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Sample records for circulating human epidermal-growth-factor-like

  1. Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Andersen, Rikke Fredslund; Aalund Olsen, Dorte

    2017-01-01

    High tumor expression of epidermal growth factor-like domain 7 (EGFL7) has been associated with a poor prognosis in colorectal cancer. The aim of the current study was to investigate the possible prognostic impact of circulating EGFL7 (cir-EGFL7), combined with single nucleotide polymorphism (SNP...

  2. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter

    1994-01-01

    The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225-262 amino acid residues. FA1 has six well conserved epidermal...... extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact...... to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating...

  3. The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans

    NARCIS (Netherlands)

    Stacey, Martin; Chang, Gin-Wen; Davies, John Q.; Kwakkenbos, Mark J.; Sanderson, Ralph D.; Hamann, Jörg; Gordon, Siamon; Lin, Hsi-Hsien

    2003-01-01

    Using multivalent protein probes, an evolutionarily conserved endogenous ligand for EMR2, a human myeloid cell-restricted EGF-TM7 receptor, was identified on the surface of a number of adherent cell lines. In addition, in situ staining of the ligand has revealed specific in vivo patterns consistent

  4. Suppression of the Epidermal Growth Factor-like Domain 7 and Inhibition of Migration and Epithelial-Mesenchymal Transition in Human Pancreatic Cancer PANC-1 Cells.

    Science.gov (United States)

    Wang, Yun-Liang; Dong, Feng-Lin; Yang, Jian; Li, Zhi; Zhi, Qiao-Ming; Zhao, Xin; Yang, Yong; Li, De-Chun; Shen, Xiao-Chun; Zhou, Jin

    2015-01-01

    Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted protein specifically expressed by endothelial cells during embryogenesis, recently was identified as a critical gene in tumor metastasis. Epithelial-mesenchymal transition (EMT) was found to be closely related with tumor progression. Accordingly, it is important to investigate the migration and EMT change after knock-down of EGFL7 gene expression in human pancreatic cancer cells. EGFL7 expression was firstly testified in 4 pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1 cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze the migration of PANC-1 cells. Real-time PCR and western blotting were used to detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N-Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in PANC-1, NC- PANC-1, and si-PANC-1 cells, respectively. After successful plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference in si-PANC-1 group. Meanwhile, migration ability decreased significantly, compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N-Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group, indicating a reversion of EMT. Also, transcription factors snail and slug decreased significantly after RNA interference. Current study suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts through transcription factors snail and slug to induce EMT, and further study is needed to confirm this issue.

  5. The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo

    International Nuclear Information System (INIS)

    Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung; Park, Yoon-Jeong; Chung, Chong-Pyoung

    2012-01-01

    Highlights: ► HBP sequence identified from HB-EGF has cell penetration activity. ► HBP inhibits the NF-κB dependent inflammatory responses. ► HBP directly blocks phosphorylation and degradation of IκBα. ► HBP inhibits nuclear translocation of NF-κB p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-α and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-α and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-κB-dependent inflammatory responses by directly blocking the phosphorylation and degradation of IκBα and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-κB. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.

  6. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

    Science.gov (United States)

    Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

    2017-05-01

    High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

  7. Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging.

    Science.gov (United States)

    Liu, Heng; Chen, Xiao; Xue, Wei; Chu, Chengchao; Liu, Yu; Tong, Haipeng; Du, Xuesong; Xie, Tian; Liu, Gang; Zhang, Weiguo

    The highly infiltrative and invasive nature of glioma cells often leads to blurred tumor margins, resulting in incomplete tumor resection and tumor recurrence. Accurate detection and precise delineation of glioma help in preoperative delineation, surgical planning and survival prediction. In this study, recombinant epidermal growth factor-like domain-1, derived from human coagulation factor VII, was conjugated to iron oxide nanoparticles (IONPs) for targeted glioma magnetic resonance (MR) imaging. The synthesized EGF1-EGFP-IONPs exhibited excellent targeting ability toward tissue factor (TF)-positive U87MG cells and human umbilical vein endothelial cells in vitro, and demonstrated persistent and efficient MR contrast enhancement up to 12 h for preclinical glioma models with high targeting specificity in vivo. They hold great potential for clinical translation and developing targeted theranostics against brain glioma.

  8. Overexpression of Heparin-Binding Epidermal Growth Factor-Like Growth Factor Mediates Liver Fibrosis in Transgenic Mice.

    Science.gov (United States)

    Guo, Yongze; Ding, Qian; Chen, Lei; Ji, Chenguang; Hao, Huiyao; Wang, Jia; Qi, Wei; Xie, Xiaoli; Ma, Junji; Li, Aidi; Jiang, Xiaoyu; Li, Xiaotian; Jiang, Huiqing

    2017-08-01

    The role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver fibrosis is not clear and is sometimes even contradictory. To clarify this role, a HB-EGF transgenic (Tg) mouse model was, for the first time, used to evaluate the functions of HB-EGF in liver fibrosis. For the in vivo study, carbon tetrachloride injection and bile duct ligation treatment were used to induce liver fibrosis in HB-EGF Tg mice and wild-type (WT) mice, respectively. Primary hepatic satellite cells (HSCs) were isolated from HB-EGF Tg and WT mice for the in vitro study. Compared with the WT mice, HB-EGF Tg mice were shown to develop more severe liver fibrosis when treated with carbon tetrachloride or bile duct ligation, with increased matrix metalloproteinases 13 activity and enhanced expression of fibrogenic genes including α-smooth muscle actin and collagen I. HB-EGF gene transfer led to an increase in proliferation and a decrease in apoptosis in primary HSCs. The ERK signaling pathway was more highly activated in primary HSCs from HB-EGF Tg mice than in those from WT mice. Our investigation confirmed the profibrotic effect of HB-EGF on the liver using a Tg mouse model. This result may contribute to the elucidation of HB-EGF as a therapeutic target in liver fibrosis. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  9. Epidermal Growth Factor-like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Sørensen, Flemming Brandt

    2014-01-01

    The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined with bevaci...

  10. Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and active angiogenesis.

    Science.gov (United States)

    Bambino, Kathryn; Lacko, Lauretta A; Hajjar, Katherine A; Stuhlmann, Heidi

    2014-07-01

    Epidermal growth factor-like domain 7 (Egfl7) expression in the developing embryo is largely restricted to sites of mesodermal progenitors of angioblasts/hemangioblasts and the vascular endothelium. We hypothesize that Egfl7 marks the endothelial lineage during embryonic development, and can be used to define the emergence of endothelial progenitor cells, as well as to visualize newly-forming vasculature in the embryo and during the processes of physiologic and pathologic angiogenesis in the adult. We have generated a transgenic mouse strain that expresses enhanced green fluorescent protein (eGFP) under the control of a minimal Egfl7 regulatory sequence (Egfl7:eGFP). Expression of the transgene recapitulated that of endogenous Egfl7 at sites of vasculogenesis and angiogenesis in the allantois, yolk sac, and in the embryo proper. The transgene was not expressed in the quiescent endothelium of most adult organs. However, the uterus and ovary, which undergo vascular growth and remodeling throughout the estrus cycle, expressed high levels of Egfl7:eGFP. Importantly, expression of the Egfl7:eGFP transgene was induced in adult neovasculature. We also found that increased Egfl7 expression contributed to pathologic revascularization in the mouse retina. To our knowledge, this is the first mouse model that enables monitoring of endothelial cells at sites of active vasculogenesis and angiogenesis. This model also facilitated the isolation and characterization of EGFL7(+) endothelial cell populations by fluorescence activated cell sorting (FACS). Together, our results demonstrate that the Egfl7:eGFP reporter mouse is a valuable tool that can be used to elucidate the mechanisms by which blood vessels form during development and under pathologic circumstances. © 2014 Wiley Periodicals, Inc.

  11. Serum Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) as a Biomarker for Primary Ovarian Cancer.

    Science.gov (United States)

    Miyata, Kohei; Yotsumoto, Fusanori; Fukagawa, Satoshi; Kiyoshima, Chihiro; Ouk, Nam Sung; Urushiyama, Daichi; Ito, Tomohiro; Katsuda, Takahiro; Kurakazu, Masamitsu; Araki, Ryota; Sanui, Ayako; Miyahara, Daisuke; Murata, Masaharu; Shirota, Kyoko; Yagi, Hiroshi; Takono, Tadao; Kato, Kiyoko; Yaegashi, Nobuo; Akazawa, Kohei; Kuroki, Masahide; Yasunaga, Shin'ichiro; Miyamoto, Shingo

    2017-07-01

    Ovarian cancer is the most lethal malignancy among gynaecological cancers. Although many anticancer agents have been developed for the treatment of ovarian cancer, it continues to have an extremely poor prognosis. Heparin-binding epidermal growth factor-like grown factor (HB-EGF) has been reported to be a rational therapeutic target for ovarian cancer. Here, we evaluated the clinical significance of serum HB-EGF by examining the association between prognosis and serum HB-EGF levels in patients with primary ovarian cancer. We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease. In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial.

    Science.gov (United States)

    Hansen, T F; Christensen, R dP; Andersen, R F; Sørensen, F B; Johnsson, A; Jakobsen, A

    2013-09-03

    This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC). A total of 230 patients from a randomised phase III study were included. The primary microRNA-126 (pri-miRNA-126) A24G single-nucleotide polymorphism and the mature miRNA-126 were analysed by PCR using genomic DNA (full blood) and formalin-fixed paraffin-embedded tissue sections, respectively. The epidermal growth factor-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry. High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio=0.49, 95% confidence interval=0.29-0.84, P=0.009). Although not significant, a relationship between EGFL7 expression and response rates is suggested, with EGFL7 expression at the invasive front being lower in responding patients than in the non-responders (P=0.063). The results validate the previous findings on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics.

  13. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities

    Science.gov (United States)

    Long, D.L.; Ulici, V.; Chubinskaya, S.; Loeser, R.F.

    2015-01-01

    Objective We determined if the epidermal growth factor receptor ligand HB-EGF is produced in cartilage and if it regulates chondrocyte anabolic or catabolic activity. Methods HB-EGF expression was measured by quantitative PCR using RNA isolated from mouse knee joint tissues and from normal and OA human chondrocytes. Immunohistochemistry was performed on normal and OA human cartilage and meniscus sections. Cultured chondrocytes were treated with fibronectin fragments (FN-f) as a catabolic stimulus and osteogenic protein 1 (OP-1) as an anabolic stimulus. Effects of HB-EGF on cell signaling were analyzed by immunoblotting of selected signaling proteins. MMP-13 was measured in conditioned media, proteoglycan synthesis was measured by sulfate incorporation, and matrix gene expression by quantitative PCR. Results HB-EGF expression was increased in 12-month old mice at 8 weeks after surgery to induce OA and increased amounts of HB-EGF were noted in human articular cartilage from OA knees. FN-f stimulated chondrocyte HB-EGF expression and HB-EGF stimulated chondrocyte MMP-13 production. However, HB-EGF was not required for FN-f stimulation of MMP-13 production. HB-EGF activated the ERK and p38 MAP kinases and stimulated phosphorylation of Smad1 at an inhibitory serine site which was associated with inhibition of OP-1 mediated proteoglycan synthesis and reduced aggrecan (ACAN) but not COL2A1 expression. Conclusion HB-EGF is a new factor identified in OA cartilage that promotes chondrocyte catabolic activity while inhibiting anabolic activity suggesting it could contribute to the catabolic-anabolic imbalance seen in OA cartilage. PMID:25937027

  14. Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

    International Nuclear Information System (INIS)

    Huang, L.H.; Cheng, H.; Sweeney, W.V.; Pardi, A.; Tam, J.P.

    1991-01-01

    Factor IX is a blood clotting protein that contains three regions, including a γ-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel β-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp 28 , with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the β-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself

  15. Levels of the epidermal growth factor-like peptide amphiregulin in follicular fluid reflect the mode of triggering ovulation: a comparison between gonadotrophin-releasing hormone agonist and urinary human chorionic gonadotrophin

    DEFF Research Database (Denmark)

    Al Humaidan, Peter Samir Heskjær; Westergaard, Lars Grabow; Mikkelsen, Anne Lis

    2011-01-01

    . INTERVENTION(S): Ovulation triggered with either urinary hCG or GnRH agonist (GnRH-a). Controls: 15 FF samples from small antral follicles (3-9 mm) and 12 FF samples from natural cycle. MAIN OUTCOME MEASURE(S): Follicular fluid concentration of AR, P(4), E(2), vascular endothelial growth factor, and inhibin B...... antral follicles only 5 out of 15 follicles contained measurable amounts of AR. When urinary hCG and GnRH-a triggering were compared, FF P(4) was significantly higher after urinary hCG triggering, whereas no difference was seen regarding E(2), vascular endothelial growth factor, and inhibin B. A total...... of 14% more metaphase II oocytes and 11% more transferable embryos were obtained after GnRH-a triggering. CONCLUSION(S): This study suggests that oocyte competence is linked to granulosa cell AR secretion....

  16. Effect and Mechanism of EGFL7 Downregulation in Human Osteosarcoma Cells on the Biological Function of Co-cultured HUVEC

    Directory of Open Access Journals (Sweden)

    Xia Li

    2018-03-01

    Full Text Available Background: Even though epidermal growth factor-like domain 7 is known to be overexpressed in osteosarcoma and is associated with poor clinical outcome, few reports are available regarding its mechanism. Aims: The objective of this study was to explore the effect and mechanism of downregulating epidermal growth factor-like domain 7 expression in a human osteosarcoma cell line on the biological function of co-cultured human umbilical vein endothelial cells. Study Design: Cell study. Methods: In the present study, human osteosarcoma cell lines U2OS, Saos-2, HOS, and MG63, and normal human osteoblasts were cultured in Dulbecco’s Modified Eagle Medium containing 10% fetal bovine serum and 1x antibiotics at 37 °C and 5% CO2 in an incubator. Of the four osteosarcoma cell lines, U2OS expresses the highest level of epidermal growth factor-like domain 7 mRNA as determined using quantitative reverse transcription polymerase chain reaction. With the knockdown of epidermal growth factor-like domain 7 in U2OS and human umbilical vein endothelial cells by lentivirus, the proliferation and apoptosis of U2OS and human umbilical vein endothelial cells were investigated using MTT and flow cytometry assays. After the co-culture of human umbilical vein endothelial cells and epidermal growth factor-like domain 7-knockdown U2OS, the in vitro effects on cell proliferation, apoptosis, adhesion, migration, and the angiogenic ability of human umbilical vein endothelial cells were detected using MTT, flow cytometry, Transwell, and tube formation assays, respectively. The expressions of phosphoinositide 3-kinase, phospho-Akt, total Akt, and vascular endothelial growth factor in human umbilical vein endothelial cells were detected using western blot assay. Results: Lentivirus with epidermal growth factor-like domain 7 shRNA could not significantly affect the proliferation and apoptosis of both U2OS and human umbilical vein endothelial cells, whereas the knockdown of

  17. Exercise increases circulating GDF15 in humans

    Directory of Open Access Journals (Sweden)

    Maximilian Kleinert

    2018-03-01

    Full Text Available Objective: The growth differentiation factor 15 (GDF15 is a stress-sensitive circulating factor that regulates systemic energy balance. Since exercise is a transient physiological stress that has pleiotropic effects on whole-body energy metabolism, we herein explored the effect of exercise on a circulating GDF15 levels and b GDF15 release from skeletal muscle in humans. Methods: Seven healthy males either rested or exercised at 67% of their VO2max for 1 h and blood was sampled from the femoral artery and femoral vein before, during, and after exercise. Plasma GDF15 concentrations were determined in these samples. Results: Plasma GDF15 levels increased 34% with exercise (p < 0.001 and further increased to 64% above resting values at 120 min (p < 0.001 after the cessation of exercise. There was no difference between the arterial and venous GDF15 concentration before, during, and after exercise. During a resting control trial, GDF15 levels measured in the same subjects were unaltered. Conclusions: Vigorous submaximal exercise increases circulating GDF15 levels in humans, but skeletal muscle tissue does not appear to be the source. Keywords: Skeletal muscle, Growth differentiation factor 15, Recovery, Physical activity

  18. Identification of a human monoclonal antibody to replace equine diphtheria antitoxin for treatment of diphtheria intoxication.

    Science.gov (United States)

    Sevigny, Leila M; Booth, Brian J; Rowley, Kirk J; Leav, Brett A; Cheslock, Peter S; Garrity, Kerry A; Sloan, Susan E; Thomas, William; Babcock, Gregory J; Wang, Yang

    2013-11-01

    Diphtheria antitoxin (DAT) has been the cornerstone of the treatment of Corynebacterium diphtheriae infection for more than 100 years. Although the global incidence of diphtheria has declined steadily over the last quarter of the 20th century, the disease remains endemic in many parts of the world, and significant outbreaks still occur. DAT is an equine polyclonal antibody that is not commercially available in the United States and is in short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we obtained human monoclonal antibodies (hMAbs) directly from antibody-secreting cells in the circulation of immunized human volunteers. We isolated a panel of diverse hMAbs that recognized diphtheria toxoid, as well as a variety of recombinant protein fragments of diphtheria toxin. Forty-five unique hMAbs were tested for neutralization of diphtheria toxin in in vitro cytotoxicity assays with a 50% effective concentration of 0.65 ng/ml for the lead candidate hMAb, 315C4. In addition, 25 μg of 315C4 completely protected guinea pigs from intoxication in an in vivo lethality model, yielding an estimated relative potency of 64 IU/mg. In comparison, 1.6 IU of DAT was necessary for full protection from morbidity and mortality in this model. We further established that our lead candidate hMAb binds to the receptor-binding domain of diphtheria toxin and physically blocks the toxin from binding to the putative receptor, heparin-binding epidermal growth factor-like growth factor. The discovery of a specific and potent human neutralizing antibody against diphtheria toxin holds promise as a potential therapeutic.

  19. Exercise increases circulating GDF15 in humans

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Clemmensen, Christoffer; Sjøberg, Kim Anker

    2018-01-01

    OBJECTIVE: The growth differentiation factor 15 (GDF15) is a stress-sensitive circulating factor that regulates systemic energy balance. Since exercise is a transient physiological stress that has pleiotropic effects on whole-body energy metabolism, we herein explored the effect of exercise on a......) circulating GDF15 levels and b) GDF15 release from skeletal muscle in humans. METHODS: Seven healthy males either rested or exercised at 67% of their VO2max for 1 h and blood was sampled from the femoral artery and femoral vein before, during, and after exercise. Plasma GDF15 concentrations were determined...... in these samples. RESULTS: Plasma GDF15 levels increased 34% with exercise (p exercise. There was no difference between the arterial and venous GDF15 concentration before, during, and after exercise. During...

  20. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, T F; Christensen, René dePont; Andersen, R F

    2013-01-01

    Background:This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC).Methods:A total of 230 patients...... on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics....

  1. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, T F; Christensen, René dePont; Andersen, R F

    2013-01-01

    Background:This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC).Methods:A total of 230 patients......-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry.Results:High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio=0.49, 95...... on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics....

  2. Effect of epidermal growth factor-like peptides on pig cumulus cell expansion, oocyte maturation and acquisition of developmental competence in vitro: comparison with gonadotropins

    Czech Academy of Sciences Publication Activity Database

    Procházka, Radek; Petlach, Michal; Nagyová, Eva; Němcová, Lucie

    2011-01-01

    Roč. 141, č. 4 (2011), s. 425-435 ISSN 1470-1626 R&D Projects: GA ČR GA523/08/0111; GA MZe QI101A166 Institutional research plan: CEZ:AV0Z50450515 Keywords : activatd protein kinase * EGF like factor * meiotic resumption Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.090, year: 2011

  3. Gene expression analysis of pig cumulus-oocyte complexes stimulated in vitro with follicle stimulating hormone or epidermal growth factor-like peptides

    Czech Academy of Sciences Publication Activity Database

    Blaha, Milan; Němcová, Lucie; Vodičková Kepková, Kateřina; Vodička, P.; Procházka, Radek

    2015-01-01

    Roč. 13, č. 113 (2015) ISSN 1477-7827 R&D Projects: GA ČR GAP502/11/0593; GA MZe(CZ) QJ1510138 Institutional support: RVO:67985904 Keywords : FSH * growth factors * cumulus cell Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.147, year: 2015

  4. Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions.

    Science.gov (United States)

    Heitzler, P; Simpson, P

    1993-03-01

    In Drosophila each neural precursor is chosen from a group of cells through cell interactions mediated by Notch and Delta which may function as receptor and ligand (signal), respectively, in a lateral signalling pathway. The cells of a group are equipotential and express both Notch and Delta. Hyperactive mutant Notch molecules, (Abruptex), probably have an enhanced affinity for the ligand. When adjacent to wild-type cells, cells bearing the Abruptex proteins are unable to produce the signal. It is suggested that in addition to the binding of Notch molecules on one cell to the Delta molecules of opposing cells, the Notch and Delta proteins on the surface of the same cell may interact. Binding between a cell's own Notch and Delta molecules would alter the availability of these proteins to interact with their counterparts on adjacent cells.

  5. Melanin-concentrating hormone in peripheral circulation in the human.

    Science.gov (United States)

    Naufahu, J; Alzaid, F; Fiuza Brito, M; Doslikova, B; Valencia, T; Cunliffe, A; Murray, J F

    2017-03-01

    Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role. © 2017 Society for Endocrinology.

  6. Nonrandom distribution of iron in circulating human transferrin.

    Science.gov (United States)

    Zak, O; Aisen, P

    1986-07-01

    By combining the urea gel electrophoresis technique of Makey and Seal with Western immunoblotting, a method has been developed for analyzing the distribution of iron between the two sites of circulating human transferrin. The new method avoids exposure of samples to a nonphysiologic pH that may promote removal or redistribution of iron from the protein; this facilitates examination of multiple samples at one time. Analysis of 21 freshly drawn specimens from normal human subjects confirms previous reports that iron is not randomly distributed in the specific sites of transferrin. Rather, there is a considerable range in the ratio of occupancies of N-terminal and C-terminal sites (N:C ratio), from 0.31 to 6.87 in the present study, with the N-terminal site predominantly occupied in most subjects. The N:C ratio correlates modestly with serum iron concentration (r = .54). Possible flaws in studies indicating a random occupancy of the specific sites of circulating transferrin may lie in the low pH to which samples may be exposed during procedures based on isoelectric focusing or in drawing inferences from data considering only total monoferric transferrin rather than the two distinguishable monoferric species.

  7. Historical aspects and relevance of the human coronary collateral circulation.

    Science.gov (United States)

    Seiler, Christian; Meier, Pascal

    2014-02-01

    In 1669, anastomoses between the right and left coronary artery were first documented by Richard Lower of Amsterdam. Using post-mortem imaging, a debate followed on the existence of structural inter-coronary anastomoses, which was not resolved before the first half of the 20 ieth century in case of the presence of coronary artery disease (CAD), and not before the early 1960 ies in case of the normal human coronary circulation by William Fulton. Functional coronary collateral measurements during coronary interventions were first performed only in the 1970 ies, respectively in the early 1980 ies. In humans, the existence of functional coronary collaterals in the absence of CAD has not been documented before 2003. Though the coronary collateral circulation has been recognized as an alternative source of blood supply to ischemic myocardium, its prognostic significance for the CAD population as a whole has been controversial until recently. The debate was due to different populations examined (acute versus chronic CAD, varying severity of CAD), to variable definitions of the term "prognosis", to insufficient statistical power of the investigation with rare occurrence of prognostic endpoints, to short duration of follow-up and to blunt instruments employed for collateral assessment. Individually, it has been acknowledged that a well functioning collateral supply to a myocardial area at risk for necrosis reduces infarct size, preserves ventricular function, prevents ventricular remodelling and aneurysm formation. Collectively, evidence has accumulated only recently that an extensive coronary collateral circulation is a beneficial prognosticator quoad vitam. In a recent meta-analysis on the topic, the risk ratio to die from any cause for high vs low or absent collateralization in patients with subacute myocardial infarction was 0.53 (95% confidence interval 0.15-1.92; p=0.335), and for patients with acute myocardial infarction, it was 0.63 (95% confidence interval 0

  8. Local Cytokine Concentrations and Oxygen Pressure Are Related to Maturation of the Collateral Circulation in Humans

    NARCIS (Netherlands)

    Schirmer, Stephan H.; van Royen, Niels; Moerland, Perry D.; Fledderus, Joost O.; Henriques, José P.; van der Schaaf, René J.; Vis, Marije M.; Baan, Jan; Koch, Karel T.; Horrevoets, Anton J. G.; Hoefer, Imo E.; Piek, Jan J.

    2009-01-01

    Objectives Our aim was to determine cytokine and oxygen gradients over the collateral circulation in humans. Background The molecular background of the maturation of the collateral circulation in response to coronary narrowing is poorly understood in humans, partly because of difficulties in

  9. The human coronary collateral circulation: development and clinical importance.

    Science.gov (United States)

    Seiler, Christian; Stoller, Michael; Pitt, Bertram; Meier, Pascal

    2013-09-01

    Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. In comparison with other species, the human coronary collateral circulation is very well developed. Among individuals without coronary artery disease (CAD), there are preformed collateral arteries preventing myocardial ischaemia during a brief vascular occlusion in 20-25%. Determinants of such anastomoses are low heart rate and the absence of systemic arterial hypertension. In patients with CAD, collateral arteries preventing myocardial ischaemia during a brief occlusion are present in every third individual. Collateral flow sufficient to prevent myocardial ischaemia during coronary occlusion amounts to one-fifth to one-fourth the normal flow through the open vessel. Myocardial infarct size, the most important prognostic determinant after such an event, is the product of coronary artery occlusion time, area at risk for infarction, and the inverse of collateral supply. Well-developed coronary collateral arteries in patients with CAD mitigate myocardial infarcts and improve survival. Approximately one-fifth of patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting. Therapeutic promotion of collateral growth is a valuable treatment strategy in those patients. It should aim at growth of large conductive collateral arteries (arteriogenesis). Potential arteriogenic approaches include the treatment with granulocyte colony-stimulating factor, physical exercise training, and external counterpulsation.

  10. Activated T lymphocytes disappear from circulation during endotoxemia in humans

    DEFF Research Database (Denmark)

    Suarez Krabbe, Karen; Kemp, Helle Bruunsgaard; Qvist, Jesper

    2002-01-01

    of disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)). In conclusion, endotoxin-induced lymphopenia reflects the disappearance from the circulation of activated lymphocytes prone to undergo apoptosis....

  11. Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T. F.; Nielsen, Boye Schnack; Jakobsen, Anders

    2015-01-01

    Background: Understanding the biological properties of potential drug targets are important. This is especially true for anti-angiogenic therapies in the search for potential biomarkers. The aim of the present descriptive study was to analyse the intra-tumoural expressions of epidermal growth...

  12. Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T. F.; Nielsen, Boye Schnack; Jakobsen, Anders

    2015-01-01

    factor-like domain 7 (EGFL7) and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph node metastases and distant metastases. Methods: A total of 126 patients were included. Analyses were performed...

  13. Quantitative proteome profiling of normal human circulating microparticles

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer T; Iversen, Line V

    2012-01-01

    Circulating microparticles (MPs) are produced as part of normal physiology. Their numbers, origin, and composition change in pathology. Despite this, the normal MP proteome has not yet been characterized with standardized high-resolution methods. We here quantitatively profile the normal MP...... proteome using nano-LC-MS/MS on an LTQ-Orbitrap with optimized sample collection, preparation, and analysis of 12 different normal samples. Analytical and procedural variation were estimated in triply processed samples analyzed in triplicate from two different donors. Label-free quantitation was validated...... by the correlation of cytoskeletal protein intensities with MP numbers obtained by flow cytometry. Finally, the validity of using pooled samples was evaluated using overlap protein identification numbers and multivariate data analysis. Using conservative parameters, 536 different unique proteins were quantitated...

  14. Glycosylation analysis and protein structure determination of murine fetal antigen 1 (mFA1)--the circulating gene product of the delta-like protein (dlk), preadipocyte factor 1 (Pref-1) and stromal-cell-derived protein 1 (SCP-1) cDNAs

    DEFF Research Database (Denmark)

    Krogh, T N; Bachmann, E; Teisner, B

    1997-01-01

    By means of sequence analysis, murine fetal antigen 1 (mFA1) isolated from Mus musculus amniotic fluid was shown to be the circulating protein of the delta-like protein, stromal-cell-derived protein 1 (SCP-1) and preadipocyte factor 1 (Pref-1) gene products. The protein contains 36 cysteine...... residues arranged in six epidermal-growth-factor-like domains. The purification of several C-terminal peptides of varying lengths showed mFA1 to be C-terminal heterogeneous. O-linked glycosylations of the NeuNAc alpha2-3Gal beta1-3(NeuNAc alpha2-6)GalNAc type were present on all C-terminal peptides...... at residues Thr235, Thr244 and Thr248, although glycosylation on Thr244 was only partial. Three N-linked glycosylations were localized in mFA1 (Asn77, Asn142 and Asn151), two of which (Asn142 and Asn151) were in the unusual Asn-Xaa-Cys motif. Fucosylated biantennary complex-type and small amounts (less than 5...

  15. A long term model of circulation. [human body

    Science.gov (United States)

    White, R. J.

    1974-01-01

    A quantitative approach to modeling human physiological function, with a view toward ultimate application to long duration space flight experiments, was undertaken. Data was obtained on the effect of weightlessness on certain aspects of human physiological function during 1-3 month periods. Modifications in the Guyton model are reviewed. Design considerations for bilateral interface models are discussed. Construction of a functioning whole body model was studied, as well as the testing of the model versus available data.

  16. A continuum model for pressure-flow relationship in human pulmonary circulation.

    Science.gov (United States)

    Huang, Wei; Zhou, Qinlian; Gao, Jian; Yen, R T

    2011-06-01

    A continuum model was introduced to analyze the pressure-flow relationship for steady flow in human pulmonary circulation. The continuum approach was based on the principles of continuum mechanics in conjunction with detailed measurement of vascular geometry, vascular elasticity and blood rheology. The pulmonary arteries and veins were considered as elastic tubes and the "fifth-power law" was used to describe the pressure-flow relationship. For pulmonary capillaries, the "sheet-flow" theory was employed and the pressure-flow relationship was represented by the "fourth-power law". In this paper, the pressure-flow relationship for the whole pulmonary circulation and the longitudinal pressure distribution along the streamlines were studied. Our computed data showed general agreement with the experimental data for the normal subjects and the patients with mitral stenosis and chronic bronchitis in the literature. In conclusion, our continuum model can be used to predict the changes of steady flow in human pulmonary circulation.

  17. Effects of ghrelin on circulating neuropeptide Y levels in humans.

    Science.gov (United States)

    Coiro, Vittorio; Saccani-Jotti, Gloria; Rubino, Pasquale; Manfredi, Guido; Melani, Andrea; Chiodera, Paolo

    2006-12-01

    Ghrelin is a 28 amino-acid peptide with a strong GH-releasing activity and a complex role in regulation of appetite, fuel utilization, body weight and composition. Neuropeptide Y (NPY) is a well-known stimulator of pathways favouring food intake and energy storage. Recently, studies in rodents suggested a possible mediation of ghrelin action by NPY. In contrast, until now no evidence of ghrelin-NPY interaction in humans has been provided. In the present study, we examined whether ghrelin influences NPY secretion in normal men. Twelve healthy normal men (aged 24-35 years; body mass index (BMI) 22.3+/-0.93 kg/m2) were tested twice at 08.00 AM on two different days, in random order at weekly intervals, after an overnight fast and rest in bed. An intravenous bolus of 1 microg/kg body weight ghrelin (esperimental test) or an equal amount of normal saline (control test) was injected at time 0. Blood was taken before and over 90 minutes after injections, and was used for the measurement of plasma NPY levels. Plasma levels of NPY slightly, but significantly rose in response to ghrelin, with a mean peak level at 15 min after injection, whereas no significant change was observed after saline administration. Our results show a significant enhancement of plasma NPY levels under ghrelin stimulation. To our knowledge, this is the first demonstration of a ghrelin-NPY interaction in humans, which may suggest a possible mediation of ghrelin action by NPY in humans.

  18. Rethinking International Migration of Human Capital and Brain Circulation: The Case of Chinese-Canadian Academics

    Science.gov (United States)

    Blachford, Dongyan Ru; Zhang, Bailing

    2014-01-01

    This article examines the dynamics of brain circulation through a historical review of the debates over international migration of human capital and a case study on Chinese-Canadian academics. Interviews with 22 Chinese-Canadian professors who originally came from China provide rich data regarding the possibilities and problems of the contemporary…

  19. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity

    OpenAIRE

    Zhiyao Fu; Feven Berhane; Alemu Fite; Berhane Seyoum; Abdul B. Abou-Samra; Ren Zhang

    2014-01-01

    Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic ?-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N = 15) or diabetic (BMI- and age-matched; N = 14); b) lean or obese (N = 53 ...

  20. The Role of Circulating Slit2, the One of the Newly Batokines, in Human Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Yea Eun Kang

    2017-09-01

    Full Text Available BackgroundSlit2 is a new secreted protein from adipose tissue that improves glucose hemostasis in mice; however, there is no study about the serum levels and precise role of Slit2 in human. The aim of this study is to explore the serum level of Slit2 in human, and to identify the role of Slit2 in diabetes mellitus (DM.MethodsThe participants of this study consist of 38 subjects with newly diagnosed DM, and 75 healthy subjects as a control group. Serum Slit2 levels were measured using an enzyme-linked immunosorbent assay. Relationship between circulating Slit2 and diabetic related factors was investigated in diabetic group compared with non-diabetic group. Additionally, the correlations between the serum level of Slit2 and diverse metabolic parameters were analyzed.ResultsCirculating Slit2 level was more decreased in diabetic group than in control group, but there was no significant difference statistically. Interestingly, serum levels of Slit2 were significantly negatively correlated to the serum concentrations of fasting glucose (coefficient r=–0.246, P=0.008, the serum concentrations of postprandial glucose (coefficient r=–0.233, P=0.017, and glycosylated hemoglobin (HbA1c; coefficient r=–0.357, P<0.001.ConclusionFrom our study, the first report of circulating Slit2 levels in human, circulating Slit2 level significantly negatively correlated with serum glucose and HbA1c. Our results suggest that the circulating Slit2 may play a role in maintainence of glucose homeostasis in human, even though exact contribution and mechanism are not yet known.

  1. Computational Prediction of Human Salivary Proteins from Blood Circulation and Application to Diagnostic Biomarker Identification

    Science.gov (United States)

    Wang, Jiaxin; Liang, Yanchun; Wang, Yan; Cui, Juan; Liu, Ming; Du, Wei; Xu, Ying

    2013-01-01

    Proteins can move from blood circulation into salivary glands through active transportation, passive diffusion or ultrafiltration, some of which are then released into saliva and hence can potentially serve as biomarkers for diseases if accurately identified. We present a novel computational method for predicting salivary proteins that come from circulation. The basis for the prediction is a set of physiochemical and sequence features we found to be discerning between human proteins known to be movable from circulation to saliva and proteins deemed to be not in saliva. A classifier was trained based on these features using a support-vector machine to predict protein secretion into saliva. The classifier achieved 88.56% average recall and 90.76% average precision in 10-fold cross-validation on the training data, indicating that the selected features are informative. Considering the possibility that our negative training data may not be highly reliable (i.e., proteins predicted to be not in saliva), we have also trained a ranking method, aiming to rank the known salivary proteins from circulation as the highest among the proteins in the general background, based on the same features. This prediction capability can be used to predict potential biomarker proteins for specific human diseases when coupled with the information of differentially expressed proteins in diseased versus healthy control tissues and a prediction capability for blood-secretory proteins. Using such integrated information, we predicted 31 candidate biomarker proteins in saliva for breast cancer. PMID:24324552

  2. Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation.

    Directory of Open Access Journals (Sweden)

    Jiang Shu

    Full Text Available MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details.

  3. Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation

    Science.gov (United States)

    Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

    2015-01-01

    MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details. PMID:26528912

  4. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity.

    Science.gov (United States)

    Fu, Zhiyao; Berhane, Feven; Fite, Alemu; Seyoum, Berhane; Abou-Samra, Abdul B; Zhang, Ren

    2014-05-23

    Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic β-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N=15) or diabetic (BMI- and age-matched; N=14); b) lean or obese (N=53 totally) and c) fasting and 2 hours following a defined meal (N=12). Serum lipasin levels were determined by the enzyme-linked immunosorbent assay. Lipasin levels [mean±SEM] were increased by more than two fold (Plipasin levels were positively correlated with BMI (rho=0.49, Plipasin/betatrophin is nutritionally-regulated hepatokine that is increased in human type 2 diabetes and obesity.

