, where the relative phases between pulses are subject to a servomechanism, and passive methods, where phase matching is inherent to the geometry. Other experiments that combine pulses with different spectral contents, pulses that have been nonlinearly broadened or successive pulses from a mode-locked laser oscillator, are then presented. All these techniques allow access to unprecedented parameter range for fiber ultrafast sources. (topical review)

  18. Efficient power combiner for THz radiation

    Energy Technology Data Exchange (ETDEWEB)

    Seidfaraji, Hamide, E-mail: hsfaraji@unm.edu; Fuks, Mikhail I.; Christodoulou, Christos; Schamiloglu, Edl [Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, 87131-0001 (United States)

    2016-08-15

    Most dangerous explosive materials, both toxic and radioactive, contain nitrogen salts with resonant absorption lines in the frequency range 0.3-10 THz. Therefore, there has been growing interest in remotely detecting such materials by observing the spectrum of reflected signals when the suspicious material is interrogated by THz radiation. Practical portable THz sources available today generate only 20–40 mW output power. This power level is too low to interrogate suspicious material from a safe distance, especially if the material is concealed. Hence, there is a need for sources that can provide greater power in the THz spectrum. Generating and extracting high output power from THz sources is complicated and inefficient. The efficiency of vacuum electronic microwave sources is very low when scaled to the THz range and THz sources based on scaling down semiconductor laser sources have low efficiency as well, resulting in the well known “THz gap.” The reason for such low efficiencies for both source types is material losses in the THz band. In this article an efficient power combiner is described that is based on scaling to higher frequencies a microwave combiner that increases the output power in the THz range of interest in simulation studies. The proposed power combiner not only combines the THz power output from several sources, but can also form a Gaussian wavebeam output. A minimum conversion efficiency of 89% with cophased inputs in a lossy copper power combiner and maximum efficiency of 100% in a Perfect Electric Conductor (PEC)-made power combiner were achieved in simulations. Also, it is shown that the TE{sub 01} output mode is a reasonable option for THz applications due to the fact that conductive loss decreases for this mode as frequency increases.

  19. Efficient power combiner for THz radiation

    Directory of Open Access Journals (Sweden)

    Hamide Seidfaraji

    2016-08-01

    Full Text Available Most dangerous explosive materials, both toxic and radioactive, contain nitrogen salts with resonant absorption lines in the frequency range 0.3-10 THz. Therefore, there has been growing interest in remotely detecting such materials by observing the spectrum of reflected signals when the suspicious material is interrogated by THz radiation. Practical portable THz sources available today generate only 20–40 mW output power. This power level is too low to interrogate suspicious material from a safe distance, especially if the material is concealed. Hence, there is a need for sources that can provide greater power in the THz spectrum. Generating and extracting high output power from THz sources is complicated and inefficient. The efficiency of vacuum electronic microwave sources is very low when scaled to the THz range and THz sources based on scaling down semiconductor laser sources have low efficiency as well, resulting in the well known “THz gap.” The reason for such low efficiencies for both source types is material losses in the THz band. In this article an efficient power combiner is described that is based on scaling to higher frequencies a microwave combiner that increases the output power in the THz range of interest in simulation studies. The proposed power combiner not only combines the THz power output from several sources, but can also form a Gaussian wavebeam output. A minimum conversion efficiency of 89% with cophased inputs in a lossy copper power combiner and maximum efficiency of 100% in a Perfect Electric Conductor (PEC-made power combiner were achieved in simulations. Also, it is shown that the TE01 output mode is a reasonable option for THz applications due to the fact that conductive loss decreases for this mode as frequency increases.

  20. Artificial intelligence in drug combination therapy.

    Science.gov (United States)

    Tsigelny, Igor F

    2018-02-09

    Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Combined air and water pollution control system

    Science.gov (United States)

    Wolverton, Billy C. (Inventor); Jarrell, Lamont (Inventor)

    1990-01-01

    A bioaquatic air pollution control system for controlling both water and atmospheric pollution is disclosed. The pollution control system includes an exhaust for directing polluted gases out of a furnace and a fluid circulating system which circulates fluid, such as waste water, from a source, past the furnace where the fluid flow entrains the pollutants from the furnace. The combined fluid and pollutants are then directed through a rock/plant/microbial filtering system. A suction pump pumps the treated waste water from the filter system past the exhaust to again entrain more pollutants from the furnace where they are combined with the fluid (waste water) and directed to the filter system.

  2. Combined treatment for complex intracranial aneurysm

    Directory of Open Access Journals (Sweden)

    Chiriac A.

    2015-06-01

    Full Text Available Complex aneurysms often cannot be completely excluded by a single approaches. Today successful treatment of these lesions requires a combination between microsurgical and endovascular techniques. Planning of combined treatment require a very good understanding of aneurysm anatomy and a close collaboration between neurosurgeon and neuroendovascular interventionist. Endovascular coiling can usually be used as early treatment for a partially aneurysm occlusion including the ruptured area and followed by definitive clipping. On the other hand microsurgical clipping also can be used as first treatment for complex aneurysm neck reconstruction, allowing successful secondary placement of coils inside the remnant aneurysm sac

  3. Raman beam combining for laser brightness enhancement

    Science.gov (United States)

    Dawson, Jay W.; Allen, Graham S.; Pax, Paul H.; Heebner, John E.; Sridharan, Arun K.; Rubenchik, Alexander M.; Barty, Chrisopher B. J.

    2015-10-27

    An optical source capable of enhanced scaling of pulse energy and brightness utilizes an ensemble of single-aperture fiber lasers as pump sources, with each such fiber laser operating at acceptable pulse energy levels. Beam combining involves stimulated Raman scattering using a Stokes' shifted seed beam, the latter of which is optimized in terms of its temporal and spectral properties. Beams from fiber lasers can thus be combined to attain pulses with peak energies in excess of the fiber laser self-focusing limit of 4 MW while retaining the advantages of a fiber laser system of high average power with good beam quality.

  4. Maximisation of Combined Cycle Power Plant Efficiency

    Directory of Open Access Journals (Sweden)

    Janusz Kotowicz

    2015-12-01

    Full Text Available The paper presents concepts for increasing the efficiency of a modern combined cycle power plant. Improvement of gas turbine performance indicators as well as recovering heat from the air cooling the gas turbine’s flow system enable reaching gross electrical efficiencies of around 65%. Analyses for a wide range of compressor pressure ratios were performed. Operating characteristics were developed for the analysed combined cycle plant, for different types of open air cooling arrangements of the gas turbine’s expander: convective, transpiration and film.

  5. Clinical application of radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Morita, Kozo

    1978-01-01

    In clinical application of radiation therapy combined with chemotherapy, it is important to gain the maximal therapeutic benefit. At present we have no agents that improve the therapeutic ratio by enhancing the effect of radiation on the tumor cell selectively. Therefore, it is necessary to use combining some or all of following procedures: (1) the intraarterial infusion of the agents, (2) the selective localization by reason of the biological affinity of the agents, (3) the surgical removal of the non-sensitized tumor residue and (4) the selective sensitization of the tumor due to its shorter cell cycle. (author)

  6. Suction caissons subjected to monotonic combined loading

    DEFF Research Database (Denmark)

    Penzes, P.; Jensen, M.R.; Zania, Varvara

    2016-01-01

    Suction caissons are being increasingly used as offshore foundation solutions in shallow and intermediate water depths. The convenient installation method through the application of suction has rendered this type of foundation as an attractive alternative to the more traditional monopile foundation...... for offshore wind turbines. The combined loading imposed typically to a suction caisson has led to the estimation of their bearing capacity by means of 3D failure envelopes. This study aims to analyse the behaviour of suction caissons for offshore wind turbines subjected to combined loading. Finite element...

  7. RF torch discharge combined with conventional burner

    International Nuclear Information System (INIS)

    Janca, J.; Tesar, C.

    1996-01-01

    The design of the combined flame-rf-plasma reactor and experimental examination of this reactor are presented. For the determination of the temperature in different parts of the combined burner plasma the methods of emission spectroscopy were used. The temperatures measured in the conventional burner reach the maximum temperature 1900 K but in the burner with the superimposed rf discharge the neutral gas temperature substantially increased up to 2600 K but also the plasma volume increases substantially. Consequently, the resident time of reactants in the reaction zone increases

  8. Diagnostic system for combine cycle power plant

    International Nuclear Information System (INIS)

    Shimizu, Yujiro; Nomura, Masumi; Tanaka, Satoshi; Ito, Ryoji; Kita, Yoshiyuki

    2000-01-01

    We developed the Diagnostic System for Combined Cycle Power Plant which enables inexperienced operators as well as experienced operators to cope with abnormal conditions of Combined Cycle Power Plant. The features of this system are the Estimate of Emergency Level for Operation and the Prediction of Subsequent Abnormality, adding to the Diagnosis of Cause and the Operation Guidance. Moreover in this system, Diagnosis of Cause was improved by using our original method and support screens can be displayed for educational means in normal condition as well. (Authors)

  9. Combined utilization of biogas and natural gas

    International Nuclear Information System (INIS)

    Jensen, J.; Tafdrup, S.; Christensen, J.

    1997-01-01

    The Danish natural gas network has been established during the past 10 years. Running parallel with this a small but growing production of biogas from centralized biogas plants and landfills has been developed. The annual biogas production is expected to keep growing and increase tenfold in the next 25 year period with a reduction of green house gas emissions as one of the important incentives. The last years' development and expansion of the Danish biogas sector has shown a need for combined utilization of biogas and natural gas. If larger volumes of biogas are present, upgrading and distribution by the natural gas network may be an alternative to combined utilization. (au) 12 refs

  10. PANSAID-PAracetamol and NSAID in combination

    DEFF Research Database (Denmark)

    Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel

    2017-01-01

    BACKGROUND: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary...... publication to prevent outcome reporting bias and data-driven analysis results. METHODS/DESIGN: The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen...... of paracetamol and ibuprofen used in a perioperative setting. TRIAL REGISTRATION: ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015....

  11. Combined modality treatment with radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Tannock, I.F.; Toronto Univ., ON

    1989-01-01

    The present paper discusses some of the methodological issues which can confound the interpretation of clinical trials of combined modality treatment. It reviews some of the larger randomized trials which have evaluated combined modality treatment in cancers of the head and neck, lung, gastrointestinal tract and bladder. It concludes that adequate trials have yet to be performed in many of thses sites, but that at present, evidence for long-term benefit from adjunctivechemotherapy is meagre. Finally, it suggests some possible mechanisms which might heve limited the benefit of chemotherapy when added to radiation treatment. (Author). 87 refs.; 4 figs.; 4 tabs

  12. Combined effect of external and internal irradiation

    International Nuclear Information System (INIS)

    Kiradzhiev, G.

    1987-01-01

    Some of the general regularities of the combined effect of external irradiation and iodine 131 are discussed. Data are adduced showing that modification of the effects of these two radiation factors, when jointly applied, is also determined by the quantitative relations of the applied doses of external and internal irradiation, referred to a particular moment of the effects. It was shown that the effects of the radionuclides in these combined radiation injuries are basically realized by two mechanisms: 1. changes are found in the radionuclide kinetic parameters (nonspecific effects); 2. changes in their kinetic parameters are absent (specific effect). These two mechanisms underlie different approaches to therapy

  13. Chemotherapy in combined and multimodality treatment

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    It is shown that chemotherapy of tumors of various localizations developes intensively in the last few years. It is connected with discovery and adoption of new active antitumoral preparations, such as alkylating preparations, antimetabolites, antitumoral antibiotics, hormonal preparations. To create the rational effective conditions of chemotherapy a study was made on kinetics of tumor gowth, molecular mechanisms of interaction of cytostatics and cells of malignant tumor. Main factors of chemotherapy combination with radiotherapy when treating numerous malignant tumors were considered. Effectiveness of using chemotherapy in combination with other methods of treatment was shown

  14. Combining Land Capability Evaluation, Geographic Information ...

    African Journals Online (AJOL)

    Combining Land Capability Evaluation, Geographic Information Systems, AnD Indigenous Technologies for Soil Conservation in Northern Ethiopia. ... Land capability and land use status were established following the procedures of a modified treatment-oriented capability classification using GIS. The case study ...

  15. Experimenting with new combinations of old ideas

    NARCIS (Netherlands)

    Linde, J.

    2012-01-01

    Many important (economic) decisions involve risk. At the same time every decision is made within a social context. So far (experimental) research studies these two aspects in isolation from each other. Jona Linde therefore combines existing experimental protocols to examine the influence of social

  16. Rocket Based Combined Cycle (RBCC) engine inlet

    Science.gov (United States)

    2004-01-01

    Pictured is a component of the Rocket Based Combined Cycle (RBCC) engine. This engine was designed to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsion systems and ultimately a Single Stage to Orbit (SSTO) air breathing propulsion system.

  17. Combined Heat and Power and Emissions Trading

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    The aim of this IEA Information Paper is to help policy makers and other stakeholders understand the challenges facing the incorporation of high efficiency combined heat and power (CHP) into greenhouse gas (GHG) Emissions Trading Schemes (ETSs) -- and to propose options for overcoming them.

  18. A Novel in situ Trigger Combination Method

    International Nuclear Information System (INIS)

    Buzatu, Adrian; Warburton, Andreas; Krumnack, Nils; Yao, Wei-Ming

    2012-01-01

    Searches for rare physics processes using particle detectors in high-luminosity colliding hadronic beam environments require the use of multi-level trigger systems to reject colossal background rates in real time. In analyses like the search for the Higgs boson, there is a need to maximize the signal acceptance by combining multiple different trigger chains when forming the offline data sample. In such statistically limited searches, datasets are often amassed over periods of several years, during which the trigger characteristics evolve and their performance can vary significantly. Reliable production cross-section measurements and upper limits must take into account a detailed understanding of the effective trigger inefficiency for every selected candidate event. We present as an example the complex situation of three trigger chains, based on missing energy and jet energy, to be combined in the context of the search for the Higgs (H) boson produced in association with a W boson at the Collider Detector at Fermilab (CDF). We briefly review the existing techniques for combining triggers, namely the inclusion, division, and exclusion methods. We introduce and describe a novel fourth in situ method whereby, for each candidate event, only the trigger chain with the highest a priori probability of selecting the event is considered. The in situ combination method has advantages of scalability to large numbers of differing trigger chains and of insensitivity to correlations between triggers. We compare the inclusion and in situ methods for signal event yields in the CDF WH search.

  19. MANUAL: REAL TIME CONTROL OF COMBINED SEWERS

    Science.gov (United States)

    Managers, engineers, and operators of combined urban sewer systems are faced with difficult problems related to the operation and maintenance of their facilities. In addition to the issues related to the operation and upkeep of the system, many sewerage agencies are facing increa...

  20. 77 FR 60418 - Combined Notice of Filings

    Science.gov (United States)

    2012-10-03

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund Report filings...-1064-000. Applicants: Venice Gathering System, L.L.C. Description: NAESB 2.0 Compliance Filing to be...

  1. 77 FR 71408 - Combined Notice of Filings

    Science.gov (United States)

    2012-11-30

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund Report filings....m. ET 12/3/12. Docket Numbers: RP13-301-000. Applicants: Venice Gathering System, LLC. Description...

  2. 76 FR 61352 - Combined Notice of Filings

    Science.gov (United States)

    2011-10-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund Report filings....m. Eastern Time on Wednesday, October 05, 2011. Docket Numbers: RP11-2585-000. Applicants: Venice...

  3. 76 FR 55375 - Combined Notice of Filings

    Science.gov (United States)

    2011-09-07

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund Report filings..., September 12, 2011. Docket Numbers: RP11-2454-000. Applicants: Venice Gathering System, LLC. Description...

  4. 75 FR 39230 - Combined Notice of Filings

    Science.gov (United States)

    2010-07-08

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings July 1, 2010. Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund Report..., July 12, 2010. Docket Numbers: RP10-922-000. Applicants: Venice Gathering System, LLC. Description...

  5. 76 FR 353 - Combined Notice of Filings

    Science.gov (United States)

    2011-01-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings December 22, 2010. Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund... 3, 2011. Docket Numbers: RP11-1640-000. Applicants: Venice Gathering System, L.L.C. Description...

  6. 78 FR 50408 - Combined Notice of Filings

    Science.gov (United States)

    2013-08-19

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund Report filings... Numbers: RP13-1239-000. Applicants: Venice Gathering System, L.L.C. Description: Order No. 776 Compliance...

  7. 76 FR 39085 - Combined Notice of Filings

    Science.gov (United States)

    2011-07-05

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings Take notice that the Commission has received the following Natural Gas Pipeline Rate and Refund Report filings..., July 05, 2011. Docket Numbers: RP11-2205-000. Applicants: Venice Gathering System, LLC. Description...

  8. A combined experimental and theoretical study

    Indian Academy of Sciences (India)

    A combined theoretical and experimental study was also performed, which demonstrated that the clus- ters 1–3 with ... silica gel TLC plates (MERCK TLC Plates). The NMR .... tronic μ3-Se and maintains the same number of clus- ter valance ...

  9. Combinational Services for NGN based IPTV

    NARCIS (Netherlands)

    Mikóczy, E.; Schumann, S.; Stokking, H.M.; Deventer, M.O. van; Niamut, O.A.

    2009-01-01

    This paper describes the general concept of combinational/blended services for IP-based Television (IPTV) services in next generation networks towards its service oriented architecture concept (SOA). Besides introducing general approaches of service reusability (SOA concepts), the service enables

  10. Combined PET/MR imaging in neurology

    DEFF Research Database (Denmark)

    Andersen, Flemming Littrup; Ladefoged, Claes Nøhr; Beyer, Thomas

    2014-01-01

    AIM: Combined PET/MR systems have now become available for clinical use. Given the lack of integrated standard transmission (TX) sources in these systems, attenuation and scatter correction (AC) must be performed using the available MR-images. Since bone tissue cannot easily be accounted for duri...

  11. Cotard syndrome with catatonia: unique combination.

    Science.gov (United States)

    Basu, Aniruddha; Singh, Priti; Gupta, Rajiv; Soni, Sandeep

    2013-07-01

    Cotard syndrome is a rare psychiatric condition characterized by extreme nihilistic delusions. Catatonia though common, its combination with the Cotard syndrome is exceeding rare and more so the response with the pharmacotherapy as in our case. Since, both are found in organic conditions the importance of studying such a case is to understand the underlying neurobiologic determinants.

  12. Cotard Syndrome with Catatonia: Unique Combination

    OpenAIRE

    Basu, Aniruddha; Singh, Priti; Gupta, Rajiv; Soni, Sandeep

    2013-01-01

    Cotard syndrome is a rare psychiatric condition characterized by extreme nihilistic delusions. Catatonia though common, its combination with the Cotard syndrome is exceeding rare and more so the response with the pharmacotherapy as in our case. Since, both are found in organic conditions the importance of studying such a case is to understand the underlying neurobiologic determinants.

  13. Development Activities on Airbreathing Combined Cycle Engines

    Science.gov (United States)

    McArthur, J. Craig; Lyles, Garry (Technical Monitor)

    2000-01-01

    Contents include the following: Advanced reusable transportation(ART); aerojet and rocketdyne tests, RBCC focused concept flowpaths,fabricate flight weigh, test select components, document ART project, Istar (Integrated system test of an airbreathing rocket); combined cycle propulsion testbed;hydrocarbon demonstrator tracebility; Istar engine system and vehicle system closure study; and Istar project planning.

  14. Estimated combined steady state tyre slip characteristics

    NARCIS (Netherlands)

    Fernandez, A.L.A.; Pauwelussen, J.P.

    2001-01-01

    Excessive behaviour of vehicles is often the subject of study, motivated by either the development of active safety systems uch as ESP, or the improvement of vehicle performance such as for racecars. In all of these cases, combined slip needs to be taken into account. In many cases however, the full

  15. Combined effect between two functional polymorphisms of ...

    Indian Academy of Sciences (India)

    four populations (Ireland, UK, Australia and Finland) reported an allelic association between ... of two common polymorphisms on SLC6A12 gene may be associated with TLE, but the ... Li L., Liu A., Wu X., Sun W., Wang Y. and Liu Y. 2015 Combined effect between two ... epileptic control subjects of Chinese Han origin were.

  16. Combined antiretroviral and anti- tuberculosis drug resistance ...

    African Journals Online (AJOL)

    these epidemics, many challenges remain.[3] Antiretroviral and anti-TB drug resistance pose considerable threats to the control of these epidemics.[4,5]. The breakdown in HIV/TB control within prisons is another emerging threat.[6,7] We describe one of the first reports of combined antiretroviral and anti-TB drug resistance ...

  17. 77 FR 27221 - Combined Notice of Filings

    Science.gov (United States)

    2012-05-09

    ... Generator Status of Minonk Wind, LLC. Filed Date: 4/19/12. Accession Number: 20120419-5196. Comments Due: 5... Self-Certification of Exempt Wholesale Generator Status of Senate Wind, LLC. Filed Date: 4/19/12... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings Take notice...