  5. The Repeated Administration of Resveratrol Has Measurable Effects on Circulating T-Cell Subsets in Humans

    Directory of Open Access Journals (Sweden)

    J. Luis Espinoza

    2017-01-01

    Full Text Available Preclinical studies have shown that resveratrol exerts immunomodulatory effects with potential clinical value in the amelioration of autoimmune disorders and cancer prevention; however, little is known about the in vivo effects of this naturally occurring polyphenol on human immune cells. We assessed the effects of repeated doses of resveratrol (1000 mg/day for 28 days on circulating immune cells in healthy Japanese individuals. Resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating γδ T cells and regulatory T cells and resulted in small, yet significant, decreases in the plasma levels of the proinflammatory cytokines TNF-α and MCP-1 and a significant increase in the plasma antioxidant activity compared with the corresponding antioxidant baseline activity and with that in four control individuals. In in vitro studies, resveratrol significantly improved the growth of γδ T cells and regulatory T cells. These findings demonstrate that resveratrol has some clear biological effects on human circulating immune cells. Further studies are necessary to interpret the long-term immunological changes associated with resveratrol treatment.

  6. Effects of immunosuppression on circulating adeno-associated virus capsid-specific T cells in humans.

    Science.gov (United States)

    Parzych, Elizabeth M; Li, Hua; Yin, Xiangfan; Liu, Qin; Wu, Te-Lang; Podsakoff, Gregory M; High, Katherine A; Levine, Matthew H; Ertl, Hildegund C J

    2013-04-01

    In humans adeno-associated virus (AAV)-mediated gene transfer is followed by expansion of AAV capsid-specific T cells, evidence of cell damage, and loss of transgene product expression, implicating immunological rejection of vector-transduced cells, which may be prevented by immunosuppressive drugs. We undertook this study to assess the effect of immunosuppression (IS) used for organ transplantation on immune responses to AAV capsid antigens. Recipients of liver or kidney transplants were tested before and 4 weeks after induction of IS in comparison with matched samples from healthy human adults and an additional cohort with comorbid conditions similar to those of the transplant patients. Our data show that transplant patients and comorbid control subjects have markedly higher frequencies of circulating AAV capsid-specific T cells compared with healthy adults. On average, IS resulted in a reduction of AAV-specific CD4⁺ T cells, whereas numbers of circulating CD8⁺ effector and central memory T cells tended to increase. Independent of the type of transplant or the IS regimens, the trend of AAV capsid-specific T cell responses after drug treatment varied; in some patients responses were unaffected whereas others showed decreases or even pronounced increases, casting doubt on the usefulness of prophylactic IS for AAV vector recipients.

  7. Diurnal Variations of Human Circulating Cell-Free Micro-RNA.

    Directory of Open Access Journals (Sweden)

    Niels H H Heegaard

    Full Text Available A 24-hour light and dark cycle-dependent rhythmicity pervades physiological processes in virtually all living organisms including humans. These regular oscillations are caused by external cues to endogenous, independent biological time-keeping systems (clocks. The rhythm is reflected by gene expression that varies in a circadian and specific fashion in different organs and tissues and is regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This leads to well-documented oscillations of specific electrolytes, hormones, metabolites, and plasma proteins in blood samples. An emerging, important class of gene regulators is short single-stranded RNA (micro-RNA, miRNA that interferes post-transcriptionally with gene expression and thus may play a role in the circadian variation of gene expression. MiRNAs are promising biomarkers by virtue of their disease-specific tissue expression and because of their presence as stable entities in the circulation. However, no studies have addressed the putative circadian rhythmicity of circulating, cell-free miRNAs. This question is important both for using miRNAs as biological markers and for clues to miRNA function in the regulation of circadian gene expression. Here, we investigate 92 miRNAs in plasma samples from 24 young male, healthy volunteers repeatedly sampled 9 times during a 24-hour stay in a regulated environment. We demonstrate that a third (26/79 of the measurable plasma miRNAs (using RT-qPCR on a microfluidic system exhibit a rhythmic behavior and are distributed in two main phase patterns. Some of these miRNAs weakly target known clock genes and many have strong targets in intracellular MAPK signaling pathways. These novel findings highlight the importance of considering bio-oscillations in miRNA biomarker studies and suggest the further study of a set of specific circulating miRNAs in the regulation and functioning of biological clocks.

  8. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders.

    Science.gov (United States)

    Barnig, Cindy; Alsaleh, Ghada; Jung, Nicolas; Dembélé, Doulaye; Paul, Nicodème; Poirot, Anh; Uring-Lambert, Béatrice; Georgel, Philippe; de Blay, Fréderic; Bahram, Seiamak

    2015-01-01

    Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology.

  9. Evaluation of Two Commercial Enzyme-Linked Immunosorbent Assay Kits for the Detection of Human Circulating Metrnl.

    Science.gov (United States)

    Zheng, Si-Li; Li, Zhi-Yong; Zhang, Zheng; Wang, Dong-Sheng; Xu, Jian; Miao, Chao-Yu

    2018-04-01

    Metrnl is a newly discovered secreted protein with neurotrophic activity and metabolic effect, while in earlier studies its circulating level in human was not explored. We evaluated two commercial enzyme-linked immunosorbent assay kits (DY7867-05, R&D Systems and SK00478-02, Aviscera Bioscience) for the detection of human circulating Metrnl. The DY7867-05 kit showed superiority over the SK00478-02 kit since it generated better curve fitting degree, smaller variation among tests, higher inter-assay reproducibility and better specificity, and could effectively detect human Metrnl in six types of blood samples. Subsequent analysis was performed using the DY7867-05 kit. Sample storage conditions were investigated. No gender difference in circulating Metrnl levels was found, while people with newly diagnosed type 2 diabetes mellitus (T2DM) had significantly lower Metrnl levels compared to the healthy controls.

  10. Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie; Fritzen, Andreas Mæchel; Sjøberg, Kim Anker

    2017-01-01

    OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must...... concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml(-1), p FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p ... intake and increased plasma FGF21 concentration. CONCLUSION: Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais....

  11. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

    International Nuclear Information System (INIS)

    Garcia, J.F.; Ebbe, S.N.; Hollander, L.; Cutting, H.O.; Miller, M.E.; Cronkite, E.P.

    1982-01-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 μl of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use

  12. Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates.

    Science.gov (United States)

    Lundsgaard, Anne-Marie; Fritzen, Andreas M; Sjøberg, Kim A; Myrmel, Lene S; Madsen, Lise; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2017-01-01

    Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml -1 , p FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.

  13. Simultaneous quantification of 21 water soluble vitamin circulating forms in human plasma by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Meisser Redeuil, Karine; Longet, Karin; Bénet, Sylvie; Munari, Caroline; Campos-Giménez, Esther

    2015-11-27

    This manuscript reports a validated analytical approach for the quantification of 21 water soluble vitamins and their main circulating forms in human plasma. Isotope dilution-based sample preparation consisted of protein precipitation using acidic methanol enriched with stable isotope labelled internal standards. Separation was achieved by reversed-phase liquid chromatography and detection performed by tandem mass spectrometry in positive electrospray ionization mode. Instrumental lower limits of detection and quantification reached water soluble vitamins in human plasma single donor samples. The present report provides a sensitive and reliable approach for the quantification of water soluble vitamins and main circulating forms in human plasma. In the future, the application of this analytical approach will give more confidence to provide a comprehensive assessment of water soluble vitamins nutritional status and bioavailability studies in humans. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009-2012.

    Science.gov (United States)

    Sipulwa, Lenata A; Ongus, Juliette R; Coldren, Rodney L; Bulimo, Wallace D

    2016-02-01

    Human Coronaviruses (HCoV) are a common cause of respiratory illnesses and are responsible for considerable morbidity and hospitalization across all age groups especially in individuals with compromised immunity. There are six known species of HCoV: HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS-CoV and SARS-HCoV. Although studies have shown evidence of global distribution of HCoVs, there is limited information on their presence and distribution in Kenya. HCoV strains that circulated in Kenya were retrospectively diagnosed and molecularly characterized. A total of 417 nasopharyngeal specimens obtained between January 2009 and December 2012 from around Kenya were analyzed by a real time RT-PCR using HCoV-specific primers. HCoV-positive specimens were subsequently inoculated onto monolayers of LL-CMK2 cells. The isolated viruses were characterized by RT-PCR amplification and sequencing of the partial polymerase (pol) gene. The prevalence of HCoV infection was as follows: out of the 417 specimens, 35 (8.4 %) were positive for HCoV, comprising 10 (2.4 %) HCoV-NL63, 12 (2.9 %) HCoV-OC43, 9 (2.1 %) HCoV-HKU1, and 4 (1 %) HCoV-229E. The Kenyan HCoV strains displayed high sequence homology to the prototypes and contemporaneous strains. Evolution analysis showed that the Kenyan HCoV-OC43 and HCoV-NL63 isolates were under purifying selection. Phylogenetic evolutionary analyses confirmed the identities of three HCoV-HKU1, five HCoV-NL63, eight HCoV-OC43 and three HCoV-229E. There were yearly variations in the prevalence and circulation patterns of individual HCoVs in Kenya. This paper reports on the first molecular characterization of human Coronaviruses in Kenya, which play an important role in causing acute respiratory infections among children.

  15. Correlation of circulating MMP-9 with white blood cell count in humans: effect of smoking.

    Directory of Open Access Journals (Sweden)

    Soren Snitker

    Full Text Available Matrix metalloproteinase-9 (MMP-9 is an emerging biomarker for several disease conditions, where white blood cell (WBC count is also elevated. In this study, we examined the relationship between MMP-9 and WBC levels in apparently healthy smoking and non-smoking human subjects.We conducted a cross-sectional study to assess the relationship of serum MMP-9 with WBC in 383 men and 356 women. Next, we divided the male population (women do not smoke in this population into three groups: never (n = 243, current (n = 76 and former (n = 64 smokers and compared the group differences in MMP-9 and WBC levels and their correlations within each group.Circulating MMP-9 and WBC count are significantly correlated in men (R(2 = 0.13, p<0.001 and women (R(2 = 0.19, p<0.001. After stratification by smoking status, MMP-9 level was significantly higher in current smokers (mean ± SE; 663.3±43.4 ng/ml, compared to never (529.7±20.6 and former smokers (568±39.3. WBC count was changed in a similar pattern. Meanwhile, the relationship became stronger in current smokers with increased correlation coefficient of r = 0.45 or R(2 = 0.21 (p<0.001 and steeper slope of ß = 1.16±0.30 (p<0.001 in current smokers, compared to r = 0.26 or R(2 = 0.07 (p<0.001 and ß = 0.34±0.10 (p<0.001 in never smokers.WBC count accounts for 13% and 19% of MMP-9 variance in men and women, respectively. In non-smoking men, WBC count accounts for 7% of MMP-9 variance, but in smoking subjects, it accounts for up to 21% of MMP-9 variance. Thus, we have discovered a previously unrecognized correlation between the circulating MMP-9 and WBC levels in humans.

  16. Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation

    Science.gov (United States)

    Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan; David, Tim

    2003-01-01

    A computational fluid dynamics (CFD) approach is presented to model the blood flow through the human circulatory system under altered gravity conditions. Models required for CFD simulation relevant to major hemodynamic issues are introduced such as non-Newtonian flow models governed by red blood cells, a model for arterial wall motion due to fluid-wall interactions, a vascular bed model for outflow boundary conditions, and a model for auto-regulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models are solved iteratively using the pseudocompressibility method and dual time stepping. Moving wall boundary conditions from the first-order fluid-wall interaction model are used to study the influence of arterial wall distensibility on flow patterns and wall shear stresses during the heart pulse. A vascular bed modeling utilizing the analogy with electric circuits is coupled with an auto-regulation algorithm for multiple outflow boundaries. For the treatment of complex geometry, a chimera overset grid technique is adopted to obtain connectivity between arterial branches. For code validation, computed results are compared with experimental data for steady and unsteady non-Newtonian flows. Good agreement is obtained for both cases. In sin-type Gravity Benchmark Problems, gravity source terms are added to the Navier-Stokes equations to study the effect of gravitational variation on the human circulatory system. This computational approach is then applied to localized blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other model using an anatomical data set. A three- dimensional anatomical Circle of Willis configuration is reconstructed from human-specific magnetic resonance images using an image segmentation method. The blood flow through these Circle of Willis models is simulated to provide means for studying gravitational effects on the brain

  17. An advanced computational bioheat transfer model for a human body with an embedded systemic circulation.

    Science.gov (United States)

    Coccarelli, Alberto; Boileau, Etienne; Parthimos, Dimitris; Nithiarasu, Perumal

    2016-10-01

    In the present work, an elaborate one-dimensional thermofluid model for a human body is presented. By contrast to the existing pure conduction-/perfusion-based models, the proposed methodology couples the arterial fluid dynamics of a human body with a multi-segmental bioheat model of surrounding solid tissues. In the present configuration, arterial flow is included through a network of elastic vessels. More than a dozen solid segments are employed to represent the heat conduction in the surrounding tissues, and each segment is constituted by a multilayered circular cylinder. Such multi-layers allow flexible delineation of the geometry and incorporation of properties of different tissue types. The coupling of solid tissue and fluid models requires subdivision of the arterial circulation into large and small arteries. The heat exchange between tissues and arterial wall occurs by convection in large vessels and by perfusion in small arteries. The core region, including the heart, provides the inlet conditions for the fluid equations. In the proposed model, shivering, sweating, and perfusion changes constitute the basis of the thermoregulatory system. The equations governing flow and heat transfer in the circulatory system are solved using a locally conservative Galerkin approach, and the heat conduction in the surrounding tissues is solved using a standard implicit backward Euler method. To investigate the effectiveness of the proposed model, temperature field evolutions are monitored at different points of the arterial tree and in the surrounding tissue layers. To study the differences due to flow-induced convection effects on thermal balance, the results of the current model are compared against those of the widely used modelling methodologies. The results show that the convection significantly influences the temperature distribution of the solid tissues in the vicinity of the arteries. Thus, the inner convection has a more predominant role in the human body heat

  18. CD133 antibody conjugation to decellularized human heart valves intended for circulating cell capture.

    Science.gov (United States)

    Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony

    2015-09-03

    The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.

  19. Mass spectrometry characterization of circulating human serum albumin microheterogeneity in patients with alcoholic hepatitis.

    Science.gov (United States)

    Naldi, Marina; Baldassarre, Maurizio; Domenicali, Marco; Giannone, Ferdinando Antonino; Bossi, Matteo; Montomoli, Jonathan; Sandahl, Thomas Damgaard; Glavind, Emilie; Vilstrup, Hendrik; Caraceni, Paolo; Bertucci, Carlo

    2016-04-15

    Human serum albumin (HSA) is the most abundant plasma protein, endowed with several biological properties unrelated to its oncotic power, such as antioxidant and free-radicals scavenging activities, binding and transport of many endogenous and exogenous substances, and regulation of endothelial function and inflammatory response. These non-oncotic activities are closely connected to the peculiarly dynamic structure of the albumin molecule. HSA undergoes spontaneous structural modifications, mainly by reaction with oxidants and saccharides; however, patients with cirrhosis show extensive post-transcriptional changes at several molecular sites of HSA, the degree of which parallels the severity of the disease. The present work reports the development and application of an innovative LC-MS analytical method for a rapid and reproducible determination of the relative abundance of HSA isoforms in plasma samples from alcoholic hepatitis (AH) patients. A condition of severe oxidative stress, similar to that observed in AH patients, is associated with profound changes in circulating HSA microheterogeneity. More interestingly, the high resolution provided by the analytical platform allowed the monitoring of novel oxidative products of HSA never reported before. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Circulation of canine parvovirus among dogs living in human-wildlife interface in the Atlantic forest biome, Brazil

    Directory of Open Access Journals (Sweden)

    Flávia V. Vieira

    2017-12-01

    Full Text Available Despite of the role of domestic dogs as reservoirs for threatening viral diseases for wild carnivores, few studies have focused to identify circulation of viruses among dogs living in human/wildlife interfaces. To identify canine parvovirus (CPV types circulating in dogs living in an Atlantic forest biome, faecal samples (n = 100 were collected at the same period (one week corresponding to each of four areas, during 2014 to 2016 and corresponded to 100 different individuals. CPV was isolated in cell culture from 67 out 100 (67% samples from healthy dogs. Cytopathic effects were characterized by total or partial cell culture lysis. Genome sequences of CPV-2a (10%, CPV-2b (7% and CPV-2c (50% were concomitantly detected by PCR and nucleotide sequencing. The current study addresses the importance of monitoring CPV circulation among dogs presenting potential contact with wildlife species.

  1. Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

    Directory of Open Access Journals (Sweden)

    Reed Christopher

    2009-11-01

    Full Text Available Abstract Background MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1. Total RNA from Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA. Profiling studies of messenger RNA (mRNA in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

  2. Serotype and genetic diversity of human rhinovirus strains that circulated in Kenya in 2008.

    Science.gov (United States)

    Milanoi, Sylvia; Ongus, Juliette R; Gachara, George; Coldren, Rodney; Bulimo, Wallace

    2016-05-01

    Human rhinoviruses (HRVs) are a well-established cause of the common cold and recent studies indicated that they may be associated with severe acute respiratory illnesses (SARIs) like pneumonia, asthma, and bronchiolitis. Despite global studies on the genetic diversity of the virus, the serotype diversity of these viruses across diverse geographic regions in Kenya has not been characterized. This study sought to characterize the serotype diversity of HRV strains that circulated in Kenya in 2008. A total of 517 archived nasopharyngeal samples collected in a previous respiratory virus surveillance program across Kenya in 2008 were selected. Participants enrolled were outpatients who presented with influenza-like (ILI) symptoms. Real-time RT-PCR was employed for preliminary HRV detection. HRV-positive samples were amplified using RT-PCR and thereafter the nucleotide sequences of the amplicons were determined followed by phylogenetic analysis. Twenty-five percent of the samples tested positive for HRV. Phylogenetic analysis revealed that the Kenyan HRVs clustered into three main species comprising HRV-A (54%), HRV-B (12%), and HRV-C (35%). Overall, 20 different serotypes were identified. Intrastrain sequence homology among the Kenyan strains ranged from 58% to 100% at the nucleotide level and 55% to 100% at the amino acid level. These results show that a wide range of HRV serotypes with different levels of nucleotide variation were present in Kenya. Furthermore, our data show that HRVs contributed substantially to influenza-like illness in Kenya in 2008. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  3. Circulating levels of human salusin-β, a potent hemodynamic and atherogenesis regulator.

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    Kazumi Fujimoto

    Full Text Available Using bioinformatics analysis, we previously identified salusin-β, an endogenous bioactive peptide with diverse physiological activities. Salusin-β is abundantly expressed in the neuroendocrine system and in systemic endocrine cells/macrophages. Salusin-β acutely regulates hemodynamics and chronically induces atherosclerosis, but its unique physicochemical characteristics to tightly adhere to all types of plastic and glassware have prevented elucidation of its precise pathophysiological role. To quantitate plasma total salusin-β concentrations, we produced rabbit and chicken polyclonal antibodies against the C- and N-terminal end sequences, circumvented its sticky nature, and successfully established a sandwich enzyme-linked immunosorbent assay (ELISA. Salusin-β was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to 6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed that a single immunoreactive salusin-β peak coincided with synthetic authentic salusin-β. Plasma salusin-β concentrations were unaffected by postural changes and by potent vasopressin release stimuli, such as hypertonic saline infusion or smoking. However, salusin-β concentrations showed significant circadian variation; concentrations were high during the daytime and reached the lowest concentrations in the early morning. Plasma salusin-β levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls. Patients with panhypopituitarism combined with complete central diabetes insipidus also showed significantly higher plasma salusin-β levels. Therefore, the ELISA system developed in this study will be useful for evaluating circulating total salusin-β levels and for confirming the presence of authentic salusin-β in human plasma. The obtained results suggest a limited contribution of the neuroendocrine system to peripheral total salusin

  4. Oxidative burst of circulating neutrophils following traumatic brain injury in human.

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    Yiliu Liao

    Full Text Available Besides secondary injury at the lesional site, Traumatic brain injury (TBI can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91(phox in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected

  5. Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates

    Directory of Open Access Journals (Sweden)

    Anne-Marie Lundsgaard

    2017-01-01

    Full Text Available Objective: Fibroblast-growth factor 21 (FGF21 is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. Methods: A diet enriched in carbohydrates (80 E% carbohydrate; CHO and a eucaloric control diet (CON were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy the same subjects for three days with a fat-rich diet (78 E% fat; FAT, consisting of primarily unsaturated fatty acids. The three diets were provided in random order. Results: After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml−1, p < 0.05. In contrast, after FAT only a non-significant tendency (p = 0.073 to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01 with increased leg glucose uptake (62%, p < 0.05 and increased hepatic glucose production (17%, p < 0.01, indicating increased glucose turnover. Plasma fatty acid (FA concentration was decreased by 68% (p < 0.01, supported by reduced subcutaneous adipose tissue HSL Ser660 phosphorylation (p < 0.01 and perilipin 1 protein content (p < 0.01, pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the

  6. Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects.

    Science.gov (United States)

    Mikirova, Nina A; Jackson, James A; Hunninghake, Ron; Kenyon, Julian; Chan, Kyle W H; Swindlehurst, Cathy A; Minev, Boris; Patel, Amit N; Murphy, Michael P; Smith, Leonard; Ramos, Famela; Ichim, Thomas E; Riordan, Neil H

    2010-04-08

    The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors.

  7. Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects

    Directory of Open Access Journals (Sweden)

    Minev Boris

    2010-04-01

    Full Text Available Abstract The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors.

  8. Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.

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    Bert Rutten

    Full Text Available Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs and macrophages in human atherosclerotic carotid plaques.Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP, in two independent cohorts: the Circulating Cells cohort (n = 244 and the Athero-Express cohort (n = 91. Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort. Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort.We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range: 4153 (1585-11267 area under the curve (AUC vs. 9633 (3580-21565 AUC, P<0.001. Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02. All associations remained significant after adjustment for age, sex and use of drugs against platelet activation.Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

  9. Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation

    DEFF Research Database (Denmark)

    Bailey, Damian M; Rasmussen, Peter; Evans, Kevin A

    2018-01-01

    This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials...... hypoxia (P free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = -0.397 to -0.459, P = 0.037 to 0...... with measurements taken at rest and 30min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A...

  10. Profiling of circulating microRNAs after a bout of acute resistance exercise in humans.

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    Shuji Sawada

    Full Text Available Recent studies have revealed a new aspect of physiological regulation in which microRNAs (miRNAs play fundamental roles in diverse biological and pathological processes. Furthermore, it was recently discovered that miRNAs are stably secreted into blood and that circulating miRNAs may play important roles in cell-cell communication. Here, we examined whether the circulating miRNA profile is affected by acute resistance exercise. Twelve males performed a resistance exercise session (bench press and leg press, consisting of five sets of 10 repetitions at 70% of maximum strength, with a 1 min rest between sets. Blood samples were taken before exercise, and at 0 and 60 min, 1 day, and 3 days after exercise. The circulating miRNA profile was determined by microarray analysis. Quantitative real-time PCR confirmed that the miR-149* level increased three days after resistance exercise. In contrast, the miR-146a and miR-221 levels decreased three days after resistance exercise. Our findings suggest that circulating miRNA levels change in response to acute resistance exercise, and miRNAs may play important roles in resistance-exercise-induced adaptation.

  11. Structure of human POFUT1, its requirement in ligand-independent oncogenic Notch signaling, and functional effects of Dowling-Degos mutations

    Energy Technology Data Exchange (ETDEWEB)

    McMillan, Brian J.; Zimmerman, Brandon; Egan, Emily D.; Lofgren, Michael; Xu, Xiang; Hesser, Anthony; Blacklow, Stephen C.

    2017-03-17

    Protein O-fucosyltransferase-1 (POFUT1), which transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins, is essential for Notch signal transduction in mammals. Here, we examine the consequences of POFUT1 loss on the oncogenic signaling associated with certain leukemia-associated mutations of human Notch1, report the structures of human POFUT1 in free and GDP-fucose bound states, and assess the effects of Dowling-Degos mutations on human POFUT1 function. CRISPR-mediated knockout of POFUT1 in U2OS cells suppresses both normal Notch1 signaling, and the ligand-independent signaling associated with leukemogenic mutations of Notch1. Normal and oncogenic signaling are rescued by wild-type POFUT1 but rescue is impaired by an active-site R240A mutation. The overall structure of the human enzyme closely resembles that of the Caenorhabditis elegans protein, with an overall backbone RMSD of 0.93 Å, despite primary sequence identity of only 39% in the mature protein. GDP-fucose binding to the human enzyme induces limited backbone conformational movement, though the side chains of R43 and D244 reorient to make direct contact with the fucose moiety in the complex. The reported Dowling-Degos mutations of POFUT1, except for M262T, fail to rescue Notch1 signaling efficiently in the CRISPR-engineered POFUT1-/- background. Together, these studies identify POFUT1 as a potential target for cancers driven by Notch1 mutations and provide a structural roadmap for its inhibition.

  12. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide.

    Science.gov (United States)

    Tilmanis, Danielle; van Baalen, Carel; Oh, Ding Yuan; Rossignol, Jean-Francois; Hurt, Aeron C

    2017-11-01

    Nitazoxanide is a thiazolide compound that was originally developed as an anti-parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide. An optimised cell culture-based focus reduction assay was used to determine the susceptibility of A(H1N1)pdm09, A(H3N2), and influenza B viruses circulating in the southern hemisphere from the period March 2014 to August 2016. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested, including neuraminidase inhibitor-resistant viruses, allowing the establishment of a baseline level of susceptibility for each subtype. Median EC 50 values (±IQR) of 0.48 μM (0.33-0.71), 0.62 μM (0.56-0.75), 0.66 μM (0.62-0.69), and 0.60 μM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively. There was no significant difference in the median baseline tizoxanide susceptibility for each influenza subtype tested. This is the first report on the susceptibility of circulating viruses to tizoxanide. The focus reduction assay format described is sensitive, robust, and less laborious than traditional cell based antiviral assays, making it highly suitable for the surveillance of tizoxanide susceptibility in circulating seasonal influenza viruses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

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    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.

  14. Detection of human collateral circulation by vasodilation-thallium-201 tomography

    International Nuclear Information System (INIS)

    Nienaber, C.A.; Salge, D.; Spielmann, R.P.; Montz, R.; Bleifeld, W.

    1990-01-01

    Coronary arteriolar vasodilation may provoke redistribution of flow to collateral-dependent jeopardized myocardium. To assess the physiologic significance of collaterals, 80 consecutive post-infarction patients (age 58 +/- 8 years) underwent vasodilation-redistribution thallium-201 tomographic imaging after administration of 0.56 mg of intravenous dipyridamole/kg body weight. Circumferential profile analysis of thallium-201 uptake and redistribution in representative left ventricular tomograms provided quantitative assessment of transient and fixed defects and separation between periinfarctional and distant inducible hypoperfusion. Tomographic perfusion data were correlated to wall motion and collateral circulation between distinct anatomic perfusion territories. Patients were grouped according to presence (59%) or absence (41%) of angiographically visible collateral channels to jeopardized myocardium. In the presence of collaterals, distant reversible defects were larger than in absence of collaterals (p less than 0.05); the extent of combined periinfarctional and distant redistribution was also larger in collateralized patients (p less than 0.025), whereas the size of the persistent perfusion defect was similar in both groups. By prospective analysis the tomographic perfusion pattern of combined periinfarctional and distant redistribution revealed a sensitivity of 85% and a specificity of 78% for the detection of significant collateral circulation in this group of patients. Thus, using the exhausted flow reserve as a diagnostic tool, vasodilation-thallium-201 tomography has the potential to identify and quantitate collateralized myocardium in post-infarction patients and may guide diagnostic and therapeutic decision-making

  15. Heritability of circulating growth factors involved in the angiogenesis in healthy human population.

    Science.gov (United States)

    Pantsulaia, I; Trofimov, S; Kobyliansky, E; Livshits, G

    2004-09-21

    The present study examined the extent of genetic and environmental influences on the populational variation of circulating growth factors (VEGF, EGF) involved in angiogenesis in healthy and ethnically homogeneous Caucasian families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 478 healthy individuals aged 18-75 years. Quantitative genetic analysis showed that the VEGF and EGF variation was appreciably attributable to genetic effects, with heritability estimates of 79.9% and 48.4%, respectively. Yet, common environmental factors, shared by members of the same household, also played a significant role (P growth factor-beta 1 (TGF-beta 1) or tissue inhibitors of matrix metalloproteinases 1 (TIMP-1), likewise relevant for angiogenesis. Bivariate analysis revealed significant phenotypic correlations (P < 0.002) between all pairs of variables, thus indicating the possible existence of common genetic and environmental factors. The analysis suggested that the pleiotropic genetic effects were consistently the primary (or even the sole) source of correlation between all pairs of studied molecules. The results of our study affirm the existence of specific and common genetic pathways that commonly determine the greater part of the circulating variation of these molecules.

  16. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S

    2011-01-01

    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...... an inverse correlation between anti-dsDNA antibodies and the DNA concentration in the circulation in both murine and human serum samples. High titer of anti-DNA antibodies in human sera correlated with reduced levels of circulating chromatin, and in lupus prone mice with deposition within glomeruli....... The inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect...

  17. Immunodetection of Fasciola gigantica Circulating Antigen in Sera of Infected Individuals for Laboratory Diagnosis of Human Fascioliasis

    Science.gov (United States)

    Attallah, Abdelfattah M.; Bughdadi, Faisal A.; El-Shazly, Atef M.

    2013-01-01

    Currently, the laboratory diagnosis of human fascioliasis is based on the parasitological examination of parasite eggs in stool specimens and serological detection of specific antibodies in serum samples, which are often unreliable diagnostic approaches. Ideally, a sensitive and specific diagnostic test for Fasciola infection should be based on the detection of circulating Fasciola antigen, which implies active infection. Here, a 27-kDa-molecular-mass antigen was identified in a Fasciola gigantica adult worm antigen preparation, excretory-secretory products, and sera from F. gigantica-infected individuals, and it was not detected in antigenic extracts of other parasites and sera from noninfected individuals. The target antigen was isolated and partially characterized as a protein. Immunoperoxidase staining located the target epitope within teguments and guts of F. gigantica adult worms. The performance characteristics of a newly developed enzyme-linked immunosorbent assay (ELISA) based on F. gigantica circulating antigen detection in serum (FgCA-27 ELISA) were investigated using sera of 120 parasitologically diagnosed F. gigantica-infected individuals and 80 noninfected individuals. The area under the receiving operating characteristic (ROC) curve (AUC) for ELISA was significantly high (AUC = 0.961, P 93%), and a significant correlation (r = 0.715, P fascioliasis. PMID:23945158

  18. Immunodetection of Fasciola gigantica circulating antigen in sera of infected individuals for laboratory diagnosis of human fascioliasis.

    Science.gov (United States)

    Attallah, Abdelfattah M; Bughdadi, Faisal A; El-Shazly, Atef M; Ismail, Hisham

    2013-10-01

    Currently, the laboratory diagnosis of human fascioliasis is based on the parasitological examination of parasite eggs in stool specimens and serological detection of specific antibodies in serum samples, which are often unreliable diagnostic approaches. Ideally, a sensitive and specific diagnostic test for Fasciola infection should be based on the detection of circulating Fasciola antigen, which implies active infection. Here, a 27-kDa-molecular-mass antigen was identified in a Fasciola gigantica adult worm antigen preparation, excretory-secretory products, and sera from F. gigantica-infected individuals, and it was not detected in antigenic extracts of other parasites and sera from noninfected individuals. The target antigen was isolated and partially characterized as a protein. Immunoperoxidase staining located the target epitope within teguments and guts of F. gigantica adult worms. The performance characteristics of a newly developed enzyme-linked immunosorbent assay (ELISA) based on F. gigantica circulating antigen detection in serum (FgCA-27 ELISA) were investigated using sera of 120 parasitologically diagnosed F. gigantica-infected individuals and 80 noninfected individuals. The area under the receiving operating characteristic (ROC) curve (AUC) for ELISA was significantly high (AUC = 0.961, P 93%), and a significant correlation (r = 0.715, P fascioliasis.

  19. Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus.

    Science.gov (United States)

    Dey, Ayan; Molodecky, Natalie A; Verma, Harish; Sharma, Prashant; Yang, Jae Seung; Saletti, Giulietta; Ahmad, Mohammad; Bahl, Sunil K; Wierzba, Thomas F; Nandy, Ranjan K; Deshpande, Jagadish M; Sutter, Roland W; Czerkinsky, Cecil

    2016-01-01

    The "gold standard" for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (ppoliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus. Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to

  20. Incidence of Micronuclei inversly relates with apoptosis in human circulating lymphocytes

    International Nuclear Information System (INIS)

    Jocksic, G.; Djurovic, B.; Petrovic, S.

    2004-01-01

    In this study relationship between chromosome aberrations, micronuclei, radiosensitivity and apoptosis of circulating lymphocytes of radiation workers was evaluated. Exposed group comprises 34 individuals, radiology sts, of mean age 43,35±6.02; with 14.9±5.2 years of occupational exposition to ionizing radiation. In 10 out of 34 exchange aberrations were found (dicentrics and ring chromosomes). According to chromosomal findings exposed groups was divided on two subgroups:>> dicentric positive >dicentric negative > dicentric positive >dicentric >dicentric >dicentric >dicentric >dicentric<< negative respectively. Baseline micronuclei correlates negatively with apoptosis in both exposed groups (r=0.55m p<0.45) suggesting that chronical exposure to low doses of ionizing radiation disturb the balance between pro apoptotic and anti apoptotic signals in cells. Results of our study have shown that effects of radiation-induced cytotoxicity could be characterised employing flow cytometry as precise method for measuring degradation of internucleosaomal DNA. Inversly relationship between baseline micronuclei and percent of lymphocytes undergoing apoptosis is the most important finding in this study, suggesting that assay can discriminate differences in radiation-induced cytotoxicity between individuals occupationally exposed to low doses of ionising radiation. (Author)

  1. A systematic review of genetic diversity of human rotavirus circulating in South Korea.

    Science.gov (United States)

    Than, Van Thai; Jeong, Sunyoung; Kim, Wonyong

    2014-12-01

    Rotavirus infections continue to be the leading cause of severe diarrhea in young Korean children. Rotavirus data acquired from uninterrupted surveillance studies between 1989 and 2009 in South Korea were analyzed to better understand the genetic diversity and evolution. The relationship between rotaviruses and the currently licensed rotavirus vaccine viruses was also examined. The most prevalent rotavirus strains, with genotype G1P[8], followed by G3P[8], G4P[6], and G2P[4], accounted for approximately 76.7% of the total identified strains, and more recently, rotavirus G9P[8] has significance increased to be the fifth most common genotype. Phylogenetic analyses underscored the heterogeneity between viral populations within each genotype, with different lineages and sub-lineages. Although the currently licensed rotavirus vaccines are effective, safe, and economical, additional data from rotavirus monitoring is necessary to evaluate the efficacy of these vaccines for their sustained use in South Korea. The present study provides comprehensive and up-to-date information regarding the epidemiology, genetic diversity, and evolution of the circulating rotaviruses in South Korea. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  2. Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses.

    Science.gov (United States)

    Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

    2017-09-01

    In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up

  3. Beyond the VAD: Human Factors Engineering for Mechanically Assisted Circulation in the 21st Century.

    Science.gov (United States)

    Throckmorton, Amy L; Patel-Raman, Sonna M; Fox, Carson S; Bass, Ellen J

    2016-06-01

    Thousands of ventricular assist devices (VADs) currently provide circulatory support to patients worldwide, and dozens of heart pump designs for adults and pediatric patients are under various stages of development in preparation for translation to clinical use. The successful bench-to-bedside development of a VAD involves a structured evaluation of possible system states, including human interaction with the device and auxiliary component usage in the hospital or home environment. In this study, we review the literature and present the current landscape of preclinical design and assessment, decision support tools and procedures, and patient-centered therapy. Gaps of knowledge are identified. The study findings support the need for more attention to user-centered design approaches for medical devices, such as mechanical circulatory assist systems, that specifically involve detailed qualitative and quantitative assessments of human-device interaction to mitigate risk and failure. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  4. Influenza A Virus with a Human-Like N2 Gene Is Circulating in Pigs

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    2013-01-01

    A novel reassortant influenza A virus, H1avN2hu, has been found in Danish swine. The virus contains an H1 gene similar to the hemagglutinin (HA) gene of H1N1 avian-like swine viruses and an N2 gene most closely related to the neuraminidase (NA) gene of human H3N2 viruses from the mid-1990s....

  5. Circulating CXCR5+CD4+ T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines

    Science.gov (United States)

    Matsui, Ken; Adelsberger, Joseph W.; Kemp, Troy J.; Baseler, Michael W.; Ledgerwood, Julie E.; Pinto, Ligia A.

    2015-01-01

    Through the interaction of T follicular helper (Tfh) cells and B cells, efficacious vaccines can generate high-affinity, pathogen-neutralizing antibodies, and memory B cells. Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. In this small study, we used PBMC samples from 11 Gardasil recipients, and 8 Cervarix recipients from the Vaccine Research Center 902 Study to examine the induction of circulating Tfh-like cells and IgD-CD38HiCD27+ memory B cells by flow cytometry. PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like) cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like) subset was induced by Cervarix post-first vaccination. There were also minimal changes in the other cellular subsets. In addition, Cervarix recipients had more memory B cells post-first vaccination than did Gardasil recipients at D14 and D30. We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. However, further investigations should be extended to different cohorts with larger sample size to better understand the functions of these T cells, as well as

  6. Human rotavirus genotypes circulating in Brazil before and after a nationwide rotavirus vaccination program established in 2006

    Directory of Open Access Journals (Sweden)

    Caruzo TAR

    2011-04-01

    Full Text Available Thabata AR CaruzoGenetics, Evolution and Bioagents Department, Institute of Biology, State University of Campinas, Campinas, São Paulo, BrazilAbstract: Accounting for an estimated 600,000 deaths worldwide each year, rotaviruses are recognized as the most important etiologic agents causing severe acute gastroenteritis among children under the age of five years. In Brazil, until rotavirus vaccination was established in the public health system in 2006, acute gastroenteritis striking children under five years and caused by these viruses was clearly associated with 3.5 million episodes of diarrhea, 650,000 visits to outpatient health care facilities, 92,000 hospitalizations, and 850 deaths each year. After the introduction of the rotavirus vaccine in Brazil in March 2006, studies all over the country have been comparing rotavirus genotypes circulating in the recent pre- and postvaccination era. Most of these studies have reported a high prevalence of the G2P[4] genotype and also a decrease in rotavirus detection all over Brazil after the introduction of the vaccine. So far, these are preliminary studies, as a longer period of time is necessary to establish if this high prevalence of G2P[4] is due to selective pressure by the vaccine on the circulating viruses or to a normal genotype fluctuation, and if it will have any impact on vaccine efficacy in the future. This review describes results from the most recent studies addressing this issue and on rotavirus genotypic variability in Brazil.Keywords: human rotavirus, vaccine, genotypes, prevalence, Brazil

  7. Diurnal Variations of Human Circulating Cell-Free Micro-RNA

    DEFF Research Database (Denmark)

    Heegaard, Niels H H; Carlsen, Anting Liu; Lilje, Berit

    2016-01-01

    A 24-hour light and dark cycle-dependent rhythmicity pervades physiological processes in virtually all living organisms including humans. These regular oscillations are caused by external cues to endogenous, independent biological time-keeping systems (clocks). The rhythm is reflected by gene...... expression that varies in a circadian and specific fashion in different organs and tissues and is regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This leads to well-documented oscillations of specific electrolytes, hormones, metabolites, and plasma proteins in blood samples...

  8. A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum.

    Directory of Open Access Journals (Sweden)

    Eleonora Dehlink

    Full Text Available Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI, the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.

  9. Intercontinental circulation of human influenza A(H1N2) reassortant viruses during the 2001-2002 influenza season.

    Science.gov (United States)

    Xu, Xiyan; Smith, Catherine B; Mungall, Bruce A; Lindstrom, Stephen E; Hall, Henrietta E; Subbarao, Kanta; Cox, Nancy J; Klimov, Alexander

    2002-11-15

    Reassortant influenza A viruses bearing the H1 subtype of hemagglutinin (HA) and the N2 subtype of neuraminidase (NA) were isolated from humans in the United States, Canada, Singapore, Malaysia, India, Oman, Egypt, and several countries in Europe during the 2001-2002 influenza season. The HAs of these H1N2 viruses were similar to that of the A/New Caledonia/20/99(H1N1) vaccine strain both antigenically and genetically, and the NAs were antigenically and genetically related to those of recent human H3N2 reference strains, such as A/Moscow/10/99(H3N2). All 6 internal genes of the H1N2 reassortants examined originated from an H3N2 virus. This article documents the first widespread circulation of H1N2 reassortants on 4 continents. The current influenza vaccine is expected to provide good protection against H1N2 viruses, because it contains the A/New Caledonia/20/99(H1N1) and A/Moscow/10/99(H3N2)-like viruses, which have H1 and N2 antigens that are similar to those of recent H1N2 viruses.

  10. Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C

    2017-01-01

    administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4(+)CD161(+) cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon......Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng......, HLA-DR(+)CD38(+) T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3(+)CD4(+) (P = .026), CD3(+)CD8(+) (P = .046), Tregs (P = .023), and CD4(+)CD161(+) cells (P = .042) decreased after endotoxin...

  11. Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk

    International Nuclear Information System (INIS)

    Alonso, E.M.; Whitington, P.F.; Whitington, S.H.; Rivard, W.A.; Given, G.

    1991-01-01

    To test the hypothesis that enhanced intestinal absorption of bilirubin may contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed infants, we studied a cross-section of 36 healthy infants and mothers. Milk from mothers and serum from infants were collected at 16.3 +/- 2.4 days. Milk was studied for its effect on the absorption of bilirubin labeled with carbon 14 in rats and compared with buffer and iron-fortified infant formula (Similac With Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29 +/- 4.0% when it was administered into the duodenum with buffer, 4.67 +/- 2.4% with Similac formula, and 7.7 +/- 2.9% with human milk. Linear regression analysis, using the infant's serum nonconjugated bilirubin level as the dependent variable and the percentage of (14C)bilirubin absorbed by the rat with the corresponding mother's milk as the independent variable, revealed a significant correlation (r = 0.40; p = 0.016). Inspection of the data suggested that absorptive permissiveness correlated closely with infant serum bilirubin values greater than 24 mumol/L (1.4 mg/dl) (r = 0.55; p = 0.007), whereas in those with bilirubin values less than or equal to 24 mumol/L, there was no apparent correlation. Milk was also analyzed for beta-glucuronidase, nonesterified fatty acids, and the ability to inhibit glucuronosyltransferase activity of rat liver microsomes in vitro, none of which correlated with the infant's serum bilirubin. These data support the theory that enhanced intestinal absorption of bilirubin contributes to the jaundice associated with breast-feeding

  12. Diagnostic radionuclide imaging of amyloid: biological targeting by circulating human serum amyloid P component

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, P.N.; Lavender, J.P.; Myers, M.J.; Pepys, M.B.

    1988-06-25

    The specific molecular affinity of the normal plasma protein, serum amyloid P component (SAP), for all known types of amyloid fibrils was used to develop a new general diagnostic method for in-vivo radionuclide imaging of amyloid deposits. After intravenous injection of /sup 123/I-labelled purified human SAP there was specific uptake into amyloid deposits in all affected patients, 7 with systematic AL amyloid, 5 with AA amyloid, and 2 with ..beta../sub 2/M amyloid, in contrast to the complete absence of any tissue localisation in 5 control subjects. Distinctive high-resolution scintigraphic images, even of minor deposits in the carpal regions, bone marrow, or adrenals, were obtained. This procedure should yield much information on the natural history and the management of amyloidosis, the presence of which has hitherto been confirmed only by biopsy. Clearance and metabolic studies indicated that, in the presence of extensive amyloidosis, the rate of synthesis of SAP was greatly increased despite maintenance of normal plasma levels. Futhermore, once localised to amyloid deposits the /sup 123/I-SAP persisted for long periods and was apparently protected from its normal rapid degradation. These findings shed new light on the pathophysiology of amyloid and may have implications for therapeutic strategies based upon specific molecular targeting with SAP.

  13. Identification and characterization of riboflavin-binding proteins in human circulation

    International Nuclear Information System (INIS)

    Innis-Whitehouse, W.S.A.

    1988-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis and binding was observed to vary over a greater than 10-fold range. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly, although FMN and photo-chemical degradation products were more tightly bound. Most of the binding occurred in the gamma-globulin fraction and was attributed to immunoglobulins because the binding proteins and immunoglobulins copurified using various methods, were removed by treatment of plasma with protein A-agarose, and were coincident upon immuno-electrophoresis followed by autoradiography to detect [2- 14 C]-riboflavin. Binding differences among plasma samples were reflected in the binding recovered with the immunoglobulin fractions; however, there was not a direct relationship between the amount of immunoglobulin and the amount of [2- 14 C]riboflavin bound. Hence, it appeared that the binding was due to a subfraction of immunoglobulins

  14. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution

    DEFF Research Database (Denmark)

    Aachmann-Andersen, Niels Jacob; Just Christensen, Søren; Lisbjerg, Kristian

    2014-01-01

    The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross......-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N......-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI...

  15. Circulating ApoJ is closely associated with insulin resistance in human subjects.

    Science.gov (United States)

    Seo, Ji A; Kang, Min-Cheol; Ciaraldi, Theodore P; Kim, Sang Soo; Park, Kyong Soo; Choe, Charles; Hwang, Won Min; Lim, Dong Mee; Farr, Olivia; Mantzoros, Christos; Henry, Robert R; Kim, Young-Bum

    2018-01-01

    Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100±8.3 vs. 150.6±8.5AU, Pinsulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100±13.9 vs. 77±15.2AU, P=0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.

    Directory of Open Access Journals (Sweden)

    Niels Jacob Aachmann-Andersen

    Full Text Available The membrane-assisted isoform immunoassay (MAIIA quantitates erythropoietin (EPO isoforms as percentages of migrated isoforms (PMI. We evaluated the effect of recombinant human EPO (rhEPO on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13; high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13; or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3 % (mean (SD. High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2% (p<0.00001 and 45.2 (7.3% (p<0.00001. Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8% (p<0.00001 and 46.1 (10.4% (p<0.00001. In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4% (p=0.029; low-dose Epoetin beta: 73.1 (17.8% (p=0.039. In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

  17. Human circulating monocytes internalize 125I-insulin in a similar fashion to rat hepatocytes: relevance to receptor regulation in target and nontarget tissues

    International Nuclear Information System (INIS)

    Grunberger, G.; Robert, A.; Carpentier, J.L.; Dayer, J.M.; Roth, A.; Stevenson, H.C.; Orci, L.; Gorden, P.

    1985-01-01

    Circulating monocytes bind 125 I-insulin in a specific fashion and have been used to analyze the ambient receptor status in humans. When freshly isolated circulating monocytes are incubated with 125 I-insulin and examined by electron microscopic autoradiography, approximately 18% of the labeled material is internalized after 15 minutes at 37 degrees C. By 2 hours at 37 degrees C, approximately one half of the 125 I-insulin is internalized. Internalization occurs also at 15 degrees C but at a slower rate. Furthermore, the monocytes bind and internalize 125 I-insulin in a manner that mirrors that of major target tissues, such as rat hepatocytes. These data suggest that the insulin receptor of the circulating monocyte might be regulated by adsorptive endocytosis in a manner analogous to that of target tissue, such as the liver

  18. Inner-ear circulation in humans is disrupted by extracranial venous outflow strictures: Implications for Ménière’s disease

    Directory of Open Access Journals (Sweden)

    Eleuterio F. Toro

    2018-02-01

    Full Text Available Ménière’s disease (MD is a pathology of the inner ear, the symptoms of which include tinnitus, vertigo attacks, fluctuating hearing loss, and nausea. Neither cause nor cure are currently known, though animal experiments suggest that disruption of the inner ear circulation, including venous hypertension and endolymphatic hydrops, to be hallmarks of the disease. Recent evidence for humans suggests a potential link to strictures in the extracranial venous outflow routes. The purpose of the present work is to demonstrate that the inner-ear circulation in humans is disrupted by extracranial venous outflow stricture and to discuss the implications of this finding for MD. The hypothesis linking extracranial venous outflow strictures to the altered dynamics of central nervous system (CNS fluid compartments is investigated theoretically via a global, closed-loop, multiscale mathematical model for the entire human circulation, interacting with the brain parenchyma and cerebrospinal fluid (CSF. The fluid dynamics model for the full human body includes submodels for the heart, pulmonary circulation, arterial system, microvasculature, venous system and the CSF, with a specially refined description of the inner ear vasculature. We demonstrate that extracranial venous outflow strictures disrupt inner ear circulation, and more generally, alter the dynamics of fluid compartments in the whole CNS. Specifically, as compared to a healthy control, the computational results from our model show that subjects with extracranial outflow venous strictures exhibit: altered inner ear circulation, redirection of flow to collaterals, increased intracranial venous pressure and increased intracranial pressure. Our findings are consistent with recent clinical evidence in humans that links extracranial outflow venous strictures to MD, aid the mechanistic understanding of the underlying features of the disease and lend support to recently proposed biophysically motivated

  19. Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

    Science.gov (United States)

    Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

    2017-05-01

    Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Role of ISM circulations in Western Kachchh, India during Mid-Late Holocene in disarticulation of Human Settlements

    Science.gov (United States)

    Dabhi, M.

    2017-12-01

    Paleoclimatic record indicates that one of the major factors for change in Indian Summer Monsoon (ISM) is North Atlantic Oceanic Circulation (NAO). Climatic changes have often been an influential factor in culture developments and dislocation of human settlements. The climatic transformations in Western India are affected by variation in the Indian Summer Monsoon (ISM). During last millennial scale, Indian sub-continent has observed varied climatic oscillations due to temperature variations in ocean and continent. People and society are the most affected lot due to this climate and monsoonal changes, which finally leads towards migration or colonization of people. Therefore, a high resolution data is required to delineate the complexity of monsoonal variation. This study focuses on the Mid-Late Holocene monsoonal changes from the sediment record of Western Kachchh. The field of study is at the mount of Kali River, a 45 km long river originating from the hills of Western Mainland Kachchh and debouching into Kori Creek. The exposed cross-section along the river bank has a fluvial unit (Unit-1) at the base followed by human settlement marked as Unit-2 culminating with eolian deposits (Unit-3) at the top. Multiproxy analysis (sedimentologically, optically and geochemically) were carried out to ascertain the climatic perturbations in the region. The lower Unit 1 which range in age from 6-5 Ka shows declining monsoon. The above exposed sediments with anthropogenic activity (Unit 2) cover a time span of 3-2.5 ka indicates monsoonal stability with declining trends. The general weakening of monsoon may be a major factor towards the ending or migration of the human settlement leading to the absence of archeological activity above 2.5ka in the area. The eolian sediments resting above the Unit 2 fall between 450 to 230 yrs represent the trends of Little Ice Age. Sediment record from the opposite bank of the river reveals an age of 1100 yrs supports wet condition which is co

  1. Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans.

    Science.gov (United States)

    Wong, Timothy; Wang, Zhican; Chapron, Brian D; Suzuki, Mizuki; Claw, Katrina G; Gao, Chunying; Foti, Robert S; Prasad, Bhagwat; Chapron, Alenka; Calamia, Justina; Chaudhry, Amarjit; Schuetz, Erin G; Horst, Ronald L; Mao, Qingcheng; de Boer, Ian H; Thornton, Timothy A; Thummel, Kenneth E

    2018-04-01

    Metabolism of 25-hydroxyvitamin D 3 (25OHD 3 ) plays a central role in regulating the biologic effects of vitamin D in the body. Although cytochrome P450-dependent hydroxylation of 25OHD 3 has been extensively investigated, limited information is available on the conjugation of 25OHD 3 In this study, we report that 25OHD 3 is selectively conjugated to 25OHD 3 -3- O -sulfate by human sulfotransferase 2A1 (SULT2A1) and that the liver is a primary site of metabolite formation. At a low (50 nM) concentration of 25OHD 3 , 25OHD 3 -3- O -sulfate was the most abundant metabolite, with an intrinsic clearance approximately 8-fold higher than the next most efficient metabolic route. In addition, 25OHD 3 sulfonation was not inducible by the potent human pregnane X receptor agonist, rifampicin. The 25OHD 3 sulfonation rates in a bank of 258 different human liver cytosols were highly variable but correlated with the rates of dehydroepiandrosterone sulfonation. Further analysis revealed a significant association between a common single nucleotide variant within intron 1 of SULT2A1 (rs296361; minor allele frequency = 15% in whites) and liver cytosolic SULT2A1 content as well as 25OHD 3 -3- O -sulfate formation rate, suggesting that variation in the SULT2A1 gene contributes importantly to interindividual differences in vitamin D homeostasis. Finally, 25OHD 3 -3- O -sulfate exhibited high affinity for the vitamin D binding protein and was detectable in human plasma and bile but not in urine samples. Thus, circulating concentrations of 25OHD 3 -3- O -sulfate appear to be protected from rapid renal elimination, raising the possibility that the sulfate metabolite may serve as a reservoir of 25OHD 3 in vivo, and contribute indirectly to the biologic effects of vitamin D. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Circulating species of Leishmania at microclimate area of Boulemane Province, Morocco: impact of environmental and human factors.

    Science.gov (United States)

    Hmamouch, Asmae; El Alem, Mahmoud Mohamed; Hakkour, Maryam; Amarir, Fatima; Daghbach, Hassan; Habbari, Khalid; Fellah, Hajiba; Bekhti, Khadija; Sebti, Faiza

    2017-02-22

    Cutaneous leishmaniasis (CL) is widely distributed in Morocco where its geographical range and incidence are related to environmental factors. This study aimed to examine the impact of several factors on the distribution of CL in Boulemane Province, which is characterized by several microclimates, and to identify the Leishmania species circulating in these areas. Ordinary least squares regression (OLSR) analysis was performed to study the impact of poverty, vulnerability, population density, urbanization and bioclimatic factors on the distribution of CL in this province. Molecular characterization of parasites was performed using a previously described PCR-RFLP method targeting the ITS1 of ribosomal DNA of Leishmania. A total of 1009 cases were declared in Boulemane Province between the years 2000 and 2015 with incidences fluctuating over the years (P = 0.007). Analyzing geographical maps of the study region identified four unique microclimate areas; sub-humid, semi-arid, arid and Saharan. The geographical distribution and molecular identification of species shows that the Saharan microclimate, characterized by the presence of Leishmania major was the most affected (47.78%) followed by semi-arid area where Leishmania tropica was identified in three districts. Among several environmental factors included in the study, poverty had the greatest influence on the spatial extension of the disease in this province. The incidence of CL in Boulemane Province varies between microclimate areas, and environmental factors partly explain this variation. However, the existence of CL in the most affected districts is mainly related to poverty, population movement and human behavior. To our knowledge, this the first study utilizing molecular techniques to confirm L. tropica and L. major as the causative agents of CL in Boulemane Province. Our findings indicate that the spatial and temporal distribution of CL in Boulemane Province is strongly related to poverty and population

  3. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation

    International Nuclear Information System (INIS)

    Korzeneva, Inna B.; Kostuyk, Svetlana V.; Ershova, Elizaveta S.; Skorodumova, Elena N.; Zhuravleva, Veronika F.; Pankratova, Galina V.; Volkova, Irina V.; Stepanova, Elena V.; Porokhovnik, Lev N.; Veiko, Natalia N.

    2016-01-01

    Highlights: • A transcribed region of human ribosomal repeat is resistant to double-strand breaks in the environment of a raised endonuclease activity. • Hybridization-based techniques are preferable for the analysis of damaged and/or oxidized genomic fragments, rather than the qRT-PCR method. • A chronic exposure to the low-dose IR induces an elevation of the rDNA content in the human circulating cfDNA as compared to cellular DNA. • An exposure to IR entails a decrease of the level of the human circulating satellite III (1q12) as compared to cellular DNA (RsatIII index). • The RrDNA/RsatIII ratio is a potential marker of a chronic IR individual exposure. - Abstract: A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N = 88) and tritium β-radiation (N = 88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the

  4. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190 Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Ershova, Elizaveta S. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031 (Russian Federation); Skorodumova, Elena N.; Zhuravleva, Veronika F.; Pankratova, Galina V.; Volkova, Irina V.; Stepanova, Elena V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190 Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Veiko, Natalia N. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031 (Russian Federation)

    2016-09-15

    Highlights: • A transcribed region of human ribosomal repeat is resistant to double-strand breaks in the environment of a raised endonuclease activity. • Hybridization-based techniques are preferable for the analysis of damaged and/or oxidized genomic fragments, rather than the qRT-PCR method. • A chronic exposure to the low-dose IR induces an elevation of the rDNA content in the human circulating cfDNA as compared to cellular DNA. • An exposure to IR entails a decrease of the level of the human circulating satellite III (1q12) as compared to cellular DNA (RsatIII index). • The RrDNA/RsatIII ratio is a potential marker of a chronic IR individual exposure. - Abstract: A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N = 88) and tritium β-radiation (N = 88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the

  5. Chimaeric Virus-Like Particles Derived from Consensus Genome Sequences of Human Rotavirus Strains Co-Circulating in Africa

    Science.gov (United States)

    Jere, Khuzwayo C.; O'Neill, Hester G.; Potgieter, A. Christiaan; van Dijk, Alberdina A.

    2014-01-01

    Rotavirus virus-like particles (RV-VLPs) are potential alternative non-live vaccine candidates due to their high immunogenicity. They mimic the natural conformation of native viral proteins but cannot replicate because they do not contain genomic material which makes them safe. To date, most RV-VLPs have been derived from cell culture adapted strains or common G1 and G3 rotaviruses that have been circulating in communities for some time. In this study, chimaeric RV-VLPs were generated from the consensus sequences of African rotaviruses (G2, G8, G9 or G12 strains associated with either P[4], P[6] or P[8] genotypes) characterised directly from human stool samples without prior adaptation of the wild type strains to cell culture. Codon-optimised sequences for insect cell expression of genome segments 2 (VP2), 4 (VP4), 6 (VP6) and 9 (VP7) were cloned into a modified pFASTBAC vector, which allowed simultaneous expression of up to four genes using the Bac-to-Bac Baculovirus Expression System (BEVS; Invitrogen). Several combinations of the genome segments originating from different field strains were cloned to produce double-layered RV-VLPs (dRV-VLP; VP2/6), triple-layered RV-VLPs (tRV-VLP; VP2/6/7 or VP2/6/7/4) and chimaeric tRV-VLPs. The RV-VLPs were produced by infecting Spodoptera frugiperda 9 and Trichoplusia ni cells with recombinant baculoviruses using multi-cistronic, dual co-infection and stepwise-infection expression strategies. The size and morphology of the RV-VLPs, as determined by transmission electron microscopy, revealed successful production of RV-VLPs. The novel approach of producing tRV-VLPs, by using the consensus insect cell codon-optimised nucleotide sequence derived from dsRNA extracted directly from clinical specimens, should speed-up vaccine research and development by by-passing the need to adapt rotaviruses to cell culture. Other problems associated with cell culture adaptation, such as possible changes in epitopes, can also be circumvented

  6. Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans.

    Science.gov (United States)

    Sergeant, Susan; Ruczinski, Ingo; Ivester, Priscilla; Lee, Tammy C; Morgan, Timothy M; Nicklas, Barbara J; Mathias, Rasika A; Chilton, Floyd H

    2016-01-28

    Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk.

  7. Modern embalming, circulation of fluids, and the voyage through the human arterial system: Carl L. Barnes and the culture of immortality in America.

    Science.gov (United States)

    Podgorny, Irina

    2011-01-01

    By considering the work of American embalmer, lawyer, and physician Carl Lewis Barnes (1872-1927), this paper analyzes the emergence of modern embalming in America. Barnes experimented with and exhibited the techniques by which embalming fluids travelled into the most remote cavities of the human body. In this sense, modem embalmers based their skills and methods on experimental medicine, turning the anatomy of blood vessels, physiology of circulation, and composition of blood into a circuit that allowed embalming fluids to move throughout the corpse. Embalmers in the late 19th century took ownership of the laws of hydrodynamics and the physiology of blood circulation to market their fluids and equipment, thus playing the role of physiologists of death, performing and demonstrating physiological experiments with dead bodies.

  8. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Elizaveta S; Skorodumova, Elena N; Zhuravleva, Veronika F; Pankratova, Galina V; Volkova, Irina V; Stepanova, Elena V; Porokhovnik, Lev N; Veiko, Natalia N

    A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N=88) and tritium β-radiation (N=88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the circulating cfDNA as compared with the cfDNA of non-exposed people (N=109). Such index that simultaneously displays both the increase of rDNA content and decrease of satellite III content in the cfDNA (RrDNA/RsatIII) can be recommended as a marker of chronic processes in the body that involve the elevated cell death rate and/or increased blood plasma endonuclease activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Affinity isolation of antigen-specific circulating B cells for generation of phage display-derived human monoclonal antibodies

    DEFF Research Database (Denmark)

    Ditzel, Henrik

    2009-01-01

    A method is described for affinity isolation of antigen-specific circulating B cells of interest for subsequent generation of immune antibody phage display libraries. This approach should overcome the problem of low yields of monoclonal antibodies of interest in the libraries generated from...... peripheral blood lymphocytes caused by the low abundance of antigen-specific B cells in the circulation. The preselection of B cells is based on the specificity of the surface Ig receptor and is accomplished using the antigen of interest conjugated to magnetic beads. This method should significantly increase...... the frequency of antibody phage particles of interest in the library and allow for efficient isolation monoclonal antibodies with the predefined specificity....

  10. Antigenic and genomic characterization of human influenza A and B viruses circulating in Argentina after the introduction of influenza A(H1N1)pdm09.

    Science.gov (United States)

    Russo, Mara L; Pontoriero, Andrea V; Benedetti, Estefania; Czech, Andrea; Avaro, Martin; Periolo, Natalia; Campos, Ana M; Savy, Vilma L; Baumeister, Elsa G

    2014-12-01

    This study was conducted as part of the Argentinean Influenza and other Respiratory Viruses Surveillance Network, in the context of the Global Influenza Surveillance carried out by the World Health Organization (WHO). The objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. During the study period, influenza virus circulation was detected from January to December. Influenza A and B, and all current subtypes of human influenza viruses, were present each year. Throughout the 2010 post-pandemic season, influenza A(H1N1)pdm09, unexpectedly, almost disappeared. The haemagglutinin (HA) of the A(H1N1)pdm09 viruses studied were segregated in a different genetic group to those identified during the 2009 pandemic, although they were still antigenically closely related to the vaccine strain A/California/07/2009. Influenza A(H3N2) viruses were the predominant strains circulating during the 2011 season, accounting for nearly 76 % of influenza viruses identified. That year, all HA sequences of the A(H3N2) viruses tested fell into the A/Victoria/208/2009 genetic clade, but remained antigenically related to A/Perth/16/2009 (reference vaccine recommended for this three-year period). A(H3N2) viruses isolated in 2012 were antigenically closely related to A/Victoria/361/2011, recommended by the WHO as the H3 component for the 2013 Southern Hemisphere formulation. B viruses belonging to the B/Victoria lineage circulated in 2010. A mixed circulation of viral variants of both B/Victoria and B/Yamagata lineages was detected in 2012, with the former being predominant. A(H1N1)pdm09 viruses remained antigenically closely related to the vaccine virus A/California/7/2009; A(H3N2) viruses continually evolved into new antigenic clusters and both B lineages, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, were observed

  11. Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans

    Science.gov (United States)

    Micallef, Michelle; Lexis, Louise; Lewandowski, Paul

    2007-01-01

    Background Red wine contains a naturally rich source of antioxidants, which may protect the body from oxidative stress, a determinant of age-related disease. The current study set out to determine the in vivo effects of moderate red wine consumption on antioxidant status and oxidative stress in the circulation. Methods 20 young (18–30 yrs) and 20 older (≥ 50 yrs) volunteers were recruited. Each age group was randomly divided into treatment subjects who consumed 400 mL/day of red wine for two weeks, or control subjects who abstained from alcohol for two weeks, after which they crossed over into the other group. Blood samples were collected before and after red wine consumption and were used for analysis of whole blood glutathione (GSH), plasma malondialdehyde (MDA) and serum total antioxidant status. Results Results from this study show consumption of red wine induced significant increases in plasma total antioxidant status (P < 0.03), and significant decreases in plasma MDA (P < 0.001) and GSH (P < 0.004) in young and old subjects. The results show that the consumption of 400 mL/day of red wine for two weeks, significantly increases antioxidant status and decreases oxidative stress in the circulation Conclusion It may be implied from this data that red wine provides general oxidative protection and to lipid systems in circulation via the increase in antioxidant status. PMID:17888186

  12. The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model

    International Nuclear Information System (INIS)

    Davies, Q.; Perkins, A.C.; Frier, M.; Watson, S.; Lalani, E.N.; Symonds, E.M.

    1997-01-01

    Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line. (orig.). With 4 figs., 1 tab

  13. Nutrigenomics in human peripheral blood mononuclear cells : the effects of fatty acids on gene expression profiles of human circulating cells as assessed in human intervention studies

    NARCIS (Netherlands)

    Bouwens, M.

    2009-01-01

    Research on the effects of nutrition on the function and health of organs in the human body, such as liver and intestine, is difficult, because for this research organ tissue is needed. Since nutrition research is usually performed in healthy volunteers, this tissue is difficult to obtain. However,

  14. Genetic regulation of the variation of circulating insulin-like growth factors and leptin in human pedigrees.

    Science.gov (United States)

    Pantsulaia, Ia; Pantsulaia, I; Trofimov, Svetlana; Kobyliansky, Eugene; Livshits, Gregory

    2005-07-01

    Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% +/- 9.0%), whereas for IGF-BP-1, only 23.3% +/- 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% +/- 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 +/- 0.04 and 0.15 +/- 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.

  15. Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial

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    Steele Andrew

    2012-09-01

    Full Text Available Abstract Background Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season. Methods Healthy infants aged 5–10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks or three doses of Rotarix™ (together forming the pooled Rotarix™ group or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI. Results Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443 were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6% severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo and G8 types (15 [1%] in placebo. Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%, 51.5% (95% CI:-6.5%; 77.9% and 64.4% (95% CI: 17.1%; 85.2%, respectively. Genotype P[8] was the predominant circulating P type and was detected in 38 (2.6% severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in placebo and P[6] (13 [0.9%] in placebo. Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%, P[4] was 70.9% (95% CI: 37.5%; 87

  16. Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial.

    Science.gov (United States)

    Steele, Andrew Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A; Madhi, Shabir A; Bos, Pieter; Ngwira, Bagrey; Witte, Desiree; Todd, Stacy; Louw, Cheryl; Kirsten, Mari; Aspinall, Sanet; Van Doorn, Leen Jan; Bouckenooghe, Alain; Suryakiran, Pemmaraju V; Han, Htay Htay

    2012-09-13

    Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children rotavirus vaccine Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season. Healthy infants aged 5-10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks) or three doses of Rotarix™ (together forming the pooled Rotarix™ group) or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI. Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443) were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:-6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI: 37.5%; 87.0%) and P[6] was 55.2% (95% CI: -6

  17. Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans

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    Lexis Louise

    2007-09-01

    Full Text Available Abstract Background Red wine contains a naturally rich source of antioxidants, which may protect the body from oxidative stress, a determinant of age-related disease. The current study set out to determine the in vivo effects of moderate red wine consumption on antioxidant status and oxidative stress in the circulation. Methods 20 young (18–30 yrs and 20 older (≥ 50 yrs volunteers were recruited. Each age group was randomly divided into treatment subjects who consumed 400 mL/day of red wine for two weeks, or control subjects who abstained from alcohol for two weeks, after which they crossed over into the other group. Blood samples were collected before and after red wine consumption and were used for analysis of whole blood glutathione (GSH, plasma malondialdehyde (MDA and serum total antioxidant status. Results Results from this study show consumption of red wine induced significant increases in plasma total antioxidant status (P Conclusion It may be implied from this data that red wine provides general oxidative protection and to lipid systems in circulation via the increase in antioxidant status.

  18. Characterization of the neuraminidase genes from human influenza A viruses circulating in Iran from 2010 to 2015.

    Science.gov (United States)

    Moasser, Elham; Behzadian, Farida; Moattari, Afagh; Fotouhi, Fatemeh; Zaraket, Hassan

    2018-02-01

    Characterization of influenza viruses is critical for detection of new emerging variants. Herein, we analyzed the genetic diversity and drug susceptibility of the neuraminidase gene (NAs) expressed by influenza A/H1N1pdm09 and A/H3N2 viruses circulating in Iran from 2010 to 2015. We genetically analyzed the NAs of 38 influenza A/H1N1pdm09 and 35 A/H3N2 isolates. The Iranian A/H1N1pdm09 viruses belonged to seven genogroups/subgenogroups, with the dominant groups being genogroups 6B and 6C. The A/H3N2 isolates fell into six gneogroups/subgenogroups, with the dominant genogroups being 3C and 3C.2a. The most common mutations detected among the A/H1N1pdm09 viruses included N44S, V106I, N200S, and N248D. All H1N1pdm09 viruses were genetically susceptible to the NAIs. However, one A/H1N1pdm09 virus from the 2013-2014 season possessed an NA-S247N mutation, which reduces the susceptibility to oseltamivir. In case of H3N2, none of the analyzed Iranian strains carried a substitution that might affect its susceptibility to NAIs. The ongoing evolution of influenza viruses and the detect of influenza viruses with reduced susceptibility to NAIs warrants continuous monitoring of the circulating strains.

  19. Circulating IGF-I and IGFBP3 levels control human colonic stem cell function and are disrupted in diabetic enteropathy

    Science.gov (United States)

    Maestroni, Anna; Jung, Peter; Orsenigo, Elena; Nasr, Moufida Ben; Tezza, Sara; Bassi, Roberto; Finzi, Giovanna; Marando, Alessandro; Vergani, Andrea; Frego, Roberto; Albarello, Luca; Andolfo, Annapaola; Manuguerra, Roberta; Viale, Edi; Staudacher, Carlo; Corradi, Domenico; Batlle, Eduard; Breault, David; Secchi, Antonio; Folli, Franco; Fiorina, Paolo

    2016-01-01

    Summary The role of circulating factors in regulating colonic stem cells (CoSCs) and colonic epithelial homeostasis is unclear. Individuals with long-standing type 1 diabetes (T1D) frequently have intestinal symptoms, termed diabetic enteropathy (DE), though its etiology is unknown. Here, we report T1D patients with DE exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed altered levels of insulin-like growth factor 1 (IGF-1) and its binding protein-3 (IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via binding its receptor TMEM219, in an IGF-1-independent manner, and disrupted in vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in patients with long-standing T1D via kidney-pancreas transplantation or in diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized circulating IGF-1/IGFBP3 levels and reestablished CoSC homeostasis. These findings demonstrate that peripheral IGF-1/IGFBP3 control CoSCs and their dysfunction in DE. PMID:26431183

  20. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  1. Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis.

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    Henning W Zimmermann

    Full Text Available BACKGROUND: Monocyte-derived macrophages critically perpetuate inflammatory responses after liver injury as a prerequisite for organ fibrosis. Experimental murine models identified an essential role for the CCR2-dependent infiltration of classical Gr1/Ly6C(+ monocytes in hepatic fibrosis. Moreover, the monocyte-related chemokine receptors CCR1 and CCR5 were recently recognized as important fibrosis modulators in mice. In humans, monocytes consist of classical CD14(+CD16(- and non-classical CD14(+CD16(+ cells. We aimed at investigating the relevance of monocyte subpopulations for human liver fibrosis, and hypothesized that 'non-classical' monocytes critically exert inflammatory as well as profibrogenic functions in patients during liver disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed circulating monocyte subsets from freshly drawn blood samples of 226 patients with chronic liver disease (CLD and 184 healthy controls by FACS analysis. Circulating monocytes were significantly expanded in CLD-patients compared to controls with a marked increase of the non-classical CD14(+CD16(+ subset that showed an activated phenotype in patients and correlated with proinflammatory cytokines and clinical progression. Correspondingly, CD14(+CD16(+ macrophages massively accumulated in fibrotic/cirrhotic livers, as evidenced by immunofluorescence and FACS. Ligands of monocyte-related chemokine receptors CCR2, CCR1 and CCR5 were expressed at higher levels in fibrotic and cirrhotic livers, while CCL3 and CCL4 were also systemically elevated in CLD-patients. Isolated monocyte/macrophage subpopulations were functionally characterized regarding cytokine/chemokine expression and interactions with primary human hepatic stellate cells (HSC in vitro. CD14(+CD16(+ monocytes released abundant proinflammatory cytokines. Furthermore, CD14(+CD16(+, but not CD14(+CD16(- monocytes could directly activate collagen-producing HSC. CONCLUSIONS/SIGNIFICANCE: Our data

  2. Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

    Science.gov (United States)

    Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

    2009-01-01

    Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

  3. Circulating CD14brightCD16+ 'intermediate' monocytes exhibit enhanced parasite pattern recognition in human helminth infection.

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    Joseph D Turner

    2014-04-01

    Full Text Available Circulating monocyte sub-sets have recently emerged as mediators of divergent immune functions during infectious disease but their role in helminth infection has not been investigated. In this study we evaluated whether 'classical' (CD14brightCD16-, 'intermediate' (CD14brightCD16+, and 'non-classical' (CD14dimCD16+ monocyte sub-sets from peripheral blood mononuclear cells varied in both abundance and ability to bind antigenic material amongst individuals living in a region of Northern Senegal which is co-endemic for Schistosoma mansoni and S. haematobium. Monocyte recognition of excretory/secretory (E/S products released by skin-invasive cercariae, or eggs, of S. mansoni was assessed by flow cytometry and compared between S. mansoni mono-infected, S. mansoni and S. haematobium co-infected, and uninfected participants. Each of the three monocyte sub-sets in the different infection groups bound schistosome E/S material. However, 'intermediate' CD14brightCD16+ monocytes had a significantly enhanced ability to bind cercarial and egg E/S. Moreover, this elevation of ligand binding was particularly evident in co-infected participants. This is the first demonstration of modulated parasite pattern recognition in CD14brightCD16+ intermediate monocytes during helminth infection, which may have functional consequences for the ability of infected individuals to respond immunologically to infection.