  18. Combination of scoring schemes for protein docking

    Directory of Open Access Journals (Sweden)

    Schomburg Dietmar

    2007-08-01

    Full Text Available Abstract Background Docking algorithms are developed to predict in which orientation two proteins are likely to bind under natural conditions. The currently used methods usually consist of a sampling step followed by a scoring step. We developed a weighted geometric correlation based on optimised atom specific weighting factors and combined them with our previously published amino acid specific scoring and with a comprehensive SVM-based scoring function. Results The scoring with the atom specific weighting factors yields better results than the amino acid specific scoring. In combination with SVM-based scoring functions the percentage of complexes for which a near native structure can be predicted within the top 100 ranks increased from 14% with the geometric scoring to 54% with the combination of all scoring functions. Especially for the enzyme-inhibitor complexes the results of the ranking are excellent. For half of these complexes a near-native structure can be predicted within the first 10 proposed structures and for more than 86% of all enzyme-inhibitor complexes within the first 50 predicted structures. Conclusion We were able to develop a combination of different scoring schemes which considers a series of previously described and some new scoring criteria yielding a remarkable improvement of prediction quality.

  19. Issues in automatic combination of cloud services

    NARCIS (Netherlands)

    Nguyen, D.K.; Lelli, F.; Papazoglou, M.; van den Heuvel, W.J.A.M.

    2012-01-01

    Current cloud service description languages envision the ability to automatically combine cloud service offerings across multiple abstraction layers, i.e. software, platform, and infrastructure service offerings, to achieve a common shared business goal. However, only little effort has been spent in

  20. Successive combination jet algorithm for hadron collisions

    International Nuclear Information System (INIS)

    Ellis, S.D.; Soper, D.E.

    1993-01-01

    Jet finding algorithms, as they are used in e + e- and hadron collisions, are reviewed and compared. It is suggested that a successive combination style algorithm, similar to that used in e + e- physics, might be useful also in hadron collisions, where cone style algorithms have been used previously

  1. Combining the power of searching and querying

    NARCIS (Netherlands)

    Cohen, S.; Kanza, Y.; Kogan, Y.A.; Nutt, W.; Sagiv, Y.; Serebrenik, A.; Etzion, O.; Scheuermann, P.

    2000-01-01

    EquiX is a search language for XML that combines the power of querying with the simplicity of searching. Requirements for search languages are discussed and it is shown that EquiX meets the necessary criteria. Both a graphical abstract syntax and a formal concrete syntax are presented for EquiX

  2. Epidemiological association between osteoporosis and combined ...

    African Journals Online (AJOL)

    ... higher dietary calcium intake was negatively associated with osteoporosis. Conclusions: Based on these findings, it can be concluded that the combined lifetime use of both snuff and cigarettes may increase the odds of developing osteoporosis among women who are 40 years and older. Key words: Cigarette, nicotine, ...

  3. [Combined physiotherapy of chronic infectious prostatitis].

    Science.gov (United States)

    Churakov, A A; Popkov, V M; Zemskov, S P; Glybochko, P V; Bliumberg, B I

    2007-01-01

    Our experience with therapy of 259 outpatients with chronic infectious prostatitis (CIP) aged 16-55 years has demonstrated that combined treatment of CIP with rectal digital massage of the prostate, electrophoresis of chimotripsin solution with dimexide and local magnetotherapy (Intramag unit) significantly raises treatment efficacy, shortens treatment, prevents complications.

  4. Combined solar collector and energy storage system

    Science.gov (United States)

    Jensen, R. N. (Inventor)

    1980-01-01

    A combined solar energy collector, fluid chiller and energy storage system is disclosed. A movable interior insulated panel in a storage tank is positionable flush against the storage tank wall to insulate the tank for energy storage. The movable interior insulated panel is alternately positionable to form a solar collector or fluid chiller through which the fluid flows by natural circulation.

  5. Combined testing of castings having rough surface

    International Nuclear Information System (INIS)

    Polyakov, Yu.O.; Zav'yalkin, F.M.; Moskvin, V.N.

    1988-01-01

    Mathematical models of a flaw detector for complex testing of castings, containing radiometric and pneumatic converters, are developed and investigated. The efficiency of compensation of casting thickness fluctuation effect on the results of testing in combined information processing obtained by various methods is estimated

  6. 38 CFR 21.4233 - Combination.

    Science.gov (United States)

    2010-07-01

    ...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Programs of... combination of institutional agricultural courses and concurrent agricultural employment (see § 21.4264). A... of the training bears to full time as defined in § 21.4270(c) of this part. The institutional portion...

  7. Effects of combination of ethylenediaminetetraacetic acid and ...

    African Journals Online (AJOL)

    This experiment was conducted to evaluate the combined effects of ethylene diamine tetraacetic acid (EDTA) and microbial phytase (MP) on the serum concentration and digestibility of some minerals in broiler chicks. This experiment was conducted using 360 Ross-308 male broiler chicks in a completely randomized ...

  8. Combination therapies in oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Krishnamurthi, S.; Shanta, V.

    1982-01-01

    The clinical trials are reported involving combined radiotherapy and chemotherapy in oral squamous cell carcinomas. Bleomycin was the only drug that potentiated radiation response in buccal squamous cell carcinomas. The response of the primary tumors was consistent, predictable and reproducible. The following drugs or chemicals were used: synkavit, methotrexate, metronidazole, bleomycin, pepleomycin, and hyperbaric oxygen. The results and their comparison is given in tables

  9. Apparatus for combining oxygen and hydrogen

    International Nuclear Information System (INIS)

    Betz, E.C.

    1977-01-01

    An apparatus is described for catalytically combining hydrogen and oxygen which includes two concentric catalyst chambers arranged so that the outer chamber surrounds the inner chamber and the gas stream passes radially through the outer catalyst chamber. 10 claims, 2 figures

  10. Combined optical/digital security devices

    Science.gov (United States)

    Girnyk, Vladimir I.; Tverdokhleb, Igor V.; Ivanovsky, Andrey A.

    2000-04-01

    Modern holographic security devices used as emblems against counterfeiting are being more difficult as they should oppress criminal world. 2D, 3D, 3D rainbow holograms or simple diffraction structures protecting documents can not be acceptable against illegal copying of important documents, banknotes or valuable products. Recent developments in technology of Optical variable devices permit world leaders to create more advanced security elements: Kinegrams, Exelgrams, Pixelgrams, Kineforms. These products are used for protecting the most confidential documents and banknotes, but now even their security level can not be enough and besides their automatic identification is vulnerable to factors of instability. We elaborate new visual security devices based on the usage of expensive and advanced technology of combined optical/digital security devices. The technology unites digital and analogue methods of synthesis and recording of visual security devices. The analogue methods include techniques of optical holography - different combinations of 2D/3D, 3D, 2D/3D + 3D structures. Basing on them the design with elements of 3D graphics including security elements and hidden machine- readable images are implemented. The digital methods provide synthesis of optical variable devices including special security elements, computer generated holograms and Kineforms. Using them we create determined and quasi-random machine-readable images. Recordings are carried out using the combined optical and electronic submicrometer technology elaborated by Optronics, Ltd. The results obtained show effectiveness of the combined technology permitting to increase the security level essentially that should increase tamper and counterfeit resistance during many years.

  11. Multiswitching combination–combination synchronization of chaotic ...

    Indian Academy of Sciences (India)

    2017-02-09

    Feb 9, 2017 ... restricted to single drive–response system model. It is therefore interesting to ask whether these studies ... this scheme, a universal controller is designed to realize synchronization between a combination of two ... literature [33]. In view of the above discussions, in this paper, we present a new multiswitching ...

  12. Estimation of structural reliability under combined loads

    International Nuclear Information System (INIS)

    Shinozuka, M.; Kako, T.; Hwang, H.; Brown, P.; Reich, M.

    1983-01-01

    For the overall safety evaluation of seismic category I structures subjected to various load combinations, a quantitative measure of the structural reliability in terms of a limit state probability can be conveniently used. For this purpose, the reliability analysis method for dynamic loads, which has recently been developed by the authors, was combined with the existing standard reliability analysis procedure for static and quasi-static loads. The significant parameters that enter into the analysis are: the rate at which each load (dead load, accidental internal pressure, earthquake, etc.) will occur, its duration and intensity. All these parameters are basically random variables for most of the loads to be considered. For dynamic loads, the overall intensity is usually characterized not only by their dynamic components but also by their static components. The structure considered in the present paper is a reinforced concrete containment structure subjected to various static and dynamic loads such as dead loads, accidental pressure, earthquake acceleration, etc. Computations are performed to evaluate the limit state probabilities under each load combination separately and also under all possible combinations of such loads

  13. Combined radiotherapy-chemotherapy in clinical practice

    International Nuclear Information System (INIS)

    Horwich, A.

    1989-01-01

    This paper investigates the combination of radiotherapy and chemotherapy performed over the last 15 years. The improvement of the therapeutic ratio of anti- cancer effect to normal tissue toxicity and its requirement of a thorough understanding of the biological effects of each modality and of how these effects may interact is presented. Early studies and conclusions are examined

  14. Combined matrices in special classes of matrices

    Czech Academy of Sciences Publication Activity Database

    Fiedler, Miroslav; Markham, T. L.

    2011-01-01

    Roč. 435, č. 8 (2011), s. 1945-1955 ISSN 0024-3795 Institutional research plan: CEZ:AV0Z10300504 Keywords : combined matrix * Hadamard product * positive definite matrix * M-matrix * totally positive matrix * oscillatory matrix * Cauchy matrix Subject RIV: BA - General Mathematics Impact factor: 0.974, year: 2011

  15. Combination of radiation injuries: pathogenesis, clinic, therapy

    International Nuclear Information System (INIS)

    Tsyba, A.F.; Farshatova, M.N.

    1993-01-01

    Modern notions on combined radiation injuries (CRI) are presented. Characteristic of injurious factors of nuclear explosion and common regularities of the CRI origination is given. The data on the CRI clinical peculiarities, diagnostics and treatment, principles of medical assistance for the injured on the stages of medical evacuation and recommendations on rehabilitation are presented

  16. Combination of ATLAS Higgs Boson measurements

    CERN Document Server

    Monticelli, Fernando; The ATLAS collaboration

    2018-01-01

    The results obtained from the different decay channels are combined to study the properties of the Higgs boson mass, production and decay, and test the SM theoretical precision with increased accuracy, using about 36 fb^{-1} of p-p collisions data collected at 13 TeV.

  17. Towards combined global monthly gravity field solutions

    Science.gov (United States)

    Jaeggi, Adrian; Meyer, Ulrich; Beutler, Gerhard; Weigelt, Matthias; van Dam, Tonie; Mayer-Gürr, Torsten; Flury, Jakob; Flechtner, Frank; Dahle, Christoph; Lemoine, Jean-Michel; Bruinsma, Sean

    2014-05-01

    Currently, official GRACE Science Data System (SDS) monthly gravity field solutions are generated independently by the Centre for Space Research (CSR) and the German Research Centre for Geosciences (GFZ). Additional GRACE SDS monthly fields are provided by the Jet Propulsion Laboratory (JPL) for validation and outside the SDS by a number of other institutions worldwide. Although the adopted background models and processing standards have been harmonized more and more by the various processing centers during the past years, notable differences still exist and the users are more or less left alone with a decision which model to choose for their individual applications. This procedure seriously limits the accessibility of these valuable data. Combinations are well established in the area of other space geodetic techniques, such as the Global Navigation Satellite Systems (GNSS), Satellite Laser Ranging (SLR), and Very Long Baseline Interferometry (VLBI). Regularly comparing and combining space-geodetic products has tremendously increased the usefulness of the products in a wide range of disciplines and scientific applications. Therefore, we propose in a first step to mutually compare the large variety of available monthly GRACE gravity field solutions, e.g., by assessing the signal content over selected regions, by estimating the noise over the oceans, and by performing significance tests. We make the attempt to assign different solution characteristics to different processing strategies in order to identify subsets of solutions, which are based on similar processing strategies. Using these subsets we will in a second step explore ways to generate combined solutions, e.g., based on a weighted average of the individual solutions using empirical weights derived from pair-wise comparisons. We will also assess the quality of such a combined solution and discuss the potential benefits for the GRACE and GRACE-FO user community, but also address minimum processing

  18. PHARMACOECONOMIC ANALYSIS OF ANTIHYPERTENSIVE DRUG COMBINATIONS USE

    Directory of Open Access Journals (Sweden)

    E. I. Tarlovskaya

    2015-09-01

    Full Text Available Aim. To pursue pharmacoeconomic analysis of two drug combinations of ACE inhibitor (enalapril and diuretic.Material and methods. Patients with arterial hypertension degree 2 and diabetes mellitus type 2 without ischemic heart disease (n=56 were included into the study. Blood pressure (BP dynamics and cost/effectiveness ratio were evaluated.Results. In group A (fixed combination of original enalapril/hydrochlorothiazide 61% of patients achieved target BP level with initial dose, and the rest 39% of patients – with double dose. In group B (non-fixed combination of generic enalapril/indapamide 60% of patients achieved the target BP with initial dose of drugs, 33% - with double dose of ACE inhibitor, and 7% - with additional amlodipine administration. In patients of group A systolic BP (SBP reduction was 45.82±1.23 mm Hg by the 12th week vs. 40.0±0.81 mm Hg in patients of group B; diastolic BP (DBP reduction was 22.47±1.05 mm Hg and 18.76±0.70 mm Hg, respectively, by the 12th week of treatment. In the first month of treatment costs of target BP achievement was 298.62 rubles per patient in group A, and 299.50 rubles – in group B; by the 12th week of treatment – 629.45 and 631.22 rubles, respectively. Costs of SBP and DBP reduction by 1 mm Hg during 12 weeks of therapy were 13 and 27 rubles per patient, respectively, in group A, and 16 and 34 rubles per patient, respectively, in group B.Conclusion. The original fixed combination (enalapril+hydrochlorothiazide proved to be more clinically effective and more cost effective in the treatment of hypertensive patients in comparison with the non-fixed combination of generic drugs (enalapril+indapamide.

  19. Combination N-Way Power Divider/Combiner and Noninvasive Reflected Power Detection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — An N-way RF/microwave power divider/combiner utilizes one input and N outputs, or conversely N inputs and one output to divide (or combine) RF/microwave power while...

  20. Further development of mathematical description for combined toxicity: A case study of lead–fluoride combination

    Directory of Open Access Journals (Sweden)

    Vladimir G. Panov

    2015-01-01

    Full Text Available In this article, we check and develop further some postulates of the theory and mathematical modeling of combined toxic effect that we proposed earlier [1]. To this end, we have analyzed the results of an experiment on rats exposed during 6 weeks to repeated intraperitoneal injections of lead acetate, sodium fluoride or both. The development of intoxication was estimated quantitatively with 54 functional, biochemical and morphometric indices. For mathematical description of the effect that lead and fluorine doses produced alone or in combination, we used a response surface regression model containing linear and cross terms (hyperbolic paraboloid. It is shown that the combination of lead and fluoride features the same 10 types of combined effect that we found previously for the lead and cadmium combination. Special attention is given to indices on which lead and fluorine produce an opposite effect.

  1. Combined spinal intramedullary arteriovenous malformation and lipomyelomeningocele

    Energy Technology Data Exchange (ETDEWEB)

    Weon, Y.C.; Roh, H.G.; Byun, H.S. [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology, Seoul (Korea); Chung, J.I. [Medimoa Hospital, Department of Radiology, Seoul (Korea); Eoh, W. [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea)

    2005-10-01

    Combined spinal arteriovenous malformation and lipomyelomeningocele are extremely rare. We present a rare combined case of a lipomyelomeningocele with an intramedullary arteriovenous malformation (AVM) occurred at the L3-L4 level in a 30-year-old man who suffered from low back pain radiating to the lower extremities, dysuria, and frequency for 5 years. The MR studies showed an intradural mass with high-signal intensity on both T1-weighted and T2-weighted images, intermingled with multiple signal-void structures. The mass extended extradurally toward a subcutaneously forming fatty mass on the patient's back. Spinal angiography showed an AVM supplied by the radiculopial branches of the lumbar arteries and drained by tortuous, dilated, perimedullary veins. Endovascular embolization and surgical resection were performed. (orig.)

  2. Consensus paper: combining transcranial stimulation with neuroimaging

    DEFF Research Database (Denmark)

    Siebner, Hartwig R; Bergmann, Til O; Bestmann, Sven

    2009-01-01

    neuroimaging (online approach), TMS can be used to test how focal cortex stimulation acutely modifies the activity and connectivity in the stimulated neuronal circuits. TMS and neuroimaging can also be separated in time (offline approach). A conditioning session of repetitive TMS (rTMS) may be used to induce...... information obtained by neuroimaging can be used to define the optimal site and time point of stimulation in a subsequent experiment in which TMS is used to probe the functional contribution of the stimulated area to a specific task. In this review, we first address some general methodologic issues that need......In the last decade, combined transcranial magnetic stimulation (TMS)-neuroimaging studies have greatly stimulated research in the field of TMS and neuroimaging. Here, we review how TMS can be combined with various neuroimaging techniques to investigate human brain function. When applied during...

  3. RESTAURANT RESERVATION MANAGEMENT CONSIDERING TABLE COMBINATION

    Directory of Open Access Journals (Sweden)

    Qing Miao

    Full Text Available ABSTRACT This paper presents a case study of table reservation practice for restaurant business within Walt Disney World. A unique feature here is to consider table combination to capture revenue potentials from different party sizes and at different time periods. For example, a party of large size can be served by combining two or more small tables. A mixed integer programming (MIP model is developed to make the reservation recommendation. We propose a rolling horizon reservation policy such that the value of a particular table is periodically evaluated and updated. This is a typical revenue management method in the airlines and other industries, the essence of which is to compare the future expected revenue with a currently offered price. Using historical data, numerical test shows a significant revenue improvement potential from our proposed model.

  4. Camera System MTF: combining optic with detector

    Science.gov (United States)

    Andersen, Torben B.; Granger, Zachary A.

    2017-08-01

    MTF is one of the most common metrics used to quantify the resolving power of an optical component. Extensive literature is dedicated to describing methods to calculate the Modulation Transfer Function (MTF) for stand-alone optical components such as a camera lens or telescope, and some literature addresses approaches to determine an MTF for combination of an optic with a detector. The formulations pertaining to a combined electro-optical system MTF are mostly based on theory, and assumptions that detector MTF is described only by the pixel pitch which does not account for wavelength dependencies. When working with real hardware, detectors are often characterized by testing MTF at discrete wavelengths. This paper presents a method to simplify the calculation of a polychromatic system MTF when it is permissible to consider the detector MTF to be independent of wavelength.

  5. Estimation of combined sewer overflow discharge

    DEFF Research Database (Denmark)

    Ahm, Malte; Thorndahl, Søren Liedtke; Nielsen, Jesper Ellerbæk

    2016-01-01

    Combined sewer overflow (CSO) structures are constructed to effectively discharge excess water during heavy rainfall, to protect the urban drainage system from hydraulic overload. Consequently, most CSO structures are not constructed according to basic hydraulic principles for ideal measurement......-balance in combined sewer catchments. A closed mass-balance is an advantage for calibration of all urban drainage models based on mass-balance principles. This study presents three different software sensor concepts based on local water level sensors, which can be used to estimate CSO discharge volumes from hydraulic...... complex CSO structures. The three concepts was tested and verified under real practical conditions. All three concepts were accurate when compared to electromagnetic flow measurements....

  6. Object attributes combine additively in visual search.

    Science.gov (United States)

    Pramod, R T; Arun, S P

    2016-01-01

    We perceive objects as containing a variety of attributes: local features, relations between features, internal details, and global properties. But we know little about how they combine. Here, we report a remarkably simple additive rule that governs how these diverse object attributes combine in vision. The perceived dissimilarity between two objects was accurately explained as a sum of (a) spatially tuned local contour-matching processes modulated by part decomposition; (b) differences in internal details, such as texture; (c) differences in emergent attributes, such as symmetry; and (d) differences in global properties, such as orientation or overall configuration of parts. Our results elucidate an enduring question in object vision by showing that the whole object is not a sum of its parts but a sum of its many attributes.

  7. Sensitivity of a combined gravitational antenna

    International Nuclear Information System (INIS)

    Kulagin, V.V.; Rudenko, V.N.