  4. Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

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    Gustavo Rocha Garcia

    2012-10-01

    Full Text Available HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in São José do Rio Preto – SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80% clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil.

  5. In vitro culture and characterization of human lung cancer circulating tumor cells isolated by size exclusion from an orthotopic nude-mouse model expressing fluorescent protein.

    Science.gov (United States)

    Kolostova, Katarina; Zhang, Yong; Hoffman, Robert M; Bobek, Vladimir

    2014-09-01

    In the present study, we demonstrate an animal model and recently introduced size-based exclusion method for circulating tumor cells (CTCs) isolation. The methodology enables subsequent in vitro CTC-culture and characterization. Human lung cancer cell line H460, expressing red fluorescent protein (H460-RFP), was orthotopically implanted in nude mice. CTCs were isolated by a size-based filtration method and successfully cultured in vitro on the separating membrane (MetaCell®), analyzed by means of time-lapse imaging. The cultured CTCs were heterogeneous in size and morphology even though they originated from a single tumor. The outer CTC-membranes were blebbing in general. Abnormal mitosis resulting in three daughter cells was frequently observed. The expression of RFP ensured that the CTCs originated from lung tumor. These readily isolatable, identifiable and cultivable CTCs can be used to characterize individual patient cancers and for screening of more effective treatment.

  6. A novel dendritic cell-based direct ex vivo assay for detection and enumeration of circulating antigen-specific human T cells.

    Science.gov (United States)

    Carrio, Roberto; Zhang, Ge; Drake, Donald R; Schanen, Brian C

    2018-05-07

    Although a variety of assays have been used to examine T cell responses in vitro, standardized ex vivo detection of antigen-specific CD4 + T cells from human circulatory PBMCs remains constrained by low-dimensional characterization outputs and the need for polyclonal, mitogen-induced expansion methods to generate detectable response signals. To overcome these limitations, we developed a novel methodology utilizing antigen-pulsed autologous human dendritic target cells in a rapid and sensitive assay to accurately enumerate antigen-specific CD4 + T cell precursor frequency by multiparametric flow cytometry. With this approach, we demonstrate the ability to reproducibly quantitate poly-functional T cell responses following both primary and recall antigenic stimulation. Furthermore, this approach enables more comprehensive phenotypic profiling of circulating antigen-specific CD4 + T cells, providing valuable insights into the pre-existing polarization of antigen-specific T cells in humans. Combined, this approach permits sensitive and detailed ex vivo detection of antigen-specific CD4 + T cells delivering an important tool for advancing vaccine, immune-oncology and other therapeutic studies.

  7. Human eosinophils express, relative to other circulating leukocytes, large amounts of secretory 14-kD phospholipase A2

    NARCIS (Netherlands)

    Blom, M.; Tool, A. T.; Wever, P. C.; Wolbink, G. J.; Brouwer, M. C. [=Maria Clara; Calafat, J.; Egesten, A.; Knol, E. F.; Hack, C. E.; Roos, D.; Verhoeven, A. J.

    1998-01-01

    Human eosinophils perform several functions dependent on phospholipase A2 (PLA2) activity, most notably the synthesis of platelet-activating factor (PAF) and leukotriene C4 (LTC4). Several forms of PLA2 have been identified in mammalian cells. In the present study, the 14-kD, secretory form of PLA2

  8. Circulating CXCR5⁺CD4⁺ T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines.

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    Ken Matsui

    Full Text Available Through the interaction of T follicular helper (Tfh cells and B cells, efficacious vaccines can generate high-affinity, pathogen-neutralizing antibodies, and memory B cells. Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV: Cervarix and Gardasil. In this small study, we used PBMC samples from 11 Gardasil recipients, and 8 Cervarix recipients from the Vaccine Research Center 902 Study to examine the induction of circulating Tfh-like cells and IgD-CD38HiCD27+ memory B cells by flow cytometry. PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like cells were induced and peaked on Day (D 7 post-first vaccination, but not as much on D7 post-third vaccination. We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like subset was induced by Cervarix post-first vaccination. There were also minimal changes in the other cellular subsets. In addition, Cervarix recipients had more memory B cells post-first vaccination than did Gardasil recipients at D14 and D30. We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. However, further investigations should be extended to different cohorts with larger sample size to better understand the functions of these T

  9. Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.

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    Alireza Eshaghi

    Full Text Available Human respiratory syncytial virus (HRSV is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010-2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene.Among the 201 consecutive RSV isolates studied, RSV-A (55.7% was more commonly observed than RSV-B (42.3%. 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2% clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10% NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.

  10. Human leptospirosis in Tanzania: sequencing and phylogenetic analysis confirm that pathogenic Leptospira species circulate among agro-pastoralists living in Katavi-Rukwa ecosystem.

    Science.gov (United States)

    Muller, Shabani K; Assenga, Justine A; Matemba, Lucas E; Misinzo, Gerald; Kazwala, Rudovick R

    2016-06-10

    Leptospirosis is a neglected zoonotic disease of worldwide public health importance. The disease affects humans, domestic animals and wildlife. However, leptospirosis is challenging in its diagnosis in humans. Culture technique, which is time consuming, is not recommended for clinical diagnosis. For these reasons, serological and molecular techniques remain the test of choice. The major objective of this study was to explore the genetic characteristic of Leptospira species which are prevalent among agro-pastoralists living in Katavi-Rukwa Ecosystem, Tanzania. A cross-sectional epidemiological study was carried out in the Katavi-Region South-west, Tanzania between August, 2013 and November, 2014. A total of 267 participants were randomly recruited for the study. Microscopic agglutination test (MAT) was used to detect antibody against six Leptospira antigens including local serogroups Icterohaemorrhagiae, Ballum, Grippotyphosa, Sejroe and reference serogroups Hebdomadis, and Australis. Samples with MAT titers ≥ 1:160 were scored as positive, samples with MAT titers ranging from 1:20 to 1:80 were scored as exposed to Leptospira, and absence of agglutination titers was scored as negative. All MAT positive samples, including the low titre samples were subjected to PCR using the respective 16S rRNA primers for the pathogenic and non-pathogenic species. Out of 267 samples tested, 80 (29.9 %) were positive with MAT. The major circulating leptospiral serogroups were Sejroe (15.7 %,), Icterohaemorrhagiae (8.9 %), Grippotyphosa (4.8 %), Hebdomadis (3.37 %), Australis (1.49 %) and Ballum (1.19 %). By using PCR, 33 (15.7 %) out of 210 samples were pathogenic Leptospira while no saprophytic Leptospira spp. was detected. Partial 16S rRNA gene sequences of Leptospira species which were obtained from this study were submitted to GenBank and acquired accession numbers KP313246 and KP313247. Phylogenetic analysis of the nucleotide sequences revealed that species

  11. Human exposure to Bisphenol A and liver health status: Quantification of urinary and circulating levels by LC-MS/MS.

    Science.gov (United States)

    Nicolucci, Carla; Errico, Sonia; Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina; Diano, Nadia

    2017-06-05

    A selective and highly sensitive analytical methodology for determination of Bisphenol A in human plasma was developed and validated. The method was based on selective liquid/solid extraction, combined with liquid chromatography-electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode and negative ionization. The linearity of the detector response was verified in human plasma over the concentration range 0.100-200ngmL -1 . The detection limit was 0.03ngmL -1 and the quantification limit was 0.100ngmL -1 . The analytical features of the proposed in-house validated method were satisfactory: precision was Bisphenol A was detected above the detection limit in all samples. The data show a persistence of unconjugated Bisphenol A levels in plasma and indicate a chronic Bisphenol A exposure of the target organ, suggesting an association between liver health status and Bisphenol A exposure. The results from our study are valuable for further investigation with large sample size and longitudinal study designs, necessary to confirm the observed association. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Aging and cytomegalovirus (CMV) infection differentially and jointly affect distinct circulating T cell subsets in humans1

    Science.gov (United States)

    Wertheimer, Anne M.; Bennett, Michael S.; Park, Byung; Uhrlaub, Jennifer L.; Martinez, Carmine; Pulko, Vesna; Currier, Noreen L.; Nikolich-Zugich, Dragana; Kaye, Jeffrey; Nikolich-Zugich, Janko

    2014-01-01

    The impact of intrinsic aging upon human peripheral blood T-cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly cytomegalovirus (CMV), which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21–101 years, we found that aging correlated strictly to an absolute loss of naïve CD8, but not CD4, T cells, but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naïve CD8 T cells was not altered by CMV in 239 subjects (range 21–96 years) but the decline in CD4+ naïve cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMV Ab titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans. PMID:24501199

  13. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. Copyright © 2015. Published by Elsevier B.V.

  14. Nitrogen. Too much of a good thing? An effective reduction of the overload of the nitrogen circulation on the benefit of environment and humans; Stickstoff. Zuviel des Guten? Ueberlastung des Stickstoffkreislaufs zum Nutzen von Umwelt und Mensch wirksam reduzieren

    Energy Technology Data Exchange (ETDEWEB)

    Schuetze, Gudrun; Geupel, Markus (comps.)

    2011-03-14

    The contribution under consideration reports on the influence of human activities on the circulation of nitrogen as well as on the resulting consequences for humans and environment. Thus the entry of nitrogen compounds is a main reason for the reduction of the biodiversity. The focus of this contribution is on the situation in Germany and the European bordering countries. Possibilities are pointed out, how harmful emissions of nitrogen can be reduced.

  15. Roles of circulating WNT-signaling proteins and WNT-inhibitors in human adiposity, insulin resistance, insulin secretion, and inflammation.

    Science.gov (United States)

    Almario, R U; Karakas, S E

    2015-02-01

    Wingless-type MMTV integration site family member (WNT) signaling and WNT-inhibitors have been implicated in regulation of adipogenesis, insulin resistance, pancreatic function, and inflammation. Our goal was to determine serum proteins involved in WNT signaling (WNT5 and WISP2) and WNT inhibition (SFRP4 and SFRP5) as they relate to obesity, serum adipokines, insulin resistance, insulin secretion, and inflammation in humans. Study population comprised 57 insulin resistant women with polycystic ovary syndrome (PCOS) and 27 reference women. In a cross-sectional study, blood samples were obtained at fasting, during oral, and frequently sampled intravenous glucose tolerance tests. Serum WNT5, WISP2, and SFRP4 concentrations did not differ between PCOS vs. reference women. Serum WNT5 correlated inversely with weight both in PCOS and reference women, and correlated directly with insulin response during oral glucose tolerance test in PCOS women. Serum WISP2 correlated directly with fatty acid binding protein 4. Serum SFRP5 did not differ between obese (n=32) vs. nonobese (n=25) PCOS women, but reference women had lower SFRP5 (pPCOS groups). Serum SFRP5 correlated inversely with IL-1β, TNF-α, cholesterol, and apoprotein B. These findings demonstrated that WNT5 correlated inversely with adiposity and directly with insulin response, and the WNT-inhibitor SFRP5 may be anti-inflammatory. Better understanding of the role of WNT signaling in obesity, insulin resistance, insulin secretion, lipoprotein metabolism, and inflammation is important for prevention and treatment of metabolic syndrome, diabetes and cardiovascular disease. © Georg Thieme Verlag KG Stuttgart · New York.

  16. CIRCULATING CD11B EXPRESSION CORRELATES WITH THE NEUTROPHIL RESPONSE AND AIRWAY MCD-14 EXPRESSION IS ENHANCED FOLLOWING OZONE EXPOSURE IN HUMANS

    Science.gov (United States)

    We recently reported that baseline expression of circulating CD11b is associated with the magnitude of the neutrophil response following inhaled endotoxin. In this study, we examined whether circulating CD11b plays a similar role in the inflammatory response following inhaled ozo...

  17. Oligonol supplementation attenuates body temperature and the circulating levels of prostaglandin E2 and cyclooxygenase-2 after heat stress in humans.

    Science.gov (United States)

    Shin, Young Oh; Lee, Jeong Beom; Song, Young Ju; Min, Young Ki; Yang, Hun Mo

    2013-04-01

    Oligonol, a phenolic production from lychee, has been reported to exhibit anti-oxidative and anti-inflammatory effects. This study investigated the effect of Oligonol supplementation on circulating levels of prostaglandin E2 (PGE2) and cyclooxygenase (COX)-2, as well as body temperature, after heat stress in 17 healthy human male volunteers (age, 21.6±2.1 years). All experiments were performed in an automated climate chamber (26.0°C±0.5°C, relative humidity 60%±3.0%, air velocity less than 1 m/sec) between 2 and 5 p.m. Subjects ingested an Oligonol (100 mg)-containing beverage or placebo beverage before half-body immersion into hot water (42°C±0.5°C for 30 min). Tympanic and skin temperatures were measured and mean body temperatures were calculated. Serum concentrations of PGE2 and COX-2 were analyzed before, immediately after, and 60 min after immersion. Oligonol intake significantly prevented elevation of tympanic (temperature difference: 0.17°C at Post, Pbody temperatures (temperature difference: 0.18°C at Post, Pbody temperature under heat stress, and this is associated with decreases in serum levels of PGE2 and COX-2.

  18. Cholesterol delivery to the adrenal glands estimated by adrenal venous sampling: An in vivo model to determine the contribution of circulating lipoproteins to steroidogenesis in humans.

    Science.gov (United States)

    Buitenwerf, Edward; Dullaart, Robin P F; Muller Kobold, Anneke C; Links, Thera P; Sluiter, Wim J; Connelly, Margery A; Kerstens, Michiel N

    Cholesterol, required for adrenal steroid hormone synthesis, is at least in part derived from circulating lipoproteins. The contribution of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) to adrenal steroidogenesis in humans is unclear. The aim of the study was to determine the extent to which HDL and LDL are taken up by the adrenal glands using samples obtained during adrenal venous sampling (AVS). AVS was successfully performed in 23 patients with primary aldosteronism. Samples were drawn from both adrenal veins and inferior vena cava (IVC). HDL cholesterol (HDL-C) and lipoprotein particle profiles were determined by nuclear magnetic resonance spectroscopy. Apolipoprotein (apo) A-I and apoB were assayed by immunoturbidimetry. Plasma HDL-C and HDL and LDL particle concentrations (HDL-P and LDL-P) were not lower in samples obtained from the adrenal veins compared with the IVC (HDL-C, P = .59; HDL-P, P = .06; LDL-P, P = .93). ApoB was lower in adrenal venous plasma than in IVC (P = .026; P lipoproteins and steroidogenesis. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  19. Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Seed Mike

    2012-11-01

    Full Text Available Abstract Background We present the first phase contrast (PC cardiovascular magnetic resonance (CMR measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG. Methods A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30–39 weeks. Flow was measured in the major fetal vessels and indexed to the fetal weight. Results There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96. Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO 540±101, main pulmonary artery (MPA 327±68, ascending aorta (AAo 198±38, superior vena cava (SVC 147±46, ductus arteriosus (DA 220±39,pulmonary blood flow (PBF 106±59,descending aorta (DAo 273±85, umbilical vein (UV 160±62, foramen ovale (FO107±54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60±4, AAo37±4, SVC 28±7, DA 41±8, PBF 19±10, DAo50±12, UV 30±9, FO 21±12. Conclusion This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.

  20. Genetic variability of attachment (G and Fusion (F protein genes of human metapneumovirus strains circulating during 2006-2009 in Kolkata, Eastern India

    Directory of Open Access Journals (Sweden)

    Chawla-Sarkar Mamta

    2011-02-01

    Full Text Available Abstract Background Human metapneumovirus (hMPV is associated with the acute respiratory tract infection (ARTI in all the age groups. However, there is limited information on prevalence and genetic diversity of human metapneumovirus (hMPV strains circulating in India. Objective To study prevalence and genomic diversity of hMPV strains among ARTI patients reporting in outpatient departments of hospitals in Kolkata, Eastern India. Methods Nasal and/or throat swabs from 2309 patients during January 2006 to December 2009, were screened for the presence of hMPV by RT-PCR of nucleocapsid (N gene. The G and F genes of representative hMPV positive samples were sequenced. Results 118 of 2309 (5.11% clinical samples were positive for hMPV. The majority (≈80% of the positive cases were detected during July−November all through the study period. Genetic analysis revealed that 77% strains belong to A2 subgroup whereas rest clustered in B1 subgroup. G sequences showed higher diversity at the nucleotide and amino acid level. In contrast, less than 10% variation was observed in F gene of representative strains of all four years. Sequence analysis also revealed changes in the position of stop codon in G protein, which resulted in variable length (217-231 aa polypeptides. Conclusion The study suggests that approximately 5% of ARTI in the region were caused by hMPV. This is the first report on the genetic variability of G and F gene of hMPV strains from India which clearly shows that the G protein of hMPV is continuously evolving. Though the study partially fulfills lacunae of information, further studies from other regions are necessary for better understanding of prevalence, epidemiology and virus evolution in Indian subcontinent.

  1. Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

    Directory of Open Access Journals (Sweden)

    Sarah L Appleby

    Full Text Available Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+ population of non-adherent endothelial forming cells (naEFCs which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38 together with mature endothelial cell markers (VEGFR2, CD144 and CD31. These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8 or myeloid markers (CD11b and CD14 which distinguishes them from 'early' endothelial progenitor cells (EPCs. Functional studies demonstrated that these naEFCs (i bound Ulex europaeus lectin, (ii demonstrated acetylated-low density lipoprotein uptake, (iii increased vascular cell adhesion molecule (VCAM-1 surface expression in response to tumor necrosis factor and (iv in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs. Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

  2. Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study.

    Science.gov (United States)

    Seed, Mike; van Amerom, Joshua F P; Yoo, Shi-Joon; Al Nafisi, Bahiyah; Grosse-Wortmann, Lars; Jaeggi, Edgar; Jansz, Michael S; Macgowan, Christopher K

    2012-11-26

    We present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG). A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30-39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight. There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540 ± 101, main pulmonary artery (MPA) 327 ± 68, ascending aorta (AAo) 198 ± 38, superior vena cava (SVC) 147 ± 46, ductus arteriosus (DA) 220 ± 39,pulmonary blood flow (PBF) 106 ± 59,descending aorta (DAo) 273 ± 85, umbilical vein (UV) 160 ± 62, foramen ovale (FO)107 ± 54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60 ± 4, AAo37 ± 4, SVC 28 ± 7, DA 41 ± 8, PBF 19 ± 10, DAo50 ± 12, UV 30 ± 9, FO 21 ± 12. This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.

  3. Characterization of a Distinct Population of Circulating Human Non-Adherent Endothelial Forming Cells and Their Recruitment via Intercellular Adhesion Molecule-3

    Science.gov (United States)

    Thompson, Emma J.; Barrett, Jeffrey M.; Tooley, Katie; Sen, Shaundeep; Sun, Wai Yan; Grose, Randall; Nicholson, Ian; Levina, Vitalina; Cooke, Ira; Talbo, Gert; Lopez, Angel F.; Bonder, Claudine S.

    2012-01-01

    Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133+ population of non-adherent endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8) or myeloid markers (CD11b and CD14) which distinguishes them from ‘early’ endothelial progenitor cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex europaeus lectin, (ii) demonstrated acetylated-low density lipoprotein uptake, (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in response to tumor necrosis factor and (iv) in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis. PMID:23144795

  4. Changes in the composition of circulating CD8+ T cell subsets during acute epstein-barr and human immunodeficiency virus infections in humans

    NARCIS (Netherlands)

    Roos, M. T.; van Lier, R. A.; Hamann, D.; Knol, G. J.; Verhoofstad, I.; van Baarle, D.; Miedema, F.; Schellekens, P. T.

    2000-01-01

    In response to viral infection, unprimed naive CD8(+), major histocompatibility complex class I-restricted, virus-specific T cells clonally expand and differentiate into memory- and effector-type cells. Changes in CD8(+) subset distribution were studied in 17 subjects with acute human

  5. A blood circulation model for reference man

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, R.W.; Eckerman, K.F. [Oak Ridge National Lab., TN (United States); Williams, L.R. [Indiana Univ., South Bend, IN (United States). Div. of Liberal Arts and Sciences

    1996-12-31

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86.

  6. A blood circulation model for reference man

    International Nuclear Information System (INIS)

    Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

    1996-01-01

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86

  7. Circulation of Stars

    Science.gov (United States)

    Boitani, P.

    2016-01-01

    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  8. Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus

    Directory of Open Access Journals (Sweden)

    Fuminori Sakurai

    2016-01-01

    Full Text Available Circulating tumor cells (CTCs are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP–expressing conditionally replicating adenovirus (Ad (rAd-GFP was recently developed; however, there is concern about the production of false-positive cells (GFP-positive normal blood cells when using rAd-GFP, particularly at high titers. In addition, CTCs lacking or expressing low levels of coxsackievirus–adenovirus receptor (CAR cannot be detected by rAd-GFP, because rAd-GFP is constructed based on Ad serotype 5, which recognizes CAR. In order to suppress the production of false-positive cells, sequences perfectly complementary to blood cell–specific microRNA, miR-142-3p, were incorporated into the 3′-untranslated region of the E1B and GFP genes. In addition, the fiber protein was replaced with that of Ad serotype 35, which recognizes human CD46, creating rAdF35-142T-GFP. rAdF35-142T-GFP efficiently labeled not only CAR-positive tumor cells but also CAR-negative tumor cells with GFP. The numbers of false-positive cells were dramatically lower for rAdF35-142T-GFP than for rAd-GFP. CTCs in the blood of cancer patients were detected by rAdF35-142T-GFP with a large reduction in false-positive cells.

  9. Nitrogen-doped multiple graphene aerogel/gold nanostar as the electrochemical sensing platform for ultrasensitive detection of circulating free DNA in human serum.

    Science.gov (United States)

    Ruiyi, Li; Ling, Liu; Hongxia, Bei; Zaijun, Li

    2016-05-15

    Graphene aerogel has attracted increasing attention due to its large specific surface area, high-conductivity and electronic interaction. The paper reported a facile synthesis of nitrogen-doped multiple graphene aerogel/gold nanostar (termed as N-doped MGA/GNS) and its use as the electrochemical sensing platform for detection of double stranded (dsDNA). On the one hand, the N-doped MGA offers a much better electrochemical performance compared with classical graphene aerogel. Interestingly, the performance can be enhanced by only increasing the cycle number of graphene oxide gelation. On the other hand, the hybridization with GNS further enhances the electrocatalytic activity towards Fe(CN)6(3-/4-). In addition, the N-doped MGA/GNS provides a well-defined three-dimensional architecture. The unique structure make it is easy to combine with dsDNA to form the electroactive bioconjugate. The integration not only triggers an ultrafast DNA electron and charge transfer, but also realizes a significant synergy between N-doped MGA, GNS and dsDNA. As a result, the electrochemical sensor based on the hybrid exhibits highly sensitive differential pulse voltammetric response (DPV) towards dsDNA. The DPV signal linearly increases with the increase of dsDNA concentration in the range from 1.0×10(-)(21) g ml(-)(1) to 1.0×10(-16) g ml(-1) with the detection limit of 3.9×10(-22) g ml(-1) (S/N=3). The sensitivity is much more than that of all reported DNA sensors. The analytical method was successfully applied in the electrochemical detection of circulating free DNA in human serum. The study also opens a window on the electrical properties of multiple graphene aerogel and DNA as well their hybrids to meet the needs of further applications as special nanoelectronics in molecule diagnosis, bioanalysis and catalysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.

    Science.gov (United States)

    Bailey, Damian M; Rasmussen, Peter; Overgaard, Morten; Evans, Kevin A; Bohm, Aske M; Seifert, Thomas; Brassard, Patrice; Zaar, Morten; Nielsen, Henning B; Raven, Peter B; Secher, Niels H

    2017-01-10

    The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O 2 tension and blood flow. Ten healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O 2 ) and hypoxic (10% O 2 ) trial with measurements performed at rest and after 30 minutes of cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled simultaneously from the brachial artery and internal jugular and femoral veins with plasma and RBC nitric oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow was determined by transcranial Doppler ultrasound (cerebral blood flow) and constant infusion thermodilution (femoral blood flow) with net exchange calculated via the Fick principle. Hypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow (Pflow during exercise (Pvenous; Parterial; P0.05). These findings suggest that hypoxia and, to a far greater extent, exercise independently promote arterial-venous delivery gradients of intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as the dominant mechanism underlying hypoxic vasodilation. © 2016 American Heart Association, Inc.

  11. Plants and Photosynthesis: Level III, Unit 3, Lesson 1; The Human Digestive System: Lesson 2; Functions of the Blood: Lesson 3; Human Circulation and Respiration: Lesson 4; Reproduction of a Single Cell: Lesson 5; Reproduction by Male and Female Cells: Lesson 6; The Human Reproductive System: Lesson 7; Genetics and Heredity: Lesson 8; The Nervous System: Lesson 9; The Glandular System: Lesson 10. Advanced General Education Program. A High School Self-Study Program.

    Science.gov (United States)

    Manpower Administration (DOL), Washington, DC. Job Corps.

    This self-study program for the high-school level contains lessons in the following subjects: Plants and Photosynthesis; The Human Digestive System; Functions of the Blood; Human Circulation and Respiration; Reproduction of a Single Cell; Reproduction by Male and Female Cells; The Human Reproductive System; Genetics and Heredity; The Nervous…

  12. Co-circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in Italy.

    Science.gov (United States)

    Zappa, Alessandra; Canuti, Marta; Frati, Elena; Pariani, Elena; Perin, Silvana; Ruzza, Maria Lorena; Farina, Claudio; Podestà, Alberto; Zanetti, Alessandro; Amendola, Antonella; Tanzi, Elisabetta

    2011-01-01

    The discovery of human Metapneumovirus (hMPV) and human Bocavirus (hBoV) identified the etiological causes of several cases of acute respiratory tract infections in children. This report describes the molecular epidemiology of hMPV and hBoV infections observed following viral surveillance of children hospitalized for acute respiratory tract infections in Milan, Italy. Pharyngeal swabs were collected from 240 children ≤3 years of age (130 males, 110 females; median age, 5.0 months; IQR, 2.0-12.5 months) and tested for respiratory viruses, including hMPV and hBoV, by molecular methods. hMPV-RNA and hBoV-DNA positive samples were characterized molecularly and a phylogenetical analysis was performed. PCR analysis identified 131/240 (54.6%) samples positive for at least one virus. The frequency of hMPV and hBoV infections was similar (8.3% and 12.1%, respectively). Both infections were associated with lower respiratory tract infections: hMPV was present as a single infectious agent in 7.2% of children with bronchiolitis, hBoV was associated with 18.5% of pediatric pneumonias and identified frequently as a single etiological agent. Genetically distinct hMPV and hBoV strains were identified in children examined with respiratory tract infections. Phylogenetic analysis showed an increased prevalence of hMPV genotype A (A2b sublineage) compared to genotype B (80% vs. 20%, respectively) and of the hBoV genotype St2 compared to genotype St1 (71.4% vs. 28.6%, respectively). Interestingly, a shift in hMPV infections resulting from A2 strains has been observed in recent years. In addition, the occurrence of recombination events between two hBoV strains with a breakpoint located in the VP1/VP2 region was identified. © 2010 Wiley-Liss, Inc.

  13. Circulating Autoantibodies in Age-Related Macular Degeneration Recognize Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation, and Protection from Oxidative Stress and Apoptosis.

    Directory of Open Access Journals (Sweden)

    Alessandro Iannaccone

    Full Text Available We investigated sera from elderly subjects with and without age-related macular degeneration (AMD for presence of autoantibodies (AAbs against human macular antigens and characterized their identity.Sera were collected from participants in the Age-Related Maculopathy Ancillary (ARMA Study, a cross-sectional investigation ancillary to the Health ABC Study, enriched with participants from the general population. The resulting sample (mean age: 79.2±3.9 years old included subjects with early to advanced AMD (n = 131 and controls (n = 231. Sera were tested by Western blots for immunoreactive bands against human donor macular tissue homogenates. Immunoreactive bands were identified and graded, and odds ratios (OR calculated. Based on these findings, sera were immunoprecipitated, and subjected to 2D gel electrophoresis (GE. Liquid chromatography-tandem mass spectrometry (LC-MS/MS was used to identify the targets recognized by circulating AAbs seen on 2D-GE, followed by ELISAs with recombinant proteins to confirm LC-MS/MS results, and quantify autoreactivities.In AMD, 11 immunoreactive bands were significantly more frequent and 13 were significantly stronger than in controls. Nine of the more frequent bands also showed stronger reactivity. OR estimates ranged between 4.06 and 1.93, and all clearly excluded the null value. Following immunoprecipitation, 2D-GE and LC-MS/MS, five of the possible autoreactivity targets were conclusively identified: two members of the heat shock protein 70 (HSP70 family, HSPA8 and HSPA9; another member of the HSP family, HSPB4, also known as alpha-crystallin A chain (CRYAA; Annexin A5 (ANXA5; and Protein S100-A9, also known as calgranulin B that, when complexed with S100A8, forms calprotectin. ELISA testing with recombinant proteins confirmed, on average, significantly higher reactivities against all targets in AMD samples compared to controls.Consistent with other evidence supporting the role of inflammation and the

  14. Association of cardiovascular complications with circulating levels of tribbles 3 human homolog and matrix metalloproteinases in Indian type 2 diabetic patients, with or without hypertension

    Directory of Open Access Journals (Sweden)

    Prashant Shirish Ratnaparkhi

    2018-01-01

    Full Text Available Aim and Objective: Matrix metalloproteinases (MMPs and Tribbles 3 (Trb3 human homologue have been reported to induce atherosclerosis. We wanted to evaluate the association of circulating levels of Trb3 human homologue and MMPs (MMP2 and MMP9, with possible cardiovascular complications in Indian type 2 diabetic patients (type 2 diabetes mellitus [T2DM], with or without hypertension (HT. Materials and Methods: Serum from 144 individuals, classified as follows: Group A1= (DM + HT; T2DM> 5 years + HT (n = 55; Group A2 = DM; T2DM <2 years, (n = 28; Group B1 = HT; (n = 31 and Group B2 = HC; (n = 30 age- and sex-matched healthy controls. Anthropometric measurements, biochemical profiles of sugar and lipids were established using auto analyser. MMP2, MMP9, Trb3, oxidised low-density lipoprotein cholesterol, and proinsulin were measured in the serum using ELISA. Results: Using Bonferroni correction, we found that MMP2 levels were increased in (DM + HT, when compared to individuals with DM and HT (P = 0.006 and 0.000. HT group had reduced levels of MMP2, as compared to HC, (P = 0.000. The Mann–Whitney U-test for MMP9 revealed that DM group had elevated levels of MMP9 compared to (DM + HT, HT and HC group, (P = 0.011, 0.000, and 0.001. (DM + HT had elevated levels of MMP9 when compared to HT group, (P = 0.012.. Levels of MMP9 in HT were lower than the HC group, although not significant. Levels of Trb3 were found to be elevated in (DM + HT when compared to DM, (P = 0.032. The levels of Trb3 were higher in the HT, when compared to HC group, although not statistically significant. Multiple linear regression model for Framingham Risk Score, weighted with post prandial blood sugar yielded R2 = 0.338; F = 7.602 (df = 9, P = 0.000. Trb3 (β = −0.179, P = 0.019; MMP2 (β =0.021, P = 0.787 and MMP9 (β = −0.03, P = 0.684. Conclusion: Trb3 is a useful marker for evaluating the association of cardiovascular risk in diabetic patients.

  15. Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

    Science.gov (United States)

    Ortega-Gómez, Almudena; Varela, Lourdes M; López, Sergio; Montserrat de la Paz, Sergio; Sánchez, Rosario; Muriana, Francisco J G; Bermúdez, Beatriz; Abia, Rocío

    2017-09-01

    Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe -/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1β mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation. Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Differential Relationships among Circulating Inflammatory and Immune Activation Biomediators and Impact of Aging and Human Immunodeficiency Virus Infection in a Cohort of Injection Drug Users

    Directory of Open Access Journals (Sweden)

    Gregory D. Kirk

    2017-10-01

    Full Text Available As individuals with human immunodeficiency virus (HIV infection live longer, aging and age-related chronic conditions have become major health concerns for this vulnerable population. Substantial evidence suggests that chronic inflammation and immune activation contribute significantly to chronic conditions in people aging with or without HIV infection. As a result, increasing numbers of inflammation and immune activation biomediators have been measured. While very few studies describe their in vivo relationships, such studies can serve as an important and necessary initial step toward delineating the complex network of chronic inflammation and immune activation. In this study, we evaluated in vivo relationships between serum levels of neopterin, a biomediator of immune activation, and four commonly described inflammatory biomediators: soluble tumor necrosis factor (TNF-α receptor (sTNFR-1, sTNFR-2, interleukin (IL-6, and C-reactive protein (CRP, as well as the impact of HIV infection and aging in the AIDS Linked to the Intravenous Experience (ALIVE study, a community-recruited observational study of former and current injection drug users (IDUs with or at high risk for HIV infection in Baltimore, MD, USA. The study included 1,178 participants in total with 316 HIV-infected (HV+ and 862 HIV-uninfected (HIV− IDUs. Multivariate regression analyses were employed, adjusting for age, sex, body mass index, smoking, hepatitis C virus co-infection, injection drug use, comorbidities, and HIV status (for all participants, and HIV viral load, CD4+ T-cell counts, and antiretroviral therapy (for HIV+ participants. The results showed significant impact of aging on all five biomediators and that of HIV infection on all but sTNFR-1. In the adjusted model, neopterin had positive associations with sTNFR-1 and sTNFR-2 (partial correlation coefficients: 0.269 and 0.422, respectively, for all participants; 0.292 and 0.354 for HIV+; and 0.262 and 0.435 for HIV

  17. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S

    2011-01-01

    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...

  18. Microwave circulator design

    CERN Document Server

    Linkhart, Douglas K

    2014-01-01

    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  19. Lipid peroxidation and total cholesterol in HAART-naïve patients infected with circulating recombinant forms of human immunodeficiency virus type-1 in Cameroon.

    Directory of Open Access Journals (Sweden)

    Georges Teto

    Full Text Available HIV infection has commonly been found to affect lipid profile and antioxidant defense.To determine the effects of Human Immunodeficiency Virus (HIV infection and viral subtype on patient's cholesterol and oxidative stress markers, and determine whether in the absence of Highly Active Antiretroviral Therapy (HAART, these biochemical parameters could be useful in patient's management and monitoring disease progression in Cameroon. For this purpose, we measured total cholesterol (TC, LDL cholesterol (LDLC, HDL cholesterol (HDLC, total antioxidant ability (TAA, lipid peroxidation indices (LPI, and malondialdehyde (MDA in HIV negative persons and HIV positive HAART-naïve patients infected with HIV-1 group M subtypes.We measured serum TC, LDLC, HDLC, plasma MDA, and TAA concentrations, and calculated LPI indices in 151 HIV-positive HAART-naïve patients and 134 seronegative controls. We also performed gene sequence analysis on samples from 30 patients to determine the effect of viral genotypes on these biochemical parameters. We also determined the correlation between CD4 cell count and the above biochemical parameters.We obtained the following controls/patients values for TC (1.96±0.54/1. 12±0. 48 g/l, LDLC (0. 67±0. 46/0. 43±0. 36 g/l, HDLC (105. 51±28. 10/46. 54±23. 36 mg/dl TAA (0. 63±0. 17/0. 16±0. 16 mM, MDA (0. 20±0. 07/0. 41±0. 10 µM and LPI (0. 34±0. 14/26. 02±74. 40. In each case, the difference between the controls and patients was statistically significant (p<0.05. There was a positive and statistically significant Pearson correlation between CD4 cell count and HDLC (r = +0.272; p<0.01, TAA (r = +0.199; p<0.05 and a negative and statistically significant Pearson correlation between CD4 cell count and LPI (r = -0.166; p<0.05. Pearson correlation between CD4 cell count and TC, CD4cell count and LDLC was positive but not statistically significant while it was negative but not statistically significant with MDA. The

  20. Circulation pump mounting

    International Nuclear Information System (INIS)

    Skalicky, A.

    1976-01-01

    The suspension is described of nuclear reactor circulating pumps enabling their dilatation with a minimum reverse force consisting of spacing rods supported with one end in the anchor joints and provided with springs and screw joints engaging the circulating pump shoes. The spacing rods are equipped with side vibration dampers anchored in the shaft side wall and on the body of the circulating pump drive body. The negative reverse force F of the spacing rods is given by the relation F=Q/l.y, where Q is the weight of the circulating pump, l is the spatial distance between the shoe joints and anchor joints, and y is the deflection of the circulating pump vertical axis from the mean equilibrium position. The described suspension is advantageous in that that the reverse force for the deflection from the mean equilibrium position is minimal, dynamic behaviour is better, and construction costs are lower compared to suspension design used so far. (J.B.)