    1986-01-01

    A modification of a combined optico-acoustic gravitational antenna: a long-base laser interferometer, where free masses are changed by Weber resonators, is suggested. The combined gravitational antenna can possess sensitivity h min ∼ 10 -18 without deep cooling of Weber resonators and h min ∼ 10 -19 at helium temperaure of the resonators. This antenna has the following new quantities: presence of three independent responses, that permits to a considerable extent to exclude non-gravitational effects; presence of responses of two separated Weber resonators, that permits to register the wave character of gravitational perturbation by measuring phase shift between relaxation ''tails''. It means that one may with certainty register the wave structure of gravitational radiation for perturbation of metrics h, exceeding the threshold sensitivity of the known detectors by an order

  8. Lymphocytic nucleolar index in the combined application

    Energy Technology Data Exchange (ETDEWEB)

    Kilyovska, M.; Nechev, Kh.; Vankova, P.; Tsvetkov, P.; Shopova, V. (Meditsinski Fakultet, Pleven (Bulgaria). Katedra Mediko-Sanitarna Zashtita)

    1982-01-01

    Sex mature male rats were irradiated with 5,25 and 50 rad from X-ray source. One group of irradiated animals was treated intraperitoneally with 10 mCi/animal Ce/sup 144/ or 0.04 mCi/g Sr/sup 89/. The second group was treated only with radionuclide. The nucleolar index (NI) of the lymphocytes in a blood smear was studied on the 1st, 3rd, 8th and 30th day after application. It was found that X-irradiation increased the value of NI after the 15th day, the effect being independent on the dose rates. Ce/sup 144/, applied alone in combination with external irradiation, also causes an increase of NI. Combined application of Sr/sup 89/ and external irradiation leads after one month to a decrease of NI. The results are discussed in connection with radionuclide kinetics and dose distribution.

  9. PANSAID-PAracetamol and NSAID in combination

    DEFF Research Database (Denmark)

    Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel

    2017-01-01

    in patients having total hip arthroplastic surgery. Patients, caregivers, physicians, investigators, and statisticians are blinded to the intervention. The two co-primary outcomes are 24-h consumption of morphine and proportion of patients with one or more serious adverse events within 90 days after surgery....... Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion of patients with one or more adverse events within 24 h postoperatively. DISCUSSION: PANSAID will provide a large trial with low risk of bias regarding benefits and harms of the combination......BACKGROUND: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary...

  10. Combining resummed Higgs predictions across jet bins

    Energy Technology Data Exchange (ETDEWEB)

    Boughezal, Radja [Argonne National Laboratory, IL (United States). High Energy Physics Division; Liu, Xiaohui; Petriello, Frank [Argonne National Laboratory, IL (United States). High Energy Physics Division; Northwestern Univ., Evanston, IL (United States). Dept. of Physics and Astronomy; Tackmann, Frank J. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Walsh, Jonathan R. [California Univ., Berkeley, CA (United States). Ernest Orlando Lawrence Berkeley Laboratory; California Univ., Berkeley, CA (United States). Center for Theoretical Physics

    2013-12-15

    Experimental analyses often use jet binning to distinguish between different kinematic regimes and separate contributions from background processes. To accurately model theoretical uncertainties in these measurements, a consistent description of the jet bins is required. We present a complete framework for the combination of resummed results for production processes in different exclusive jet bins, focusing on Higgs production in gluon fusion as an example. We extend the resummation of the H+1-jet cross section into the challenging low transverse momentum region, lowering the uncertainties considerably. We provide combined predictions with resummation for cross sections in the H+0-jet and H+1-jet bins, and give an improved theory covariance matrix for use in experimental studies. We estimate that the relevant theoretical uncertainties on the signal strength in the H{yields}WW{sup *} analysis are reduced by nearly a factor of 2 compared to the current value.

  11. Combination stem cell therapy for heart failure

    Directory of Open Access Journals (Sweden)

    Ichim Thomas E

    2010-04-01

    Full Text Available Abstract Patients with congestive heart failure (CHF that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a increasing stem cell migration to the heart; b augmenting stem cell activity; and c combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.

  12. Organosilicon fluid for cooling coal combine motors

    Energy Technology Data Exchange (ETDEWEB)

    Donets, I K; Dmitrenko, Yu N; Kovalev, Ye B; Sukhanov, V V; Tsingarelli, Ye P

    1983-01-01

    Results are presented of toxicological evaluation of the polymer organosilicon fluid FM-5.6AP which should be used as the cooling agent of the electric motors of coal combines. It was established that fluid FM-5.6AP belongs to the low-toxic substances that do not have skinresorptive, skin-damaging and cumulative effect, do not have a significant influence on phagocytosis of the coal dust, in depositing in the lungs and elimination. During experimental industrial tests of the motor using the fluid FM-5.6AP, no toxic effect of it on the body was revealed. The possibility is shown of using organosilicon fluid FM-5.6AP for cooling electric motors of coal combines.

  13. [Combination therapy of chronic bacterial prostatitis].

    Science.gov (United States)

    Khryanin, A A; Reshetnikov, O V

    2016-08-01

    The article discusses the possible etiological factors in the development of chronic bacterial prostatitis. The authors presented a comparative long-term analysis of morbidity from non-viral sexually transmitted infections (STIs) in Russia. Against the background of general decline in STIs incidence, a significant percentage of them is made up by urogenital trichomoniasis. The findings substantiated the advantages of combination therapy (ornidazole and ofloxacin) for bacterial urinary tract infections.

  14. Combined interferometric and polarimetric diagnostics for TEXTOR

    International Nuclear Information System (INIS)

    Soltwisch, H.

    1980-01-01

    A method for combining Faraday rotation measurements with a phase modulated HCN interferometer is described. Extended to a multichannel system this technique should allow to investigate the distributions of electron density and poloidal magnetic field in a Tokamak plasma. We discuss the principle of operation and appropriate evaluation of measured data with regard to TEXTOR parameters and give an estimate for the expected experimental accuracy. (orig./GG) 891 GG/orig.- 892 KN

  15. Rocket Based Combined Cycle (RBCC) Engine

    Science.gov (United States)

    2004-01-01

    Pictured is an artist's concept of the Rocket Based Combined Cycle (RBCC) launch. The RBCC's overall objective is to provide a technology test bed to investigate critical technologies associated with opperational usage of these engines. The program will focus on near term technologies that can be leveraged to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsions systems and ultimately a Single Stage To Orbit (SSTO) air breathing propulsion system.

  16. Multi combined Adlerian supervision in Counseling

    OpenAIRE

    Gungor, Abdi

    2017-01-01

    For counselor professional and counselor education, supervision is an important process, in which more experienced professional helps and guides less experienced professional. To provide an effective and beneficial supervision, various therapy, development, or process based approaches and models have been developed. In addition, different eclectic models integrating more than one model have been developed. In this paper, as a supervision model, multi combined Adlerian supervision model is pro...

  17. Combining data in non-destructive testing

    International Nuclear Information System (INIS)

    Lavayssiere, B.

    1994-03-01

    Non-destructive testing of some components requires quite often the use of several methods such as X-ray, ultrasonics, Eddy Currents. But the efficiency of a NDT method is highly dependent on the fact that the detectability of flaws in a specimen relies on the choice of the best method. Moreover a lot of inspection issues could benefit from the use of more than one test method, as each NDT method has its own physical properties and technological limits. Some questions still remain: how to combine data, at what level and for what functionality. Simple monomethod processes are well-known now. They include techniques like reconstruction which belongs to the so-called ill-posed problems in the field of mathematics. For NDT data processing, it has the ability to estimate real data from distorted ones coming from a probe. But, up to now there has been very few approaches for computer aided combination of results from different advanced techniques. This report presents the various mathematical fields involved towards that goal (statistical decision theory which allows the use of multiple hypothesis, non-linear decision theory for its capability to classify and to discriminate, graph theory to find the optimal path in an hypothesis graph and also fuzzy logic, multiple resolution analysis, artificial intelligence,...) and which combinations of methods are useful. Some images will illustrate this topic in which EDF is involved, and will explain what are the major goals of this work. Combining is not only an improvement of 3D visualisation which would allow to display simultaneously CAD or NDT data for example, but it consists in exploiting multisensor data collected via a variety of sophisticated techniques and presenting this information to the operator without overloading the operator/system capacities in order to reduce the uncertainty and to resolve the ambiguity inherent to mono method inspection. (author). 7 figs., 35 refs

  18. ACCOUNTING FOR CONTINGENT CONSIDERATIONS IN BUSINESS COMBINATIONS

    OpenAIRE

    Gurgen KALASHYAN

    2017-01-01

    According to IFRS 3 Business Combinations contingent considerations must be included in the total consideration given for the acquired entity along with cash, other assets, ordinary or preference equity instruments, options, warrants. The contingent consideration is the determined amount which acquiring entity has to pay to acquired entity provided, that certain conditions will be fulfilled in the future. In case the provisions are not satisfied, we will get the situation when the amount of c...

  19. Screening for severe combined immunodeficiency in neonates

    OpenAIRE

    Kelly, Brian T; Tam, Jonathan S; Verbsky, James W; Routes, John M

    2013-01-01

    Brian T Kelly,1 Jonathan S Tam,1 James W Verbsky,1,2 John M Routes1,2 1Department of Pediatrics, 2Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA Abstract: Severe combined immunodeficiency (SCID) is a rare disease that severely affects the cellular and humoral immune systems. Patients with SCID present with recurrent or severe infections and often with chronic diarrhea and failure to thrive. The disease is uniformly fatal, making early diag...

  20. Combined analog-to-digital converter

    International Nuclear Information System (INIS)

    Zhukov, A.V.; Rzhendinskaya, S.N.

    1983-01-01

    A 10-bit analog-to-digital converter (ADC) designed for operating in spectrometers with time-dependent filters is described. The ADC operation is based on combining the parallel reading and sequential counting methods. At maximum conversion time of 12 μs, timing series frequency of 25 MHz and foUr reference levels the differential nonlinearity withoUt statistical smoothing (maximum relative channel width deviation from average value) is not more than 4%

  1. Suction caissons subjected to monotonic combined loading

    OpenAIRE

    Penzes, P.; Jensen, M.R.; Zania, Varvara

    2016-01-01

    Suction caissons are being increasingly used as offshore foundation solutions in shallow and intermediate water depths. The convenient installation method through the application of suction has rendered this type of foundation as an attractive alternative to the more traditional monopile foundation for offshore wind turbines. The combined loading imposed typically to a suction caisson has led to the estimation of their bearing capacity by means of 3D failure envelopes. This study aims to anal...

  2. Combined confinement system applied to tokamaks

    International Nuclear Information System (INIS)

    Ohkawa, Tihiro

    1986-01-01

    From particle orbit point of view, a tokamak is a combined confinement configuration where a closed toroidal volume is surrounded by an open confinement system like a magnetic mirror. By eliminating a cold halo plasma, the energy loss from the plasma becomes convective. The H-mode in diverted tokamaks is an example. Because of the favorable scaling of the energy confinement time with temperature, the performance of the tokamak may be significantly improved by taking advantage of this effect. (author)

  3. Coherent beam combination via microparticle plasma modes

    International Nuclear Information System (INIS)

    Rogovin, D.; Shen, T.P.

    1988-01-01

    Recently, there have been interesting observations and calculations on phase conjugation via degenerate four-wave mixing in gold colloids. The generation of phase conjugate radiation in these media arises from and reflects the creation of static index grating imposed on the electronic wave functions within the microparticles. These encouraging findings motivate us to consider the possibility of generating moving index gratings in these media with possible applications to coherent beam combination

  4. Combination of irradiation and thermal processing

    International Nuclear Information System (INIS)

    Hozova, B.; Sorman, L.

    1991-01-01

    Recently, the technology and methods of food preservation have searched for ever better and less destructive methods and procedures which prolong the shelf-life of the primary products so that they do not undergo degradation processes. New non-traditional methods of preservation, as well as the procedures based on scientifically controlled combination of two or more preservation methods give increasingly higher chances for the improvement of the quality of canned products. Such combinations should reduce the intensity of the adverse effects of separately applied preservation methods. The aim is to achieve synergic or additive effects of the decisive factors, which would ensure microbiological adequacy and storage stability of canned foods, including maximum retention of their nutritional and sensory characteristics. If the published scientific papers dealing with non-traditional methods of food preservation and application of combination of preservation methods are evaluated, it can be seen that there is no work which provides an analysis of this problem. The use of ionizing radiation can reduce the number of microorganisms on foods and doses of up to 10 kGy are not considered to present any toxicological risks. However results have not been satisfactory mainly due to the interaction of ionizing radiation with the components of the irradiated foods. It is desirable to reduce the side effects of radiosterilizing doses by reducing the dose and using another method to complete the processing. Special attention is paid particularly to the use of combinations of heat and irradiation, since this is suitable mainly for the preservation of meat products but can also be applied to vegetables and other products. (author)

  5. Cost allocation. Combined heat and power production

    International Nuclear Information System (INIS)

    Sidzikauskas, V.

    2002-01-01

    The benefits of Combined Heat and Power (CHP) generation are discussed. The include improvement in energy intensity of 1% by 2010, 85-90% efficiency versus 40-50% of condensation power and others. Share of CHP electricity production in ERRA countries is presented.Solutions for a development CHP cost allocation are considered. Conclusion are presented for CHP production cost allocation. (R.P.)

  6. On Coding Non-Contiguous Letter Combinations

    Directory of Open Access Journals (Sweden)

    Frédéric eDandurand

    2011-06-01

    Full Text Available Starting from the hypothesis that printed word identification initially involves the parallel mapping of visual features onto location-specific letter identities, we analyze the type of information that would be involved in optimally mapping this location-specific orthographic code onto a location-invariant lexical code. We assume that some intermediate level of coding exists between individual letters and whole words, and that this involves the representation of letter combinations. We then investigate the nature of this intermediate level of coding given the constraints of optimality. This intermediate level of coding is expected to compress data while retaining as much information as possible about word identity. Information conveyed by letters is a function of how much they constrain word identity and how visible they are. Optimization of this coding is a combination of minimizing resources (using the most compact representations and maximizing information. We show that in a large proportion of cases, non-contiguous letter sequences contain more information than contiguous sequences, while at the same time requiring less precise coding. Moreover, we found that the best predictor of human performance in orthographic priming experiments was within-word ranking of conditional probabilities, rather than average conditional probabilities. We conclude that from an optimality perspective, readers learn to select certain contiguous and non-contiguous letter combinations as information that provides the best cue to word identity.

  7. Regulatory requirements for marketing fixed dose combinations

    Directory of Open Access Journals (Sweden)

    B G Jayasheel

    2010-01-01

    Full Text Available The development of fixed-dose combinations (FDCs is becoming increasingly important from a public health perspective. FDCs have advantages when there is an identifiable patient population for whom treatment with a particular combination of actives in a fixed ratio is safe and effective and when all of the actives contribute to the overall therapeutic effect. Such combinations of drugs are particularly useful in the management of chronic diseases. In addition, there can be real clinical benefits in the form of increased efficacy and/or a reduced incidence of adverse effects. Additional advantages of FDCs are potentially lower costs of manufacturing compared to the costs of producing separate products administered concurrently, simpler logistics of distribution and reduced development of resistance in the case of antimicrobials. Above all, FDC therapy reduces pill burden and improves medication compliance. Although, FDCs seem to be ideal under certain pre-defined circumstances, if a dosing adjustment is warranted, there may not be an FDC available in the most appropriate strength for the patient and if an adverse drug reaction occurs from using an FDC, it may be difficult to identify the active ingredient responsible for causing the reaction. Appendix VI of Schedule Y (Drugs & Cosmetics Rules 1945, India states the requirements for marketing approval of various types of FDCs. The same is further elaborated in this article to provide a detailed guidance including the clinical trial requirements. However, the heterogeneity of the therapeutic field makes it difficult to develop a standard guidance document.

  8. Combined effects of radiation and trauma

    Science.gov (United States)

    Messerschmidt, Otfried

    Injuries, caused by both whole-body irradiation and wounds or burns, have been relatively little studied. Possibly because many investigators think that these injuries are just modified radiation-induced diseases for which the same treatment principles are valid. Other authors had the impression that, for instance, the radiation burn trauma is a new kind of disease which differs significantly from either radiation syndrome alone or from burn disease. There are many experimental data on animals which suggest that the pathology of combined injuries differs significantly from that of radiation-induced disease or of thermal or mechanical traumas. Wounds or burns which, in general, do not cause septicaemia could become entrance ports for bacteria when animals are exposed to whole-body irradiation. Thrombocytopenia is the reason for hemorrhages in wounds. The susceptibility to shock is increased considerably in combined injuries and the formation of callus in the bone fractures is significantly delayed. The healing of wounds and burns in the initial phase of the radiation syndrome does not always differ from healing in the non-irradiated organism. However, a few days or weeks later very serious wound infections and hemorrhages can occur. The additional injuries almost always worsen the development and prognosis of radiation-induced disease. The recommended treatment for combined injuries will differ in many respects from the treatment of wounds and burns or the radiation syndrome.

  9. Reports from the Combined Performance Working Groups

    CERN Multimedia

    S. Haywood

    The main goal of the Combined Performance Groups is to study the detector performance for physics, as well as to monitor the effect of changes to the detector layout and the evolution of the software. The groups combine the expertise available in several different subdetectors. In addition, they are responsible for developing combined reconstruction algorithms and are involved in the calibration of energy scales and optimising resolutions. For the Workshop, the four groups made a real effort to compare the reconstruction in Athena (the "New" C++ software framework) and Atrecon (the "Old" software used for the TDR studies). b-tagging Working Group: Over the last few months, the description of the Inner Detector in the simulation has become more realistic, following the evolution of the detector design. This has caused the amount of material in the simulation to increase and the Pixel B-layer has been moved to a larger radius to allow for a wider beam-pipe. Nevertheless, the good performance of the b-tagging (...

  10. Genetic compatibility determines endophyte-grass combinations.

    Directory of Open Access Journals (Sweden)

    Kari Saikkonen

    Full Text Available Even highly mutually beneficial microbial-plant interactions, such as mycorrhizal- and rhizobial-plant exchanges, involve selfishness, cheating and power-struggles between the partners, which depending on prevailing selective pressures, lead to a continuum of interactions from antagonistic to mutualistic. Using manipulated grass-endophyte combinations in a five year common garden experiment, we show that grass genotypes and genetic mismatches constrain genetic combinations between the vertically (via host seeds transmitted endophytes and the out-crossing host, thereby reducing infections in established grass populations. Infections were lost in both grass tillers and seedlings in F(1 and F(2 generations, respectively. Experimental plants were collected as seeds from two different environments, i.e., meadows and nearby riverbanks. Endophyte-related benefits to the host included an increased number of inflorescences, but only in meadow plants and not until the last growing season of the experiment. Our results illustrate the importance of genetic host specificity and trans-generational maternal effects on the genetic structure of a host population, which act as destabilizing forces in endophyte-grass symbioses. We propose that (1 genetic mismatches may act as a buffering mechanism against highly competitive endophyte-grass genotype combinations threatening the biodiversity of grassland communities and (2 these mismatches should be acknowledged, particularly in breeding programmes aimed at harnessing systemic and heritable endophytes to improve the agriculturally valuable characteristics of cultivars.

  11. Unsupervised Retinal Vessel Segmentation Using Combined Filters.

    Directory of Open Access Journals (Sweden)

    Wendeson S Oliveira

    Full Text Available Image segmentation of retinal blood vessels is a process that can help to predict and diagnose cardiovascular related diseases, such as hypertension and diabetes, which are known to affect the retinal blood vessels' appearance. This work proposes an unsupervised method for the segmentation of retinal vessels images using a combined matched filter, Frangi's filter and Gabor Wavelet filter to enhance the images. The combination of these three filters in order to improve the segmentation is the main motivation of this work. We investigate two approaches to perform the filter combination: weighted mean and median ranking. Segmentation methods are tested after the vessel enhancement. Enhanced images with median ranking are segmented using a simple threshold criterion. Two segmentation procedures are applied when considering enhanced retinal images using the weighted mean approach. The first method is based on deformable models and the second uses fuzzy C-means for the image segmentation. The procedure is evaluated using two public image databases, Drive and Stare. The experimental results demonstrate that the proposed methods perform well for vessel segmentation in comparison with state-of-the-art methods.

  12. The 2004 ATLAS Combined Test Beam

    CERN Multimedia

    The ATLAS CTB Team, .

    2004-01-01

    In the year 2004, ATLAS has been involved in a huge combined test beam (CTB) effort in H8. A complete slice of the barrel detector and of the Muon End-cap has been tested, with the following clear goals: pre-commission the final elements and study the detector performance in a realistic combined data taking. Thanks to this experience, a lot of expertise in the operations has been acquired and much data (~ 4.6 TB of data, ~ 90 million events on castor) has been collected and is already under analysis. The CTB has been characterized by different phases with an incremental presence of sub-detectors modules and associated DAQ infrastructure, as well as incremental improvement of analysis tools for prompt data certification. The physics goals of the CTB have been defined in consultation with the physics coordinator, all the sub-detector representatives and the combined performance group representative. With all these indications, a detailed run plan day-by-day schedule was defined before the CTB start and was foll...

  13. Fixed Dose Combination for TB treatment

    Directory of Open Access Journals (Sweden)

    Tjandra Y. Aditama

    2003-06-01

    Full Text Available According to the World Health Organization, a third of the world’s population is infected with tuberculosis. The disease is responsible for nearly 2 million deaths each year and over 8 million were developing active diseases. Moreover, according to WHO (2000, tuberculosis deaths are estimated to increase to 35 million between 2000-2020. The majority of tuberculosis patients worldwide are still treated with single drugs, or with 2-drug fixed-dose combinations (FDCs. To improve tuberculosis treatment, 2- and 3-drug FDCs were recommended by the World Health Organization (WHO as part of the DOTS strategy. Since 1999 a 4-drug FDC was included on the WHO Model List of Essential Drugs. Today, FDCs are important tools to further improve the quality of care for people with TB, and accelerate DOTS expansion to reach the global TB control targets. Fixed dose combination TB drugs could simplifies both treatment and management of drug supply, and may prevent the emergence of drug resistance .Prevention of drug resistance is just one of the potential benefits of the use of FDCs. FDCs simplify administration of drugs by reducing the number of pills a patient takes each day and decreasing the risk of incorrect prescriptions. Most tuberculosis patients need only take 3–4 FDCs tablets per day during the intensive phase of treatment, instead of the 15–16 tablets per day that is common with single-drug formulations It is much simpler to explain to patients that they need to take four tablets of the same type and colour, rather than a mixture of tablets of different shapes, colours and sizes. Also, the chance of taking an incomplete combination of drugs is eliminated, since the four essential drugs are combined into one tablet. FDCs are also simpler for care-givers as they minimize the risk of confusion. Finally, drug procurement, in all its components (stock management, shipping, distribution, is simplified by FDCs. Adverse reactions to drugs are not more

  14. All-fiber 7x1 signal combiner for incoherent laser beam combining

    DEFF Research Database (Denmark)

    Noordegraaf, Danny; Maack, Martin D.; Skovgaard, Peter M. W.

    2011-01-01

    We demonstrate an all-fiber 7x1 signal combiner for incoherent laser beam combining. This is a potential key component for reaching several kW of stabile laser output power. The combiner couples the output from 7 single-mode (SM) fiber lasers into a single multi-mode (MM) fiber. The input signal ...... in device temperature is observed. At an intermediate power level of 600 W a beam parameter product (BPP) of 2.22 mm x mrad is measured, corresponding to an M2 value of 6.5. These values are approaching the theoretical limit dictated by brightness conservation....

  15. Combining disparate data for decision making

    Science.gov (United States)

    Gettings, M. E.

    2010-12-01

    Combining information of disparate types from multiple data or model sources is a fundamental task in decision making theory. Procedures for combining and utilizing quantitative data with uncertainties are well-developed in several approaches, but methods for including qualitative and semi-quantitative data are much less so. Possibility theory offers an approach to treating all three data types in an objective and repeatable way. In decision making, biases are frequently present in several forms, including those arising from data quality, data spatial and temporal distribution, and the analyst's knowledge and beliefs as to which data or models are most important. The latter bias is particularly evident in the case of qualitative data and there are numerous examples of analysts feeling that a qualitative dataset is more relevant than a quantified one. Possibility theory and fuzzy logic now provide fairly general rules for quantifying qualitative and semi-quantitative data in ways that are repeatable and minimally biased. Once a set of quantified data and/or model layers is obtained, there are several methods of combining them to obtain insight useful in decision making. These include: various combinations of layers using formal fuzzy logic (for example, layer A and (layer B or layer C) but not layer D); connecting the layers with varying influence links in a Fuzzy Cognitive Map; and using the set of layers for the universe of discourse for agent based model simulations. One example of logical combinations that have proven useful is the definition of possible habitat for valley fever fungus (Coccidioides sp.) using variables such as soil type, altitude, aspect, moisture and temperature. A second example is the delineation of the lithology and possible mineralization of several areas beneath basin fill in southern Arizona. A Fuzzy Cognitive Map example is the impacts of development and operation of a hypothetical mine in an area adjacent to a city. In this model

  16. IMPLICATION OF THE FIXED COMBINATIONS IN THE HYPERTENSION TREATMENT

    Directory of Open Access Journals (Sweden)

    Z. D. Kobalava

    2010-01-01

    Full Text Available The role of fixed combinations in the hypertension (HT treatment is discussed. Theoretical and practical aspects of combination therapy, principles of rational combination therapy are present. Current guidelines on the use of fixed dose combinations, including start antihypertensive therapy are analyzed. Classification of combinations, advantages and limitations of some of them implementation are also presented. Significance of beta-blocker bisoprolol and thiazide diuretic hydrochlorothiazide fixed combination (Lodoz is shown in HT treatment.

  17. Spectral beam combining of diode lasers with high efficiency

    DEFF Research Database (Denmark)

    Müller, André; Vijayakumar, Deepak; Jensen, Ole Bjarlin

    2012-01-01

    Based on spectral beam combining we obtain 16 W of output power, combining two 1063 nm DBR-tapered diode lasers. The spectral separation within the combined beam can be used for subsequent sum-frequency generation.......Based on spectral beam combining we obtain 16 W of output power, combining two 1063 nm DBR-tapered diode lasers. The spectral separation within the combined beam can be used for subsequent sum-frequency generation....

  18. VLBI TRF Combination Using GNSS Software

    Directory of Open Access Journals (Sweden)

    Younghee Kwak

    2013-12-01

    Full Text Available Space geodetic techniques can be used to obtain precise shape and rotation information of the Earth. To achieve this, the representative combination solution of each space geodetic technique has to be produced, and then those solutions need to be combined. In this study, the representative combination solution of very long baseline interferometry (VLBI, which is one of the space geodetic techniques, was produced, and the variations in the position coordinate of each station during 7 years were analyzed. Products from five analysis centers of the International VLBI Service for Geodesy and Astrometry (IVS were used as the input data, and Bernese 5.0, which is the global navigation satellite system (GNSS data processing software, was used. The analysis of the coordinate time series for the 43 VLBI stations indicated that the latitude component error was about 15.6 mm, the longitude component error was about 37.7 mm, and the height component error was about 30.9 mm, with respect to the reference frame, International Terrestrial Reference Frame 2008 (ITRF2008. The velocity vector of the 42 stations excluding the YEBES station showed a magnitude difference of 7.3 mm/yr (30.2% and a direction difference of 13.8° (3.8%, with respect to ITRF2008. Among these, the 10 stations in Europe showed a magnitude difference of 7.8 mm/yr (30.3% and a direction difference of 3.7° (1.0%, while the 14 stations in North America showed a magnitude difference of 2.7 mm/yr (15.8% and a direction difference of 10.3° (2.9%.

  19. Modeling of a combined cycle power plant

    International Nuclear Information System (INIS)

    Faridah Mohamad Idris

    2001-01-01

    The combined cycle power plant is a non-linear, closed loop system, which consists of high-pressure (HP) superheater, HP evaporator, HP economizer, low-pressure (LP) evaporator, HP drum, HP deaerator, condenser, HP and LP steam turbine and gas turbine. The two types of turbines in the plant for example the gas turbine and the HP and LP steam turbines operate concurrently to generate power to the plant. The exhaust gas which originate from the combustion chamber drives the gas turbine, after which it flows into the heat recovery steam generator (HRSG) to generate superheated steam to be used in driving the HP and LP steam turbines. In this thesis, the combined cycle power plant is modeled at component level using the physical method. Assuming that there is delay in transport, except for the gas turbine system, the mass and heat balances are applied on the components of the plant to derive the governing equations of the components. These time dependent equations, which are of first order differential types, are then solved for the mass and enthalpy of the components. The solutions were simulated using Matlab Simulink using measured plant data. Where necessary there is no plant data available, approximated data were used. The generalized regression neural networks are also used to generate extra sets of simulation data for the HRSG system. Comparisons of the simulation results with its corresponding plant data showed good agreements between the two and indicated that the models developed for the components could be used to represent the combined cycle power plant under study. (author)

  20. Preventive treatment of combined radiation injuries

    International Nuclear Information System (INIS)

    Boudagov, R.; Uljanova, L.; Makarov, G.

    1996-01-01

    The risk of sepsis development increases when thermal burns and other trauma occur in combination with exposure to radiation. Only surgical correction of the life-threatening state recommends within 48 hours after irradiation. All other arrangements have to carry out when hemopoiesis recovery will complete. However exposed patients with combined injuries (CI) die during the first two or three weeks mainly due to sepsis. Therefore prophylaxis and preventive therapy of infectious complications are need early. Actual difficulties in choice of valid treatment procedure for acute radiation syndrome (ARS) exhibit additional aggravation under CI. The available facts prove decreasing early therapy efficiency for rather high dose exposure and wound trauma occurrence. The own results showed that bacterial polysaccharide pyrogenal, glycopin (synthetic analogue of muramil-dipeptide), thymus preparations (thymozin, thymotropin, thymogen), tuftsin, heterologic human and bovine immunoglobulins did not modify the low values of 30-day survival under CI (irradiation + thermal burn). Single injection of prodigiozan, zymozan and some other yeast polysaccharides in 1 hr after CI resulted at moderate increasing of survival. The main purpose of this study, which bases upon our understanding of CI pathogenesis, was search more effective means for preventive treatment of combined radiation injuries. Two groups of remedies were under study. The first group included so called 'biological response modifiers' (BRM). These agents may increase host defences to infection, macrophage's activity and hemopoietic growth factor's secretion. The second group included antibiotics that should be directed against the potential gram-negative as well as gram-positive pathogens and simultaneously be useful for selective decontamination of gastrointestinal tract. (author)

  1. Binocular combination in abnormal binocular vision.

    Science.gov (United States)

    Ding, Jian; Klein, Stanley A; Levi, Dennis M

    2013-02-08

    We investigated suprathreshold binocular combination in humans with abnormal binocular visual experience early in life. In the first experiment we presented the two eyes with equal but opposite phase shifted sine waves and measured the perceived phase of the cyclopean sine wave. Normal observers have balanced vision between the two eyes when the two eyes' images have equal contrast (i.e., both eyes contribute equally to the perceived image and perceived phase = 0°). However, in observers with strabismus and/or amblyopia, balanced vision requires a higher contrast image in the nondominant eye (NDE) than the dominant eye (DE). This asymmetry between the two eyes is larger than predicted from the contrast sensitivities or monocular perceived contrast of the two eyes and is dependent on contrast and spatial frequency: more asymmetric with higher contrast and/or spatial frequency. Our results also revealed a surprising NDE-to-DE enhancement in some of our abnormal observers. This enhancement is not evident in normal vision because it is normally masked by interocular suppression. However, in these abnormal observers the NDE-to-DE suppression was weak or absent. In the second experiment, we used the identical stimuli to measure the perceived contrast of a cyclopean grating by matching the binocular combined contrast to a standard contrast presented to the DE. These measures provide strong constraints for model fitting. We found asymmetric interocular interactions in binocular contrast perception, which was dependent on both contrast and spatial frequency in the same way as in phase perception. By introducing asymmetric parameters to the modified Ding-Sperling model including interocular contrast gain enhancement, we succeeded in accounting for both binocular combined phase and contrast simultaneously. Adding binocular contrast gain control to the modified Ding-Sperling model enabled us to predict the results of dichoptic and binocular contrast discrimination experiments

  2. Combination TLD/TED dose assessment

    International Nuclear Information System (INIS)

    Parkhurst, M.A.

    1992-11-01

    During the early 1980s, an appraisal of dosimetry programs at US Department of Energy (DOE) facilities identified a significant weakness in dose assessment in fast neutron environments. Basing neutron dose equivalent on thermoluminescence dosimeters (TLDS) was not entirely satisfactory for environments that had not been well characterized. In most operational situations, the dosimeters overrespond to neutrons, and this overresponse could be further exaggerated with changes in the neutron quality factor (Q). Because TLDs are energy dependent with an excellent response to thermal and low-energy neutrons but a weak response to fast neutrons, calibrating the dosimetry system to account for mixed and moderated neutron energy fields is a difficult and seldom satisfactory exercise. To increase the detection of fast neutrons and help improve the accuracy of dose equivalent determinations, a combination dosimeter was developed using TLDs to detect thermal and low-energy neutrons and a track-etch detector (TED) to detect fast neutrons. By combining the albedo energy response function of the TLDs with the track detector elements, the dosimeter can nearly match the fluence-to-dose equivalent conversion curve. The polymer CR-39 has neutron detection characteristics superior to other materials tested. The CR-39 track detector is beta and gamma insensitive and does not require backscatter (albedo) from the body to detect the exposure. As part of DOE's Personnel Neutron and Upgrade Program, we have been developing a R-39 track detector over the past decade to address detection and measurement of fast neutrons. Using CR-39 TEDs in combination with TLDs will now allow us to detect the wide spectrum of occupational neutron energies and assign dose equivalents much more confidently

  3. The combination of electrospray and flow focusing

    Science.gov (United States)

    Gañán-Calvo, Alfonso M.; López-Herrera, José M.; Riesco-Chueca, Pascual

    2006-11-01

    An ultra-fine liquid atomization procedure combining the advantages of electrospray and flow focusing is presented. Both techniques are known to produce strikingly small and steady liquid micro-jets issuing from menisci held by capillary forces. Such menisci take the form of a cusp-like drop attached to the feeding tube (flow focusing: FF) or a Taylor cone (electrospray: ES). The issuing micro-jets are forced or ‘sucked’ from the parent meniscus either by pressure or electrohydrodynamic forces. Subsequent capillary breakup of the jet leads to fine sprays of remarkable quality. Here we describe the joint effect of pressurization and electrification in a flow focusing device, and the subsequent coupling of both ES and FF phenomena. For any given liquid and flow rate, the combined procedure gives rise to significantly smaller droplet sizes than observed in any of the source techniques. The co-flowing gas stream removes space charges; in addition, the perforated plate facing the feed tube provides an electric barrier, shielding the jet-meniscus or ‘production’ area from the spray or ‘product’ area. As a result, space charges and electrified droplets are removed from the production area, thus avoiding the ambient electric saturation which becomes a limiting factor in ES-spraying: a significantly enhanced spraying stability ensues, with a much wider operation range than FF or ES. Other unexpected outcomes from the combination are also shown. A theoretical model is developed to predict the emitted droplet size: a first integral of the momentum equation yielding a generalized Bernoulli equation, and an explicit approximation for the jet diameter and droplet size, accurate within a broad parametrical band.

  4. Combining cluster number counts and galaxy clustering

    Energy Technology Data Exchange (ETDEWEB)

    Lacasa, Fabien; Rosenfeld, Rogerio, E-mail: fabien@ift.unesp.br, E-mail: rosenfel@ift.unesp.br [ICTP South American Institute for Fundamental Research, Instituto de Física Teórica, Universidade Estadual Paulista, São Paulo (Brazil)

    2016-08-01

    The abundance of clusters and the clustering of galaxies are two of the important cosmological probes for current and future large scale surveys of galaxies, such as the Dark Energy Survey. In order to combine them one has to account for the fact that they are not independent quantities, since they probe the same density field. It is important to develop a good understanding of their correlation in order to extract parameter constraints. We present a detailed modelling of the joint covariance matrix between cluster number counts and the galaxy angular power spectrum. We employ the framework of the halo model complemented by a Halo Occupation Distribution model (HOD). We demonstrate the importance of accounting for non-Gaussianity to produce accurate covariance predictions. Indeed, we show that the non-Gaussian covariance becomes dominant at small scales, low redshifts or high cluster masses. We discuss in particular the case of the super-sample covariance (SSC), including the effects of galaxy shot-noise, halo second order bias and non-local bias. We demonstrate that the SSC obeys mathematical inequalities and positivity. Using the joint covariance matrix and a Fisher matrix methodology, we examine the prospects of combining these two probes to constrain cosmological and HOD parameters. We find that the combination indeed results in noticeably better constraints, with improvements of order 20% on cosmological parameters compared to the best single probe, and even greater improvement on HOD parameters, with reduction of error bars by a factor 1.4-4.8. This happens in particular because the cross-covariance introduces a synergy between the probes on small scales. We conclude that accounting for non-Gaussian effects is required for the joint analysis of these observables in galaxy surveys.

  5. Combined Pulmonary Fibrosis and Emphysema Syndrome

    Science.gov (United States)

    Rounds, Sharon I. S.

    2012-01-01

    There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

  6. Combined constraints on holographic bosonic technicolor

    International Nuclear Information System (INIS)

    Carone, Christopher D.; Primulando, Reinard

    2010-01-01

    We consider a model of strong electroweak symmetry breaking in which the expectation value of an additional, possibly composite, scalar field is responsible for the generation of fermion masses. The dynamics of the strongly coupled sector is defined and studied via its holographic dual, and does not correspond to a simple, scaled-up version of QCD. We consider the bounds from perturbative unitarity, the S parameter, and the mass of the Higgs-like scalar. We show that the combination of these constraints leaves a relatively limited region of parameter space viable, and suggests the qualitative features of the model that might be probed at the LHC.

  7. Biopiles and biofilters combined for soil cleanup

    International Nuclear Information System (INIS)

    Lei, J.; Sansregret, J.L.; Cyr, B.

    1994-01-01

    Bioremediation of hydrocarbon-contaminated soils can be completed using a combination of biopile and biofiltration technologies. Target contaminants, such as gasoline, jet fuel, diesel fuel and other petroleum-derived products are removed from the soil by biodegradation and volatilization in the biopile. Air emissions from the biopile containing volatile hydrocarbons are treated subsequently in a biofilter, where the pollutants are degraded and mineralized by heterotrophic aerobic microorganisms. In the biopile process, contaminated soil is excavated and stockpiled in a treatment area. Remediation of the soil relies on microbial degradation and volatilization of hydrocarbons under controlled treatment conditions

  8. Combination of behavioural and cognitive techniques

    Directory of Open Access Journals (Sweden)

    Leonida Rotvejn Pajič

    2001-03-01

    Full Text Available The cognitive - behavioral approach in the treatment of behavioral disorders, emotional disorders and learning difficulties is not limited to a single theoretical principle or technique, but integrates different techniques. The variants techniques are derived from theoretical and empirical findings in different domains of developmental psychology (self-control, social cognition, memory, metacognitive and attritional processes. The aim of the article is to present some basic cognitive and behavioral techniques that are individually adapted during therapy and mutually complete each other. A practical case of combining techniques is presented.

  9. Combining accounting approaches to practice valuation.

    Science.gov (United States)

    Schwartzben, D; Finkler, S A

    1998-06-01

    Healthcare organizations that wish to acquire physician or ambulatory care practices can choose from a variety of practice valuation approaches. Basic accounting methods assess the value of a physician practice on the basis of a historical, balance-sheet description of tangible assets. Yet these methods alone are inadequate to determine the true financial value of a practice. By using a combination of accounting approaches to practice valuation that consider factors such as fair market value, opportunity cost, and discounted cash flow over a defined time period, organizations can more accurately assess a practice's actual value.

  10. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki

    2016-09-01

    Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

  11. Combining or Separating Forward and Reverse Logistics

    DEFF Research Database (Denmark)

    Herbert-Hansen, Zaza Nadja Lee; Larsen, Samuel; Nielsen, Anders

    2018-01-01

    Purpose – While forward logistics handles and manages the flow of goods downstream in the supply chain from suppliers to customers, reverse logistics (RL) manages the flow of returned goods upstream. A firm can combine reverse logistics with forward logistics, keep the flows separated, or choose......-research addresses intra-RL issues while the relationship between forward and reverse logistics is under-researched. This paper contributes to RL-theory by identifying the contextual factors that determine the most advantageous relationship between forward and reverse logistics, and proposes a novel decision making...

  12. A Combined Preconditioning Strategy for Nonsymmetric Systems

    KAUST Repository

    Ayuso Dios, Blanca

    2014-01-01

    We present and analyze a class of nonsymmetric preconditioners within a normal (weighted least-squares) matrix form for use in GMRES to solve nonsymmetric matrix problems that typically arise in finite element discretizations. An example of the additive Schwarz method applied to nonsymmetric but definite matrices is presented for which the abstract assumptions are verified. A variable preconditioner, combining the original nonsymmetric one and a weighted least-squares version of it, is shown to be convergent and provides a viable strategy for using nonsymmetric preconditioners in practice. Numerical results are included to assess the theory and the performance of the proposed preconditioners.

  13. Targeting IAP proteins in combination with radiotherapy

    International Nuclear Information System (INIS)

    Fulda, Simone

    2015-01-01

    The efficacy of radiotherapy critically depends on the activation of intrinsic cell death programs in cancer cells. This implies that evasion of cell death, a hallmark of human cancers, can contribute to radioresistance. Therefore, novel strategies to reactivate cell death programs in cancer cells are required in order to overcome resistance to radiotherapy. Since Inhibitor of Apoptosis (IAP) proteins are expressed at high levels in multiple cancers and block cell death induction at a central point, therapeutic targeting of IAP proteins represents a promising approach to potentiate the efficacy of radiotherapy. The current review discusses the concept of targeting IAP proteins in combination with radiotherapy

  14. Combined cycle plant controls retrofit case history

    International Nuclear Information System (INIS)

    Tenney, D.; Pieszchala, T.