  1. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Lawrence J.; Bower, Amy S.; Kö hl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-01-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented

  2. The 78 kDa glucose-regulated protein (GRP78/BIP) is expressed on the cell membrane, is released into cell culture medium and is also present in human peripheral circulation.

    Science.gov (United States)

    Delpino, Andrea; Castelli, Mauro

    2002-01-01

    In human rabdomiosarcoma cells (TE671/RD) chronic exposure to 500 nM thapsigargin (a powerful inhibitor of the endoplasmic reticulum Ca2+-ATPases) resulted in the induction of the stress protein GRP78/BIP. Making use of the surface biotinylation method, followed by the isolation of the GRP78 using ATP-agarose affinity chromatography, it was found that a fraction of the thapsigargin-induced GRP78 is expressed on the cell surface. The presence of GRP78 on the membrane of thapsigargin-treated cells was confirmed by fractionation of cell lysates into a soluble and a membrane fraction, followed by Western blot analysis with an anti-GRP78 antibody. It was also found that conspicuous amounts of GRP78 are present in the culture medium collected from thapsigargin-treated cultures. This extracellular GRP78 originates mostly by an active release from intact cells and does not result solely from the leakage of proteins from dead cells. Moreover, small amounts of circulating, free GRP78 and naturally-occurring anti-GRP78 autoantibodies were detected in the peripheral circulation of healthy human individuals.

  3. Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides.

    Directory of Open Access Journals (Sweden)

    Lygia T Budnik

    Full Text Available There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD but (mostly lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001. The decreased integrity of mtDNA (mtDNA-230/mtDNA-79 in exposed individuals implicates apoptotic processes (p = 0.015. The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001. Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

  4. Tracing How Arts and Humanities Research Translates, Circulates and Consolidates in Society.. How Have Scholars Been Reacting to Diverse Impact and Public Value Agendas?

    Science.gov (United States)

    Benneworth, Paul

    2015-01-01

    Arts and humanities research appears to have a problem when it comes to making an argument that it matters to society. Despite widespread efforts within and beyond the field to document how arts and humanities research creates social value, these arguments have had little traction within public policy debates. The paper argues that other…

  5. Tracing how arts and humanities research translates, circulates and consolidates in society.. How have scholars been reacting to diverse impact and public value agendas?

    NARCIS (Netherlands)

    Benneworth, Paul Stephen

    2014-01-01

    Arts and humanities research appears to have a problem when it comes to making an argument that it matters to society. Despite widespread efforts within and beyond the field to document how arts and humanities research creates social value, these arguments have had little traction within public

  6. Circulating interleukin-10 levels and human papilloma virus and Epstein-Barr virus-associated cancers: evidence from a Mendelian randomization meta-analysis based on 11,170 subjects.

    Science.gov (United States)

    Qu, Kai; Pang, Qing; Lin, Ting; Zhang, Li; Gu, Mingliang; Niu, Wenquan; Liu, Chang; Zhang, Ming

    2016-01-01

    Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that determines antiviral immune response and is related to virus-associated cancers. However, whether genetically elevated circulating IL-10 levels are associated with the risk of human papilloma virus and Epstein-Barr virus-associated cancers (HEACs) is still unclear. Mendelian randomization method was implemented to meta-analyze available observational studies by employing IL-10 three variants (-592C>A, -819C>T, and -1082A>G) as instruments. A total of 24 articles encompassing 11,170 subjects were ultimately eligible for the meta-analysis. Overall, there was a significant association between IL-10 promoter variant -1082A>G and HEACs under allelic and dominant models (both PG was significant for nasopharyngeal cancer under allelic, homozygous genotypic and dominant models (all P<0.001). Moreover by ethnicity, carriers of -1082G allele had a 74% increased risk for nasopharyngeal cancer in Asians under dominant model (odds ratio [OR] =1.737; 95% confidence interval [CI]: 1.280-2.358; P<0.001). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 levels was 1.14 (95% CI: 1.01-16.99) in HEACs. Our findings provided strong evidence for a critical role of genetically elevated circulating IL-10 levels in the development of HEACs, especially in Asian population and for nasopharyngeal cancer.

  7. Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: Effect on outcome.

    Science.gov (United States)

    Chan, Adeline; Yan, Jun; Csurhes, Peter; Greer, Judith; McCombe, Pamela

    2015-09-15

    The aim of this study was to measure the levels of circulating BDNF and the frequency of BDNF-producing T cells after acute ischaemic stroke. Serum BDNF levels were measured by ELISA. Flow cytometry was used to enumerate peripheral blood leukocytes that were labelled with antibodies against markers of T cells, T regulatory cells (Tregs), and intracellular BDNF. There was a slight increase in serum BDNF levels after stroke. There was no overall difference between stroke patients and controls in the frequency of CD4(+) and CD8(+) BDNF(+) cells, although a subgroup of stroke patients showed high frequencies of these cells. However, there was an increase in the percentage of BDNF(+) Treg cells in the CD4(+) population in stroke patients compared to controls. Patients with high percentages of CD4(+) BDNF(+) Treg cells had a better outcome at 6months than those with lower levels. These groups did not differ in age, gender or initial stroke severity. Enhancement of BDNF production after stroke could be a useful means of improving neuroprotection and recovery after stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects.

    Science.gov (United States)

    Lee, Sang-Rok; Schriefer, Johnhenry M; Gunnels, Trint A; Harvey, Innocence C; Bloomer, Richard J

    2013-10-21

    Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist-possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6-8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. A condition effect was noted for both FFA (p 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p < 0.0001), with values higher for supplement compared to placebo. Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine contributes little to the increase in these hemodynamic variables. These findings are in reference to young, healthy and active men and women.

  9. FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest

    DEFF Research Database (Denmark)

    Søberg, Susanna; Andersen, Emilie S; Dalgaard, Niels B

    2018-01-01

    . KLB encodes β-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and human Fgf21 variants are enriched among heavy drinkers. Thus, the liver may limit alcohol consumption by secreting FGF21. However, whether full-length, active...... plasma FGF21 (FGF21 (1-181)) levels in humans increase acutely or sub-chronically in response to alcohol ingestion is uncertain. METHODS: We recruited 10 healthy, fasted male subjects to receive an oral water or alcohol bolus with concurrent blood sampling for FGF21 (1-181) measurement in plasma...... correlated fasting FGF21 (1-181) levels in 49 healthy, non-alcoholic subjects of mixed sex with self-reports of alcohol-related behaviors, emotional responses, and problems. Finally, we characterized the effect of recombinant human FGF21 injection on ad libitum alcohol intake in mice. RESULTS: We show...

  10. Arctic circulation regimes.

    Science.gov (United States)

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L

    2015-10-13

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. © 2015 The Authors.

  11. Impact of interocean exchange on the Atlantic overturning circulation

    NARCIS (Netherlands)

    Weijer, W.

    2000-01-01

    The awareness that human activity could change climate has greatly raised public and scientific interest in climate. One issue of present-day climate research is the stability of the thermohaline circulation. This overturning circulation, popularly known as the `conveyor belt', redistributes

  12. Detection of circulating immune complexes of human IgA and beta 2 glycoprotein I in patients with antiphospholipid syndrome symptomatology.

    Science.gov (United States)

    Martínez-Flores, José A; Serrano, Manuel; Pérez, Dolores; Lora, David; Paz-Artal, Estela; Morales, José M; Serrano, Antonio

    2015-07-01

    Patients with antiphospholipid syndrome (APS) have a hypercoagulable condition associated with the presence of antiphospholipid autoantibodies (aPL). Consensus antibodies for diagnosis are lupus anticoagulant, anti-beta2 glycoprotein I (B2GPI) and anticardiolipin (IgG or IgM). Circulating immunocomplexes (CIC) of B2GPI associated with IgM or IgG were reported. Isolated IgA aB2GPI antibodies have achieved high diagnostic value although specific CIC of B2GPI bounded to IgA (B2A-CIC) has still not been described. CIC detection assays are mainly based on interaction with complement and are not appropriate to detect B2A-CIC because IgA does not fix complement using the classical pathway. Sera from healthy blood donors (N= 247) and from patients with thrombosis background and isolate positive for IgA aB2GPI (N = 68) were studied in a case-control study. Two methods were applied, these being a capture ELISA to quantify specific B2A-CIC and quantification of total IgA anti-B2GPI after dissociating CIC. B2A-CIC values in APS-patients were 19.27 ± 2.6 AU vs 6.1 ± 0.4 AU in blood donors (p < 0.001). There were 36.4% B2A-CIC positive patients (cutoff 21 AU) versus 5.5% in blood donors (p < 0.001). Dissociated IgA aB2GPI levels (total IgA aB2GPI) were 146.8 ± 10.8 IU/mL in patients vs. 22.4 IU/mL in controls (p < 0.001). B2A-CIC was independent of B2GPI and autoantibodies IgA aB2GPI serum levels. B2A-CIC can be identified and quantified in an easy and reproducible manner using two complement-independent methods. The use of these tests in prospective studies will allow better understanding of the prognosis and outcome of patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Systems engineering requirements impacting MHTGR circulator design

    International Nuclear Information System (INIS)

    Chi, H.W.; Baccaglini, G.M.; Potter, R.C.; Shenoy, A.S.

    1988-01-01

    At the initiation of the MHTGR program, an important task involved translating the plant users' requirements into design conditions. This was particularly true in the case of the heat transport and shutdown cooling systems since these embody many components. This paper addresses the two helium circulators in these systems. An integrated approach is being used in the development of design and design documentation for the MHTGR plant. It is an organized and systematic development of plant functions and requirements, determined by top-down design, performance, and cost trade-off studies and analyses, to define the overall plant systems, subsystems, components, and human actions. These studies, that led to the identification of the major design parameters for the two circulators, are discussed in this paper. This includes the performance information, steady state and transient data, and the various interface requirements. The design of the circulators used in the MHTGR is presented. (author). 1 ref., 17 figs

  14. Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes

    Directory of Open Access Journals (Sweden)

    Nathalie Kin

    2015-05-01

    Full Text Available Human coronavirus OC43 (HCoV-OC43 is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.

  15. Controlled humidity gas circulators

    International Nuclear Information System (INIS)

    Gruner, S.M.

    1981-01-01

    A programmable circulator capable of regulating the humidity of a gas stream over a wide range of humidity is described. An optical dew-point hygrometer is used as a feedback element to control the addition or removal of water vapor. Typical regulation of the gas is to a dew-point temperature of +- 0.2 0 C and to an accuracy limited by the dew-point hygrometer

  16. Fluid circulation control device

    International Nuclear Information System (INIS)

    Benard, Henri; Henocque, Jean.

    1982-01-01

    Horizontal fluid circulation control device, of the type having a pivoting flap. This device is intended for being fitted in the pipes of hydraulic installation, particularly in a bleed and venting system of a nuclear power station shifting radioactive or contaminated liquids. The characteristic of this device is the cut-out at the top of the flap to allow the air contained in the pipes to flow freely [fr

  17. Molecular characterization of canine distemper vi- rus circulating in ...

    African Journals Online (AJOL)

    2OIE Collaborating Centre for Diseases at Animal and Human Interface, FAO Reference Centre for Rabies, Viale ... Asia-1 lineage canine distemper virus is circulating in outbreak. .... jected to cell culture on Vero cell lines for virus isolation.

  18. Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

    DEFF Research Database (Denmark)

    Fismen, S; Hedberg, A; Fenton, K A

    2009-01-01

    Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal i......Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo......-epidermal immune complex deposits have similar molecular composition as glomerular deposits, (ii) whether chromatin fragments bind dermo-epidermal structures, and (iii) whether deposits in nephritic glomeruli predispose for accumulation of similar deposits in skin. Paired skin and kidney biopsies from nephritic...... (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i...

  19. Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans.

    Science.gov (United States)

    Cruz, E; Vieira, J; Gonçalves, R; Alves, H; Almeida, S; Rodrigues, P; Lacerda, R; Porto, G

    2004-07-01

    Variability in T-lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T-lymphocyte numbers. Two approaches were used. Association studies between T-cell counts (CD4(+) and CD8(+)) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T-cell counts in relation to HLA-HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA-A*01 with high numbers of CD8(+) T cells and a less powerful association with the HLA-A*24 with low numbers of CD8(+) T cells. Sibpair correlations revealed the most significant correlation for CD8(+) T-cell numbers for sibpairs with HLA-HFE-identical haplotypes. This was not observed for CD4(+) T cells. These results show that the MHC region is involved in the genetic regulation of CD8(+) T-cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications.

  20. BIM-Enabled Conceptual Modelling and Representation of Building Circulation

    Directory of Open Access Journals (Sweden)

    Jin Kook Lee

    2014-08-01

    Full Text Available This paper describes how a building information modelling (BIM-based approach for building circulation enables us to change the process of building design in terms of its computational representation and processes, focusing on the conceptual modelling and representation of circulation within buildings. BIM has been designed for use by several BIM authoring tools, in particular with the widely known interoperable industry foundation classes (IFCs, which follow an object-oriented data modelling methodology. Advances in BIM authoring tools, using space objects and their relations defined in an IFC's schema, have made it possible to model, visualize and analyse circulation within buildings prior to their construction. Agent-based circulation has long been an interdisciplinary topic of research across several areas, including design computing, computer science, architectural morphology, human behaviour and environmental psychology. Such conventional approaches to building circulation are centred on navigational knowledge about built environments, and represent specific circulation paths and regulations. This paper, however, places emphasis on the use of ‘space objects’ in BIM-enabled design processes rather than on circulation agents, the latter of which are not defined in the IFCs' schemas. By introducing and reviewing some associated research and projects, this paper also surveys how such a circulation representation is applicable to the analysis of building circulation-related rules.

  1. Method validation for preparing serum and plasma samples from human blood for downstream proteomic, metabolomic, and circulating nucleic acid-based applications.

    Science.gov (United States)

    Ammerlaan, Wim; Trezzi, Jean-Pierre; Lescuyer, Pierre; Mathay, Conny; Hiller, Karsten; Betsou, Fay

    2014-08-01

    Formal method validation for biospecimen processing in the context of accreditation in laboratories and biobanks is lacking. Serum and plasma processing protocols were validated for fitness-for-purpose in terms of key downstream endpoints, and this article demonstrates methodology for biospecimen processing method validation. Serum and plasma preparation from human blood was optimized for centrifugation conditions with respect to microparticle counts. Optimal protocols were validated for methodology and reproducibility in terms of acceptance criteria based on microparticle counts, DNA and hemoglobin concentration, and metabolomic and proteomic profiles. These parameters were also used to evaluate robustness for centrifugation temperature (4°C versus room temperature [RT]), deceleration (low, medium, high) and blood stability (after a 2-hour delay). Optimal protocols were 10-min centrifugation for serum and 20-min for plasma at 2000 g, medium brake, RT. Methodology and reproducibility acceptance criteria were met for both protocols except for reproducibility of plasma metabolomics. Overall, neither protocol was robust for centrifugation at 4°C versus RT. RT gave higher microparticles and free DNA yields in serum, and fewer microparticles with less hemolysis in plasma. Overall, both protocols were robust for fast, medium, and low deceleration, with a medium brake considered optimal. Pre-centrifugation stability after a 2-hour delay was seen at both temperatures for hemoglobin concentration and proteomics, but not for microparticle counts. We validated serum and plasma collection methods suitable for downstream protein, metabolite, or free nucleic acid-based applications. Temperature and pre-centrifugation delay can influence analytic results, and laboratories and biobanks should systematically record these conditions in the scope of accreditation.

  2. Human immunodeficiency virus type 1 subtype B ancestral envelope protein is functional and elicits neutralizing antibodies in rabbits similar to those elicited by a circulating subtype B envelope.

    Science.gov (United States)

    Doria-Rose, N A; Learn, G H; Rodrigo, A G; Nickle, D C; Li, F; Mahalanabis, M; Hensel, M T; McLaughlin, S; Edmonson, P F; Montefiori, D; Barnett, S W; Haigwood, N L; Mullins, J I

    2005-09-01

    Human immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine development, in part because of its ever-expanding genetic diversity and attendant capacity to escape immunologic recognition. Vaccine efficacy might be improved by maximizing immunogen antigenic similarity to viruses likely to be encountered by vaccinees. To this end, we designed a prototype HIV-1 envelope vaccine using a deduced ancestral state for the env gene. The ancestral state reconstruction method was shown to be >95% accurate by computer simulation and 99.8% accurate when estimating the known inoculum used in an experimental infection study in rhesus macaques. Furthermore, the deduced ancestor gene differed from the set of sequences used to derive the ancestor by an average of 12.3%, while these latter sequences were an average of 17.3% different from each other. A full-length ancestral subtype B HIV-1 env gene was constructed and shown to produce a glycoprotein of 160 kDa that bound and fused with cells expressing the HIV-1 coreceptor CCR5. This Env was also functional in a virus pseudotype assay. When either gp160- or gp140-expressing plasmids and recombinant gp120 were used to immunize rabbits in a DNA prime-protein boost regimen, the artificial gene induced immunoglobulin G antibodies capable of weakly neutralizing heterologous primary HIV-1 strains. The results were similar for rabbits immunized in parallel with a natural isolate, HIV-1 SF162. Further design efforts to better present conserved neutralization determinants are warranted.

  3. Radiology of liver circulation

    International Nuclear Information System (INIS)

    Hermine, C.L.

    1985-01-01

    This book proposes that careful evaluation of the arterioportogram is the cornerstone in assessing portal flow obstruction, being the most consistent of all observations including liver histology, portal venous pressure, size and number of portosystemic collaterals, and wedged hepatic venous pressure. Very brief chapters cover normal hepatic circulation and angiographic methods. Contrast volumes and flow rates for celiac, hepatic, and superior mesenteric injection are given, with the timing for venous phase radiographs. In the main body of the text, portal obstruction is divided very simply into presinusoidal (all proximal causes) and postsinusoidal (all distal causes, including Budd-Chiari). Changes are discussed regarding the splenic artery and spleen; hepatic artery and its branches; portal flow rate and direction; and arterioportal shunting and portosystemic collateral circulation in minimal, moderate, severe, and very severe portal obstruction and in recognizable entities such as prehepatic portal and hepatic venous obstructions. The major emphasis in this section is the recognition and understanding of flow changes by which level and severity of obstruction are assessed (not simply the anatomy of portosystemic collateral venous flow). Excellent final chapters discuss the question of portal hypertension without obstruction, and the contribution of arterioportography to the treatment of portal hypertension, again with an emphasis on hemodynamics before and after shunt surgery. There is a fascinating final chapter on segmental intrahepatic obstruction without portal hypertension that explains much of the unusual contrast enhancement sometimes seen in CT scanning of hepatic mass lesions

  4. Circulation Systems Past and Present

    Directory of Open Access Journals (Sweden)

    Maurice J. Freedman

    1981-01-01

    Full Text Available A review of the development of circulation systems shows two areas of change. The librarian's perception of circulation control has shifted from a broad service orientation to a narrow record-keeping approach and recently back again. The technological development of circulation sys-tems has evolved from manual systems to the online systems of today. The trade-offs and deficiencies of earlier systems in relation to the comprehensive services made possible by the online computer are detailed.

  5. The ocean circulation inverse problem

    National Research Council Canada - National Science Library

    Wunsch, C

    1996-01-01

    .... This book addresses the problem of inferring the state of the ocean circulation, understanding it dynamically, and even forecasting it through a quantitative combination of theory and observation...

  6. Persistent sample circulation microextraction combined with graphite furnace atomic absorption spectroscopy for trace determination of heavy metals in fish species marketed in Kermanshah, Iran, and human health risk assessment.

    Science.gov (United States)

    Safari, Yahya; Karimaei, Mostafa; Sharafi, Kiomars; Arfaeinia, Hossein; Moradi, Masoud; Fattahi, Nazir

    2018-06-01

    Persistent sample circulation microextraction (PSCME) combined with graphite furnace atomic absorption spectrometry (GFAAS) was developed as a high pre-concentration technique for the determination of heavy metals in fish species. In this method, a few microliters of organic solvent (40.0 µL carbon tetrachloride) was transferred to the bottom of a conical sample cup. Then 10.0 mL of aqueous solution was transformed to fine droplets while passing through the organic solvent. At this stage, metal-ligand hydrophobic complex was extracted into the organic solvent. After extraction, 20 µL of extraction solvent was injected into the graphite tube using an auto-sampler. Under optimal conditions, enrichment factors and enhancement factor were in the range of 180-240 and 155-214, respectively. The calibration curves were linear in the range of 0.03-200 µg kg -1 and the limits of detection (LODs) were in the range of 0.01-0.05 µg kg -1 . Repeatability (intra-day) and reproducibility (inter-day) for 0.50 µg L -1 Hg and 0.10 µg L -1 Cd and Pb were in the range of 3.1-4.2% (n = 7) and 4.3-6.1% (n = 7), respectively. Potential human health risk assessment was conducted by calculating estimated weekly intake (EWI) of the metals from eating fish and comparison of these values with provisional tolerable weekly intake (PTWI) values. EWI data for the studied metals through fish consumption were lower than the PTWI values. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  7. Sino-Danish Brain Circulation

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe

    2014-01-01

    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  8. Circulating elastin peptides, role in vascular pathology.

    Science.gov (United States)

    Robert, L; Labat-Robert, J

    2014-12-01

    The atherosclerotic process starts with the degradation of elastic fibers. Their presence was demonstrated in the circulation as well as several of their biological properties elucidated. We described years ago a procedure to obtain large elastin peptides by organo-alkaline hydrolysis, κ-elastin. This method enabled also the preparation of specific antibodies used to determine elastin peptides, as well as anti-elastin antibodies in body fluids and tissue extracts. Elastin peptides were determined in a large number of human blood samples. Studies were carried out to explore their pharmacological properties. Similar recent studies by other laboratories confirmed our findings and arose new interest in circulating elastin peptides for their biological activities. This recent trend justified the publication of a review of the biological and pathological activities of elastin peptides demonstrated during our previous studies, subject of this article. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Natural Circulation with Boiling

    Energy Technology Data Exchange (ETDEWEB)

    Mathisen, R P

    1967-09-15

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed.

  10. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Science.gov (United States)

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Köhl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24°N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model's winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow.

  11. Fragment Length of Circulating Tumor DNA.

    Science.gov (United States)

    Underhill, Hunter R; Kitzman, Jacob O; Hellwig, Sabine; Welker, Noah C; Daza, Riza; Baker, Daniel N; Gligorich, Keith M; Rostomily, Robert C; Bronner, Mary P; Shendure, Jay

    2016-07-01

    Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.

  12. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  13. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  14. Proper Sizing of Circulation Pumps

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Nørgaard, Jørgen

    2007-01-01

    The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust, but the r......The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust...

  15. Circulating immune complexes – reviewing the biological roles in ...

    African Journals Online (AJOL)

    Circulating immune complexes – reviewing the biological roles in human immune function and exercise. ... studies that have investigated CIC's following exercise and proposes that a comprehensive understanding and interpretation of immune system responses to exercise should take these complexes into consideration.

  16. [Entomologic situation regarding arbovirus circulation in the Guajaibon area].

    Science.gov (United States)

    Fuentes González, O; Fernández Martínez, A; Castex Rodríguez, M; Pelegrino Martínez, J L

    1989-01-01

    The collections of culicidae made in the Guajaibón area, North coast of Havana province, are analyzed with arbovirologic purposes. The predominance of Aedes scapularis in the human bait collections is confirmed. The possibility of arbovirus circulation in the area is suggested.

  17. VanderLaan Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Hongyan Pan

    2015-01-01

    Full Text Available Circulant matrices have become a satisfactory tools in control methods for modern complex systems. In the paper, VanderLaan circulant type matrices are presented, which include VanderLaan circulant, left circulant, and g-circulant matrices. The nonsingularity of these special matrices is discussed by the surprising properties of VanderLaan numbers. The exact determinants of VanderLaan circulant type matrices are given by structuring transformation matrices, determinants of well-known tridiagonal matrices, and tridiagonal-like matrices. The explicit inverse matrices of these special matrices are obtained by structuring transformation matrices, inverses of known tridiagonal matrices, and quasi-tridiagonal matrices. Three kinds of norms and lower bound for the spread of VanderLaan circulant and left circulant matrix are given separately. And we gain the spectral norm of VanderLaan g-circulant matrix.

  18. Serological evaluation of Crimean-Congo hemorrhagic fever in humans with high-risk professions living in enzootic regions of Isfahan province of Iran and genetic analysis of circulating strains

    DEFF Research Database (Denmark)

    Chinikar, Sadegh; Ghiasi, Seyed Mojtaba; Naddaf, Saeed

    2012-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease that is asymptomatic in infected livestock, but causes a serious threat to humans with a mortality rate up to 50%. Although the CCHF virus (CCHFV) is often transmitted by ticks, livestock-to-human and human-to-human transmission a...

  19. Circulating cell-free DNA and circulating tumor cells, the "liquid biopsies" in ovarian cancer.

    Science.gov (United States)

    Cheng, Xianliang; Zhang, Lei; Chen, Yajuan; Qing, Chen

    2017-11-13

    Limited understanding of ovarian cancer (OC) genome portrait has hindered the therapeutic advances. The serial monitoring of tumor genotypes is becoming increasingly attainable with circulating cell-free DNA (cf-DNA) and circulating tumor cells (CTCs) emerging as "liquid biopsies". They represent non-invasive biomarkers and are viable, as they can be isolated from human plasma, serum and other body fluids. Molecular characterization of circulating tumor DNA (ct-DNA) and CTCs offer unique potentials to better understand the biology of metastasis and resistance to therapies. The liquid biopsies may also give innovative insights into the process of rapid and accurate identification, resistant genetic alterations and a real time monitoring of treatment responses. In addition, liquid biopsies are shedding light on elucidating signal pathways involved in invasiveness and metastasis competence; but the detection and molecular characterization of ct-DNA and CTCs are still challenging, since they are rare, and the amount of available samples are very limited. This review will focus on the clinical potential of ct-DNA and CTCs in both the early and advanced diagnosis, prognosis, and in the identification of resistance mutations in OC.

  20. Atmospheric circulation classification comparison based on wildfires in Portugal

    Science.gov (United States)

    Pereira, M. G.; Trigo, R. M.

    2009-04-01

    Atmospheric circulation classifications are not a simple description of atmospheric states but a tool to understand and interpret the atmospheric processes and to model the relation between atmospheric circulation and surface climate and other related variables (Radan Huth et al., 2008). Classifications were initially developed with weather forecasting purposes, however with the progress in computer processing capability, new and more robust objective methods were developed and applied to large datasets prompting atmospheric circulation classification methods to one of the most important fields in synoptic and statistical climatology. Classification studies have been extensively used in climate change studies (e.g. reconstructed past climates, recent observed changes and future climates), in bioclimatological research (e.g. relating human mortality to climatic factors) and in a wide variety of synoptic climatological applications (e.g. comparison between datasets, air pollution, snow avalanches, wine quality, fish captures and forest fires). Likewise, atmospheric circulation classifications are important for the study of the role of weather in wildfire occurrence in Portugal because the daily synoptic variability is the most important driver of local weather conditions (Pereira et al., 2005). In particular, the objective classification scheme developed by Trigo and DaCamara (2000) to classify the atmospheric circulation affecting Portugal have proved to be quite useful in discriminating the occurrence and development of wildfires as well as the distribution over Portugal of surface climatic variables with impact in wildfire activity such as maximum and minimum temperature and precipitation. This work aims to present: (i) an overview the existing circulation classification for the Iberian Peninsula, and (ii) the results of a comparison study between these atmospheric circulation classifications based on its relation with wildfires and relevant meteorological

  1. The Donders model of the circulation in normo- and pathophysiology

    DEFF Research Database (Denmark)

    Noordergraaf, Gerrit J.; Ottesen, Johnny T.; Kortsmit, Wil J.P.M.

    2006-01-01

    the continuum of physiological conditions to cardiopulmonary resuscitation effects within the circulation.   Within the model, Harvey's view of the circulation has been broadened to include impedance-defined flow as a unifying concept. The cardiac function curve, the relation between ventricular filling...... and output, changes during exercise. First, it rotates counterclockwise and stretches along the output axis, second, it shifts along the filling axis. The first is induced by sympathetic control, the second by respiratory control. The model shows that depth of respiration, sympathetic stimulation of cardiac......A model of the closed human cardiovascular loop is developed. This model, using one set of 88 equations, allows variations from normal resting conditions to exercise, as well as to the extreme condition of a circulation following cardiac arrest. The principal purpose of the model is to evaluate...

  2. Journalism as Cultures of Circulation

    DEFF Research Database (Denmark)

    Bødker, Henrik

    2013-01-01

    The universe of journalism has always consisted of interspersed texts, meanings and practices. Yet, much journalism research has often isolated either texts and/or contexts and as such assumed relations between professional practices, informed (rational) readers and (conceived) core texts...... of journalism. It is, however, more important than ever to shift attention away from texts to the processes through which they are circulated. This is partly because the many cultural forms of journalism (textual, institutional, technological, material, behavioural and imagined) are undergoing significant......, likes, comments, searches, journalist roles, writing and reading positions and identities etc. Such forms will be traced within the mediation of a specific event with the overall aim of beginning a theorization of the landscape of journalism as highly interrelated cultures of circulation....

  3. Radioisotopic evaluation of portal circulation

    International Nuclear Information System (INIS)

    Maliska, C.; Rosenthal, D.

    1986-01-01

    The use of a radio-tracer of portal circulation through the intestine, should prevent cruel punctures in the portal-vein or spleen as it is usually the case with traditional methods in the study of portal-system. The absorption of I-131 and Tc-99m, previously cheked in rabbits presented similar results in dogs. The time of circulation between terminal large-intestine and the liver (t-RF) was determined by external counting at hepatic level by recording radioactivity variation-time. In healthy animals the t-RF was from 20to 60 seconds, with average time of 42 seconds. In 2 animals with partial binding of portal-vein the t-RF went up to 110 and 120 seconds. (Author) [pt

  4. Ocean circulation generated magnetic signals

    DEFF Research Database (Denmark)

    Manoj, C.; Kuvshinov, A.; Maus, S.

    2006-01-01

    Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification...... of ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume...... of the magnetic field, as compared to the ECCO simulation. Besides the expected signatures of the global circulation patterns, we find significant seasonal variability of ocean magnetic signals in the Indian and Western Pacific Oceans. Compared to seasonal variation, interannual variations produce weaker signals....

  5. Observations of Local Seychelles Circulation

    Science.gov (United States)

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Observations of Local Seychelles Circulation Geno...goal for the proposed work is to develop predictive capabilities for physical oceanography for the Seychelles region in support of locally relevant...observations in the Seychelles region that will lead to long-term data collection efforts. In collaboration with local partnerships, we will carry out

  6. Circulating nucleic acids and evolution.

    Science.gov (United States)

    Anker, Philippe; Stroun, Maurice

    2012-06-01

    J.B. Lamarck in 1809 was the first to present a theory of evolution. He proposed it was due to the adaptation of species to environmental changes, this adaptation being acquired by the offspring. In 1868, Darwin suggested that cells excrete gemmules, which circulate through the body and reach the gonads where they are transmitted to the next generation. His main argument came from graft hybrids. In the fifties and sixties, Russian geneticists, rejecting neo-Darwinism, said that acquired characteristics were the basis of evolution. The main experiments on which they based their theory were the transmission of hereditary characteristics by a special technique of grafting between two varieties of plants. We repeated this kind of experiment and also succeeded in obtaining hereditary modifications of the pupil plants that acquired some characteristics of the mentor variety. Rather than adopting the views of the Russian scientists, we suggested that DNA was circulating between the mentor and pupil plants. Hirata's group have shown recently, by using molecular techniques such as cloning, RFLP PCR and sequencing some genes of their graft hybrids of pepper plants, that transfer of informative molecules from the mentor to the pupil plant does exist. Nucleic acids are actively released by cells; they circulate in the body. They can transform oncogenically or trigger antibody response but the only genetic transformation showing that DNA can go from the soma to the germen comes from graft hybrids. This suggests that circulating nucleic acids, in this case DNA, like Darwin's gemmules, play a role in the mechanism of evolution.

  7. Improvement of Classification of Enterprise Circulating Funds

    OpenAIRE

    Rohanova Hanna O.

    2014-01-01

    The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, ...

  8. Hall Effect Gyrators and Circulators

    Science.gov (United States)

    Viola, Giovanni; DiVincenzo, David P.

    2014-04-01

    The electronic circulator and its close relative the gyrator are invaluable tools for noise management and signal routing in the current generation of low-temperature microwave systems for the implementation of new quantum technologies. The current implementation of these devices using the Faraday effect is satisfactory but requires a bulky structure whose physical dimension is close to the microwave wavelength employed. The Hall effect is an alternative nonreciprocal effect that can also be used to produce desired device functionality. We review earlier efforts to use an Ohmically contacted four-terminal Hall bar, explaining why this approach leads to unacceptably high device loss. We find that capacitive coupling to such a Hall conductor has much greater promise for achieving good circulator and gyrator functionality. We formulate a classical Ohm-Hall analysis for calculating the properties of such a device, and show how this classical theory simplifies remarkably in the limiting case of the Hall angle approaching 90°. In this limit, we find that either a four-terminal or a three-terminal capacitive device can give excellent circulator behavior, with device dimensions far smaller than the ac wavelength. An experiment is proposed to achieve GHz-band gyration in millimeter (and smaller) scale structures employing either semiconductor heterostructure or graphene Hall conductors. An inductively coupled scheme for realizing a Hall gyrator is also analyzed.

  9. Encoders for block-circulant LDPC codes

    Science.gov (United States)

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2009-01-01

    Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

  10. Early concepts and charts of ocean circulation

    Science.gov (United States)

    Peterson, R. G.; Stramma, L.; Kortum, G.

    Charts of ocean currents from the late nineteenth century show that already by then the patterns of surface circulation in regions away from polar latitudes were well understood. This fundamental knowledge accumulated gradually through centuries of sea travel and had reached a state of near correctness by the time dedicated research cruises, full-depth measurements and the practical application of the dynamical method were being instituted. Perhaps because of the foregoing, many of the pioneering works, critical to establishing what the upper-level circulation is like, the majority of the charts accompanying them, and several of the groundbreaking theoretical treatments on the physics of currents, are only poorly known to present-day oceanographers. In this paper we trace Western developments in knowledge and understanding of ocean circulation from the earliest times to the late-1800s transition into the modern era. We also discuss certain peripheral advances that proved critical to the subject. The earliest known ideas, dating from the Bronze Age and described by Homer, necessarily reflect severe limitations to geographical knowledge, as well as basic human predilections toward conjecture and exaggeration in the face of inadequate information. People considered the earth to be flat and circular, with the ocean flowing like a river around it. They also believed in horrific whirlpools, a concept that persisted into the Renaissance and which would later provide subject material for modern literature. From the Greek Classical Age, we find hydrologic theories of Earth's interior being laced with subterranean channels (Socrates) and all motion deriving from a divine force forever propelling the heavens toward the west, the primum mobile (Aristotle). These ideas, particularly the latter, dominated opinions about ocean circulation into the late Renaissance. By late Antiquity mariners had very likely acquired intimate knowledge of coastal currents in the Mediterranean, but

  11. Large scale atmospheric tropical circulation changes and consequences during global warming

    International Nuclear Information System (INIS)

    Gastineau, G.

    2008-01-01

    The changes of the tropical large scale circulation during climate change can have large impacts on human activities. In a first part, the meridional atmospheric tropical circulation was studied in the different coupled models. During climate change, we find, on the one hand, that the Hadley meridional circulation and the subtropical jet are significantly shifted poleward, and on the other hand, that the intensity of the tropical circulation weakens. The slow down of the atmospheric circulation results from the dry static stability changes affecting the tropical troposphere. Secondly, idealized simulations are used to explain the tropical circulation changes. Ensemble simulation using the model LMDZ4 are set up to study the results from the coupled model IPSLCM4. The weakening of the large scale tropical circulation and the poleward shift of the Hadley cells are explained by both the uniform change and the meridional gradient change of the sea surface temperature. Then, we used the atmospheric model LMDZ4 in an aqua-planet configuration. The Hadley circulation changes are explained in a simple framework by the required poleward energy transport. In a last part, we focus on the water vapor distribution and feedback in the climate models. The Hadley circulation changes were shown to have a significant impact on the water vapour feedback during climate change. (author)

  12. Diarrhea caused by circulating agents.

    Science.gov (United States)

    Fabian, Elisabeth; Kump, Patrizia; Krejs, Guenter J

    2012-09-01

    Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Vasculitis of the mesenteric circulation.