    1991-01-01

    The Comanche Power Station, Public Service of Oklahoma's combined cycle generating facility, underwent a controls and operator panel retrofit at the end of 1988. The plant consists of two gas turbines, two heat recovery boilers and a steam turbine along with three generators. This paper examines the extent to which the original goals and specifications were met. Costs, operating principles and modifications since the original installation are discussed. Operating procedures are compared with the original system. The future of the plant is discussed and the impact on the power system grid is analyzed

  15. COMBINED SURGERY OF SPREAD THYROID CANCER

    Directory of Open Access Journals (Sweden)

    V. Zh. Brzhezovsky

    2014-01-01

    Full Text Available Results of treating of 99 patients with differentiated thyroid cancer spreading beyond the capsule of the organ were analysed. In most cases with spreading the tumor to the tracheal rings performing of organ-preserving operations (from “window-like” tracheal resections to circular tracheal resection with intertracheal anastomosis is possible. Choosing of type of operation to be performed depends on localisation and spread of tumor invasion of trachea, pharynx and esophagus. Using of combined operations in patients with locally-spread thyroid cancer allows to achieve long and stable remission in most of the cases.

  16. Trial of radiation therapy combined with hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Takegawa, Y; Fujiwara, K; Oe, J; Nagase, M; Akiyama, H [Tokushima Univ. (Japan). School of Medicine

    1978-08-01

    Nine patients were treated by the combination therapy of external irradiation and hyperthermia, 5 patients with metastatic lesions; two breast cancer, one lung cancer, one malignant melanoma, one vulva cancer, 1 patient with recurrent lesion of skin cancer and 3 patients with bladder cancer. All patients were treated by heating locally (42/sup 0/C, 30 min) followed by external irradiation with 4,000 - 5,000 rad over 4 to 5 weeks. No local recurrence was found in 4 of 9 patients.

  17. Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Fatehi Elnour Elzein

    2016-01-01

    Full Text Available The mortality in Strongyloides hyperinfection syndrome (SHS is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli urosepsis and CMV infection.

  18. A Combined Preconditioning Strategy for Nonsymmetric Systems

    Energy Technology Data Exchange (ETDEWEB)

    de Dios, B. Ayuso [Univ. of Bologna (Italy). Dept. of Mathematics; King Abdullah Univ. of Science and Technology, Thuwal (Saudi Arabia); Barker, A. T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vassilevski, P. S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-11-04

    Here, we present and analyze a class of nonsymmetric preconditioners within a normal (weighted least-squares) matrix form for use in GMRES to solve nonsymmetric matrix problems that typically arise in finite element discretizations. An example of the additive Schwarz method applied to nonsymmetric but definite matrices is presented for which the abstract assumptions are verified. Variable preconditioner, which combines the original nonsymmetric one and a weighted least-squares version of it, and it is shown to be convergent and provides a viable strategy for using nonsymmetric preconditioners in practice. Numerical results are included to assess the theory and the performance of the proposed preconditioners.

  19. High performance integrated solar combined cycles with minimum modifications to the combined cycle power plant design

    International Nuclear Information System (INIS)

    Manente, Giovanni

    2016-01-01

    Highlights: • Off-design model of a 390 MW_e three pressure combined cycle developed and validated. • The off-design model is used to evaluate different hybridization schemes with solar. • Power boosting and fuel saving with different design modifications are considered. • Maximum solar share of total electricity is only 1% with the existing equipment. • The maximum incremental solar radiation-to-electrical efficiency approaches 29%. - Abstract: The integration of solar energy into natural gas combined cycles has been successfully demonstrated in several integrated solar combined cycles since the beginning of this decade in many countries. There are many motivations that drive investments on integrated solar combined cycles which are primarily the repowering of existing power plants, the compliance with more severe environmental laws on emissions and the mitigation of risks associated with large solar projects. Integrated solar combined cycles are usually developed as brownfield facilities by retrofitting existing natural gas combined cycles and keeping the existing equipment to minimize costs. In this work a detailed off-design model of a 390 MW_e three pressure level natural gas combined cycle is built to evaluate different integration schemes of solar energy which either keep the equipment of the combined cycle unchanged or include new equipment (steam turbine, heat recovery steam generator). Both power boosting and fuel saving operation strategies are analyzed in the search for the highest annual efficiency and solar share. Results show that the maximum incremental power output from solar at design solar irradiance is limited to 19 MW_e without modifications to the existing equipment. Higher values are attainable only including a larger steam turbine. High solar radiation-to-electrical efficiencies in the range 24–29% can be achieved in the integrated solar combined cycle depending on solar share and extension of tube banks in the heat recovery

  20. Combining radiotherapy and immunotherapy: A revived partnership

    International Nuclear Information System (INIS)

    Demaria, Sandra; Bhardwaj, Nina; McBride, William H.; Formenti, Silvia C.

    2005-01-01

    Ionizing radiation therapy (RT) is an important local modality for the treatment of cancer. The current rationale for its use is based largely on the ability of RT to kill the cancer cells by a direct cytotoxic effect. Nevertheless, considerable evidence indicates that RT effects extend beyond the mere elimination of the more radiosensitive fraction of cancer cells present within a tumor at the time of radiation exposure. For instance, a large body of evidence is accumulating on the ability of RT to modify the tumor microenvironment and generate inflammation. This might have far-reaching consequences regarding the response of a patient to treatment, especially if radiation-induced tumor cell kill were to translate into the generation of effective antitumor immunity. Although much remains to be learned about how radiation can impact tumor immunogenicity, data from preclinical studies provide the proof of principle that different immunotherapeutic strategies can be combined with RT to enhance antitumor effects. Conversely, RT could be a useful tool to combine with immunotherapy. This article will briefly summarize what is known about the impact of RT on tumor immunity, including tumor-associated antigens, antigen-presenting cells, and effector mechanisms. In addition, the experimental evidence supporting the contention that RT can be used as a tool to induce antitumor immunity is discussed, and a new approach to radioimmunotherapy of cancer is proposed

  1. Checkpoint blockade in combination with cancer vaccines.

    Science.gov (United States)

    Morse, Michael A; Lyerly, H Kim

    2015-12-16

    Checkpoint blockade, prevention of inhibitory signaling that limits activation or function of tumor antigen-specific T cells responses, is revolutionizing the treatment of many poor prognosis malignancies. Indeed monoclonal antibodies that modulate signaling through the inhibitory molecules CTLA-4 and PD-1 are now clinically available; however, many tumors, demonstrate minimal response suggesting the need for combinations with other therapeutic strategies. Because an inadequate frequency of activated tumor antigen-specific T cells in the tumor environment, the so-called non-inflamed phenotype, is observed in some malignancies, other rationale partners are modalities that lead to enhanced T cell activation (vaccines, cytokines, toll-like receptor agonists, and other anticancer therapies such as chemo-, radio- or targeted therapies that lead to release of antigen from tumors). This review will focus on preclinical and clinical data supporting the use of cancer vaccines with anti-CTLA-4 and anti-PD-1/PD-L1 antibodies. Preliminary preclinical data demonstrate enhanced antitumor activity although the results in human studies are less clear. Broader combinations of multiple immune modulators are now under study. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Irradiation in combined treatments and food safety

    International Nuclear Information System (INIS)

    Lacroix Monique; Dussault Dominic; Turgis Melanie; Salmieri Stephane; Perlette Takala; Vu Dang Khanh; Ayari Samia

    2013-01-01

    Irradiation combined with other processes can contribute to insuring food safety to consumers and controlling severe losses during transportation and commercialisation. We have demonstrated that using in synergy with other treatments; a lower dose could be used to eliminate pathogenic bacteria and permit a better protection of the sensorial quality and to prolong the shelf life of foods. Results indicated that some bacteria are more sensitive to irradiation under modified atmosphere (MAP) and the presence of active compound can increase the bacterial radiosensitivity by more than 4 times under air and by more than 10 times under MAP. Mild heat treatment or addition of natural antimicrobial compounds before irradiation treatment has also permitted an increase of Bacillus cereus radiosensitization. An increase of the bacterial radiosensitization of 1.5 and 1.56 was respectively observed. The effectiveness of the use of edible coating containing natural antimicrobial compounds, modified atmosphere packaging (MAP) or mild treatment before irradiation treatment was demonstrated in order to inactivate Listeria monocytogenes, Salmonella typhimurium, Escherichia coli and Bacillus cereus growth or B. cereus spore germination, to increase the bacterial sensitivity to irradiation, to reduce the water loss and to extend the shelf life of the food when stored at 4 deg C. Also, the use of edible coating previously crosslinked by irradiation have permitted a better control of the active compounds release. Studies of combined treatments were used in ready to eat vegetables, fruits and meat products. (author)

  3. Combining rhinoplasty with septal perforation repair.

    Science.gov (United States)

    Foda, Hossam M T; Magdy, Emad A

    2006-11-01

    A combined septal perforation repair and rhinoplasty was performed in 80 patients presenting with septal perforations (size 1 to 5 cm) and external nasal deformities. The external rhinoplasty approach was used for all cases and the perforation was repaired using bilateral intranasal mucosal advancement flaps with a connective tissue interposition graft in between. Complete closure of the perforation was achieved in 90% of perforations of size up to 3.5 cm and in only 70% of perforations that were larger than 3.5 cm. Cosmetically, 95% were very satisfied with their aesthetic result. The external rhinoplasty approach proved to be very helpful in the process of septal perforation repair especially in large and posteriorly located perforations and in cases where the caudal septal cartilage was previously resected. Our results show that septal perforation repair can be safely combined with rhinoplasty and that some of the routine rhinoplasty maneuvers, such as medial osteotomies and dorsal lowering, could even facilitate the process of septal perforation repair.

  4. Reproductive cloning combined with genetic modification.

    Science.gov (United States)

    Strong, C

    2005-11-01

    Although there is widespread opposition to reproductive cloning, some have argued that its use by infertile couples to have genetically related children would be ethically justifiable. Others have suggested that lesbian or gay couples might wish to use cloning to have genetically related children. Most of the main objections to human reproductive cloning are based on the child's lack of unique nuclear DNA. In the future, it may be possible safely to create children using cloning combined with genetic modifications, so that they have unique nuclear DNA. The genetic modifications could be aimed at giving such children genetic characteristics of both members of the couple concerned. Thus, cloning combined with genetic modification could be appealing to infertile, lesbian, or gay couples who seek genetically related children who have genetic characteristics of both members. In such scenarios, the various objections to human reproductive cloning that are based on the lack of genetic uniqueness would no longer be applicable. The author argues that it would be ethically justifiable for such couples to create children in this manner, assuming these techniques could be used safely.

  5. Single maximal versus combination punch kinematics.

    Science.gov (United States)

    Piorkowski, Barry A; Lees, Adrian; Barton, Gabor J

    2011-03-01

    The aim of this study was to determine the influence of punch type (Jab, Cross, Lead Hook and Reverse Hook) and punch modality (Single maximal, 'In-synch' and 'Out of synch' combination) on punch speed and delivery time. Ten competition-standard volunteers performed punches with markers placed on their anatomical landmarks for 3D motion capture with an eight-camera optoelectronic system. Speed and duration between key moments were computed. There were significant differences in contact speed between punch types (F(2,18,84.87) = 105.76, p = 0.001) with Lead and Reverse Hooks developing greater speed than Jab and Cross. There were significant differences in contact speed between punch modalities (F(2,64,102.87) = 23.52, p = 0.001) with the Single maximal (M+/- SD: 9.26 +/- 2.09 m/s) higher than 'Out of synch' (7.49 +/- 2.32 m/s), 'In-synch' left (8.01 +/- 2.35 m/s) or right lead (7.97 +/- 2.53 m/s). Delivery times were significantly lower for Jab and Cross than Hook. Times were significantly lower 'In-synch' than a Single maximal or 'Out of synch' combination mode. It is concluded that a defender may have more evasion-time than previously reported. This research could be of use to performers and coaches when considering training preparations.

  6. Combining Search Engines for Comparative Proteomics

    Science.gov (United States)

    Tabb, David

    2012-01-01

    Many proteomics laboratories have found spectral counting to be an ideal way to recognize biomarkers that differentiate cohorts of samples. This approach assumes that proteins that differ in quantity between samples will generate different numbers of identifiable tandem mass spectra. Increasingly, researchers are employing multiple search engines to maximize the identifications generated from data collections. This talk evaluates four strategies to combine information from multiple search engines in comparative proteomics. The “Count Sum” model pools the spectra across search engines. The “Vote Counting” model combines the judgments from each search engine by protein. Two other models employ parametric and non-parametric analyses of protein-specific p-values from different search engines. We evaluated the four strategies in two different data sets. The ABRF iPRG 2009 study generated five LC-MS/MS analyses of “red” E. coli and five analyses of “yellow” E. coli. NCI CPTAC Study 6 generated five concentrations of Sigma UPS1 spiked into a yeast background. All data were identified with X!Tandem, Sequest, MyriMatch, and TagRecon. For both sample types, “Vote Counting” appeared to manage the diverse identification sets most effectively, yielding heightened discrimination as more search engines were added.

  7. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  8. Dextromethorphan and Quinidine Combination for Heroin Detoxification

    Science.gov (United States)

    Akerele, Evaristo; Bisaga, Adam; Sullivan, Maria A.; Garawi, Fatima; Comer, Sandra D.; Thomas, Anil A.; Nunes, Edward V.; Kleber, Herbert D.

    2015-01-01

    Dextromethorphan (DM) is a low-affinity, non-competitive NMDA receptor antagonist that has shown promise in pre-clinical and preliminary clinical studies for the reduction of opioid withdrawal symptoms, but when used at higher doses, it is associated with deleterious side effects attributed to its metabolite, dextrorphan. A clinical trial was therefore conducted to test the withdrawal-suppressant effect of a combination of dextromethorphan with quinidine (DM/Q). Quinidine inhibits the metabolism of dextromethorphan, reducing dextrorphan levels. Opioid-dependent patients were admitted to an inpatient unit, stabilized for three days on morphine (25 mg, sc, every six hours), and randomly assigned on day 2 to DM/Q (30 mg/30 mg, twice a day) (n = 22) or matching placebo (n = 9) prior to the discontinuation of morphine on day 4. Withdrawal symptoms, measured with the Modified Himmelsbach Opioid Withdrawal Scale (MHOWS), increased significantly on days 4 and 5 (Z = 3.70, p = .0002), and by day 6, 90% of the sample (28/31) had dropped out of the study. There were no differences between treatment groups on either outcome measure. The combination of dextromethorphan and quinidine appears ineffective as a primary treatment for opioid withdrawal. Future studies should examine dextromethorphan as an adjunct to other anti-withdrawal medications and focus more on the relationship between dextrorphan levels and withdrawal suppression. PMID:18463993

  9. ACCOUNTING FOR CONTINGENT CONSIDERATIONS IN BUSINESS COMBINATIONS

    Directory of Open Access Journals (Sweden)

    Gurgen KALASHYAN

    2017-07-01

    Full Text Available According to IFRS 3 Business Combinations contingent considerations must be included in the total consideration given for the acquired entity along with cash, other assets, ordinary or preference equity instruments, options, warrants. The contingent consideration is the determined amount which acquiring entity has to pay to acquired entity provided, that certain conditions will be fulfilled in the future. In case the provisions are not satisfied, we will get the situation when the amount of contingent consideration has been included in the total consideration given in the business combination, but in fact, the acquirer has not paid that amount. In its turn, the acquired entity will recognize the contingent consideration as a financial asset according to IFRS 9 Financial Instruments. In that case, it would be appropriately to recognize the contingent consideration as a contingent asset applying IAS 37. In the Article the author will explore the challenges of contingent consideration accounting and suggest the ways of solving the above mentioned problems.

  10. Combined experiment Phase 2 data characterization

    Energy Technology Data Exchange (ETDEWEB)

    Miller, M.S.; Shipley, D.E.; Young, T.S.; Robinson, M.C.; Luttges, M.W. [Colorado Univ., Boulder, CO (United States); Simms, D.A. [National Renewable Energy Lab., Golden, CO (United States)

    1995-11-01

    The National Renewable Energy Laboratory`s ``Combined Experiment`` has yielded a large quantity of experimental data on the operation of a downwind horizontal axis wind turbine under field conditions. To fully utilize this valuable resource and identify particular episodes of interest, a number of databases were created that characterize individual data events and rotational cycles over a wide range of parameters. Each of the 59 five-minute data episodes collected during Phase 11 of the Combined Experiment have been characterized by the mean, minimum, maximum, and standard deviation of all data channels, except the blade surface pressures. Inflow condition, aerodynamic force coefficient, and minimum leading edge pressure coefficient databases have also been established, characterizing each of nearly 21,000 blade rotational cycles. In addition, a number of tools have been developed for searching these databases for particular episodes of interest. Due to their extensive size, only a portion of the episode characterization databases are included in an appendix, and examples of the cycle characterization databases are given. The search tools are discussed and the FORTRAN or C code for each is included in appendices.

  11. Spatial aspects of combined modality radiotherapy

    International Nuclear Information System (INIS)

    Bodey, Rachel K.; Evans, Phil M.; Flux, Glenn D.

    2005-01-01

    Background and purpose: A combined modality radiotherapy (CMRT) incorporates both external beam radiotherapy (EBT) and targeted radionuclide therapy (TRT) components. The spatial aspects of this combination were explored by utilising intensity modulated radiotherapy (IMRT) to provide a non-uniform EBT dose distribution. Patients and methods: Three methods of prescribing the required non-uniform distribution of EBT dose are described, based on both physical and biological criteria according to the distribution of TRT uptake. The results and consequences of these prescriptions are explored by application to three examples of patient data. Results: The planning procedure adopted allowed IMRT plans to be produced that met the prescription requirements. However, when the treatment was planned as a CMRT, compared with the use of EBT alone, more satisfactory target doses could be achieved with lower doses to normal tissues. The effects of errors in EBT delivery and in the functional data were found to cause a non-uniform prescription to tend towards the uniform case. Conclusions: The methods and results are relevant for more general biological treatment planning, in which IMRT may be used to produce dose distributions prescribed according to tumour function. The effects of delivery and dose calculation errors can have a significant impact on how such treatments should be planned

  12. The lysine deacetylase inhibitor givinostat inhibits ß-cell IL-1ß induced IL-1ß transcription and processing

    DEFF Research Database (Denmark)

    Dahllöf, Mattias Salling; Christensen, Dan P; Lundh, Morten

    2012-01-01

    . Further, IL-1R antagonism improves normoglycemia and ß-cell function in type 2 diabetic patients. Inhibition of lysine deacetylases (KDACi) counteracts ß-cell toxicity induced by the combination of IL-1 and IFN¿ and reduces diabetes incidence in non-obese diabetic (NOD) mice. We hypothesized that KDACi......Aims: Pro-inflammatory cytokines and chemokines, in particular IL-1ß, IFN¿, and CXCL10, contribute to ß-cell failure and loss in DM via IL-1R, IFN¿R, and TLR4 signaling. IL-1 signaling deficiency reduces diabetes incidence, islet IL-1ß secretion, and hyperglycemia in animal models of diabetes...

  13. All-fiber 7x1 signal combiner for incoherent laser beam combining

    Science.gov (United States)

    Noordegraaf, D.; Maack, M. D.; Skovgaard, P. M. W.; Johansen, J.; Becker, F.; Belke, S.; Blomqvist, M.; Laegsgaard, J.

    2011-02-01

    We demonstrate an all-fiber 7x1 signal combiner for incoherent laser beam combining. This is a potential key component for reaching several kW of stabile laser output power. The combiner couples the output from 7 single-mode (SM) fiber lasers into a single multi-mode (MM) fiber. The input signal fibers have a core diameter of 17 μm and the output MM fiber has a core diameter of 100 μm. In a tapered section light gradually leaks out of the SM fibers and is captured by a surrounding fluorine-doped cladding. The combiner is tested up to 2.5 kW of combined output power and only a minor increase in device temperature is observed. At an intermediate power level of 600 W a beam parameter product (BPP) of 2.22 mm x mrad is measured, corresponding to an M2 value of 6.5. These values are approaching the theoretical limit dictated by brightness conservation.

  14. [Results of combined endotrabeculectomy and phacoemulsification surgery].

    Science.gov (United States)

    Novytskyy, I Ya; Novytskyy, M I

    2015-01-01

    to identify indications and evaluate the efficacy of combined endotrabeculectomy and phacoemulsification surgery. A total of 172 patients (193 eyes) with open-angle glaucoma and cataract were enrolled. Group 1 included 102 patients (118 eyes), who were considered surgical candidates due to decompensation of IOP, group 2--70 patients (75 eyes), in whom IOP control could only be achieved with a multidrug regimen (two or more ocular hypotensive medications). The mean preoperative IOP measured with Maklakov tonometer was 26.4 ± 1.8 mmHg in group 1 and 20.5 ± 1.7 mmHg in group 2. In 134 eyes the extent of retention of intraocular fluid was determined intraoperatively by provoking blood reflux into Schlemm's canal. In 6 out of 134 eyes (4.5%) Schlemm's canal was not at all filled with blood, which was considered a contraindication for endotrabeculectomy. Partial filling of Schlemm's canal with blood was observed in 26 out of 134 eyes (19.4%), complete--in 102 eyes (76.1%). All but 6 patients underwent endotrabeculectomy (ab interno trabecular excision with original forceps through the anterior chamber angle) combined with cataract phacoemulsification and intraocular lens implantation. In 11 out of 126 cases, insignificant bleeding occurred during sample acquisition. No other complications were registered. Six months after the surgery, IOP was reduced by the mean of 7.0 ± 0.6 mmHg (26.5% from the baseline) in group 1 and by 2.2 ± 0.2 mmHg (10.7% from the baseline) in group 2. The number of hypotensive medications by that time has been decreased from 2.3 ± 0.3 to 0.8 ± 0.2 in group 1 and from 1.6 ± 0.3 to 0.4 ± 0.1 in group 2. Combined endotrabeculectomy and phacoemulsification surgery is a pathogenically oriented procedure, which improves ocular hydrodynamics and has a significant hypotensive effect.

  15. Combining solid biomass combustion and stirling technology

    Energy Technology Data Exchange (ETDEWEB)

    Siemers, W.; Senkel, N. [CUTEC-Institut GmbH, Clausthal-Zellerfeld (Germany)], e-mail: werner.siemers@cutec.de

    2012-11-01

    Decentralised electricity production in combination with and based on biomass still finds some difficulties in real applications. One concept favoured in a recent project is the connection of a wood chip furmace with a Stirling engine. Because the direct exposure of the Stirling head causes numerous problems, the solution is sought in designing an indirect heat transfer system. The main challenge is the temperature level, which should be reached for high electrical efficiencies. Temperatures above 1000 deg C at the biomass combustion side are needed for an efficient heat transfer at some 850 deg C at the Stirling engine in theory. Measurements on both installations have been conducted and analyzed. After this, the design phase is started. However, no final choice on the design has been taken.

  16. Combined hydraulic and regenerative braking system

    Science.gov (United States)

    Venkataperumal, R.R.; Mericle, G.E.

    1979-08-09

    A combined hydraulic and regenerative braking system and method for an electric vehicle is disclosed. The braking system is responsive to the applied hydraulic pressure in a brake line to control the braking of the vehicle to be completely hydraulic up to a first level of brake line pressure, to be partially hydraulic at a constant braking force and partially regenerative at a linearly increasing braking force from the first level of applied brake line pressure to a higher second level of brake line pressure, to be partially hydraulic at a linearly increasing braking force and partially regenerative at a linearly decreasing braking force from the second level of applied line pressure to a third and higher level of applied line pressure, and to be completely hydraulic at a linearly increasing braking force from the third level to all higher applied levels of line pressure.

  17. Improved particle swarm optimization combined with chaos

    International Nuclear Information System (INIS)

    Liu Bo; Wang Ling; Jin Yihui; Tang Fang; Huang Dexian

    2005-01-01

    As a novel optimization technique, chaos has gained much attention and some applications during the past decade. For a given energy or cost function, by following chaotic ergodic orbits, a chaotic dynamic system may eventually reach the global optimum or its good approximation with high probability. To enhance the performance of particle swarm optimization (PSO), which is an evolutionary computation technique through individual improvement plus population cooperation and competition, hybrid particle swarm optimization algorithm is proposed by incorporating chaos. Firstly, adaptive inertia weight factor (AIWF) is introduced in PSO to efficiently balance the exploration and exploitation abilities. Secondly, PSO with AIWF and chaos are hybridized to form a chaotic PSO (CPSO), which reasonably combines the population-based evolutionary searching ability of PSO and chaotic searching behavior. Simulation results and comparisons with the standard PSO and several meta-heuristics show that the CPSO can effectively enhance the searching efficiency and greatly improve the searching quality

  18. LNG plant combined with power plant

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, I; Kikkawa, Y [Chiyoda Chemical Engineering and Construction Co. Ltd., Tokyo (Japan)

    1997-06-01

    The LNG plant consumers a lot of power of natural gas cooling and liquefaction. In some LNG plant location, a rapid growth of electric power demand is expected due to the modernization of area and/or the country. The electric power demand will have a peak in day time and low consumption in night time, while the power demand of the LNG plant is almost constant due to its nature. Combining the LNG plant with power plant will contribute an improvement the thermal efficiency of the power plant by keeping higher average load of the power plant, which will lead to a reduction of electrical power generation cost. The sweet fuel gas to the power plant can be extracted from the LNG plant, which will be favorable from view point of clean air of the area. (Author). 5 figs.

  19. Theoretically palatable flavor combinations of astrophysical neutrinos

    International Nuclear Information System (INIS)

    Bustamante, Mauricio

    2015-07-01

    The flavor composition of high-energy astrophysical neutrinos can reveal the physics governing their production, propagation, and interaction. The IceCube Collaboration has published the first experimental determination of the ratio of the flux in each flavor to the total. We present, as a theoretical counterpart, new results for the allowed ranges of flavor ratios at Earth for arbitrary flavor ratios in the sources. Our results will allow IceCube to more quickly identify when their data imply standard physics, a general class of new physics with arbitrary (incoherent) combinations of mass eigenstates, or new physics that goes beyond that, e.g., with terms that dominate the Hamiltonian at high energy.

  20. Combining multiple decisions: applications to bioinformatics

    International Nuclear Information System (INIS)

    Yukinawa, N; Ishii, S; Takenouchi, T; Oba, S

    2008-01-01

    Multi-class classification is one of the fundamental tasks in bioinformatics and typically arises in cancer diagnosis studies by gene expression profiling. This article reviews two recent approaches to multi-class classification by combining multiple binary classifiers, which are formulated based on a unified framework of error-correcting output coding (ECOC). The first approach is to construct a multi-class classifier in which each binary classifier to be aggregated has a weight value to be optimally tuned based on the observed data. In the second approach, misclassification of each binary classifier is formulated as a bit inversion error with a probabilistic model by making an analogy to the context of information transmission theory. Experimental studies using various real-world datasets including cancer classification problems reveal that both of the new methods are superior or comparable to other multi-class classification methods

  1. Combining triggers in HEP data analysis

    International Nuclear Information System (INIS)

    Lendermann, Victor; Herbst, Michael; Krueger, Katja; Schultz-Coulon, Hans-Christian; Stamen, Rainer; Haller, Johannes

    2009-01-01

    Modern high-energy physics experiments collect data using dedicated complex multi-level trigger systems which perform an online selection of potentially interesting events. In general, this selection suffers from inefficiencies. A further loss of statistics occurs when the rate of accepted events is artificially scaled down in order to meet bandwidth constraints. An offline analysis of the recorded data must correct for the resulting losses in order to determine the original statistics of the analysed data sample. This is particularly challenging when data samples recorded by several triggers are combined. In this paper we present methods for the calculation of the offline corrections and study their statistical performance. Implications on building and operating trigger systems are discussed. (orig.)

  2. Combining triggers in HEP data analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lendermann, Victor; Herbst, Michael; Krueger, Katja; Schultz-Coulon, Hans-Christian; Stamen, Rainer [Heidelberg Univ. (Germany). Kirchhoff-Institut fuer Physik; Haller, Johannes [Hamburg Univ. (Germany). Institut fuer Experimentalphysik

    2009-01-15

    Modern high-energy physics experiments collect data using dedicated complex multi-level trigger systems which perform an online selection of potentially interesting events. In general, this selection suffers from inefficiencies. A further loss of statistics occurs when the rate of accepted events is artificially scaled down in order to meet bandwidth constraints. An offline analysis of the recorded data must correct for the resulting losses in order to determine the original statistics of the analysed data sample. This is particularly challenging when data samples recorded by several triggers are combined. In this paper we present methods for the calculation of the offline corrections and study their statistical performance. Implications on building and operating trigger systems are discussed. (orig.)

  3. A combinational fast algorithm for image reconstruction

    International Nuclear Information System (INIS)

    Wu Zhongquan

    1987-01-01

    A combinational fast algorithm has been developed in order to increase the speed of reconstruction. First, an interpolation method based on B-spline functions is used in image reconstruction. Next, the influence of the boundary conditions assumed here on the interpolation of filtered projections and on the image reconstruction is discussed. It is shown that this boundary condition has almost no influence on the image in the central region of the image space, because the error of interpolation rapidly decreases by a factor of ten in shifting two pixels from the edge toward the center. In addition, a fast algorithm for computing the detecting angle has been used with the mentioned interpolation algorithm, and the cost for detecting angle computaton is reduced by a factor of two. The implementation results show that in the same subjective and objective fidelity, the computational cost for the interpolation using this algorithm is about one-twelfth of the conventional algorithm

  4. Combined heat and power in the City

    Energy Technology Data Exchange (ETDEWEB)

    Crafter, A. [Corporation of London (United Kingdom). Dept. of Technical Services

    2002-03-01

    This article reports on the development of a large-scale combined heat and power community energy scheme within the City of London. Supported by the Corporation of London and using its own buildings to provide the heating and cooling loads, the scheme has established a power plant close to Smithfield Meat Market and supplies district heating and chilled water for air conditioning to its own properties and some private customers in the nearby districts. Details are given of the power plant which is sited in a conservation area with limited access, the use of absorption chillers to produce the chilled water, the estimated amount of carbon dioxide emissions saved, and the financial benefits of the scheme.

  5. Sjogren's syndrome combined with MALT lymphoma

    International Nuclear Information System (INIS)

    Han, Won Jeong; Cha, Sang Yun; Kim, Eun Kyung

    2000-01-01

    Sjogren's syndrome is a chronic inflammatory disease that predominantly affects salivary, lacrimal, and other exocrine glands. We report a case of Sjogren's syndrome combined with MALT (mucose associated lymphoid tissue) lymphoma which occurred in the parotid gland. A 57-year-old female with the complaint of painful swelling and lymph node enlargement was referred to our department. Sialograms of both parotid glands showed globular collections of contrast material uniformly distributed throughout the parotid gland. Salivary scintigraphy showed decreased uptake of the parotid gland. CT scan showed larger, slightly more dense parotid gland than normal and honeycomb glandular appearance. Also, It showed discrete, slightly more enhanced round mass in the left parotid gland. Histopathological finding showed replacement of salivary gland parenchyma with dense small lymphocytic infiltration having the feature of epimyoepithelial islands. Kappa light chain restriction of interglandular plasma cell could be seen.

  6. Green ergonomics: combining sustainability and ergonomics.

    Science.gov (United States)

    Pilczuk, Davana; Barefield, Kevin

    2014-01-01

    When discussing ergonomics, the term 'sustainability' usually refers to the preservation of the human workforce. However, in 2010 Gulfstream Aerospace Corporation made a conscious effort to combine ergonomics and environmental sustainability in order to increase employee engagement for both programs. They introduced a companywide campaign called Green Ergo which is the idea of creating ergonomic solutions from scrap material found on site. This concept embraced the true meaning of 'green' and encouraged engineers and employees all across the company to design innovative green ergonomic solutions. The idea generated over 35 new ergo solutions, reduced waste production, and solved over 700 ergo problems for a fraction of the cost of newly purchased items. The demand for these items grew large enough that the company outsourced their manufacturing to a local non-profit. The Green Ergo campaign has changed the culture of the company and has increased the level of buy-in for both the ergonomics and sustainability programs.

  7. High Efficiency Ka-Band Spatial Combiner

    Directory of Open Access Journals (Sweden)

    D. Passi

    2014-12-01

    Full Text Available A Ka-Band, High Efficiency, Small Size Spatial Combiner (SPC is proposed in this paper, which uses an innovatively matched quadruple Fin Lines to microstrip (FLuS transitions. At the date of this paper and at the Author's best knowledge no such FLuS innovative transitions have been reported in literature before. These transitions are inserted into a WR28 waveguide T-junction, in order to allow the integration of 16 Monolithic Microwave Integrated Circuit (MMIC Solid State Power Amplifiers (SSPA's. A computational electromagnetic model using the finite elements method has been implemented. A mean insertion loss of 2 dB is achieved with a return loss better the 10 dB in the 31-37 GHz bandwidth.

  8. Combining Stocks and Flows of Knowledge

    DEFF Research Database (Denmark)

    Ambos, Tina C.; Nell, Phillip Christopher; Pedersen, Torben

    In the area of knowledge management and knowledge governance, previous research has mostly focused on either knowledge stocks or knowledge flows of firms or organizational units. Contrary to this work, our study is among the first to integrate these two perspectives in order to shed light...... on the complementarity effects of different types of knowledge stocks and flows in the multinational corporation (MNC). We investigate intra-functional as well as cross-functional complementarity effects from the perspective of the knowledge recipient. We test the impact of stocks on flows on the benefit that is created...... for MNC units. Based on a comprehensive sample of 324 relationships between MNC units we find that both types of complementarity create benefits for these units, but that the effects from intra-functional combinations of knowledge stocks and flows are significantly stronger than from cross...

  9. [Combined forecasting system of peritonitis outcome].

    Science.gov (United States)

    Lebedev, N V; Klimov, A E; Agrba, S B; Gaidukevich, E K

    To create a reliable system for assessing of severity and prediction of the outcome of peritonitis. Critical analysis of the systems for peritonitis severity assessment is presented. The study included outcomes of 347 patients who admitted at the Department of Faculty Surgery of Peoples' Friendship University of Russia in 2015-2016. The cause of peritonitis were destructive forms of acute appendicitis, cholecystitis, perforated gastroduodenal ulcer, various perforation of small and large intestines (including tumor). Combined forecasting system for peritonitis severity assessment is created. The system includes clinical, laboratory data, assessment of systemic inflammatory response (SIRS) and severity of organ failure (qSOFA). The authors focused on easily identifiable parameters which are available in virtually any surgical hospital. Threshold value (lethal outcome probability over 50%) is 8 scores in this system. Sensitivity, specificity and accuracy were 93.3, 99.7 and 98.9%, respectively according to ROC-curve that exceeds those parameters of MPI and APACHE II.

  10. A puzzling combination: disorder X order

    International Nuclear Information System (INIS)

    Hasenfratz, P.

    1979-01-01

    There are several examples indicating that the operator combination 'disorder X order' creates anomalous spin and/or statistics. In 2 + 1 dimensions there is a similar anomaly related to the disorder operator carrying Z(N) topological charge believed to have an important role in quark confinement. The conventionally defined total angular momentum has an anomalous term 1/2 sigma 3 ((1/√3) lambda 8 ) and can take the values 1/2 (1/3) in the presence of 'disorder X order' in 2 + 1 dimensional SU(2) (SU(3)) gauge theories. It is argued that the existence of a stable soliton solution or the introduction of Higgs fields are not important for the anomaly. (Auth.)

  11. LNG plant combined with power plant

    International Nuclear Information System (INIS)

    Aoki, I.; Kikkawa, Y.

    1997-01-01

    The LNG plant consumers a lot of power of natural gas cooling and liquefaction. In some LNG plant location, a rapid growth of electric power demand is expected due to the modernization of area and/or the country. The electric power demand will have a peak in day time and low consumption in night time, while the power demand of the LNG plant is almost constant due to its nature. Combining the LNG plant with power plant will contribute an improvement the thermal efficiency of the power plant by keeping higher average load of the power plant, which will lead to a reduction of electrical power generation cost. The sweet fuel gas to the power plant can be extracted from the LNG plant, which will be favorable from view point of clean air of the area. (Author). 5 figs

  12. Combining GLP-1 receptor agonists with insulin

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Vilsbøll, T

    2013-01-01

    Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control. However, there is a degree of inertia among...... physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose......, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin. Data from clinical studies support the therapeutic...

  13. Medicine as combining natural and human science.

    Science.gov (United States)

    Dreyfus, Hubert L

    2011-08-01

    Medicine is unique in being a combination of natural science and human science in which both are essential. Therefore, in order to make sense of medical practice, we need to begin by drawing a clear distinction between the natural and the human sciences. In this paper, I try to bring the old distinction between the Geistes and Naturwissenschaften up to date by defending the essential difference between a realist explanatory theoretical study of nature including the body in which the scientist discovers the causal properties of natural kinds and the interpretive understanding of human beings as embodied agents which, as Charles Taylor has convincingly argued, requires a hermeneutic account of self-interpreting human practices.

  14. Malignant mesothelioma clinical trial combines immunotherapy drugs.

    Science.gov (United States)

    Chatwal, Monica S; Tanvetyanon, Tawee

    2018-04-01

    Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1 inhibitor for mesothelioma have reported tumor response rates in approximately 10-20% of patients treated. Given the success of combining these agents with CTLA-4 inhibitor in melanoma, there is a strong rationale to study it in mesothelioma. Recently results from clinical trials investigating this approach have been released. Though limited by small sample size, the studies conclusively demonstrated feasibility and suggested a modestly higher tumor response rate than one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor. Nevertheless, toxicity was also increased. Immunotherapy-related deaths due to encephalitis, renal failure and hepatitis were observed. Further studies are warranted.

  15. Combined Waste Form Cost Trade Study

    International Nuclear Information System (INIS)

    Gombert, Dirk; Piet, Steve; Trickel, Timothy; Carter, Joe; Vienna, John; Ebert, Bill; Matthern, Gretchen

    2008-01-01

    A new generation of aqueous nuclear fuel reprocessing, now in development under the auspices of the DOE Office of Nuclear Energy (NE), separates fuel into several fractions, thereby partitioning the wastes into groups of common chemistry. This technology advance enables development of waste management strategies that were not conceivable with simple PUREX reprocessing. Conventional wisdom suggests minimizing high level waste (HLW) volume is desirable, but logical extrapolation of this concept suggests that at some point the cost of reducing volume further will reach a point of diminishing return and may cease to be cost-effective. This report summarizes an evaluation considering three groupings of wastes in terms of cost-benefit for the reprocessing system. Internationally, the typical waste form for HLW from the PUREX process is borosilicate glass containing waste elements as oxides. Unfortunately several fission products (primarily Mo and the noble metals Ru, Rh, Pd) have limited solubility in glass, yielding relatively low waste loading, producing more glass, and greater disposal costs. Advanced separations allow matching the waste form to waste stream chemistry, allowing the disposal system to achieve more optimum waste loading with improved performance. Metals can be segregated from oxides and each can be stabilized in forms to minimize the HLW volume for repository disposal. Thus, a more efficient waste management system making the most effective use of advanced waste forms and disposal design for each waste is enabled by advanced separations and how the waste streams are combined. This trade-study was designed to juxtapose a combined waste form baseline waste treatment scheme with two options and to evaluate the cost-benefit using available data from the conceptual design studies supported by DOE-NE

  16. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition

    Science.gov (United States)

    Hubers, Scott A.; Brown, Nancy J.

    2016-01-01

    Heart failure affects approximately 5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the FDA approved the first of a new class of drugs for the treatment of heart failure; valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses two of the pathophysiologic mechanisms of heart failure - activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared to enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacologic properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension. PMID:26976916

  17. Combination and interpretation of observables in Cosmology

    Directory of Open Access Journals (Sweden)

    Virey Jean-Marc

    2010-04-01

    Full Text Available The standard cosmological model has deep theoretical foundations but need the introduction of two major unknown components, dark matter and dark energy, to be in agreement with various observations. Dark matter describes a non-relativistic collisionless fluid of (non baryonic matter which amount to 25% of the total density of the universe. Dark energy is a new kind of fluid not of matter type, representing 70% of the total density which should explain the recent acceleration of the expansion of the universe. Alternatively, one can reject this idea of adding one or two new components but argue that the equations used to make the interpretation should be modified consmological scales. Instead of dark matter one can invoke a failure of Newton's laws. Instead of dark energy, two approaches are proposed : general relativity (in term of the Einstein equation should be modified, or the cosmological principle which fixes the metric used for cosmology should be abandonned. One of the main objective of the community is to find the path of the relevant interpretations thanks to the next generation of experiments which should provide large statistics of observationnal data. Unfortunately, cosmological in formations are difficult to pin down directly fromt he measurements, and it is mandatory to combine the various observables to get the cosmological parameters. This is not problematic from the statistical point of view, but assumptions and approximations made for the analysis may bias our interprettion of the data. Consequently, a strong attention should be paied to the statistical methods used to make parameters estimation and for model testing. After a review of the basics of cosmology where the cosmological parameters are introduced, we discuss the various cosmological probes and their associated observables used to extract cosmological informations. We present the results obtained from several statistical analyses combining data of diferent nature but

  18. Combination Therapy for Airflow Limitation In COPD

    Directory of Open Access Journals (Sweden)

    Jafar Aslani

    2012-08-01

    Full Text Available Background and the purpose of the study Existing evidence confirms that no pharmacologic agent ameliorates the decline in the lung function or changes the prognosis of chronic obstructive pulmonary disease (COPD. We tried a critical combination therapy for management of COPD. Methods Current or past smoker (passive or active COPD patients with moderate to severe COPD who did not respond to primitive therapy (i.e., oral prednisolone (50 mg in the morning for 5 days; with Beclomethasone Fort (3 puff q12h, totally 1500 micrograms/day, Salmeterol (2 puffs q12h, 50 micrograms/puff and ipratropium bromide (4 puffs q8h for two months, enrolled to study. Furthermore they were received N-Acetylcysteine (1200 mg/daily, Azithromycin (tablet 250 mg/every other day and Theophylline (100 mg BD.Results The study group consisted of 44 men and 4 women, with a mean age and standard deviation of 63.6+/-12.7 years (range 22-86 years. Thirteen of 48 patients (27.0% was responder based on 15% increasing in FEV 1 (27.7+/-7.9 after 6.7+/-6.1 months (57.9+/-12.9 year old. There were statistically significant differences in age and smoking between responders and nonresponders (P value was 0.05 and 0.04 respectively. There was no difference in emphysema and air trapping between two groups (p=0.13. Conclusion Interestingly considerable proportion of patients with COPD can be reversible using combination drug therapy and patients will greatly benefit from different and synergic action of the drugs. The treatment was more effective in younger patients who smoke less.