    Science.gov (United States)

    Koster, Matthew J; Warrington, Kenneth J

    2017-02-01

    Vasculitis of the mesenteric circulation is an uncommon but life-threatening manifestation of systemic vasculitis. Initial symptoms are frequently non-specific and therefore patients often present to primary care physicians and gastroenterologists with abdominal pain or gastrointestinal bleeding. Given the severity of the conditions associated with mesenteric vasculitis, it is imperative to appropriately diagnose and initiate treatment of suspected cases. This review will focus on diseases commonly associated with vasculitis of the mesenteric vessels. Imaging characteristics and clinical features assisting in diagnosis as well as initial approaches to treatment are emphasized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  15. Novel reassortant swine influenza viruses are circulating in Danish pigs

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    of the reassortant viruses comprised a HA gene similar to H1 of H1N1 avian-like swine influenza virus (SIV) and a NA gene most closely related to N2 gene of human H3N2 influenza virus that circulated in humans in the mid 1990s. The internal genes of this reassortant virus with the subtype H1avN2hu all belonged...... to the H1N1 avian-like SIV lineages. Until now this novel virus H1avN2hu has only been detected in Danish swine. The other novel reassortant virus contained the HA gene from H1N1pdm09 virus and a NA gene similar to the N2 gene of H3N2 SIV that have been circulating in European swine since the mid 1980s...

  16. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  17. Roadmap for cardiovascular circulation model

    Science.gov (United States)

    Bradley, Christopher P.; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R.; Omholt, Stig W.; Chase, J. Geoffrey; Müller, Lucas O.; Watanabe, Sansuke M.; Blanco, Pablo J.; de Bono, Bernard; Hunter, Peter J.

    2016-01-01

    Abstract Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well‐established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo‐skeletal system. The computational infrastructure for the cardiovascular model should provide for near real‐time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model. PMID:27506597

  18. Serological evaluation of Crimean-Congo hemorrhagic fever in humans with high-risk professions living in enzootic regions of Isfahan province of Iran and genetic analysis of circulating strains.

    Science.gov (United States)

    Chinikar, Sadegh; Ghiasi, Seyed M; Naddaf, Saeed; Piazak, Norair; Moradi, Maryam; Razavi, Mohammad R; Afzali, Neda; Haeri, Ali; Mostafavizadeh, Kamyar; Ataei, Behrouz; Khalilifard-Brojeni, Mohammad; Husseini, Sayed M; Bouloy, Michele

    2012-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease that is asymptomatic in infected livestock, but causes a serious threat to humans with a mortality rate up to 50%. Although the CCHF virus (CCHFV) is often transmitted by ticks, livestock-to-human and human-to-human transmission also occurs. In the current study, we focused on CCHF in the province of Isfahan, located in the center of Iran and deemed to be the second most infected province. Human and livestock sera and resident ticks in the livestock are collected from different regions of the province and analyzed with specific IgG ELISA and RT-PCR tests. Overall, 12% and 12.7% of studied human and livestock populations were IgG positive, respectively. The genome of CCHFV was detected in 9% of ticks resident in livestock involved in this survey. The CCHFV isolates from infected ticks were genetically examined. Nucleotide sequence of the S-segment revealed that the different isolates were closely related to each other, with nucleotide sequence identities higher than 98%. Phylogenetic analysis demonstrated that a variant isolate clustered with the Iraq strain. This high proportion of IgG-positive sera and nearly high proportion of infected ticks increases the risk of CCHF outbreaks in the province and probably posits a great danger to other provinces.

  19. Stressed lungs: unveiling the role of circulating stress ...

    Science.gov (United States)

    Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction with lung lining components causing local oxidative changes, which then leads to cell damage and recruitment of inflammatory cells. It is postulated that the spillover of reactive intermediates and pro-inflammatory molecules from lung to systemic circulation mediates extra-pulmonary effects. However, recent work from our laboratory supports an alternative hypothesis that circulating stress hormones, such as epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects. We have shown in rats and humans that ozone increases the levels of circulating stress hormones through activation of the hypothalamus- pituitary-adrenal (HPA) axis before any measurable effects are observed in the lung. The surgical removal of adrenals diminishes circulating stress hormones and at the same time, the pulmonary effects of ozone suggesting a significant contribution of these hormones in ozone-induced lung injury and inflammation. While ozone effects in the lung have been extensively studied, the contribution of central nervous system -mediated hormonal stress response has not been examined. In order to understand the signaling pathways that might be involved in ozone-induced lun

  20. Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss.

    Science.gov (United States)

    Rivolta, C; Sweklo, E A; Berson, E L; Dryja, T P

    2000-06-01

    Microdeletions Glu767(1-bp del), Thr967(1-bp del), and Leu1446(2-bp del) in the human USH2A gene have been reported to cause Usher syndrome type II, a disorder characterized by retinitis pigmentosa (RP) and mild-to-severe hearing loss. Each of these three frameshift mutations is predicted to lead to an unstable mRNA transcript that, if translated, would result in a truncated protein lacking the carboxy terminus. Here, we report Cys759Phe, a novel missense mutation in this gene that changes an amino-acid residue within the fifth laminin-epidermal growth factor-like domain of the USH2A gene and that is associated with recessive RP without hearing loss. This single mutation was found in 4.5% of 224 patients with recessive RP, suggesting that USH2A could cause more cases of nonsyndromic recessive RP than does any other gene identified to date.

  1. Uranus atmospheric dynamics and circulation

    Science.gov (United States)

    Allison, Michael; Beebe, Reta F.; Conrath, Barney J.; Hinson, David P.; Ingersoll, Andrew P.

    1991-01-01

    The observations, models, and theories relevant to the atmospheric dynamics and meteorology of Uranus are discussed. The available models for the large-scale heat transport and atmospheric dynamics as well as diagnostic interpretations of the Voyager data are reviewed. Some pertinent ideas and questions regarding the global circulation balance are considered, partly in comparison with other planetary atmospheres. The available data indicate atmospheric rotation at midlatitudes nearly 200 m/s faster than that of the planetary magnetic field. Analysis of the dynamical deformation of the shape and size of isobaric surfaces measured by the Voyager radio-occultation experiment suggests a subrotating equator at comparable altitudes. Infrared temperature retrievals above the cloud deck indicate a smaller equator-to-pole contrast than expected for purely radiative-convective equilibrium, but show local variations implying a latitudinally correlated decrease with altitude in the cloud-tracked wind.

  2. Improvement of Classification of Enterprise Circulating Funds

    Directory of Open Access Journals (Sweden)

    Rohanova Hanna O.

    2014-02-01

    Full Text Available The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, which clearly shows the role of circulating funds in managing enterprise finance and economy in general. The article supplements and groups classification features of enterprise circulating funds by: the organisation level, functioning character, sources of formation and their cost, and level of management efficiency. The article shows that the provided grouping of classification features of circulating funds allows exerting all-sided and purposeful influence upon indicators of efficiency of circulating funds functioning and facilitates their rational management in general. The prospect of further studies in this direction is identification of the level of attraction of loan resources by production enterprises for financing circulating funds.

  3. NPP Krsko natural circulation performance evaluation

    International Nuclear Information System (INIS)

    Segon, Velimir; Bajs, Tomislav; Frogheri, Monica

    1999-01-01

    The present document deals with an evaluation of the natural circulation performance of the Krsko nuclear power plant. Two calculation have been performed using the NPP Krsko nodalization (both similar to the LOBI A2-77 natural circulation experiment) - the first with the present steam generators at NPP Krsko (Westinghouse, 18% plugged), the second with the future steam generators (Siemens, 0% plugged). The results were evaluated using the natural circulation flow map derived in /1/, and were compared to evaluate the influence of the new steam generators on the natural circulation performance. (author)

  4. Basic natural circulation characteristics of SBWR

    International Nuclear Information System (INIS)

    Kuran, S.; Soekmen, C. N.

    2001-01-01

    Natural circulation is an important passive heat removal mechanism for both existing and next generation light water reactors. Simplified Boiling Water Reactor (SBWR) is one of the advanced light water reactors that rely on natural circulation for normal as well as emergency core cooling. In this study, basic natural circulation characteristics of this reactor are examined on a flow loop that simulates the operation of SBWR. On this model, effect of system operating parameters on the steady state natural circulation characteristics inside the loop is studied via solving the transcendental equation for loop flow rate

  5. Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells

    Science.gov (United States)

    Fan, Rong; Emery, Travis; Zhang, Yongguo; Xia, Yuxuan; Sun, Jun; Wan, Jiandi

    2016-06-01

    During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm2), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of β-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model, and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis.

  6. Natural circulation in reactor coolant system

    International Nuclear Information System (INIS)

    Han, J.T.

    1987-01-01

    Reactor coolant system (RCS) natural circulation in a PWR is the buoyancy-driven coolant circulation between the core and the upper-plenum region (in-vessel circulation) with or without a countercurrent flow in the hot leg piping between the vessel and steam generators (ex-vessel circulation). This kind of multidimensional bouyancy-driven flow circulation serves as a means of transferring the heat from the core to the structures in the upper plenum, hot legs, and possibly steam generators. As a result, the RCS piping and other pressure boundaries may be heated to high temperatures at which the structural integrity is challenged. RCS natural circulation is likely to occur during the core uncovery period of the TMLB' accident in a PWR when the vessel upper plenum and hot leg are already drained and filled with steam and possibly other gaseous species. RCS natural circulation is being studied for the Surry plant during the TMLB' accident in which station blackout coincides with the loss of auxiliary feedwater and no operator actions. The effects of the multidimensional RCS natural circulation during the TMLB' accident are discussed

  7. Circulating follistatin in relation to energy metabolism

    DEFF Research Database (Denmark)

    Hansen, Jakob Schiøler; Plomgaard, Peter

    2016-01-01

    a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated...

  8. Extraembryonic origin of circulating endothelial cells.

    Directory of Open Access Journals (Sweden)

    Luc Pardanaud

    Full Text Available Circulating endothelial cells (CEC are contained in the bone marrow and peripheral blood of adult humans and participate to the revascularization of ischemic tissues. These cells represent attractive targets for cell or gene therapy aimed at improving ischemic revascularization or inhibition of tumor angiogenesis. The embryonic origin of CEC has not been addressed previously. Here we use quail-chick chimeras to study CEC origin and participation to the developing vasculature. CEC are traced with different markers, in particular the QH1 antibody recognizing only quail endothelial cells. Using yolk-sac chimeras, where quail embryos are grafted onto chick yolk sacs and vice-versa, we show that CEC are generated in the yolk sac. These cells are mobilized during wound healing, demonstrating their participation to angiogenic repair processes. Furthermore, we found that the allantois is also able to give rise to CEC in situ. In contrast to the yolk sac and allantois, the embryo proper does not produce CEC. Our results show that CEC exclusively originate from extra-embryonic territories made with splanchnopleural mesoderm and endoderm, while definitive hematopoietic stem cells and endothelial cells are of intra-embryonic origin.

  9. Extraembryonic origin of circulating endothelial cells.

    Science.gov (United States)

    Pardanaud, Luc; Eichmann, Anne

    2011-01-01

    Circulating endothelial cells (CEC) are contained in the bone marrow and peripheral blood of adult humans and participate to the revascularization of ischemic tissues. These cells represent attractive targets for cell or gene therapy aimed at improving ischemic revascularization or inhibition of tumor angiogenesis. The embryonic origin of CEC has not been addressed previously. Here we use quail-chick chimeras to study CEC origin and participation to the developing vasculature. CEC are traced with different markers, in particular the QH1 antibody recognizing only quail endothelial cells. Using yolk-sac chimeras, where quail embryos are grafted onto chick yolk sacs and vice-versa, we show that CEC are generated in the yolk sac. These cells are mobilized during wound healing, demonstrating their participation to angiogenic repair processes. Furthermore, we found that the allantois is also able to give rise to CEC in situ. In contrast to the yolk sac and allantois, the embryo proper does not produce CEC. Our results show that CEC exclusively originate from extra-embryonic territories made with splanchnopleural mesoderm and endoderm, while definitive hematopoietic stem cells and endothelial cells are of intra-embryonic origin.

  10. Collateral Circulation in Chronic Total Occlusions - An Interventional Perspective

    Science.gov (United States)

    Choo, Gim-Hooi

    2015-01-01

    Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

  11. Collateral Circulation in Chronic Total Occlusions - an interventional perspective.

    Science.gov (United States)

    Choo, Gim-Hooi

    2015-09-09

    Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

  12. Moderator circulation in CANDU reactors

    International Nuclear Information System (INIS)

    Fath, H.E.S.; Hussein, M.A.

    1989-01-01

    A two-dimensional computer code that is capable of predicting the moderator flow and temperature distribution inside CANDU calandria is presented. The code uses a new approach to simulate the calandria tube matrix by blocking the cells containing the tubes in the finite difference mesh. A jet momentum-dominant flow pattern is predicted in the nonisothermal case, and the effect of the buoyancy force, resulting from nuclear heating, is found to enhance the speed of circulation. Hot spots are located in low-velocity areas at the top of the calandria and below the inlet jet level between the fuel channels. A parametric study is carried out to investigate the effect of moderator inlet velocity,moderator inlet nozzle location, and geometric scaling. The results indicate that decreasing the moderator inlet velocity has no significant influence on the general features of the flow pattern (i.e., momentum dominant); however, too many high-temperature hot spots appear within the fuel channels

  13. Numerical Modeling of Ocean Circulation

    Science.gov (United States)

    Miller, Robert N.

    2007-01-01

    The modelling of ocean circulation is important not only for its own sake, but also in terms of the prediction of weather patterns and the effects of climate change. This book introduces the basic computational techniques necessary for all models of the ocean and atmosphere, and the conditions they must satisfy. It describes the workings of ocean models, the problems that must be solved in their construction, and how to evaluate computational results. Major emphasis is placed on examining ocean models critically, and determining what they do well and what they do poorly. Numerical analysis is introduced as needed, and exercises are included to illustrate major points. Developed from notes for a course taught in physical oceanography at the College of Oceanic and Atmospheric Sciences at Oregon State University, this book is ideal for graduate students of oceanography, geophysics, climatology and atmospheric science, and researchers in oceanography and atmospheric science. Features examples and critical examination of ocean modelling and results Demonstrates the strengths and weaknesses of different approaches Includes exercises to illustrate major points and supplement mathematical and physical details

  14. Circulating microparticles: square the circle

    Science.gov (United States)

    2013-01-01

    Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

  15. Vertical mixing by Langmuir circulations

    International Nuclear Information System (INIS)

    McWilliams, James C.; Sullivan, Peter P.

    2001-01-01

    Wind and surface wave frequently induce Langmuir circulations (LC) in the upper ocean, and the LC contribute to mixing materials down from the surface. In this paper we analyze large-eddy simulation (LES) cases based on surface-wave-averaged, dynamical equations and show that the effect of the LC is a great increase in the vertical mixing efficiency for both material properties and momentum. We provide new confirmation that the previously proposed K-profile parameterization (KPP) model accurately characterizes the turbulent transport in a weakly convective, wind-driven boundary layer with stable interior stratification. We also propose a modest generalization of KPP for the regime of weakly convective Langmuir turbulence. This makes the KPP turbulent flux profiles match those in the LES case with LC present fairly well, especially so for material properties being transported downwards from the ocean surface. However, some open issues remain about how well the present LES and KPP formulations represent Langmuir turbulence, in part because wave-breaking effects are not yet included. (Author)

  16. 46 CFR 56.50-45 - Circulating pumps.

    Science.gov (United States)

    2010-10-01

    ... APPURTENANCES Design Requirements Pertaining to Specific Systems § 56.50-45 Circulating pumps. (a) A main circulating pump and emergency means for circulating water through the main condenser shall be provided. The... circulating pump and the condenser. (b) Independent sea suctions shall be provided for the main circulating...

  17. Development of CO2 circulators

    International Nuclear Information System (INIS)

    Donaldson, J.

    1988-01-01

    The development of the basic machine types we have supplied has not been without problems. The Windscale AGR (the prototype AGR) was a small 1.2 MW vertically up circulator with an inlet temperature of 237 deg. C (459 deg. F). Oil leakage problems occurred and were cured in the works test facility and the machine went into service with no other problems. The Horizontal 5 MW machines for Hinkley/Hunterston were not so fortunate with vibration problems, interface corrosion problems (effecting the whole reactor) and material dimensional stability problems. Oil ingress problems did not show up in test work but were later reported from site. These reports were initially exagerated due to the measuring techniques which took the operators some time to resolve. In the vertical 5 MW machines for Hartlepool and Heysham 1 there are two interesting factors, firstly a spar failure and secondly shaft axial stability. Many of the problems were due to modifications at site or our inability to model all aspects of site installation from which lessons for the future can be learned. The latest stations Torness and Heysham II incorporate these lessons. The machines have been designed with so much margin that during the resolution of the reactor control rod gag problems the machines were run continuously at 20% overload (6.3 MW). From an initial accident case of 350 deg. C inlet temperature, this increased to 458 deg. C and now stands at 585 deg. C. No modifications to the impeller were required. The site experience to date is good with no operational problems reported. (author). 4 figs

  18. SpaceX Dragon Air Circulation System

    Science.gov (United States)

    Hernandez, Brenda; Piatrovich, Siarhei; Prina, Mauro

    2011-01-01

    The Dragon capsule is a reusable vehicle being developed by Space Exploration Technologies (SpaceX) that will provide commercial cargo transportation to the International Space Station (ISS). Dragon is designed to be a habitable module while it is berthed to ISS. As such, the Dragon Environmental Control System (ECS) consists of pressure control and pressure equalization, air sampling, fire detection, illumination, and an air circulation system. The air circulation system prevents pockets of stagnant air in Dragon that can be hazardous to the ISS crew. In addition, through the inter-module duct, the air circulation system provides fresh air from ISS into Dragon. To utilize the maximum volume of Dragon for cargo packaging, the Dragon ECS air circulation system is designed around cargo rack optimization. At the same time, the air circulation system is designed to meet the National Aeronautics Space Administration (NASA) inter-module and intra-module ventilation requirements and acoustic requirements. A flight like configuration of the Dragon capsule including the air circulation system was recently assembled for testing to assess the design for inter-module and intra-module ventilation and acoustics. The testing included the Dragon capsule, and flight configuration in the pressure section with cargo racks, lockers, all of the air circulation components, and acoustic treatment. The air circulation test was also used to verify the Computational Fluid Dynamics (CFD) model of the Dragon capsule. The CFD model included the same Dragon internal geometry that was assembled for the test. This paper will describe the Dragon air circulation system design which has been verified by testing the system and with CFD analysis.

  19. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A.

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management....

  20. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

    Science.gov (United States)

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  1. Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects.

    Directory of Open Access Journals (Sweden)

    María Moreno

    Full Text Available A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans.Circulating irisin levels (ELISA and metabolic parameters were analyzed in 428 subjects (195 men/233 women. Participants were classified according to their self-reported physical activity and to their area of residence.Circulating irisin levels were higher in active than in sedentary subjects (p = 0.006. Rural inhabitants showed higher circulating irisin levels than urban subjects (p < 0.0001. The increase in irisin levels related to an active lifestyle was only observed in rural citizens (p = 0.014. Among sedentary participants, irisin levels were positively associated with metabolic risk factors (BMI, fasting insulin, HOMA and fasting triglycerides. The area of residence (β = - 0.592, p = < 0.0001 contributed independently to circulating irisin levels variance after controlling for age, gender, BMI, HOMAIR, triglycerides and physical activity.In sedentary participants, circulating irisin levels were positively associated with parameters related to an increased cardiometabolic risk. The present study confirmed that an active lifestyle increases circulating irisin levels, but only among subjects living in a rural environment. Area of residence might be a determinant of irisin levels.

  2. Circulating leptin and thyroid dysfunction

    DEFF Research Database (Denmark)

    Zimmermann-Belsing, Tina; Brabant, Georg; Holst, Jens Juul

    2003-01-01

    and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid...

  3. Pleiotrophin levels are associated with improved coronary collateral circulation.

    Science.gov (United States)

    Türker Duyuler, Pinar; Duyuler, Serkan; Gök, Murat; Kundi, Harun; Topçuoğlu, Canan; Güray, Ümit

    2018-01-01

    Elucidation of the underlying mechanisms of angiogenesis and arteriogenesis in coronary collateral formation is necessary for new therapies. Pleiotrophin is a secreted multifunctional cytokine and associated with the formation of functional cardiovascular neovascularization in a series of experimental animal models. We aimed to evaluate the serum levels of pleiotrophin in patients with chronic total coronary artery occlusion and poor or good collateral development. We included 88 consecutive patients (mean age of the entire population: 63.7±12.1 years, 68 male patients) with stable angina pectoris who underwent coronary angiography and had chronic total occlusion in at least one major coronary artery. Collateral grading was performed according to the Rentrop classification. After grading, patients were divided into poor collateral circulation (Rentrop grade 0 and 1) and good collateral circulation (Rentrop grades 2 and 3) groups. Serum pleiotrophin levels were measured using a commercial human ELISA kit. Fifty-eight patients had good and 30 patients had poor coronary collaterals. The good collateral group had higher serum pleiotrophin levels than the poor collateral group (690.1±187.9 vs. 415.3±165.9 ng/ml, Pcollateral development (odds ratio: 1.007; confidence interval: 1.003-1.012; P=0.002). This study showed that increased serum pleiotrophin levels are associated with better developed coronary collateral circulation. Further studies are needed to better understand the relationship.

  4. Circulating microRNAs as Potential Biomarkers of Infectious Disease

    Science.gov (United States)

    Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

    2017-01-01

    microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

  5. [Circulating endothelial cells: biomarkers for monitoring activity of antiangiogenic therapy].

    Science.gov (United States)

    Farace, Françoise; Bidart, Jean-Michel

    2007-07-01

    Tumor vessel formation is largely dependent on the recruitment of endothelial cells. Rare in healthy individuals, circulating endothelial cells (CEC) are shed from vessel walls and enter the circulation reflecting endothelial damage or dysfunction. Increased numbers of CEC have been documented in different types of cancer. Recent studies have suggested the role for CEC in tumor angiogenesis, but whose presence could also reflect normal endothelium perturbation in cancer. Originating from the bone marrow rather than from vessel walls, endothelial progenitor cells (EPC) are mobilized following tissue ischemia and may be recruited to complement local angiogenesis supplied by existing endothelium. Recently, studies in mouse models suggest that the circulating fraction of endothelial progenitors (CEP) is involved in tumor angiogenesis but their contribution is less clear in humans. The detection of CEC and CEP is difficult and impeded by the rarity of these cells. They may have important clinical implication as novel biomarkers susceptible to predict more efficiently and rapidly the therapeutic response to anti-angiogenic treatments. However, a methodological consensus would be necessary in order to correctly evaluate the clinical interest of CEC and CEP in patients.

  6. Seawater circulating system in an aquaculture laboratory

    Digital Repository Service at National Institute of Oceanography (India)

    Chatterji, A.; Ingole, B.S.; Parulekar, A.H.

    The note gives an account, for the first time in India, of an Aquaculture Laboratory with open type seawater circulating system developed at the National Institute of Oceanography, Goa, India. Besides describing the details of the system...

  7. EOP MIT General Circulation Model (MITgcm)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data contains a regional implementation of the Massachusetts Institute of Technology general circulation model (MITgcm) at a 1-km spatial resolution for the...

  8. Seasonal Overturning Circulation in the Red Sea

    Science.gov (United States)

    Yao, F.; Hoteit, I.; Koehl, A.

    2010-12-01

    The Red Sea exhibits a distinct seasonal overturning circulation. In winter, a typical two-layer exchange structure, with a fresher inflow from the Gulf of Aden on top of an outflow from the Red Sea, is established. In summer months (June to September) this circulation pattern is changed to a three-layer structure: a surface outflow from the Red Sea on top of a subsurface intrusion of the Gulf of Aden Intermediate Water and a weakened deep outflow. This seasonal variability is studied using a general circulation model, MITgcm, with 6 hourly NCEP atmospheric forcing. The model is able to reproduce the observed seasonal variability very well. The forcing mechanisms of the seasonal variability related to seasonal surface wind stress and buoyancy flux, and water mass transformation processes associated with the seasonal overturning circulation are analyzed and presented.

  9. Blocking device especially for circulating pumps

    International Nuclear Information System (INIS)

    Susil, J.; Vychodil, V.; Lorenc, P.

    1976-01-01

    The claim of the invention is a blocking device which blocks reverse flow occurring after the shutdown of circulating pumps, namely in the operation of nuclear power plants or in pumps with a high delivery head. (F.M.)

  10. Estuarine turbidity, flushing, salinity, and circulation

    Science.gov (United States)

    Pritchard, D. W.

    1972-01-01

    The effects of estuarine turbidity, flushing, salinity, and circulation on the ecology of the Chesapeake Bay are discussed. The sources of fresh water, the variations in salinity, and the circulation patterns created by temperature and salinity changes are analyzed. The application of remote sensors for long term observation of water temperatures is described. The sources of sediment and the biological effects resulting from increased sediments and siltation are identified.

  11. [Circulating tumor cells: cornerstone of personalized medicine].

    Science.gov (United States)

    Rafii, A; Vidal, F; Rathat, G; Alix-Panabières, C

    2014-11-01

    Cancer treatment has evolved toward personalized medicine. It is mandatory for clinicians to ascertain tumor biological features in order to optimize patients' treatment. Identification and characterization of circulating tumor cells demonstrated a prognostic value in many solid tumors. Here, we describe the main technologies for identification and characterization of circulating tumor cells and their clinical application in gynecologic and breast cancers. Copyright © 2014. Published by Elsevier Masson SAS.

  12. Themes on circulation in the third world.

    Science.gov (United States)

    Chapman, M; Prothero, R M

    1983-01-01

    "This article focuses upon circulation, or reciprocal flows of people, with specific reference to Third World societies." Aspects considered include attempts to standardize terminology and to formulate typologies of population movement; the development of explanatory models of circulation and modernization, social networks, family welfare, and capitalism; and "the transfer of methods and concepts to societies and populations different from those from which they initially evolved and in which they were first tested." excerpt

  13. Surgical myocardial revascularization without extracorporeal circulation

    Directory of Open Access Journals (Sweden)

    Salomón Soriano Ordinola Rojas

    2003-05-01

    Full Text Available OBJECTIVE: To assess the immediate postoperative period of patients undergoing myocardial revascularization without extracorporeal circulation with different types of grafts. METHODS: One hundred and twelve patients, 89 (79.5% of whom were males, were revascularized without extracorporeal circulation. Their ages ranged from 39 to 85 years. The criteria for indicating myocardial revascularization without extracorporeal circulation were as follows: revascularized coronary artery caliber > 1.5 mm, lack of intramyocardial trajectory on coronary angiography, noncalcified coronary arteries, and tolerance of the heart to the different rotation maneuvers. RESULTS: Myocardial revascularization without extracorporeal circulation was performed in 112 patients. Three were converted to extracorporeal circulation, which required a longer hospital stay but did not impact mortality. During the procedure, the following events were observed: atrial fibrillation in 10 patients, ventricular fibrillation in 4, total transient atrioventricular block in 2, ventricular extrasystoles in 58, use of a device to retrieve red blood cells in 53, blood transfusion in 8, and arterial hypotension in 89 patients. Coronary angiography was performed in 20 patients on the seventh postoperative day when the grafts were patent. CONCLUSION: Myocardial revascularization without extracorporeal circulation is a reproducible technique that is an alternative for treating ischemic heart disease.

  14. Circulating microRNA Profile throughout the menstrual cycle.

    Directory of Open Access Journals (Sweden)

    Kadri Rekker

    Full Text Available Normal physiological variables, such as age and gender, contribute to alterations in circulating microRNA (miRNA expression levels. The changes in the female body during the menstrual cycle can also be reflected in plasma miRNA expression levels. Therefore, this study aimed to determine the plasma miRNA profile of healthy women during the menstrual cycle and to assess which circulating miRNAs are derived from blood cells. The plasma miRNA expression profiles in nine healthy women were determined by quantitative real time PCR using Exiqon Human Panel I assays from four time-points of the menstrual cycle. This platform was also used for studying miRNAs from pooled whole blood RNA samples at the same four time-points. Our results indicated that circulating miRNA expression levels in healthy women were not significantly altered by the processes occurring during the menstrual cycle. No significant differences in plasma miRNA expression levels were observed between the menstrual cycle time-points, but the number of detected miRNAs showed considerable variation among the studied individuals. miRNA analysis from whole blood samples revealed that majority of miRNAs in plasma are derived from blood cells. The most abundant miRNA in plasma and blood was hsa-miR-451a, but a number of miRNAs were only detected in one or the other sample type. In conclusion, our data suggest that the changes in the female body during the menstrual cycle do not affect the expression of circulating miRNAs at measurable levels.

  15. Hypoxia, leukocytes, and the pulmonary circulation.

    Science.gov (United States)

    Stenmark, Kurt R; Davie, Neil J; Reeves, John T; Frid, Maria G

    2005-02-01

    Data are rapidly accumulating in support of the idea that circulating monocytes and/or mononuclear fibrocytes are recruited to the pulmonary circulation of chronically hypoxic animals and that these cells play an important role in the pulmonary hypertensive process. Hypoxic induction of monocyte chemoattractant protein-1, stromal cell-derived factor-1, vascular endothelial growth factor-A, endothelin-1, and tumor growth factor-beta(1) in pulmonary vessel wall cells, either directly or indirectly via signals from hypoxic lung epithelial cells, may be a critical first step in the recruitment of circulating leukocytes to the pulmonary circulation. In addition, hypoxic stress appears to induce release of increased numbers of monocytic progenitor cells from the bone marrow, and these cells may have upregulated expression of receptors for the chemokines produced by the lung circulation, which thus facilitates their specific recruitment to the pulmonary site. Once present, macrophages/fibrocytes may exert paracrine effects on resident pulmonary vessel wall cells stimulating proliferation, phenotypic modulation, and migration of resident fibroblasts and smooth muscle cells. They may also contribute directly to the remodeling process through increased production of collagen and/or differentiation into myofibroblasts. In addition, they could play a critical role in initiating and/or supporting neovascularization of the pulmonary artery vasa vasorum. The expanded vasa network may then act as a conduit for further delivery of circulating mononuclear cells to the pulmonary arterial wall, creating a feedforward loop of pathological remodeling. Future studies will need to determine the mechanisms that selectively induce leukocyte/fibrocyte recruitment to the lung circulation under hypoxic conditions, their direct role in the remodeling process via production of extracellular matrix and/or differentiation into myofibroblasts, their impact on the phenotype of resident smooth muscle

  16. Gemfibrozil disrupts the metabolism of circulating lipids in bobwhite quails.

    Science.gov (United States)

    Bussière-Côté, Sophie; Omlin, Teye; de Càssia Pinheiro, Eliana; Weber, Jean-Michel

    2016-01-01

    The circulating lipids of birds play essential roles for egg production and as an energy source for flight and thermogenesis. How lipid-lowering pharmaceuticals geared to prevent heart disease in humans and that are routinely released in the environment affect their metabolism is unknown. This study assesses the impact of the popular drug gemfibrozil (GEM) on the plasma phospholipids (PL), neutral lipids (NL), and nonesterified fatty acids (NEFA) of bobwhite quails (Colinus virginianus). Results show that bird lipoproteins are rapidly altered by GEM, even at environmentally-relevant doses. After 4 days of exposure, pharmacological amounts cause an 83% increase in circulating PL levels, a major decrease in average lipoprotein size measured as a 56% drop in the NL/PL ratio, and important changes in the fatty acid composition of PL and NEFA (increases in fatty acid unsaturation). The levels of PL carrying all individual fatty acids except arachidonate are strongly stimulated. The large decrease in bird lipoprotein size may reflect the effects seen in humans: lowering of LDL that can cause atherosclerosis and stimulation of HDL that promote cholesterol disposal. Lower (environmental) doses of GEM cause a reduction of %palmitate in all the plasma lipid fractions of quails, but particularly in the core triacylglycerol of lipoproteins (NL). No changes in mRNA levels of bird peroxisome proliferator-activated receptor (PPAR) could be demonstrated. The disrupting effects of GEM on circulating lipids reported here suggest that the pervasive presence of this drug in the environment could jeopardize reproduction and migratory behaviours in wild birds. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Circulating water pumps for nuclear power stations

    International Nuclear Information System (INIS)

    Satoh, Hiroshi; Ohmori, Tsuneaki

    1979-01-01

    Shortly, the nuclear power station with unit power output of 1100 MW will begin the operation, and the circulating water pumps manufactured recently are those of 2.4 to 4 m bore, 840 to 2170 m 3 /min discharge and 2100 to 5100 kW driving power. The circulating water pumps are one of important auxiliary machines, because if they fail, power generation capacity lowers immediately. Enormous quantity of cooling water is required to cool condensers, therefore in Japan, sea water is usually used. As siphon is formed in circulating water pipes, the total head of the pumps is not very high. The discharge of the pumps is determined so as to keep the temperature rise of discharged water lower than 7 deg. C. The quantity of cooling water for nuclear power generation is about 50% more as compared with thermal power generation because of the difference in steam conditions. The total head of the pumps is normally from 8 to 15 m. The circulating water pumps rarely stop after they started the operation, therefore it is economical to determine the motor power so that it can withstand 10% overload for a short period, instead of large power. At present, vertical shaft, oblique flow circulating water pumps are usually employed. Recently, movable blade pumps are adopted. The installation, construction and materials of the pumps and the problems are described. (Kako, I.)

  18. Cascade of circulations in fluid turbulence.

    Science.gov (United States)

    Eyink, Gregory L

    2006-12-01

    Kelvin's theorem on conservation of circulations is an essential ingredient of Taylor's theory of turbulent energy dissipation by the process of vortex-line stretching. In previous work, we have proposed a nonlinear mechanism for the breakdown of Kelvin's theorem in ideal turbulence at infinite Reynolds number. We develop here a detailed physical theory of this cascade of circulations. Our analysis is based upon an effective equation for large-scale coarse-grained velocity, which contains a turbulent-induced vortex force that can violate Kelvin's theorem. We show that singularities of sufficient strength, which are observed to exist in turbulent flow, can lead to nonvanishing dissipation of circulation for an arbitrarily small coarse-graining length in the effective equations. This result is an analog for circulation of Onsager's theorem on energy dissipation for singular Euler solutions. The physical mechanism of the breakdown of Kelvin's theorem is diffusion of lines of large-scale vorticity out of the advected loop. This phenomenon can be viewed as a classical analog of the Josephson-Anderson phase-slip phenomenon in superfluids due to quantized vortex lines. We show that the circulation cascade is local in scale and use this locality to develop concrete expressions for the turbulent vortex force by a multiscale gradient expansion. We discuss implications for Taylor's theory of turbulent dissipation and we point out some related cascade phenomena, in particular for magnetic flux in magnetohydrodynamic turbulence.

  19. Circulation as Assessment: Collection Development Policies Evaluated in Terms of Circulation at a Small Academic Library.

    Science.gov (United States)

    Dinkins, Debbi

    2003-01-01

    Discusses the use of academic library circulation statistics to assess whether user needs are being met and describes a study at Stetson University that investigated collection development practices by comparing circulation statistics for books selected by faculty in support of departmental curricula with those of librarian selections. (Author/LRW)

  20. Lower peripheral circulation in eumenorrheic young women with premenstrual symptoms

    Directory of Open Access Journals (Sweden)

    Tatsumi Noriyuki

    2007-03-01

    Full Text Available Abstract Background A majority of women from all cultures and socioeconomic levels experience diverse psychosomatic and behavioral symptoms premenstrually, a phenomenon commonly termed premenstrual syndrome, although symptoms and discomfort levels vary from woman to woman. The underlying pathological mechanisms of premenstrual syndrome remain unknown; however, altered function or even slight disorder of the blood circulation system, which contributes to the orchestrations of the human internal environment, could cause bio-psychological changes leading to complaints and ultimately compromising a woman's overall health. The present study, therefore, investigates to what extent and how the menstrual cyclicity of peripheral circulation is associated with premenstrual symptomatology. Methods Twenty-one eumenorrheic young women participated in this study. All subjects were investigated during the follicular and late luteal phases. Cycle phase was determined by the onset of menstruation and oral temperature and was verified by concentrations of ovarian hormones, estrone, and pregnanediol in a urine sample taken early in the morning. Peripheral circulation was evaluated with the Astrim (Sysmex, Kobe, a portable non-invasive monitoring device using the principle of near-infrared spectroscopy, which calculates the venous oxygenation index (VOI based on the ratio of light absorption of oxyhemoglobin and deoxyhemoglobin, a proven reliable indicator of peripheral blood circulation. The Menstrual Distress Questionnaire was applied to measure physical, emotional, and behavioral symptoms accompanying the menstrual cycle of the subjects. Results The oral temperature and urinary ovarian hormones adjusted for creatinine significantly increased in the late luteal phase in all subjects. While 10 subjects experienced no symptoms during the menstrual cycle, 11 subjects had apparent physical and psychological discomfort in the late luteal phase. We found that VOI

  1. Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

    Science.gov (United States)

    Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

    2015-01-01

    Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

  2. Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects.