  19. Combined shearing interferometer and hartmann wavefront sensor

    International Nuclear Information System (INIS)

    Hutchin, R. A.

    1985-01-01

    A sensitive wavefront sensor combining attributes of both a Hartmann type of wavefront sensor and an AC shearing interferometer type of wavefront sensor. An incident wavefront, the slope of which is to be detected, is focussed to first and second focal points at which first and second diffraction gratings are positioned to shear and modulate the wavefront, which then diverges therefrom. The diffraction patterns of the first and second gratings are positioned substantially orthogonal to each other to shear the wavefront in two directions to produce two dimensional wavefront slope data for the AC shearing interferometer portion of the wavefront sensor. First and second dividing optical systems are positioned in the two diverging wavefronts to divide the sheared wavefront into an array of subapertures and also to focus the wavefront in each subaperture to a focal point. A quadrant detector is provided for each subaperture to detect the position of the focal point therein, which provides a first indication, in the manner of a Hartmann wavefront sensor, of the local wavefront slope in each subaperture. The total radiation in each subaperture, as modulated by the diffraction grating, is also detected by the quadrant detector which produces a modulated output signal representative thereof, the phase of which relative to modulation by the diffraction grating provides a second indication of the local wavefront slope in each subaperture, in the manner of an AC shearing interferometer wavefront sensor. The data from both types of sensors is then combined by long term averaging thereof to provide an extremely sensitive wavefront sensor

  20. Combining human and machine processes (CHAMP)

    Science.gov (United States)

    Sudit, Moises; Sudit, David; Hirsch, Michael

    2015-05-01

    Machine Reasoning and Intelligence is usually done in a vacuum, without consultation of the ultimate decision-maker. The late consideration of the human cognitive process causes some major problems in the use of automated systems to provide reliable and actionable information that users can trust and depend to make the best Course-of-Action (COA). On the other hand, if automated systems are created exclusively based on human cognition, then there is a danger of developing systems that don't push the barrier of technology and are mainly done for the comfort level of selected subject matter experts (SMEs). Our approach to combining human and machine processes (CHAMP) is based on the notion of developing optimal strategies for where, when, how, and which human intelligence should be injected within a machine reasoning and intelligence process. This combination is based on the criteria of improving the quality of the output of the automated process while maintaining the required computational efficiency for a COA to be actuated in timely fashion. This research addresses the following problem areas: • Providing consistency within a mission: Injection of human reasoning and intelligence within the reliability and temporal needs of a mission to attain situational awareness, impact assessment, and COA development. • Supporting the incorporation of data that is uncertain, incomplete, imprecise and contradictory (UIIC): Development of mathematical models to suggest the insertion of a cognitive process within a machine reasoning and intelligent system so as to minimize UIIC concerns. • Developing systems that include humans in the loop whose performance can be analyzed and understood to provide feedback to the sensors.

  1. Combined debridement in chronic wounds: a literature review

    OpenAIRE

    Liu, Wan-Lin; Jiang, Yun-Lan; Wang, Yan-Qiao; Li, Ying-Xin; Liu, Yi-Xian

    2017-01-01

    Wounds debridement is important for healing of chronic wounds. Combined debridement is a new technique to deal with the complex chronic wounds. This review introduces several topical methods of combined debridement according to the various color classifications. Methods include combined sharp and hydrogel debridement, combined ultrasonic and enzymatic debridement, ultrasonic debridement combined with surgical debridement and vacuum aspiration on debridement, and other types of debridement. Th...

  2. Using data from monitoring combined sewer overflows to assess, improve, and maintain combined sewer systems

    OpenAIRE

    Montserrat Royuela, Albert; Bosch, Ll.; Kiser, M.A.; Poch, Manuel; Corominas Tabares, Lluís

    2015-01-01

    Using low-cost sensors, data can be collected on the occurrence and duration of overflows in each combined sewer overflow (CSO) structure in a combined sewer system (CSS). The collection and analysis of real data can be used to assess, improve, and maintain CSSs in order to reduce the number and impact of overflows. The objective of this study was to develop a methodology to evaluate the performance of CSSs using low-cost monitoring. This methodology includes (1) assessing the capacity of a C...

  3. Combining the Observations from Different GNSS (Invited)

    Science.gov (United States)

    Dach, R.; Lutz, S.; Schaer, S.; Bock, H.; Jäggi, A.; Meindl, M.; Ostini, L.; Thaller, D.; Steinbach, A.; Beutler, G.; Steigenberger, P.

    2009-12-01

    For a very long time GPS has clearly dominated the use of GNSS measurements for scientific purposes. This picture is changing: we are moving from a GPS-only to a multi-GNSS world. This is, e.g., reflected by changing the meaning of the abbreviation IGS in March 2005 from International GPS to GNSS Service. The current situation can be described as follows: GPS has the leading role in the GNSS because it has provided a very stable satellite constellation over many years. Some of the currently active GPS satellites are nearly 15 years old. These old satellites are expected to be decommissioned within the next years. On the other hand, due to the increasing number of active GLONASS satellites and the improved density of multi-GNSS tracking stations in the IGS network, the quality of the GLONASS orbits has drastically improved during the last years. The European Galileo system is under development: currently two test satellites (GIOVE-A and GIOVE-B) are in orbit. The IOV (in-orbit-validation phase) will start soon. Also the first test satellites for the Chinese Compass system are in space. For the maximum benefit the observations of these GNSS will be processed in a combined multi-GNSS analysis in future. CODE (Center for Orbit Determination in Europe) is a joint venture between the Astronomical Institute of the University Bern (AIUB, Bern, Switzerland), the Federal Office of Topography (swisstopo, Wabern, Switzerland), the Federal Agency for Cartography and Geodesy (BKG, Frankfurt am Main, Germany), and the Institut für Astronomische und Physikalische Geodäsie of the Technische Universität München (IAPG/TUM, Munich, Germany). It acts as one of the global analysis centers of the IGS and has started in May 2003 with a rigorous combined processing of GPS and GLONASS measurements for the final, rapid, and even ultra-rapid product lines. All contributions from CODE to the IGS are in fact multi-GNSS products -- the only exception is the satellite and receiver clock

  4. EGSIEM combination service: combination of GRACE monthly K-band solutions on normal equation level

    Science.gov (United States)

    Meyer, Ulrich; Jean, Yoomin; Arnold, Daniel; Jäggi, Adrian

    2017-04-01

    The European Gravity Service for Improved Emergency Management (EGSIEM) project offers a scientific combination service, combining for the first time monthly GRACE gravity fields of different analysis centers (ACs) on normal equation (NEQ) level and thus taking all correlations between the gravity field coefficients and pre-eliminated orbit and instrument parameters correctly into account. Optimal weights for the individual NEQs are commonly derived by variance component estimation (VCE), as is the case for the products of the International VLBI Service (IVS) or the DTRF2008 reference frame realisation that are also derived by combination on NEQ-level. But variance factors are based on post-fit residuals and strongly depend on observation sampling and noise modeling, which both are very diverse in case of the individual EGSIEM ACs. These variance factors do not necessarily represent the true error levels of the estimated gravity field parameters that are still governed by analysis noise. We present a combination approach where weights are derived on solution level, thereby taking the analysis noise into account.

  5. Combinations of genetic variants associated with bipolar disorder

    DEFF Research Database (Denmark)

    Mellerup, Erling; Andreassen, Ole A; Bennike, Bente

    2017-01-01

    The main objective of the study was to find genetic variants that in combination are significantly associated with bipolar disorder. In previous studies of bipolar disorder, combinations of three and four single nucleotide polymorphisms (SNP) genotypes taken from 803 SNPs were analyzed, and five...... clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of ten SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from......, heterozygote or variant homozygote. In the combinations containing 10 SNP genotypes almost all the genotypes were the normal homozygote. Such a finding may indicate that accumulation in the genome of combinations containing few SNP genotypes may be a risk factor for bipolar disorder when those combinations...

  6. API and ISO standards can be combined

    International Nuclear Information System (INIS)

    Weightman, R.T.; Warnack, M.F.

    1992-01-01

    This paper reports that oil field equipment and product manufacturers can maintain a competitive advantage and minimize costs by integrating American Petroleum Institute (API) licensing programs with International Standards Organization (ISO) 9001 standards under one quality system. A combined quality system approach can position a company for quality system certification under ISO 9001 while maintaining API specifications. Furthermore, only one quality system manual is needed for API licensing and ISO certification, avoiding duplication of effort. The benefits of a documented quality program include the flowing: Job descriptions and personnel qualification requirements are documented; The improved documentation allows direct tracing of specific production activities; Laboratory test methods and calibration of test equipment follow accepted standards for more reliable and reproducible test data; Quality control becomes proactive, not reactive, through internal process controls previously not implemented; Employee attitudes improve through appreciation for the overall goals of the company; Ambiguous quality issues, such as documenting special customer requirements, are easily resolved; and The company image improves with customers, particularly for those that require API Specification Q1 or ISO 9001 compliance or those having their own quality performance standards

  7. Combined natural gas and electricity network pricing

    Energy Technology Data Exchange (ETDEWEB)

    Morais, M.S.; Marangon Lima, J.W. [Universidade Federal de Itajuba, Rua Dr. Daniel de Carvalho, no. 296, Passa Quatro, Minas Gerais, CEP 37460-000 (Brazil)

    2007-04-15

    The introduction of competition to electricity generation and commercialization has been the main focus of many restructuring experiences around the world. The open access to the transmission network and a fair regulated tariff have been the keystones for the development of the electricity market. Parallel to the electricity industry, the natural gas business has great interaction with the electricity market in terms of fuel consumption and energy conversion. Given that the transmission and distribution monopolistic activities are very similar to the natural gas transportation through pipelines, economic regulation related to the natural gas network should be coherent with the transmission counterpart. This paper shows the application of the main wheeling charge methods, such as MW/gas-mile, invested related asset cost (IRAC) and Aumman-Shapley allocation, to both transmission and gas network. Stead-state equations are developed to adequate the various pricing methods. Some examples clarify the results, in terms of investments for thermal generation plants and end consumers, when combined pricing methods are used for transmission and gas networks. The paper also shows that the synergies between gas and electricity industry should be adequately considered, otherwise wrong economic signals are sent to the market players. (author)

  8. Combined rankine and vapor compression cycles

    Science.gov (United States)

    Radcliff, Thomas D.; Biederman, Bruce P.; Brasz, Joost J.

    2005-04-19

    An organic rankine cycle system is combined with a vapor compression cycle system with the turbine generator of the organic rankine cycle generating the power necessary to operate the motor of the refrigerant compressor. The vapor compression cycle is applied with its evaporator cooling the inlet air into a gas turbine, and the organic rankine cycle is applied to receive heat from a gas turbine exhaust to heat its boiler within one embodiment, a common condenser is used for the organic rankine cycle and the vapor compression cycle, with a common refrigerant, R-245a being circulated within both systems. In another embodiment, the turbine driven generator has a common shaft connected to the compressor to thereby eliminate the need for a separate motor to drive the compressor. In another embodiment, an organic rankine cycle system is applied to an internal combustion engine to cool the fluids thereof, and the turbo charged air is cooled first by the organic rankine cycle system and then by an air conditioner prior to passing into the intake of the engine.

  9. Combining engineering and data-driven approaches

    DEFF Research Database (Denmark)

    Fischer, Katharina; De Sanctis, Gianluca; Kohler, Jochen

    2015-01-01

    Two general approaches may be followed for the development of a fire risk model: statistical models based on observed fire losses can support simple cost-benefit studies but are usually not detailed enough for engineering decision-making. Engineering models, on the other hand, require many assump...... to the calibration of a generic fire risk model for single family houses to Swiss insurance data. The example demonstrates that the bias in the risk estimation can be strongly reduced by model calibration.......Two general approaches may be followed for the development of a fire risk model: statistical models based on observed fire losses can support simple cost-benefit studies but are usually not detailed enough for engineering decision-making. Engineering models, on the other hand, require many...... assumptions that may result in a biased risk assessment. In two related papers we show how engineering and data-driven modelling can be combined by developing generic risk models that are calibrated to statistical data on observed fire events. The focus of the present paper is on the calibration procedure...

  10. Combination microwave ovens: an innovative design strategy.

    Science.gov (United States)

    Tinga, Wayne R; Eke, Ken

    2012-01-01

    Reducing the sensitivity of microwave oven heating and cooking performance to load volume, load placement and load properties has been a long-standing challenge for microwave and microwave-convection oven designers. Conventional design problem and solution methods are reviewed to provide greater insight into the challenge and optimum operation of a microwave oven after which a new strategy is introduced. In this methodology, a special load isolating and energy modulating device called a transducer-exciter is used containing an iris, a launch box, a phase, amplitude and frequency modulator and a coupling plate designed to provide spatially distributed coupling to the oven. This system, when applied to a combined microwave-convection oven, gives astounding performance improvements to all kinds of baked and roasted foods including sensitive items such as cakes and pastries, with the only compromise being a reasonable reduction in the maximum available microwave power. Large and small metal utensils can be used in the oven with minimal or no performance penalty on energy uniformity and cooking results. Cooking times are greatly reduced from those in conventional ovens while maintaining excellent cooking performance.

  11. Combined treatment of uveal melanoma liver metastases

    Directory of Open Access Journals (Sweden)

    Brasiuniene B

    2011-02-01

    Full Text Available Abstract Uveal melanoma (UM is the most prevalent intraocular malignant tumor in the Western world. The prognosis of survival in the presence of metastatic disease is 2-7 months, depending on the treatment applied. This article presents a case of metastatic UM with successful complex treatment of liver metastases. A 49-year old female, underwent removal of the right eyeball in 1996 due to a histologically confirmed uveal melanoma. After 11 years, CT revealed a mass in the left kidney and multiple metastases in the liver. After left nephrectomy, 6 chemotherapy courses with dacarbazine were performed. The increasing liver metastases were observed. Additional 4 intraarterial (i/a chemotherapy courses were administered using cisplatin, doxorubicin, fluorouracil, and interferon alfa. After few courses increase in CTC Grade 4 liver transaminases was seen. A partial response was observed, and in December 2008 the patient underwent surgery removing all liver metastases by 7 wedge or atypical resections. All margins were tumor-free. 21 months after liver resections and 14 years since diagnosis, the patient is alive without evidence of disease. Successful treatment of metastatic uveal melanoma was due to a timely application of a combination of several treatment methods and good prognostic factors of the patient.

  12. Small scale combined woodgas power plant

    International Nuclear Information System (INIS)

    Gulbis, V.

    2003-01-01

    As a first attempt to introduce biomass gasification technology in Latvia at the Faculty of Engineering of Latvia University of Agriculture an integral small scale combined heat and power (CHP) system based on a used Russian-made diesel-alternator set with electrical output 100 kWe was developed. The diesel is converted to dual fuel gas engine, using producer gas as the main fuel and gas oil as pilot fuel. To get sufficiently clean (tar content ≤ 250 mg/m 3 ) woodgas for using in IC engine a downdraft type of gasifier was chosen designed and constructed on the IMBERT gasifier principles. The test runs of the first experimental model showed that the engine does not develop expected power because of high resistance of gasifier and gas cleaning system does not work sufficiently enough. There was rather high level of tar content in woodgas because the temperature in the reduction zone was low. Calculations were carried out and new technological scheme of gasification system was worked out, introducing innovative ideas aimed on improving the working parameters (author)

  13. Transformative combinations: women's health and human rights.

    Science.gov (United States)

    Yamin, A E

    1997-01-01

    From the human rights perspective proposed in this article, a woman's good or ill health reflects more than biology or individual behaviors; it reflects her enjoyment (or lack thereof) of fundamental human rights that enable her to exercise basic power over the course and quality of her life. The "structural" view of health that such a human rights perspective suggests is concerned first with identifying the effects of social, economic, and political relations on women's health and then with promoting "interventions" aimed at transforming the laws, institutions, and structures that deny women's rights and well-being. Yet, traditional human rights law and practice have been limited to narrowly defined abuses by public officials against individuals that fail to capture the most pervasive denials of women's rights, which, though rooted in systematic discrimination, are frequently played out in so-called "private" institutions, primarily within the family. The experiences of women's health advocates in addressing complex women's health issues makes it clear that women's lack of access to economic and political power in the public sphere creates the conditions under which they are discriminated against and physically and sexually abused in the private sphere. Combining the pragmatic understanding of women's health professionals with an expansive conception of human rights norms has the potential to transform the fields of women's health and human rights.

  14. Combined Heuristic Attack Strategy on Complex Networks

    Directory of Open Access Journals (Sweden)

    Marek Šimon

    2017-01-01

    Full Text Available Usually, the existence of a complex network is considered an advantage feature and efforts are made to increase its robustness against an attack. However, there exist also harmful and/or malicious networks, from social ones like spreading hoax, corruption, phishing, extremist ideology, and terrorist support up to computer networks spreading computer viruses or DDoS attack software or even biological networks of carriers or transport centers spreading disease among the population. New attack strategy can be therefore used against malicious networks, as well as in a worst-case scenario test for robustness of a useful network. A common measure of robustness of networks is their disintegration level after removal of a fraction of nodes. This robustness can be calculated as a ratio of the number of nodes of the greatest remaining network component against the number of nodes in the original network. Our paper presents a combination of heuristics optimized for an attack on a complex network to achieve its greatest disintegration. Nodes are deleted sequentially based on a heuristic criterion. Efficiency of classical attack approaches is compared to the proposed approach on Barabási-Albert, scale-free with tunable power-law exponent, and Erdős-Rényi models of complex networks and on real-world networks. Our attack strategy results in a faster disintegration, which is counterbalanced by its slightly increased computational demands.

  15. Sweden: Combining childbearing and gender equality

    Directory of Open Access Journals (Sweden)

    Eva Bernhardt

    2008-07-01

    Full Text Available Sweden is the forerunner of the Second Demographic Transition. Fertility trends have fluctuated greatly since the 1960s, and the 1990s showed both European-highest and lowest-ever-in-Sweden levels, while the cohort pattern has been relatively stable. Period fluctuations have been accompanied by a postponement of entering committed partnerships and parenthood as well as an increasing instability of family relationships. The awareness and the availability of effective contraceptives have been extensive since the mid-1970s, the year the liberal abortion law was introduced. Post-modern values are dominant in this highly secularized society, but ideal family size is among the highest in the European Union, and childlessness has remained at a relatively low level. Ethnic diversification has increased over time, with about one-fifth of the population having a 'foreign background' in the early 2000s. The level of female labor-force participation is the highest in Europe (although mothers of pre-schoolers often work part-time, and young women are just as highly educated as men. Family policies, based on the principle of equality across social groups and gender, seem to play an important role in keeping fertility relatively high. In combination with other factors, family policies also play a role in the fluctuations of fertility rates, as eligibility to parental-leave and benefits as well as the availability of public childcare are linked to parents' labor-force attachment.

  16. Combined genetic effects of chemicals and radiation

    International Nuclear Information System (INIS)

    Kada, T.; Inoue, T.; Yokoiyama, A.; Russell, L.B.

    1979-01-01

    The interactions of chemicals and radiation are complex, and there may exist other unexpected patterns. The photodynamic induction of mutation by fluorescein dyes, and the radiosensitization with iodine compounds are classified as the interactions of chemicals and radiation outside cells. On the other hand, the antimutagenic effects of cobaltous chloride is concerned with the events taking place in the cells that had already been exposed to mutagenic agents. It is likely that the action of mutagenic agents is not direct, and that cellular functions, such as mutators or repair systems, are involved in the mutagenesis initiated by the agents. Such cellular functions can be affected by a second agent. In sexually reproducing organisms, two agents can also act on separate cells (male and female germ cells) which subsequently fuse. In mice, the experiments combining the radiation applied to one sex with the chemicals given to the other sex are only in early stages. Males were irradiated with X-ray (spermatozoa and spermatids sampled) and females (mature oocytes) were treated with caffeine. When the endpoint was dominant lethal, the level of X-ray effect induced in the male genome was independent of the caffeine treatment of the female. However, when the endpoint was sex-chromosome-loss, and a different strain of female was used, the caffeine potentiation was statistically significant at 5% level. (Yamashita, S.)

  17. Combined "dual" absorption and fluorescence smartphone spectrometers.

    Science.gov (United States)

    Arafat Hossain, Md; Canning, John; Ast, Sandra; Cook, Kevin; Rutledge, Peter J; Jamalipour, Abbas

    2015-04-15

    A combined "dual" absorption and fluorescence smartphone spectrometer is demonstrated. The optical sources used in the system are the white flash LED of the smartphone and an orthogonally positioned and interchangeable UV (λex=370  nm) and blue (λex=450  nm) LED. The dispersive element is a low-cost, nano-imprinted diffraction grating coated with Au. Detection over a 300 nm span with 0.42 nm/pixel resolution was carried out with the camera CMOS chip. By integrating the blue and UV excitation sources into the white LED circuitry, the entire system is self-contained within a 3D printed case and powered from the smartphone battery; the design can be scaled to add further excitation sources. Using a customized app, acquisition of absorption and fluorescence spectra are demonstrated using a blue-absorbing and green-emitting pH-sensitive amino-naphthalimide-based fluorescent probe and a UV-absorbing and blue-emitting Zn2+-sensitive fluoro-ionophore.

  18. Combined radioimmunoassay for triiodothyronine and thyroxine

    International Nuclear Information System (INIS)

    Denning, C.E.; Schick, L.A.

    1980-01-01

    A method for the combined radioimmunoassay for the hormones triiodothyronine (T-3) and thyroxine (T-4) in serum or plasma, wherein the radiolabeled t-3 and t-4 reagents are t-3 and t-4 labeled with the same radioisotope. The hormones are extracted from the serum or plasma sample and separated from their binding proteins by adsorption to a crosslinked dextran gel at a highly alkaline ph. After washing away the dissociated proteins, a predetermined limiting amount of t-3 antibody is incubated with the gel and thereafter radiolabeled t-3 which has become extracted from the gel by antibody binding is washed away. Excess t-3 antibody and a predetermined limiting amount of t-4 antibody are then incubated with the gel and radiolabeled t-3 and t-4 which has become extracted from the gel by antibody binding are thereafter washed away. The respective relative amounts of radiolabeled t-3 and t-4 retained by the gel after the incubations with the respective limiting amounts of t-3 and t-4 antibody are compared with standard results to quantitate the hormones in the sample. The use of excess t-3 antibody in the t-4 antibody incubation is critical to the accuracy of the method, enabling the use of the same radioisotope for radiolabeling t-3 and t-4

  19. Combining forecast weights: Why and how?

    Science.gov (United States)

    Yin, Yip Chee; Kok-Haur, Ng; Hock-Eam, Lim

    2012-09-01

    This paper proposes a procedure called forecast weight averaging which is a specific combination of forecast weights obtained from different methods of constructing forecast weights for the purpose of improving the accuracy of pseudo out of sample forecasting. It is found that under certain specified conditions, forecast weight averaging can lower the mean squared forecast error obtained from model averaging. In addition, we show that in a linear and homoskedastic environment, this superior predictive ability of forecast weight averaging holds true irrespective whether the coefficients are tested by t statistic or z statistic provided the significant level is within the 10% range. By theoretical proofs and simulation study, we have shown that model averaging like, variance model averaging, simple model averaging and standard error model averaging, each produces mean squared forecast error larger than that of forecast weight averaging. Finally, this result also holds true marginally when applied to business and economic empirical data sets, Gross Domestic Product (GDP growth rate), Consumer Price Index (CPI) and Average Lending Rate (ALR) of Malaysia.

  20. PANSAID - PAracetamol and NSAID in combination

    DEFF Research Database (Denmark)

    Thybo, Kasper Højgaard; Hägi-Pedersen, Daniel; Wetterslev, Jørn

    2017-01-01

    compared to monotherapy. The objective of this trial is to investigate the analgesic effects and safety of paracetamol and ibuprofen alone and in combination in different dosages after THA. METHODS: PANSAID is a placebo-controlled, parallel four-group, multicentre trial with centralised computer......-generated allocation sequence and allocation concealment and with varying block size and stratification by site. Blinding of assessor, investigator, caregivers, patients and statisticians. Patients are randomised to four groups: (A) paracetamol 1 g × 4 and ibuprofen 400 mg × 4, (B) paracetamol 1 g × 4 and placebo, (C......) placebo and ibuprofen 400 mg × 4 and (D) paracetamol 0.5 g × 4 and ibuprofen 200 mg. The two co-primary outcomes are 24-h consumption of morphine and number of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest...

  1. Pixel-Tilecal-MDT Combined Test Beam

    CERN Multimedia

    B. Di Girolamo

    A test with many expectations When an additional week of running (from September 11th to 18th) was allocated for the test-beam, it was decided to give priority to a combined run with the participation of the Pixel, Tilecal and MDT sub-detectors. The integration of these three sub-detectors was possible as they all use the baseline (DAQ-1/EF based) DAQ for test beams (as reported in a previous e-news). The tests and the addition of a common trigger and busy were organized in a short timescale by experts from the three sub-detectors and DAQ/EF. The expectations were many; both looking for problems and finding solutions. The setup The setup, shown in the figure, consisted of the Pixel telescope normally used during the sub-detector tests, two Tilecal barrel modules, two Tilecal extended barrel modules, and six MDT barrel chambers. This fully occupied a length of some 30 meters in the H8 line of the SPS North Area. Each sub-detector used their own specialized front-end electronics. The data collected by modu...

  2. Combined gas and steam power plant

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, D T; Davis, J P

    1977-06-02

    The invention concerns a combination of internal combustion engine and steam turbine, where not only the heat of the hot exhaust gases of the internal combustion engine, but also the heat in the coolant of the internal combustion engine is used for power generation. The working fluid of the steam turbine is an organic fluid of low boiling point. A mixture of 85 mol% of tri-fluoro ethanol and 15 mol% of water is the most suitable fluid. The combustion engine (a Diesel engine is the most suitable), drives a working machine, e.g. a generator. The hot combustion exhaust gases produce evaporation of the working fluid in an HP evaporator. The superheated steam gives up its energy in the HP turbine stage, flows through the feed preheater of the fluid, and is condensed in the condenser. A pump pumps the fluid via control valve to heat the feed preheater of the fluid, from which it returns to the HP evaporator. At the same time evaporated coolant flows into an LP evaporator in counter-flow to the working fluid, condenses, and is returned to the cooling circuit of the combustion engine. The working fluid in the LP evaporator is heated to its boiling point, gives up its energy in the LP stage of the steam turbine is condensed, pumped to the preheater and returns to the LP evaporator. The two rotors of the turbine stages (HP and LP stages) are mounted on the same shaft, which drives a working machine or a generator.

  3. Linear combinations come alive in crossover designs.

    Science.gov (United States)

    Shuster, Jonathan J

    2017-10-30

    Before learning anything about statistical inference in beginning service courses in biostatistics, students learn how to calculate the mean and variance of linear combinations of random variables. Practical precalculus examples of the importance of these exercises can be helpful for instructors, the target audience of this paper. We shall present applications to the "1-sample" and "2-sample" methods for randomized short-term 2-treatment crossover studies, where patients experience both treatments in random order with a "washout" between the active treatment periods. First, we show that the 2-sample method is preferred as it eliminates "conditional bias" when sample sizes by order differ and produces a smaller variance. We also demonstrate that it is usually advisable to use the differences in posttests (ignoring baseline and post washout values) rather than the differences between the changes in treatment from the start of the period to the end of the period ("delta of delta"). Although the intent is not to provide a definitive discussion of crossover designs, we provide a section and references to excellent alternative methods, where instructors can provide motivation to students to explore the topic in greater detail in future readings or courses. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Expert judgement combination using moment methods

    International Nuclear Information System (INIS)

    Wisse, Bram; Bedford, Tim; Quigley, John

    2008-01-01

    Moment methods have been employed in decision analysis, partly to avoid the computational burden that decision models involving continuous probability distributions can suffer from. In the Bayes linear (BL) methodology prior judgements about uncertain quantities are specified using expectation (rather than probability) as the fundamental notion. BL provides a strong foundation for moment methods, rooted in work of De Finetti and Goldstein. The main objective of this paper is to discuss in what way expert assessments of moments can be combined, in a non-Bayesian way, to construct a prior assessment. We show that the linear pool can be justified in an analogous but technically different way to linear pools for probability assessments, and that this linear pool has a very convenient property: a linear pool of experts' assessments of moments is coherent if each of the experts has given coherent assessments. To determine the weights of the linear pool we give a method of performance based weighting analogous to Cooke's classical model and explore its properties. Finally, we compare its performance with the classical model on data gathered in applications of the classical model

  5. Efficient Generation and Selection of Combined Features for Improved Classification

    KAUST Repository

    Shono, Ahmad N.

    2014-05-01

    This study contributes a methodology and associated toolkit developed to allow users to experiment with the use of combined features in classification problems. Methods are provided for efficiently generating combined features from an original feature set, for efficiently selecting the most discriminating of these generated combined features, and for efficiently performing a preliminary comparison of the classification results when using the original features exclusively against the results when using the selected combined features. The potential benefit of considering combined features in classification problems is demonstrated by applying the developed methodology and toolkit to three sample data sets where the discovery of combined features containing new discriminating information led to improved classification results.

  6. [Combined treatment of endometriosis: radical yet gentle].

    Science.gov (United States)

    Alkatout, Ibrahim; Wedel, Thilo; Maass, Nicolai

    2018-02-01

    Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the management of individual patients. This should take into account the severity of the disease and whether the patient desires to have children. Particular emphasis is laid on the anatomical intersections which, when injured, can lead to persistent damage of the anterior, middle or posterior compartment and are not infrequently the cause of urological and urogynaecological follow-up measures. Typical symptoms of endometriosis include chronic pelvic pain, subfertility, dysmenorrhoea, deep dyspareunia, cyclical bowel or bladder symptoms (e. g. dyschezia, bloating, constipation, rectal bleeding, diarrhoea and haematuria), abnormal menstrual bleeding, chronic fatigue and low back pain. Approx. 50 % of all female teenagers and up to 32 % of all women of reproductive age who have been operated for chronic pelvic pain or dysmenorrhoea suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 % and > 60 % and is very much dependent on integrated management and surgical skills. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should be reserved to appropriate

  7. Energy uses in combination processes applying irradiation

    International Nuclear Information System (INIS)

    Brynjolfsson, A.

    1998-01-01

    The costs of energy in the food system are significant and have increased as a result of the growth in population worldwide. This, in turn, demands an increased harvest per area of land, and thus intensive agriculture. The energy used in the food system is not only a drain on limited resources but also has an adverse impact on the environment. It is therefore important to devise methods that reduce energy in all undertakings. The energy used in food irradiation is relatively low compared with other methods and relative to the amount of energy used in producing food. for this reason, food irradiation is an environmentally friendly method and the costs of processing and preserving food do not depend greatly on the fluctuating costs of renewable energy sources such as oil. Irradiation in 60 Co facilities uses a very small amount of energy, about 0.032-0.0465 MJ/kg for radicidation doses of 3 kGy. Irradiation in 5 MV DC electron accelerator facilities uses about twice as much energy; 10 MV travelling wave accelerator facilities use about five times as much and 5 MV X ray facilities about 25 times as much as 60 Co facilities. In practice, X ray facilities are employed only for low dose applications such as sprout inhibition, inactivation of trichina in pork products and disinfestation of fruits, therefore the energy used in low. Frequently, irradiation can be used in combination with other low energy methods such as the sun drying of spices, condiments, vegetables and fish. The overall method of preservation is then particularly environmentally friendly and results in microbiologically safe and wholesome food. (author)

  8. Combined SRCT & FXCT - The next steps

    Science.gov (United States)

    Hall, C.; Acres, R. G.; Winnett, A.; Wang, F.

    2016-03-01

    One of the goals in developing synchrotron radiation x-ray computed tomography (SRCT) for biomedical specimens, is allowing particular tissues and cell types to be marked in the images. This is equivalent to the staining in histology, which enables researchers to visualise and measure tissue structure and biochemical processes within the specimen. Some progress in this direction for SRCT is being made, using a variety of contrast agents that alter the natural x-ray attenuation of the marked tissue [1]. However there are limits to the usefulness of these attenuation altering techniques. Often high concentrations of potentially disruptive chemicals are required with reduced compatibility for in-vivo studies. Another image highlighting technique which might prove more sensitive is x-ray fluorescence imaging. In this case usually endogenous elemental markers are visualised. We would like to develop a lower resolution, but wider field of view means of three-dimensional (3-D) fluorescence imaging compatible with SRCT. We have previously proposed a technique in which x-ray fluorescence CT (FXCT) and SRCT data can be collected simultaneously [2]. This work resulted in proof of concept modelling, and a simple experiment test system. We show data here which demonstrate a two-dimensional (2-D) reconstruction of an iodine fluorescence map from a phantom. Measurements were performed with a fixed beam modulating mask using the Imaging and Medical beam line (IMBL) at the Australian Synchrotron. Fluorescence data was obtained during a CT scan using a single point detector, while transmission data was simultaneously collected using an area detector. A maximum likelihood expectation maximisation (MLEM) iterative algorithm was used to reconstruct the fluorescence map. We report on technique development and now believe compressive sensing (CS) imaging techniques suit SRCT and may overcome the issues encountered so far in combining SRCT and FXCT.

  9. Combined performance studies for electrons at the 2004 ATLAS combined test-beam

    International Nuclear Information System (INIS)

    Abat, E; Arik, E; Abdallah, J M; Addy, T N; Adragna, P; Aharrouche, M; Ahmad, A; Akesson, T P A; Aleksa, M; Anghinolfi, F; Baron, S; Alexa, C; Anderson, K; Andreazza, A; Banfi, D; Antonaki, A; Arabidze, G; Atkinson, T; Baines, J; Baker, O K

    2010-01-01

    In 2004 at the ATLAS (A Toroidal LHC ApparatuS) combined test beam, one slice of the ATLAS barrel detector (including an Inner Detector set-up and the Liquid Argon calorimeter) was exposed to particles from the H8 SPS beam line at CERN. It was the first occasion to test the combined electron performance of ATLAS. This paper presents results obtained for the momentum measurement p with the Inner Detector and for the performance of the electron measurement with the LAr calorimeter (energy E linearity and resolution) in the presence of a magnetic field in the Inner Detector for momenta ranging from 20 GeV/c to 100 GeV/c. Furthermore the particle identification capabilities of the Transition Radiation Tracker, Bremsstrahlungs-recovery algorithms relying on the LAr calorimeter and results obtained for the E/p ratio and a way how to extract scale parameters will be discussed.

  10. Combined performance studies for electrons at the 2004 ATLAS combined test-beam

    Energy Technology Data Exchange (ETDEWEB)

    Abat, E; Arik, E [Bogazici University, Faculty of Sciences, Department of Physics, TR - 80815 Bebek-Istanbul (Turkey); Abdallah, J M [Institut de Fisica d' Altes Energies, IFAE, Universitat Autonoma de Barcelona, Edifici Cn, ES - 08193 Bellaterra, Barcelona Spain (Spain); Addy, T N [Hampton University, Department of Physics, Hampton, VA 23668 (United States); Adragna, P [Queen Mary, University of London, Mile End Road, E1 4NS, London (United Kingdom); Aharrouche, M [Universitaet Mainz, Institut fuer Physik, Staudinger Weg 7, DE 55099 (Germany); Ahmad, A [Insitute of Physics, Academia Sinica, TW - Taipei 11529, Taiwan (China); Akesson, T P A [Lunds universitet, Naturvetenskapliga fakulteten, Fysiska institutionen, Box 118, SE - 221 00, Lund (Sweden); Aleksa, M; Anghinolfi, F; Baron, S [European Laboratory for Particle Physics (CERN), CH-1211 Geneva 23 (Switzerland); Alexa, C [National Institute of Physics and Nuclear Engineering (Bucharest -IFIN-HH), P.O. Box MG-6, R-077125 Bucharest (Romania); Anderson, K [University of Chicago, Enrico Fermi Institute, 5640 S. Ellis Avenue, Chicago, IL 60637 (United States); Andreazza, A; Banfi, D [INFN Sezione di Milano, via Celoria 16, IT - 20133 Milano (Italy); Antonaki, A; Arabidze, G [University of Athens, Nuclear and Particle Physics Department of Physics, Panepistimiopouli Zografou, GR 15771 Athens (Greece); Atkinson, T [School of Physics, University of Melbourne, AU - Parkvill, Victoria 3010 (Australia); Baines, J [Rutherford Appleton Laboratory, Science and Technology Facilities Council, Harwell Science and Innovation Campus, Didcot OX11 0QX (United Kingdom); Baker, O K, E-mail: robert.froeschl@cern.c [Yale University, Department of Physics, PO Box 208121, New Haven, CT06520-8121 (United States)

    2010-11-15

    In 2004 at the ATLAS (A Toroidal LHC ApparatuS) combined test beam, one slice of the ATLAS barrel detector (including an Inner Detector set-up and the Liquid Argon calorimeter) was exposed to particles from the H8 SPS beam line at CERN. It was the first occasion to test the combined electron performance of ATLAS. This paper presents results obtained for the momentum measurement p with the Inner Detector and for the performance of the electron measurement with the LAr calorimeter (energy E linearity and resolution) in the presence of a magnetic field in the Inner Detector for momenta ranging from 20 GeV/c to 100 GeV/c. Furthermore the particle identification capabilities of the Transition Radiation Tracker, Bremsstrahlungs-recovery algorithms relying on the LAr calorimeter and results obtained for the E/p ratio and a way how to extract scale parameters will be discussed.

  11. Combinations of Genetic Variants Occurring Exclusively in Patients

    Directory of Open Access Journals (Sweden)

    Erling Mellerup

    Full Text Available In studies of polygenic disorders, scanning the genetic variants can be used to identify variant combinations. Combinations that are exclusively found in patients can be separated from those combinations occurring in control persons. Statistical analyses can be performed to determine whether the combinations that occur exclusively among patients are significantly associated with the investigated disorder. This research strategy has been applied in materials from various polygenic disorders, identifying clusters of patient-specific genetic variant combinations that are significant associated with the investigated disorders. Combinations from these clusters are found in the genomes of up to 55% of investigated patients, and are not present in the genomes of any control persons. Keywords: Genetic variants, Polygenic disorder, Combinations of genetic variants, Patient-specific combinations

  12. Combined Effects of Medicinal Plants on Induced Upper ...

    African Journals Online (AJOL)

    Combined Effects of Medicinal Plants on Induced Upper Gastrointestinal Tract Injury ... treated in different doses of single and combined extracts of Allium sativum, ... was no visible sign of ulceration or perforation observed on the stomach and ...

  13. Treatment of premature ejaculation: a new combined approach

    Directory of Open Access Journals (Sweden)

    Adel Kurkar

    2015-01-01

    Causes of PE differ considerably. In this paper, we compared the outcomes of two single treatment lines together with a combination of both. The combination therapy was more effective than either line alone.

  14. Smoking and Bone Healing - A Risky Surgical Combination

    Science.gov (United States)

    ... Risky Surgical Combination A A A | Print | Share Smoking and Bone Healing – A Risky Surgical Combination Imagine ... saying that they'd prefer patients to quit smoking. There hasn't been a great deal of ...

  15. Combination syringe provides air-free blood samples

    Science.gov (United States)

    Pool, S. L.

    1970-01-01

    Standard syringe and spinal needle are combined in unique manner to secure air-free blood samples. Combination syringe obtains air free samples because air bubbles become insignificant when samples greater than 1 cc are drawn.

  16. A combined constraint handling framework: an empirical study

    DEFF Research Database (Denmark)

    Si, Chengyong; Hu, Junjie; Lan, Tian

    2017-01-01

    This paper presents a new combined constraint handling framework (CCHF) for solving constrained optimization problems (COPs). The framework combines promising aspects of different constraint handling techniques (CHTs) in different situations with consideration of problem characteristics. In order...

  17. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  18. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  19. Locations of Combined Sewer Overflow Outfalls - US EPA Region 3

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data layer identifies the locations of Combined sewer overflow outfalls. Combined sewer systems are sewers that are designed to collect rainwater runoff,...

  20. Performance Evaluation of the Combined Agent Fire Fighting System (CAFFS)

    National Research Council Canada - National Science Library

    Kalberer, Jennifer

    2003-01-01

    ... of the location. The Combined Agent Fire Fighting System (CAFFS) employs innovations in nozzle design, lightweight composites and combination agents to design a system with extinguishment capabilities of much larger ARFF vehicles...