    Science.gov (United States)

    Moreno, María; Moreno-Navarrete, José María; Serrano, Marta; Ortega, Francisco; Delgado, Elías; Sanchez-Ragnarsson, Cecilia; Valdés, Sergio; Botas, Patricia; Ricart, Wifredo; Fernández-Real, José Manuel

    2015-01-01

    A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans. Circulating irisin levels (ELISA) and metabolic parameters were analyzed in 428 subjects (195 men/233 women). Participants were classified according to their self-reported physical activity and to their area of residence. Circulating irisin levels were higher in active than in sedentary subjects (p = 0.006). Rural inhabitants showed higher circulating irisin levels than urban subjects (p sedentary participants, irisin levels were positively associated with metabolic risk factors (BMI, fasting insulin, HOMA and fasting triglycerides). The area of residence (β = - 0.592, p = sedentary participants, circulating irisin levels were positively associated with parameters related to an increased cardiometabolic risk. The present study confirmed that an active lifestyle increases circulating irisin levels, but only among subjects living in a rural environment. Area of residence might be a determinant of irisin levels.

  3. Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate.

    Science.gov (United States)

    Goulay, Romain; Flament, Julien; Gauberti, Maxime; Naveau, Michael; Pasquet, Nolwenn; Gakuba, Clement; Emery, Evelyne; Hantraye, Philippe; Vivien, Denis; Aron-Badin, Romina; Gaberel, Thomas

    2017-08-01

    Subarachnoid hemorrhage (SAH) is a devastating form of stroke with neurological outcomes dependent on the occurrence of delayed cerebral ischemia. It has been shown in rodents that some of the mechanisms leading to delayed cerebral ischemia are related to a decreased circulation of the cerebrospinal fluid (CSF) within the brain parenchyma. Here, we evaluated the cerebral circulation of the CSF in a nonhuman primate in physiological condition and after SAH. We first evaluated in physiological condition the circulation of the brain CSF in Macaca facicularis , using magnetic resonance imaging of the temporal DOTA-Gd distribution after its injection into the CSF. Then, animals were subjected to a minimally invasive SAH before an MRI evaluation of the impact of SAH on the brain parenchymal CSF circulation. We first demonstrate that the CSF actively penetrates the brain parenchyma. Two hours after injection, almost the entire brain is labeled by DOTA-Gd. We also show that our model of SAH in nonhuman primate displays the characteristics of SAH in humans and leads to a dramatic impairment of the brain parenchymal circulation of the CSF. The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH. © 2017 American Heart Association, Inc.

  4. Experimental study of the natural circulation phenomena

    International Nuclear Information System (INIS)

    Sabundjian, Gaiane; Andrade, Delvonei Alves de; Umbehaun, Pedro E.; Torres, Walmir M.; Castro, Alfredo Jose Alvim de; Belchior Junior, Antonio; Rocha, Ricardo Takeshi Vieira da; Damy, Osvaldo Luiz de Almeida; Torres, Eduardo

    2006-01-01

    The objective of this paper is to study the natural circulation in experimental loops and extend the results to nuclear facilities. New generation of compact nuclear power plants use the natural circulation as cooling and residual heat removal systems in case of accidents or shutdown. Lately the interest in this phenomenon, by scientific community, has increased. The experimental loop, described in this paper, was assembled at Escola Politecnica - USP at the Chemical Engineering Department. It is the goal to generate information to help with the understanding of the one and two phase natural circulation phenomena. Some experiments were performed with different levels of heat power and different flow of the cooling water at the secondary circuit. The data generated from these experiments are going to be used to validate some computational thermal hydraulic codes. Experimental results for one and two phase regimes are presented as well as the proposed model to simulate the flow regimes with the RELAP5 code. (author)

  5. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in ...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.......Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...

  6. Adjustable speed drives improve circulating water system

    International Nuclear Information System (INIS)

    Dent, R.A.; Dicic, Z.

    1994-01-01

    This paper illustrates the integration of electrical and mechanical engineering requirements to produce a solution to past problems and future operating demands. The application of adjustable speed drives in the modifications of the circulating water system at Indian Point No. 3 Nuclear Power Plant provided increased operating flexibility, efficiency and avoided otherwise costly renovations to the plant electrical systems. Rectification of the original inadequate design of the circulating water system, in addition to maximizing plant efficiency consistent with environmental considerations, formed the basis for this modification. This entailed replacement of all six circulating water pumps and motors and physical modifications to the intake system. This paper details the methodology used in this engineering task. The new system was installed successfully and has been operating reliably and economically for the past eight years

  7. Natural circulation in a scaled PWR integral test facility

    International Nuclear Information System (INIS)

    Kiang, R.L.; Jeuck, P.R. III

    1987-01-01

    Natural circulation is an important mechanism for cooling a nuclear power plant under abnormal operating conditions. To study natural circulation, we modeled a type of pressurized water reactor (PWR) that incorporates once-through steam generators. We conducted tests of single-phase natural circulations, two-phase natural circulations, and a boiler condenser mode. Because of complex geometry, the natural circulations observed in this facility exhibit some phenomena not commonly seen in a simple thermosyphon loop

  8. Experimental study of natural circulation circuit

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, Wanderley F.; Su, Jian, E-mail: wlemos@lasme.coppe.ufrj.br, E-mail: sujian@lasme.coppe.ufrj.br [Coordenacao dos Programas de Pos-Graduacao de Engenharia (LASME/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Lab. de Simulacao e Metodos Numericos; Faccini, Jose L.H., E-mail: faccini@ien.gov.br [Instituto de Engenharia Nuclear (LTE/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab. de Termo-Hidraulica Experimental

    2011-07-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  9. Fort St. Vrain circulator operating experience

    Energy Technology Data Exchange (ETDEWEB)

    Brey, H. L.

    1988-08-15

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs.

  10. Experimental study of natural circulation circuit

    International Nuclear Information System (INIS)

    Lemos, Wanderley F.; Su, Jian; Faccini, Jose L.H.

    2011-01-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  11. Fort St. Vrain circulator operating experience

    International Nuclear Information System (INIS)

    Brey, H.L.

    1988-01-01

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs

  12. Doppler ultrasonography of the human fetal pulmonary circulation

    NARCIS (Netherlands)

    J.A.M. Laudij (Jacqueline)

    2000-01-01

    textabstractPulmonary hypoplasia is a condition characterized by a decrease in the number of lung cells, airways and alveoli with a resulting decrease in organ size and weight. The reported incidence of pulmonary hypoplasia in the general population is about 1 per 1000 live births and it is one of

  13. Light microscope observation of circulating human lymphocytes cultured in vitro

    Directory of Open Access Journals (Sweden)

    Naila Francis Paulo de Oliveira

    2010-10-01

    Full Text Available The purpose of this work was to study the isolation and a light microscopy technique for cultured lymphocytes. Blood samples were obtained by venipuncture with an anticoagulant added and centrifuged in a Percoll density gradient to separate the leukocytes. Lymphocytes were placed in 25 cm ³ tissue culture flasks at 37ºC. After culturing, they were fixed and stained with the methods used for blood smears. Results showed that not all fixing solutions and stains were an equally good choice for cultured lymphocytes.Os linfócitos são células importantes do sistema imune e têm sido largamente utilizados em estudos morfológicos. Entretanto, a literatura sobre técnicas de preparação dessas células é escassa e antiga, especialmente para linfócitos cultivados in vitro. Portanto, o objetivo desse estudo foi relatar com detalhes as técnicas de isolamento e microscopia de luz de linfócitos mantidos em cultura. Amostras de sangue foram obtidas por punção venosa e centrifugadas em gradiente de densidade de Percoll, para separar os leucócitos. Os linfócitos foram mantidos em frascos de cultura de 25 cm³ a 37ºC. Após a cultura, as células foram fixadas e coradas de acordo com a metodologia utilizada para esfregaços sanguíneos. Nossos resultados mostraram que nem todos os fixadores e corantes utilizados para esfregaços sanguíneos são uma boa escolha para linfócitos cultivados in vitro.

  14. Circulating Red Cell–derived Microparticles in Human Malaria

    Science.gov (United States)

    Nantakomol, Duangdao; Dondorp, Arjen M.; Krudsood, Srivicha; Udomsangpetch, Rachanee; Pattanapanyasat, Kovit; Combes, Valery; Grau, Georges E.; White, Nicholas J.; Viriyavejakul, Parnpen; Day, Nicholas P.J.

    2011-01-01

    In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell–derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/μL [range, 13–4,342 RMPs/μL]), Plasmodium vivax (n = 5; median, 409 RMPs/μL [range, 281–503/μL]), and Plasmodium malariae (n = 2; median, 163 RMPs/μL [range, 127–200 RMPs/μL]) compared with those in healthy subjects (n = 11; median, 8 RMPs/μL [range, 3–166 RMPs/μL]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced >10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs. PMID:21282195

  15. Circulating red cell-derived microparticles in human malaria.

    Science.gov (United States)

    Nantakomol, Duangdao; Dondorp, Arjen M; Krudsood, Srivicha; Udomsangpetch, Rachanee; Pattanapanyasat, Kovit; Combes, Valery; Grau, Georges E; White, Nicholas J; Viriyavejakul, Parnpen; Day, Nicholas P J; Chotivanich, Kesinee

    2011-03-01

    In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell-derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/μL [range, 13-4,342 RMPs/μL]), Plasmodium vivax (n = 5; median, 409 RMPs/μL [range, 281-503/μL]), and Plasmodium malariae (n = 2; median, 163 RMPs/μL [range, 127-200 RMPs/μL]) compared with those in healthy subjects (n = 11; median, 8 RMPs/μL [range, 3-166 RMPs/μL]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced >10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs.

  16. Quenching phenomena in natural circulation loop

    International Nuclear Information System (INIS)

    Umekawa, Hisashi; Ozawa, Mamoru; Ishida, Naoki

    1995-01-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity

  17. Labour circulation and the urban labour process.

    Science.gov (United States)

    Standing, G

    1986-01-01

    The author investigates aspects of labor circulation, which he defines as "temporary movement between geographical areas for work or in search of work....[He attempts to determine] what roles have been played by labour circulation in the development of urban-industrial labour forces in the transition to industrial capitalism." Factors considered include the exploitation and oppression of labor migrants; the industrial-urban labor reserve; urban socioeconomic stratification and discrimination by age, sex, or race; the division of labor; and policy options. excerpt

  18. An elementary model of money circulation

    Science.gov (United States)

    Pokrovskii, Vladimir N.; Schinckus, Christophe

    2016-12-01

    This paper investigates money circulation for a system, consisting of a production system, the government, a central bank, commercial banks and many customers of the commercial banks. A set of equations for the system is written; the theory determines the main features of interaction between production and money circulation. Investigation of the equations in a steady-state situation reveals some relationship among output of the production system and monetary variables. The relation of quantity theory of money is confirmed, whereas a new concept of the efficiency of the system is introduced.

  19. Engineering Judgment and Natural Circulation Calculations

    International Nuclear Information System (INIS)

    Ferreri, J.C.; Ferreri, J.C.

    2011-01-01

    The analysis performed to establish the validity of computer code results in the particular field of natural circulation flow stability calculations is presented in the light of usual engineering practice. The effects of discretization and closure correlations are discussed and some hints to avoid undesired mistakes in the evaluations performed are given. Additionally, the results are presented for an experiment relevant to the way in which a (small) number of skilled, nuclear safety analysts and researchers react when facing the solution of a natural circulation problem. These results may be also framed in the concept of Engineering Judgment and are potentially useful for Knowledge Management activities.

  20. First circulating beam in the AA

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    On 3 July 1980, two years after project authorization, beam circulated for the first time in the AA. It was a 3.56 GeV/c proton test beam. We see an expecting crowd, minutes before the happy event. The persons are too numerous to name them all, but the 3 most prominent ones are at the centre (left to right): Roy Billinge (Joint AA Project Leader, with his hand on the control box), Eifionydd Jones (white shirt), Simon van der Meer (spiritus rector and Joint AA Project Leader). The first antiprotons were injected, made to circulate and cooled soon after, on 14 July 1980.

  1. Quenching phenomena in natural circulation loop

    Energy Technology Data Exchange (ETDEWEB)

    Umekawa, Hisashi; Ozawa, Mamoru [Kansai Univ., Osaka (Japan); Ishida, Naoki [Daihatsu Motor Company, Osaka (Japan)

    1995-09-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity.

  2. Stabilization and augmentation of circulating AIM in mice by synthesized IgM-Fc.

    Directory of Open Access Journals (Sweden)

    Toshihiro Kai

    Full Text Available Owing to rapid and drastic changes in lifestyle and eating habits in modern society, obesity and obesity-associated diseases are among the most important public health problems. Hence, the development of therapeutic approaches to regulate obesity is strongly desired. In view of previous work showing that apoptosis inhibitor of macrophage (AIM blocks lipid storage in adipocytes, thereby preventing obesity caused by a high-fat diet, we here explored a strategy to augment circulating AIM levels. We synthesized the Fc portion of the soluble human immunoglobulin (IgM heavy chain and found that it formed a pentamer containing IgJ as natural IgM does, and effectively associated with AIM in vitro. When we injected the synthesized Fc intravenously into mice lacking circulating IgM, it associated with endogenous mouse AIM, protecting AIM from renal excretion and preserving the circulating AIM levels. As the synthesized Fc lacked the antigen-recognizing variable region, it provoked no undesired immune response. In addition, a challenge with the Fc-human AIM complex in wild-type mice, which exhibited normal levels of circulating IgM and AIM, successfully maintained the levels of the human AIM in mouse blood. We also observed that the human AIM was effectively incorporated into adipocytes in visceral fat tissue, suggesting its functionality against obesity. Thus, our findings reveal potent strategies to safely increase AIM levels, which could form the basis for developing novel therapies for obesity.

  3. Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy subjects

    DEFF Research Database (Denmark)

    Barbieri, Michelangela; Paolisso, Giuseppe; Kimura, Masayuki

    2009-01-01

    Mutations that inhibit the insulin-like growth factor-1 (IGF-1) extend the lifespan of worms, flies and mice. However, it appears that relatively low circulating levels of IGF-1 in humans are associated with aging-related diseases and diminished longevity. As leukocyte telomere length (LTL) is os...

  4. Circulating Follistatin Is Liver-Derived and Regulated by the Glucagon-to-Insulin Ratio

    DEFF Research Database (Denmark)

    Hansen, Jakob S; Rutti, Sabine; Arous, Caroline

    2016-01-01

    CONTEXT: Follistatin is a plasma protein recently reported to increase under conditions with negative energy balance, such as exercise and fasting in humans. Currently, the perception is that circulating follistatin is a result of para/autocrine actions from various tissues. The large and acute i...

  5. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    Directory of Open Access Journals (Sweden)

    José María Moreno-Navarrete

    Full Text Available Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity. Circulating zonulin increased with body mass index (BMI, waist to hip ratio (WHR, fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002 contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01 contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  6. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    Science.gov (United States)

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  7. Bed system performance in helium circulation mode

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yean Jin; Jung, Kwang Jin; Ahn, Do Hee; Chung, Hong Suk [UST, Daejeon (Korea, Republic of); Kang, Hee Suk [KAERI, Daejeon (Korea, Republic of); Yun, Sei Hun [NFRI, Deajeon (Korea, Republic of)

    2016-05-15

    As a part of the International Thermonuclear Experimental Reactor (ITER) Project, We have conducted an experiment for storing hydrogen to depleted uranium and zirconium cobalt. The helium blanket effect has been observed in experiments using metal hydrides. The collapse of the hydrogen isotopes are accompanied by the decay heat and helium-3. Helium-3 dramatically reduces the hydrogen isotope storage capacity by surrounding the metal. This phenomenon is called a helium blanket effect. In addition the authors are working on the recovery and removal techniques of helium-3. In this paper, we discuss the equipment used to test the helium blanket effect and the results of a helium circulation experiment. The helium-3 produced surrounds the storage material surface and thus disturbs the reaction of the storage material and the hydrogen isotope. Even if the amount of helium-3 is small, the storage capacity of the SDS bed significantly drops. This phenomenon is the helium blanket effect. To resolve this phenomenon, a circulating loop was introduced. Using a circulating system, helium can be separated from the storage material. We made a helium loop that includes a ZrCo bed. Then using a metal bellows pump, we tested the helium circulation.

  8. Periodontitis and increase in circulating oxidative stress

    Directory of Open Access Journals (Sweden)

    Takaaki Tomofuji

    2009-05-01

    Full Text Available Reactive oxygen species (ROS are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress. Such oxidation may be detrimental to systemic health. For instance, previous animal studies suggested that experimental periodontitis induces oxidative damage of the liver and descending aorta by increasing circulating oxidative stress. In addition, it has been revealed that clinical parameters in chronic periodontitis patients showed a significant improvement 2 months after periodontal treatment, which was accompanied by a significant reduction of reactive oxygen metabolites in plasma. Improvement of periodontitis by periodontal treatment could reduce the occurrence of circulating oxidative stress. Furthermore, recent studies indicate that the increase in circulating oxidative stress following diabetes mellitus and inappropriate nutrition damages periodontal tissues. In such cases, therapeutic approaches to systemic oxidative stress might be necessary to improve periodontal health.

  9. Natural circulation under severe accident conditions

    International Nuclear Information System (INIS)

    Pafford, D.J.; Hanson, D.J.; Tung, V.X.; Chmielewski, S.V.

    1992-01-01

    Research is being conducted to better understand natural circulation phenomena in mixtures of steam and noncondensibles and its influence on the temperature of the vessel internals and the hot leg, pressurizer surge line, and steam generator tubes. The temperature of these structures is important because their failure prior to reactor vessel lower head failure could reduce the likelihood of containment failure as a result of direct containment heating. Computer code calculations (MELPROG, SCDAP/RELAP5/MOD3) predict high fluid temperatures in the upper plenum resulting from in-vessel natural circulation. Using a simple model for the guide tube phenomena, high upper plenum temperatures are shown to be consistent with the relatively low temperatures that were deduced metallurgically from leadscrews removed from the TMI-2 upper plenum. Evaluation of the capabilities of the RELAP5/MOD3 computer code to predict natural circulation behavior was also performed. The code was used to model the Westinghouse natural circulation experimental facility. Comparisons between code calculations and results from experiments show good agreement

  10. Detecting Holocene changes in thermohaline circulation

    OpenAIRE

    Keigwin, L. D.; Boyle, E. A.

    2000-01-01

    Throughout the last glacial cycle, reorganizations of deep ocean water masses were coincident with rapid millennial-scale changes in climate. Climate changes have been less severe during the present interglacial, but evidence for concurrent deep ocean circulation change is ambiguous.

  11. Opportunities in CARICOM Migration : Brain Circulation, Diasporic ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Opportunities in CARICOM Migration : Brain Circulation, Diasporic Tourism, and Investment. Between 1965 and 2000, about 12% of the Caribbean labour force moved to Canada and other developed countries, making the Caribbean the largest per capita source of emigrants in the world. Remittances from these emigrants ...

  12. Oceanic Circulation. A Programmed Unit of Instruction.

    Science.gov (United States)

    Marine Maritime Academy, Castine.

    This booklet contains a programmed lesson on oceanic circulation. It is designed to allow students to progress through the subject at their own speed. Since it is written in linear format, it is suggested that students proceed through the program from "frame" to succeeding "frame." Instructions for students on how to use the booklet are included.…

  13. 3D Visualization of Global Ocean Circulation

    Science.gov (United States)

    Nelson, V. G.; Sharma, R.; Zhang, E.; Schmittner, A.; Jenny, B.

    2015-12-01

    Advanced 3D visualization techniques are seldom used to explore the dynamic behavior of ocean circulation. Streamlines are an effective method for visualization of flow, and they can be designed to clearly show the dynamic behavior of a fluidic system. We employ vector field editing and extraction software to examine the topology of velocity vector fields generated by a 3D global circulation model coupled to a one-layer atmosphere model simulating preindustrial and last glacial maximum (LGM) conditions. This results in a streamline-based visualization along multiple density isosurfaces on which we visualize points of vertical exchange and the distribution of properties such as temperature and biogeochemical tracers. Previous work involving this model examined the change in the energetics driving overturning circulation and mixing between simulations of LGM and preindustrial conditions. This visualization elucidates the relationship between locations of vertical exchange and mixing, as well as demonstrates the effects of circulation and mixing on the distribution of tracers such as carbon isotopes.

  14. Efficient Circulation of Railway Rolling Stock

    NARCIS (Netherlands)

    Alfieri, A.; Groot, R.; Kroon, L.G.; Schrijver, A.

    2006-01-01

    Railway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of rolling

  15. Efficient Circulation of Railway Rolling Stock

    NARCIS (Netherlands)

    A. Alfieri (Arianna); R. Groot (Rutger); L.G. Kroon (Leo); A. Schrijver (Lex)

    2002-01-01

    textabstractRailway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of

  16. Circulation of Coxiella burnetii in a Naturally Infected Flock of Dairy Sheep: Shedding Dynamics, Environmental Contamination, and Genotype Diversity

    OpenAIRE

    Joulié, A.; Laroucau, K.; Bailly, X.; Prigent, M.; Gasqui, P.; Lepetitcolin, E.; Blanchard, B.; Rousset, E.; Sidi-Boumedine, K.; Jourdain, E.

    2015-01-01

    Q fever is a worldwide zoonosis caused by Coxiella burnetii. Domestic ruminants are considered to be the main reservoir. Sheep, in particular, may frequently cause outbreaks in humans. Because within-flock circulation data are essential to implementing optimal management strategies, we performed a follow-up study of a naturally infected flock of dairy sheep. We aimed to (i) describe C. burnetii shedding dynamics by sampling vaginal mucus, feces, and milk, (ii) assess circulating strain divers...

  17. Dynamic Regulation of Circulating microRNAs During Acute Exercise and Long-Term Exercise Training in Basketball Athletes

    OpenAIRE

    Yongqin Li; Mengchao Yao; Qiulian Zhou; Yan Cheng; Lin Che; Jiahong Xu; Junjie Xiao; Zhongming Shen; Yihua Bei

    2018-01-01

    Emerging evidence indicates the beneficial effects of physical exercise on human health, which depends on the intensity, training time, exercise type, environmental factors, and the personal health status. Conventional biomarkers provide limited insight into the exercise-induced adaptive processes. Circulating microRNAs (miRNAs, miRs) are dynamically regulated in response to acute exhaustive exercise and sustained rowing, running and cycling exercises. However, circulating miRNAs in response ...

  18. Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance

    OpenAIRE

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measure...

  19. Observations of the summer Red Sea circulation

    Science.gov (United States)

    Sofianos, Sarantis S.; Johns, William E.

    2007-06-01

    Aiming at exploring and understanding the summer circulation in the Red Sea, a cruise was conducted in the basin during the summer of 2001 involving hydrographic, meteorological, and direct current observations. The most prominent feature, characteristic of the summer circulation and exchange with the Indian Ocean, is a temperature, salinity, and oxygen minimum located around a depth of 75 m at the southern end of the basin, associated with Gulf of Aden Intermediate Water inflowing from the Gulf of Aden during the summer season as an intruding subsurface layer. Stirring and mixing with ambient waters lead to marked increases in temperature (from 16.5 to almost 33°C) and salinity (from 35.7 to more than 38 psu) in this layer by the time it reaches midbasin. The observed circulation presents a very vigorous pattern with strong variability and intense features that extend the width of the basin. A permanent cyclone, detected in the northern Red Sea, verifies previous observations and modeling studies, while in the central sector of the basin a series of very strong anticyclones were observed with maximum velocities exceeding 1 m/s. The three-layer flow pattern, representative of the summer exchange between the Red Sea and the Gulf of Aden, is observed in the strait of Bab el Mandeb. In the southern part of the basin the layer flow is characterized by strong banking of the inflows and outflows against the coasts. Both surface and intermediate water masses involved in the summer Red Sea circulation present prominent spatial variability in their characteristics, indicating that the eddy field and mixing processes play an important role in the summer Red Sea circulation.

  20. Decontamination of CAGR gas circulator components

    International Nuclear Information System (INIS)

    Rogers, L.N.; Hooper, A.J.

    1985-01-01

    This paper describes the development and full-scale trial of two methods for removal of radioactive contamination on the surfaces of CAGR gas circulator components. The two methods described are a particle impact cleaning (PIC) decontamination technique and an electrochemical technique, 'electro-swabbing', which is based on the principle of decontamination by electro-polishing. In developing these techniques it was necessary to take account of the physical and chemical nature of the surface deposits on the gas circulator components; these were shown to consist of magnetite-type oxide and carbonaceous material. In order to follow the progress of the decontamination it was also necessary to develop a surface sampling technique which was effective and precise under these conditions; an electrochemical technique, employing similar principles to the electro-swabbing process, was developed for this purpose. The full-scale trial of the PIC decontamination technique was carried out on an inlet guide vane (IGV) assembly, this having been identified as the component from the gas circulator which contributes most to the radiation dose accumulated during routine circulator maintenance. The technique was shown to be practically viable and some 99% of the radioactive contamination was readily removed from the treated surfaces with only negligible surface damage being caused. The full-scale trial of the electro-swabbing decontamination technique was carried out on a gas circulator impeller. High decontamination factors were again achieved with ≥ 99% of the radioactive contamination being removed from the treated surfaces. The technique has practical limitations in terms of handling and treatment of waste-arisings. However, the use of specially-designed swabbing electrodes may allow the treatment of constricted geometries inaccessible to techniques such as PIC. The technique is also highly suitable for the treatment of soft-finish materials and of components fabricated from a

  1. Serological Evidence of Orthopoxvirus Circulation Among Equids, Southeast Brazil

    Directory of Open Access Journals (Sweden)

    Iara A. Borges

    2018-03-01

    Full Text Available Since 1999 Vaccinia virus (VACV outbreaks involving bovines and humans have been reported in Brazil; this zoonosis is known as Bovine Vaccinia (BV and is mainly an occupational disease of milkers. It was only in 2008 (and then again in 2011 and 2014 however, that VACV was found causing natural infections in Brazilian equids. These reports involved only equids, no infected humans or bovines were identified, and the sources of infections remain unknown up to date. The peculiarities of Equine Vaccinia outbreaks (e.g., absence of human infection, the frequently shared environments, and fomites by equids and bovines in Brazilian farms and the remaining gaps in BV epidemiology incited a question over OPV serological status of equids in Brazil. For this report, sera from 621 equids - representing different species, ages, sexes and locations of origin within Minas Gerais State, southeast Brazil – were examined for the presence of anti-Orthopoxvirus (OPV antibodies. Only 74 of these were sampled during an Equine Vaccinia outbreak, meaning some of these specific animals presented typical lesions of OPV infections. The majority of sera, however, were sampled from animals without typical signs of OPV infection and during the absence of reported Bovine or Equine Vaccinia outbreaks. Results suggest the circulation of VACV among equids of southeast Brazil even prior to the time of the first VACV outbreak in 2008. There is a correlation of OPVs outbreaks among bovines and equids although many gaps remain to our understanding of its nature. The data obtained may even be carefully associated to recent discussion over OPVs history. Moreover, data is available to improve the knowledge and instigate new researches regarding OPVs circulation in Brazil and worldwide.

  2. Experimental investigation on natural circulation and air-injection enhanced circulation in a simple loop

    International Nuclear Information System (INIS)

    Walter Ambrosini; Nicola Forgione; Francesco Oriolo; Filippo Pellacani; Mariano Tarantino; Claudio Struckmann

    2005-01-01

    Full text of publication follows: Natural circulation represents an interesting phenomenon because of both the complex aspects characterising it and for the widespread application in industry. On the other hand, injection of a gas into a rising branch of a loop represents a means to establish or to enhance a circulation flow, as it occurs in the so-called 'air-lift' loops. Both natural circulation and gas-injection enhanced circulation are presently considered for cooling Accelerator Driven System (ADS) reactors. These are subcritical reactors in which the fission reaction chain is maintained by the injection of neutrons obtained by spallation reactions in a target through a high energy proton beam generated in an external accelerator. The capability of such reactors to be used as incinerators of long lived fission products makes them particularly interesting in the light of the closure of the nuclear fuel cycle. Some of the fluids proposed as coolants for these reactors are liquid metals, with main interest for lead and lead-bismuth eutectic (LBE). Experimental activities are being performed in support to the design of the reactor prototype by different organisations. The university of Pisa, in addition to provide cooperation in these large scale activities performed with LBE has set up a specific experimental program aimed at studying the fundamental mechanisms involved in natural circulation and gas-injection enhanced circulation. The adopted experimental facility consists in a simple loop, having a rectangular lay-out (roughly, 4 m tall and 1 m wide), equipped with a 5 kW, 1 m tall heater, a 2 m long pipe-in-pipe heat exchanger, an air injection device and a separator. The fluid adopted in the tests performed up to now is water, though studies for evaluating the feasibility of the adoption of different fluids have been undertaken. Experimental data reported in previous publications concerning this research were related to a relatively high range of gas

  3. Study in rabbits of portal circulation by a radioisotopic method

    International Nuclear Information System (INIS)

    Maliska, C.

    1980-01-01

    The development of a precocius - and noninvasive method for the detection of portal circulation alterations by means of time interval measurements between the rectal administration of radiotracers and their detection in liver and head is aimed at. The pertecnetate ( 99 sup(m)Tc)- and iodate ( 131 I) absorption by the terminal large intestine was tested in 22 rabbits. The time iinterval between rectal administration of the radiotracer and its appearance in liver and head was determined in 12 rabbits, by external detection with a scintillation camera. The same parameters were studied in 9 animals submitted to the ligature of the portal vein. Iodate and pertecnetate are absorbed by the terminal large intestine, the pertecnetate absorption being significantly smaller than that of iodate. The pertecnetate distribution volume is smaller than that of iodate; the rectum - liver - and rectum - head time intervals is increased in animals with the ligature of portal vein. Application of the method to larger animals will permit the necessary improvements for its utilization as a precocius - noninvasive - and inocuous test in the evaluation of alteration of the human portal circulation. (Author) [pt

  4. Money circulation and debt circulation: A restatement of quantity theory of money

    OpenAIRE

    Xing, Xiaoyun; Xiong, Wanting; Chen, Liujun; Chen, Jiawei; Wang, Yougui; Stanley, H. Eugene

    2018-01-01

    Both money and debt are products of credit creation of banks. Money is always circulating among traders by facilitating commodity transactions. In contrast, debt is created by borrowing and annihilated by repayment as it is matured. However, when this creation- annihilation process is mediated by banks which are constrained by a credit capacity, there exists continuous transfer of debt among debtors, which can be defined as debt circulation. This paper presents a multi-agent model in which in...

  5. Grazing Affects Exosomal Circulating MicroRNAs in Cattle

    Science.gov (United States)

    Muroya, Susumu; Ogasawara, Hideki; Hojito, Masayuki

    2015-01-01

    Circulating microRNAs (c-miRNAs) are associated with physiological adaptation to acute and chronic aerobic exercise in humans. To investigate the potential effect of grazing movement on miRNA circulation in cattle, here we profiled miRNA expression in centrifugally prepared exosomes from the plasma of both grazing and housed Japanese Shorthorn cattle. Microarray analysis of the c-miRNAs resulted in detection of a total of 231 bovine exosomal miRNAs in the plasma, with a constant expression level of let-7g across the duration and cattle groups. Expression of muscle-specific miRNAs such as miR-1, miR-133a, miR-206, miR-208a/b, and miR-499 were undetectable, suggesting the mildness of grazing movement as exercise. According to validation by quantitative RT-PCR, the circulating miR-150 level in the grazing cattle normalized by the endogenous let-7g level was down-regulated after 2 and 4 months of grazing (P cattle equalized when the grazing cattle were returned to a housed situation. Likewise, the levels of miR-19b, miR-148a, miR-221, miR-223, miR-320a, miR-361, and miR-486 were temporarily lowered in the cattle at 1 and/or 2 month of grazing compared to those of the housed cattle (P cattle at 2 months of grazing (P = 0.044). The elevation of miR-451 level in the plasma was coincident with that in the biceps femoris muscle of the grazing cattle (P = 0.008), which suggests the secretion or intake of miR-451 between skeletal muscle cells and circulation during grazing. These results revealed that exosomal c-miRNAs in cattle were affected by grazing, suggesting their usefulness as molecular grazing markers and functions in physiological adaptation of grazing cattle associated with endocytosis, focal adhesion, axon guidance, and a variety of intracellular signaling, as predicted by bioinformatic analysis. PMID:26308447

  6. Comparison of Print Monograph Acquisitions Strategies Finds Circulation Advantage to Firm Orders

    Directory of Open Access Journals (Sweden)

    Laura Costello

    2017-12-01

    Full Text Available A Review of: Ke, I., Gao, W., & Bronicki, J. (2017. Does title-by-title selection make a difference? A usage title analysis on print monograph purchasing. Collection Management, 42(1, 34-47. http://dx.doi.org/10.1080/01462679.2016.1249040 Abstract Objective – To compare usage of print monographs acquired through firm order to those acquired through approval plans. Design – Quantitative study. Setting – A public research university serving an annual enrollment of over 43,500 students and employing more than 2,600 faculty members in the South Central United States. Subjects – Circulation and call number data from 21,356 print books acquired through approval plans, and 23,920 print books acquired through firm orders. Methods – Item records for print materials purchased between January 1, 2011 and December 31, 2014 were extracted from the catalog and separated by acquisitions strategy into firm order and approval plan lists. Items without call numbers and materials that had been placed on course reserves were removed from the lists. The authors examined accumulated circulation counts and conducted trend analyses to examine year-to-year usage. The authors also measured circulation performance in each Library of Congress call number class; they grouped these classes into science, social science, and humanities titles. Main Results – The authors found that 31% of approval plan books and 39% of firm order books had circulated at least once. The firm order books that had circulated were used an average of 1.87 times, compared to approval plan books which were used an average of 1.47 times. The year-to-year analysis showed that the initial circulation rate for approval plan books decreased from 42% in 2011 to 14% in 2014, and from 46% to 24% for firm order books. Subject area analysis showed that medicine and military science had the highest circulation rates at over 45%, and that agriculture and bibliography titles had the lowest circulation

  7. Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

    Science.gov (United States)

    Zengel, James; Phan, Shannon I; Pickar, Adrian; Xu, Pei; He, Biao

    2017-07-13

    Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Bond Graph Model of Cerebral Circulation: Toward Clinically Feasible Systemic Blood Flow Simulations

    Science.gov (United States)

    Safaei, Soroush; Blanco, Pablo J.; Müller, Lucas O.; Hellevik, Leif R.; Hunter, Peter J.

    2018-01-01

    We propose a detailed CellML model of the human cerebral circulation that runs faster than real time on a desktop computer and is designed for use in clinical settings when the speed of response is important. A lumped parameter mathematical model, which is based on a one-dimensional formulation of the flow of an incompressible fluid in distensible vessels, is constructed using a bond graph formulation to ensure mass conservation and energy conservation. The model includes arterial vessels with geometric and anatomical data based on the ADAN circulation model. The peripheral beds are represented by lumped parameter compartments. We compare the hemodynamics predicted by the bond graph formulation of the cerebral circulation with that given by a classical one-dimensional Navier-Stokes model working on top of the whole-body ADAN model. Outputs from the bond graph model, including the pressure and flow signatures and blood volumes, are compared with physiological data. PMID:29551979

  9. Quantitative measurement of blood circulation in tests of rats using nuclear medical methods

    International Nuclear Information System (INIS)

    Ripke, R.

    1980-01-01

    The experiments show that is it is possible to quantitatively assess the blood circulation and, within limits, the germinative function of tests by measuring the impulses of an incorporated radionuclide (99-Tc-pertechnetate) using an uptake measuring instrument. This is a rapid and unbloody method to be adopted in human medicine. 'Acute tests' or pre-damaged tests can thus be exactly diagnosed. In the former case the circulation modification and in the latter the evaluation of the germinative function ability is of main interest. The most important measuring criterion is the 15-minute-uptake U; it represents the blood circulation in the tests measured. The germinative function ability is evaluated on the basis of the accumulation activity Nsub(max). (orig./MG) [de

  10. [Applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis].

    Science.gov (United States)

    Wang, Feng-Qin; Chen, Cen; Xia, Zhi-Ning; Yang, Feng-Qing

    2014-08-01

    Thrombotic diseases in different forms become a great threat to human health. Such anti-platelet aggregation drugs as aspirin and clopidogrel are common drugs in clinic. However, along with the appearance of resistance and side effects of western anti-platelet aggregation drugs, anti-platelet aggregation traditional Chinese medicines promoting blood circulation to remove blood stasis have gradually become an important study orientation. Platelet is one of major participant in thrombosis, and plays an important role as a bioactive material in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, mainly involving two aspects--the evaluation for the anti-platelet aggregation activity of traditional Chinese medicines and the screening of their active components. This paper summarized the applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, so as to provide basis for further studies.

  11. Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Ringholm, Lene; Søstrup, Birgitte

    2014-01-01

    is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.......OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones...... there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors. SAMPLES: Serum samples from nonpregnant and pregnant women. METHODS: The effect of serum from pregnant women...

  12. Modelling the Seasonal Overturning Circulation in the Red Sea

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry; Bower, Amy; Koehl, Armin; Gopalakrishnan, Ganesh

    2015-01-01

    The overturning circulation in the Red Sea exhibits a distinct seasonally reversing pattern and is studied using 50-year, high-resolution MIT general circulation model simulations. The seasonal water exchange in the Strait of Bab el Mandeb

  13. Silent Circulation of Ross River Virus in French Polynesia

    Directory of Open Access Journals (Sweden)

    Maite Aubry

    2015-08-01

    Discussion: Our results support the existence of autochthonous RRV transmission and suggest that this pathogen has silently circulated in French Polynesia. These findings raise the question of possible undetected circulation of RRV in other Pacific Island Countries and Territories.

  14. Circulating dendritic cells in pediatric patients with nephrotic syndrome

    African Journals Online (AJOL)

    EL-HAKIM

    nephrotic syndrome, circulating DCs were measured by flowcytometry. Results: Circulating DC count ... parents or caregivers of each child before enrollment in the study. ..... role in initiating the primary immune response. On the basis of the ...

  15. Distinct proteome pathology of circulating microparticles in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer Tandrup; Tanassi, Julia T

    2017-01-01

    BACKGROUND: The pathogenesis of systemic lupus erythematosus (SLE) is poorly understood but has been linked to defective clearance of subcellular particulate material from the circulation. This study investigates the origin, formation, and specificity of circulating microparticles (MPs) in patients...

  16. Circulation induced by diffused aeration in a shallow lake

    African Journals Online (AJOL)

    2017-01-01

    Jan 1, 2017 ... Lastly, a simple returning flow model was proposed to describe the circulation flow patterns ... method to describe the circulation patterns induced by the bub- ... 160 holes of 1 mm, which was designed to promote high mix-.

  17. Uptake and degradation of circulating proteins by the liver.

    NARCIS (Netherlands)

    Buys, Carolus Henricus Cornelis Maria

    1976-01-01

    Circulating proteins, like all proteins in a living animal, are subject to continual replacement or turnover. This process implies both synthesis and degradation, This thesis deals with the degradative part of turnover of circulating proteins. ... Summary

  18. Anti-cyclonic circulation driven by the estuarine circulation in a gulf type ROFI

    Science.gov (United States)

    Fujiwara, T.; Sanford, L. P.; Nakatsuji, K.; Sugiyama, Y.

    1997-08-01

    Baroclinic residual circulation processes are examined in gulf type Regions Of Freshwater Influence (ROFIs), which have large rivers discharging into a rounded head wider than the Rossby internal deformation radius. Theoretical and observational investigations concentrate on Ise Bay, Japan, with supporting data from Osaka Bay and Tokyo Bay. Simplified analytical solutions are derived to describe the primary features of the circulation. Three dimensional residual current data collected using moored current meters and shipboard acoustic doppler current profilers (ADCPs), satellite imagery and density structure data observed using STDs, are presented for comparison to the theoretical predictions. There are three key points to understanding the resulting circulation in gulf type ROFIs. First, there are likely to be three distinct water masses: the river plume, a brackish upper layer, and a higher salinity lower layer. Second, baroclinic processes in gulf type ROFIs are influenced by the Earth's rotation at first order. Residual currents are quasi-geostrophic and potential vorticity is approximately conserved. Third, the combined effects of a classical longitudinal estuarine circulation and the Earth's rotation are both necessary to produce the resulting circulation. Anti-cyclonic vorticity is generated in the upper layer by the horizontal divergence associated with upward entrainment, which is part of the estuarine circulation. The interaction between anti-cyclonic vorticity and horizontal divergence results in two regions of qualitatively different circulation, with gyre-like circulation near the bay head and uniformly seaward anti-cyclonicly sheared flow further towards the mouth. The stagnation point separating the two regions is closer to (further away from) the bay head for stronger (weaker) horizontal divergence, respectively. The vorticity and spin-up time of this circulation are-(ƒ-ω 1)/2 and h/2w 0, respectively, where ƒ is the Coriolis parameter, ω 1 is

  19. Producing superfluid circulation states using phase imprinting

    Science.gov (United States)

    Kumar, Avinash; Dubessy, Romain; Badr, Thomas; De Rossi, Camilla; de Goër de Herve, Mathieu; Longchambon, Laurent; Perrin, Hélène

    2018-04-01

    We propose a method to prepare states of given quantized circulation in annular Bose-Einstein condensates (BEC) confined in a ring trap using the method of phase imprinting without relying on a two-photon angular momentum transfer. The desired phase profile is imprinted on the atomic wave function using a short light pulse with a tailored intensity pattern generated with a spatial light modulator. We demonstrate the realization of "helicoidal" intensity profiles suitable for this purpose. Due to the diffraction limit, the theoretical steplike intensity profile is not achievable in practice. We investigate the effect of imprinting an intensity profile smoothed by a finite optical resolution onto the annular BEC with a numerical simulation of the time-dependent Gross-Pitaevskii equation. This allows us to optimize the intensity pattern for a given target circulation to compensate for the limited resolution.

  20. Natural circulation in pressurized water reactors

    International Nuclear Information System (INIS)

    Bastos, J.L.F.; Loureiro, L.V.; Rocha, R.T.V. da; Umbehaun, P.E.

    1992-01-01

    Several analytical modelling have been done for steady-state and slow transients conditions, besides more sophisticated studies considering two and three dimensional effects in a very simple geometry. Under severe accident conditions for PWR a code to analyse natural circulation has been developed by Westinghouse. This paper discusses the problem of natural circulation in a complex geometry similar to that of nuclear power plants. A first experiment has been done at the integral test facility of 'Co-ordination of Special Projects-Ministry of Naval Affairs' (Coordenadoria para Projetos Especiais -Ministerio da Marinha, COPESP) for several flux conditions. The results obtained were compared with numerical simulations for the steady-state regime. 09 refs, 05 figs, 01 tab. (B.C.A.)

  1. Circulation policies in health science libraries.

    Science.gov (United States)

    Watkins, C; Coker, N C

    1970-10-01

    There is general agreement that library policies have considerable influence on the use of libraries. Medical school (health science) libraries of this country were surveyed as to their policies in respect to whether faculty and student use were regulated by a single policy, circulation regulations, hours library was accessible to users, accessibility of reserve material, interlibrary loan, policy on overdue material, and exit control. THE LIBRARIES WERE THEN DIVIDED INTO THREE GROUPS, HIGH, MIDDLE, AND LOW ACCORDING TO THE FOLLOWING CHARACTERISTICS: size of student body, size of faculty, size of holdings, size of library staff, annual budget, and annual circulation. Our findings would indicate that schools falling in a high category based upon these criteria tend to be more restrictive in their policies and to have different regulations for faculty and students than do schools in the low category.These findings warrant further study.

  2. Natural circulation in simulated LMFBR fuel assemblies

    International Nuclear Information System (INIS)

    Levin, A.E.; Carbajo, J.J.; Lloyd, D.B.; Montgomery, B.H.; Rose, S.D.; Wantland, J.L.

    1985-01-01

    Natural circulation experiments have been performed using simulated liquid metal fast breeder reactor fuel assemblies in the Thermal-Hydraulic Out-of-Reactor Safety (THORS) facility, an engineering-scale sodium loop. Objective of these tests has been to provide experimental data under conditions that might be encountered during a partial or total loss of the shutdown heat removal system (SHRS) in a reactor. The experiments have included single- and two-phase tests under quasi-steady and transient conditions, at both nominal and non-nominal system conditions. Results from these test indicate that the potential for reactor damage during degraded SHRS operation is extremely slight, and that natural circulation can be a major contributor to safe operation of the system in both single- and two-phase flow during such operation

  3. Genetic architecture of circulating lipid levels

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; Amin, Najaf; Isaacs, Aaron

    2011-01-01

    Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid...... the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify...... an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models...

  4. On-Chip Microwave Quantum Hall Circulator

    Directory of Open Access Journals (Sweden)

    A. C. Mahoney

    2017-01-01

    Full Text Available Circulators are nonreciprocal circuit elements that are integral to technologies including radar systems, microwave communication transceivers, and the readout of quantum information devices. Their nonreciprocity arises from the interference of microwaves over the centimeter scale of the signal wavelength, in the presence of bulky magnetic media that breaks time-reversal symmetry. Here, we realize a completely passive on-chip microwave circulator with size 1/1000th the wavelength by exploiting the chiral, “slow-light” response of a two-dimensional electron gas in the quantum Hall regime. For an integrated GaAs device with 330  μm diameter and about 1-GHz center frequency, a nonreciprocity of 25 dB is observed over a 50-MHz bandwidth. Furthermore, the nonreciprocity can be dynamically tuned by varying the voltage at the port, an aspect that may enable reconfigurable passive routing of microwave signals on chip.

  5. Correlates of Circulating 25-Hydroxyvitamin D

    OpenAIRE

    McCullough, Marjorie L.; Weinstein, Stephanie J.; Freedman, D. Michal; Helzlsouer, Kathy; Flanders, W. Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong

    2010-01-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geogra...

  6. Circulating fluidized bed boilers design and operations

    CERN Document Server

    Basu, Prabir

    1991-01-01

    This book provides practicing engineers and students with insight into the design and operation of circulating fluidized bed (CFB) boilers. Through a combination of theoretical concepts and practical experience, this book gives the reader a basic understanding of the many aspects of this subject.Important environmental considerations, including solid waste disposal and predicted emissions, are addressed individually in separate chapters. This book places an emphasis on combustion, hydrodynamics, heat transfer, and material issues, and illustrates these concepts with numerous examples of pres

  7. Music Circulation and Transmission in Tbilisi, Georgia

    OpenAIRE

    Sebald, Brigita

    2013-01-01

    This dissertation, based upon two years research in Tbilisi, Georgia, questions how popular music travels from the performer to the audience and how it circulates among audience members. After the disintegration of the Soviet Union in the early 1990s, the state-run music industry collapsed, taking the infrastructure for music distribution with it. In the years since, a music industry has not been rebuilt due to uncertain economic realities and a shaky political situation. Because of this, per...

  8. Periodontitis and increase in circulating oxidative stress

    OpenAIRE

    Takaaki Tomofuji; Koichiro Irie; Toshihiro Sanbe; Tetsuji Azuma; Daisuke Ekuni; Naofumi Tamaki; Tatsuo Yamamoto; Manabu Morita

    2009-01-01

    Reactive oxygen species (ROS) are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress). Such oxidation may be detrimental to systemic health. Fo...

  9. Engineering Judgment and Natural Circulation Calculations

    OpenAIRE

    Ferreri, J. C.

    2011-01-01

    The analysis performed to establish the validity of computer code results in the particular field of natural circulation flow stability calculations is presented in the light of usual engineering practice. The effects of discretization and closure correlations are discussed and some hints to avoid undesired mistakes in the evaluations performed are given. Additionally, the results are presented for an experiment relevant to the way in which a (small) number of skilled, nuclear safety analysts...

  10. Nitric oxide : An ally in extracorporeal circulation?

    OpenAIRE

    Melki, Vilyam

    2016-01-01

    Many complications associated with heart surgery are due to the negative effects of extracorporeal circulation (ECC). Some of these complications may be attributed to ECC-induced activation of inflammation and coagulation pathways. The inflammatory reaction may be caused by the interaction of blood components with air and the artificial surfaces of the ECC, from substances produced due to ischaemia-reperfusion injury of the heart and lungs, and from increased release of endotoxin from ischemi...

  11. The creation and circulation of public geographies

    OpenAIRE

    Kitchin, Rob; Linehan, Denis; O'Callaghan, Cian; Lawton, Philip

    2013-01-01

    In response to the commentaries, we discuss further how social media disrupts and remakes the creation and circulation of geographical knowledges and potentially reconfigures the moral economy of the social sciences. In particular, we examine questions of what is meant by public geography, the publics which such geographies serve, alternative and complementary approaches to social media, the politics of authorship within collective blogs, the politics and mechanisms of knowledge c...

  12. NUCLA Circulating Atmospheric Fluidized Bed Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    1992-02-01

    The objective of this DOE Cooperative Agreement is to conduct a cost-shared clean coal technology project to demonstrate the feasibility of circulating fluidized bed combustion technology and to evaluate economic, environmental, and operational benefits of CFB steam generators on a utility scale. At the conclusion of the Phase 2 program, testing related to satisfying these objectives was completed. Data analysis and reporting are scheduled for completion by October 1991. (VC)

  13. First circulating beam in the AA

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    On 3 July 1980, two years after project authorization, beam circulated for the first time in the AA. It was a 3.5 GeV/c proton test beam. We see an expecting crowd, minutes before the happy event. The persons are to numerous to name them all. Heribert Koziol, apparently asleep, is answering the call from an impatient director. See also 8007094.

  14. Circulating procoagulant microparticles in cancer patients

    OpenAIRE

    Thaler, Johannes; Ay, Cihan; Weinstabl, Harald; Dunkler, Daniela; Simanek, Ralph; Vormittag, Rainer; Freyssinet, Jean-Marie; Zielinski, Christoph; Pabinger, Ingrid

    2010-01-01

    Abstract Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vien...

  15. Circulation in a Short Cylindrical Couette System

    Energy Technology Data Exchange (ETDEWEB)

    Akira Kageyama; Hantao Ji; Jeremy Goodman

    2003-07-08

    In preparation for an experimental study of magnetorotational instability (MRI) in liquid metal, we explore Couette flows having height comparable to the gap between cylinders, centrifugally stable rotation, and high Reynolds number. Experiments in water are compared with numerical simulations. The flow is very different from that of an ideal, infinitely long Couette system. Simulations show that endcaps co-rotating with the outer cylinder drive a strong poloidal circulation that redistributes angular momentum. Predicted toroidal flow profiles agree well with experimental measurements. Spin-down times scale with Reynolds number as expected for laminar Ekman circulation; extrapolation from two-dimensional simulations at Re less than or equal to 3200 agrees remarkably well with experiment at Re approximately equal to 106. This suggests that turbulence does not dominate the effective viscosity. Further detailed numerical studies reveal a strong radially inward flow near both endcaps. After turning vertically along the inner cylinder, these flows converge at the midplane and depart the boundary in a radial jet. To minimize this circulation in the MRI experiment, endcaps consisting of multiple, differentially rotating rings are proposed. Simulations predict that an adequate approximation to the ideal Couette profile can be obtained with a few rings.

  16. Circulation in a Short Cylindrical Couette System

    International Nuclear Information System (INIS)

    Akira Kageyama; Hantao Ji; Jeremy Goodman

    2003-01-01

    In preparation for an experimental study of magnetorotational instability (MRI) in liquid metal, we explore Couette flows having height comparable to the gap between cylinders, centrifugally stable rotation, and high Reynolds number. Experiments in water are compared with numerical simulations. The flow is very different from that of an ideal, infinitely long Couette system. Simulations show that endcaps co-rotating with the outer cylinder drive a strong poloidal circulation that redistributes angular momentum. Predicted toroidal flow profiles agree well with experimental measurements. Spin-down times scale with Reynolds number as expected for laminar Ekman circulation; extrapolation from two-dimensional simulations at Re less than or equal to 3200 agrees remarkably well with experiment at Re approximately equal to 106. This suggests that turbulence does not dominate the effective viscosity. Further detailed numerical studies reveal a strong radially inward flow near both endcaps. After turning vertically along the inner cylinder, these flows converge at the midplane and depart the boundary in a radial jet. To minimize this circulation in the MRI experiment, endcaps consisting of multiple, differentially rotating rings are proposed. Simulations predict that an adequate approximation to the ideal Couette profile can be obtained with a few rings

  17. When Prostate Cancer Circulates in the Bloodstream

    Directory of Open Access Journals (Sweden)

    Virginie Vlaeminck-Guillem

    2015-10-01

    Full Text Available Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine, reliable evaluation of the intrinsic molecular biology of the tumor is warranted, and particularly for all tumor sites (primary tumors and secondary sites at any time of the disease progression. As a consequence of their natural tendency to grow (passive invasion or as a consequence of an active blood vessel invasion by metastase-initiating cells, tumors shed various materials into the bloodstream. Major efforts have been recently made to develop powerful and accurate methods able to detect, quantify and/or analyze all these circulating tumor materials: circulating tumors cells, disseminating tumor cells, extracellular vesicles (including exosomes, nucleic acids, etc. The aim of this review is to summarize current knowledge about these circulating tumor materials and their applications in translational research.

  18. Diagnosis of boundary-layer circulations.

    Science.gov (United States)

    Beare, Robert J; Cullen, Michael J P

    2013-05-28

    Diagnoses of circulations in the vertical plane provide valuable insights into aspects of the dynamics of the climate system. Dynamical theories based on geostrophic balance have proved useful in deriving diagnostic equations for these circulations. For example, semi-geostrophic theory gives rise to the Sawyer-Eliassen equation (SEE) that predicts, among other things, circulations around mid-latitude fronts. A limitation of the SEE is the absence of a realistic boundary layer. However, the coupling provided by the boundary layer between the atmosphere and the surface is fundamental to the climate system. Here, we use a theory based on Ekman momentum balance to derive an SEE that includes a boundary layer (SEEBL). We consider a case study of a baroclinic low-level jet. The SEEBL solution shows significant benefits over Ekman pumping, including accommodating a boundary-layer depth that varies in space and structure, which accounts for buoyancy and momentum advection. The diagnosed low-level jet is stronger than that determined by Ekman balance. This is due to the inclusion of momentum advection. Momentum advection provides an additional mechanism for enhancement of the low-level jet that is distinct from inertial oscillations.

  19. The dynamics of the coronary collateral circulation.

    Science.gov (United States)

    Zimarino, Marco; D'Andreamatteo, Mariangela; Waksman, Ron; Epstein, Stephen E; De Caterina, Raffaele

    2014-04-01

    Coronary collaterals are present at birth, with wide interindividual variation in their functional capacity. These vessels protect jeopardized myocardium, and the number of collaterals and the extent of their coverage are associated with improved survival in patients with coronary heart disease. The collateral circulation is not a permanent set of structures, but undergoes dynamic changes with important consequences for cardioprotection. If a severe atherosclerotic lesion develops in an artery supplying tissue downstream of a total occlusion through collateral blood flow, pressure gradients across the collateral bed change. The result is that some of the collateral flow previously supplying the perfusion territory of the totally occluded artery is redirected to the perfusion territory of the donor artery, thus producing a 'collateral steal'. The collateral circulation can regress once antegrade flow in the main dependent artery is re-established, as occurs following the recanalization of a chronic total occlusion. The clinical benefits of coronary revascularization must be cautiously weighed against the risk of reducing the protective support derived from coronary collaterals. Consequently, pharmacological, gene-based, and cell-based therapeutic attempts have been made to enhance collateral function. Although such approaches have so far yielded no, or modest, beneficial results, the rapidly accruing data on coronary collateral circulation will hopefully lead to new effective therapeutic strategies.

  20. Circulation of a triaxial, charged ellipsoidal droplet

    International Nuclear Information System (INIS)

    Graber, J.L.; Rosensteel, G.

    2002-01-01

    The Kelvin circulation, which is the Casimir invariant of the general collective motion gcm(3) Lie algebra, is determined for a rapidly rotating triaxial nucleus in the classical domain. The potential energy is approximated by the sum of Coulomb repulsion and attractive surface energy terms, and the kinetic energy is adopted from the Riemann ellipsoidal model. An accurate approximation valid for both small and large deformations is reported for the potential energy. The Riemann ellipsoid theory allows for collective rotation in the continuum from rigid body motion to irrotational flow; the rigidity parametrizes this kinematical continuum. Analytic formulas are derived for the circulation, angular momentum, and energy as functions of the axis lengths, fissility, and rigidity. In particular, the bifurcation point to Jacobi triaxial shapes from noncollective oblate spheroids is given by a simple analytic formula. For a given fissility, the bifurcation point depends sensitive- ly on the rigidity. The Kelvin circulation remains approximately constant for triaxial ellipsoids as the angular momentum increases. This implies that gcm(3) is an approximate partial dynamical symmetry for rapidly rotating triaxial nuclei

  1. Formation of germline chimera Gaok chicken used circulation primordial germ cells (circulation PGCs fresh and thawed

    Directory of Open Access Journals (Sweden)

    Kostaman T

    2014-03-01

    Full Text Available Formation of germline chimeras by transfer of chicken primordial germ cells (PGCs is one of the effective techniques for preservation and regeneration of genetic resources in chickens. This study attempted to form germline chimeras of Gaok chicken buy purifying circulated PGCs of donor embryo before it is transferred to the recipient (White Leghorn chickens=WL and studied the ability of recipient embryo on survival in incubators, and hatchability. This study used 200 fertile eggs of Gaok and 90 fertile WL breed all of the eggs was incubated at 380C and 60% humidity in a portable incubator. PGCs-circulation of the blood collected Gaok embryos at stage 14-16 were taken from the dorsal aorta, and then purified by centrifugation method using nycodenz. PGCs-circulation results further purification frozen in liquid nitrogen before being transferred to the recipient embryo. The results showed that for the development of embryos transferred to the fresh circulation of PGCs-circulation as many as 25 cells can survive up to day 14, while one of the transferred of 50 and 100 cells into recipient embryos was hatched (10%. On the contrari recipient embryos that are transferred to the frozen PGCs-circulation the embryos development was shorter, and only survived until day 10th (treatment 25 cells, day 14th (treatment of 50 cells and day 17th (treatment of 100 cells. It is concluded that the amount of PGCs-circulation embryos transferred to the recipient is one factor that influence the success of the development germline chimeras.

  2. 19 CFR 207.63 - Circulation of draft questionnaires.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Circulation of draft questionnaires. 207.63... SUBSIDIZED EXPORTS TO THE UNITED STATES Five-Year Reviews § 207.63 Circulation of draft questionnaires. (a) The Director shall circulate draft questionnaires to the parties for comment in each full review. (b...

  3. Characteristics of the Current Sales and Circulation System in China

    Institute of Scientific and Technical Information of China (English)

    our reporter

    2001-01-01

    <正> 5 Former circulation enterprises finding new market position Those large-sized auto circulation enterprises, which used to lead the circulation system, have been suffering the twist and turns from the new system oriented by automakers. Their market shares shapely fell down and have emerged into chaos. Parts of them that are powerful enough have established new sales companies controlled by the jointly

  4. Exact Inverse Matrices of Fermat and Mersenne Circulant Matrix

    Directory of Open Access Journals (Sweden)

    Yanpeng Zheng

    2015-01-01

    Full Text Available The well known circulant matrices are applied to solve networked systems. In this paper, circulant and left circulant matrices with the Fermat and Mersenne numbers are considered. The nonsingularity of these special matrices is discussed. Meanwhile, the exact determinants and inverse matrices of these special matrices are presented.

  5. Appraisal of circulation routine duties in academic libraries | Hassan ...

    African Journals Online (AJOL)

    ... of brown charging system, book reservation, keeping of reserved collection, circulation of reserved books, treatment of overdue, lost of books on loan and library statistics among other as duties perform in circulation department of libraries. Keywords: Library Service, Circulation Duties, Challenges, Academic Libraries ...

  6. The stability of the thermohaline circulation in a coupled ocean-atmosphere general circulation model

    Energy Technology Data Exchange (ETDEWEB)

    Schiller, A. [Max-Planck-Institut fuer Meteorologie, Hamburg (Germany); Mikolajewicz, U. [Max-Planck-Institut fuer Meteorologie, Hamburg (Germany); Voss, R. [Deutsches Klimarechenzentrum (DKRZ), Hamburg (Germany)

    1996-02-01

    The stability of the Atlantic thermohaline circulation against meltwater input is investigated in a coupled ocean-atmosphere general circulation model. The meltwater input to the Labrador Sea is increased linearly for 250 years to a maximum input of 0.625 Sv and then reduced again to 0 (both instantaneously and slowly decreasing over 250 years). The resulting freshening forces a shutdown of the formation of North Atlantic deepwater and a subsequent reversal of the thermohaline circulation of the Atlantic, filling the deep Atlantic with Antarctic bottom water. The change in the overturning pattern causes a drastic reduction of the Atlantic northward heat transport, resulting in a strong cooling with maximum amplitude over the northern North Atlantic and a southward shift of the sea-ice margin in the Atlantic. Due to the increased meridional temperature gradient, the Atlantic intertropical convergence zone is displaced southward and the westerlies in the northern hemisphere gain strength. We identify four main feedbacks affecting the stability of the thermohaline circulation: the change in the overturning circulation of the Atlantic leads to longer residence times of the surface waters in high northern latitudes, which allows them to accumulate more precipitation and runoff from the continents, which results in an increased stability in the North Atlantic.

  7. Seasonal overturning circulation in the Red Sea: 1. Model validation and summer circulation

    KAUST Repository

    Yao, Fengchao

    2014-04-01

    The overturning circulation in the Red Sea exhibits a distinct seasonally reversing pattern and is studied using high-resolution MIT general circulation model simulations. In the first part of this study, the vertical and horizontal structure of the summer overturning circulation and its dynamical mechanisms are presented from the model results. The seasonal water exchange in the Strait of Bab el Mandeb is successfully simulated, and the structures of the intruding subsurface Gulf of Aden intermediate water are in good agreement with summer observations in 2011. The model results suggest that the summer overturning circulation is driven by the combined effect of the shoaling of the thermocline in the Gulf of Aden resulting from remote winds in the Arabian Sea and an upward surface slope from the Red Sea to the Gulf of Aden set up by local surface winds in the Red Sea. In addition, during late summer two processes associated, respectively, with latitudinally differential heating and increased salinity in the southern Red Sea act together to cause the reversal of the contrast of the vertical density structure and the cessation of the summer overturning circulation. Dynamically, the subsurface northward pressure gradient force is mainly balanced by vertical viscosity resulting from the vertical shear and boundary friction in the Strait of Bab el Mandeb. Unlike some previous studies, the three-layer summer exchange flows in the Strait of Bab el Mandeb do not appear to be hydraulically controlled.

  8. Seasonal overturning circulation in the Red Sea: 1. Model validation and summer circulation

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Zhai, Ping; Kö hl, Armin; Gopalakrishnan, Ganesh

    2014-01-01

    The overturning circulation in the Red Sea exhibits a distinct seasonally reversing pattern and is studied using high-resolution MIT general circulation model simulations. In the first part of this study, the vertical and horizontal structure of the summer overturning circulation and its dynamical mechanisms are presented from the model results. The seasonal water exchange in the Strait of Bab el Mandeb is successfully simulated, and the structures of the intruding subsurface Gulf of Aden intermediate water are in good agreement with summer observations in 2011. The model results suggest that the summer overturning circulation is driven by the combined effect of the shoaling of the thermocline in the Gulf of Aden resulting from remote winds in the Arabian Sea and an upward surface slope from the Red Sea to the Gulf of Aden set up by local surface winds in the Red Sea. In addition, during late summer two processes associated, respectively, with latitudinally differential heating and increased salinity in the southern Red Sea act together to cause the reversal of the contrast of the vertical density structure and the cessation of the summer overturning circulation. Dynamically, the subsurface northward pressure gradient force is mainly balanced by vertical viscosity resulting from the vertical shear and boundary friction in the Strait of Bab el Mandeb. Unlike some previous studies, the three-layer summer exchange flows in the Strait of Bab el Mandeb do not appear to be hydraulically controlled.

  9. Bioimpedance harmonic analysis as a tool to simultaneously assess circulation and nervous control.

    Science.gov (United States)

    Mudraya, I S; Revenko, S V; Nesterov, A V; Gavrilov, I Yu; Kirpatovsky, V I

    2011-07-01

    Multicycle harmonic (Fourier) analysis of bioimpedance was employed to simultaneously assess circulation and neural activity in visceral (rat urinary bladder) and somatic (human finger) organs. The informative value of the first cardiac harmonic of the bladder impedance as an index of bladder circulation is demonstrated. The individual reactions of normal and obstructive bladders in response to infusion cystometry were recorded. The potency of multicycle harmonic analysis of bioimpedance to assess sympathetic and parasympathetic neural control in urinary bladder is discussed. In the human finger, bioimpedance harmonic analysis revealed three periodic components at the rate of the heart beat, respiration and Mayer wave (0.1 Hz), which were observed under normal conditions and during blood flow arrest in the hand. The revealed spectrum peaks were explained by the changes in systemic blood pressure and in regional vascular tone resulting from neural vasomotor control. During normal respiration and circulation, two side cardiac peaks were revealed in a bioimpedance amplitude spectrum, whose amplitude reflected the depth of amplitude respiratory modulation of the cardiac output. During normal breathing, the peaks corresponding to the second and third cardiac harmonics were split, reflecting frequency respiratory modulation of the heart rate. Multicycle harmonic analysis of bioimpedance is a novel potent tool to examine the interaction between the respiratory and cardiovascular system and to simultaneously assess regional circulation and neural influences in visceral and somatic organs.

  10. Gas Cooled Fast Breeder Reactor cost estimate for a circulator test facility (modified HTGR circulator test facility)

    International Nuclear Information System (INIS)

    1979-10-01

    This is a conceptual design cost estimate for a Helium Circulator Test Facility to be located at the General Atomic Company, San Diego, California. The circulator, drive motors, controllers, thermal barrier, and circulator service module installation costs are part of the construction cost included

  11. Explicit Determinants of the RFPrLrR Circulant and RLPrFrL Circulant Matrices Involving Some Famous Numbers

    Directory of Open Access Journals (Sweden)

    Tingting Xu

    2014-01-01

    Full Text Available Circulant matrices may play a crucial role in solving various differential equations. In this paper, the techniques used herein are based on the inverse factorization of polynomial. We give the explicit determinants of the RFPrLrR circulant matrices and RLPrFrL circulant matrices involving Fibonacci, Lucas, Pell, and Pell-Lucas number, respectively.

  12. Gas cooled fast breeder reactor design for a circulator test facility (modified HTGR circulator test facility)

    Energy Technology Data Exchange (ETDEWEB)

    1979-10-01

    A GCFR helium circulator test facility sized for full design conditions is proposed for meeting the above requirements. The circulator will be mounted in a large vessel containing high pressure helium which will permit testing at the same power, speed, pressure, temperature and flow conditions intended in the demonstration plant. The electric drive motor for the circulator will obtain its power from an electric supply and distribution system in which electric power will be taken from a local utility. The conceptual design decribed in this report is the result of close interaction between the General Atomic Company (GA), designer of the GCFR, and The Ralph M. Parson Company, architect/engineer for the test facility. A realistic estimate of total project cost is presented, together with a schedule for design, procurement, construction, and inspection.

  13. Power limit and quality limit of natural circulation reactor

    International Nuclear Information System (INIS)

    Zhao Guochang; Ma Changwen

    1997-01-01

    The circulation characteristics of natural circulation reactor in boiling regime are researched. It is found that, the circulation mass flow rate and the power have a peak value at a mass quality respectively. Therefore, the natural circulation reactor has a power limit under certain technological condition. It can not be increased steadily by continually increasing the mass quality. Corresponding to this, the mass quality of natural circulation reactor has a reasonable limit. The relations between the maximum power and the reactor parameters, such as the resistance coefficient, the working pressure and so on, are analyzed. It is pointed out that the power limit of natural circulation reactor is about 1000 MW at present technological condition. Taking the above result and low quality stability experimental result into account, the authors recommend that the reasonable mass quality of natural circulation reactor working in boiling regime is from 2% to 3% under the researched working pressure

  14. Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes?

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2017-02-01

    Full Text Available Precision medicine and personalized medicine are based on the development of biomarkers, and liquid biopsy has been reported to be able to detect biomarkers that carry information on tumor development and progression. Compared with traditional ‘solid biopsy’, which cannot always be performed to determine tumor dynamics, liquid biopsy has notable advantages in that it is a noninvasive modality that can provide diagnostic and prognostic information prior to treatment, during treatment and during progression. In this review, we describe the source, characteristics, technology for detection and current situation of circulating tumor cells, circulating free DNA and exosomes used for diagnosis, recurrence monitoring, prognosis assessment and medication planning.

  15. Seawater bicarbonate removal during hydrothermal circulation

    Science.gov (United States)

    Proskurowski, G. K.; Seewald, J.; Sylva, S. P.; Reeves, E.; Lilley, M. D.

    2013-12-01

    High temperature fluids sampled at hydrothermal vents represent a complex alteration product of water-rock reactions on a multi-component mixture of source fluids. Sources to high-temperature hydrothermal samples include the 'original' seawater present in the recharge limb of circulation, magmatically influenced fluids added at depth as well as any seawater entrained during sampling. High-temperature hydrothermal fluids are typically enriched in magmatic volatiles, with CO2 the dominant species, characterized by concentrations of 10's-100's of mmol/kg (1, 2). Typically, the high concentration of CO2 relative to background seawater bicarbonate concentrations (~2.3 mmol/kg) obscures a full analysis of the fate of seawater bicarbonate during high-temperature hydrothermal circulation. Here we present data from a suite of samples collected over the past 15 years from high-temperature hydrothermal vents at 9N, Endeavour, Lau Basin, and the MAR that have endmember CO2 concentrations less than 10 mmol/kg. Using stable and radiocarbon isotope measurements these samples provide a unique opportunity to examine the balance between 'original' seawater bicarbonate and CO2 added from magmatic sources. Multiple lines of evidence from multiple hydrothermal settings consistently points to the removal of ~80% of the 'original' 2.3 mmol/kg seawater bicarbonate. Assuming that this removal occurs in the low-temperature, 'recharge' limb of hydrothermal circulation, this removal process is widely occurring and has important contributions to the global carbon cycle over geologic time. 1. Lilley MD, Butterfield DA, Lupton JE, & Olson EJ (2003) Magmatic events can produce rapid changes in hydrothermal vent chemistry. Nature 422(6934):878-881. 2. Seewald J, Cruse A, & Saccocia P (2003) Aqueous volatiles in hydrothermal fluids from the Main Endeavour Field, northern Juan de Fuca Ridge: temporal variability following earthquake activity. Earth and Planetary Science Letters 216(4):575-590.

  16. Bottom water circulation in Cascadia Basin

    Science.gov (United States)

    Hautala, Susan L.; Paul Johnson, H.; Hammond, Douglas E.

    2009-10-01

    A combination of beta spiral and minimum length inverse methods, along with a compilation of historical and recent high-resolution CTD data, are used to produce a quantitative estimate of the subthermocline circulation in Cascadia Basin. Flow in the North Pacific Deep Water, from 900-1900 m, is characterized by a basin-scale anticyclonic gyre. Below 2000 m, two water masses are present within the basin interior, distinguished by different potential temperature-salinity lines. These water masses, referred to as Cascadia Basin Bottom Water (CBBW) and Cascadia Basin Deep Water (CBDW), are separated by a transition zone at about 2400 m depth. Below the depth where it freely communicates with the broader North Pacific, Cascadia Basin is renewed by northward flow through deep gaps in the Blanco Fracture Zone that feeds the lower limb of a vertical circulation cell within the CBBW. Lower CBBW gradually warms and returns to the south at lighter density. Isopycnal layer renewal times, based on combined lateral and diapycnal advective fluxes, increase upwards from the bottom. The densest layer, existing in the southeast quadrant of the basin below ˜2850 m, has an advective flushing time of 0.6 years. The total volume flushing time for the entire CBBW is 2.4 years, corresponding to an average water parcel residence time of 4.7 years. Geothermal heating at the Cascadia Basin seafloor produces a characteristic bottom-intensified temperature anomaly and plays an important role in the conversion of cold bottom water to lighter density within the CBBW. Although covering only about 0.05% of the global seafloor, the combined effects of bottom heat flux and diapycnal mixing within Cascadia Basin provide about 2-3% of the total required global input to the upward branch of the global thermohaline circulation.

  17. Containment air circulation for optimal hydrogen recombination

    International Nuclear Information System (INIS)

    Spinks, N.; Krause, M.

    1997-01-01

    An accepted first-line defense for hydrogen mitigation is to design for the hydrogen to be rapidly mixed with the containment atmosphere and diluted to below flammability concentrations. Then, as hydrogen continues to be produced in the longer term, recombiners can be used to remove hydrogen: recombiners can be located in forced-air ducts or passive recombiners can be distributed within containment and the heat of recombination used to promote local air circulation. However, this principle does not eliminate the possibility of high hydrogen concentrations at locations removed from the recombiners. An improvement on this strategy is to arrange for a specific, buoyancy-driven, overall circulation of the containment atmosphere such that the recombiners can be located within the recirculation flow, immediately downstream of the hydrogen source. This would make the mixing process more predictable and solve the mass-transfer problem associated with distributed recombiners. Ideally, the recombiners would be located just above the hydrogen source so that the heat of recombination would assist the overall circulation. In this way, the hydrogen would be removed as close as possible to the source, thereby minimizing the amount of hydrogen immediately downstream of the source and reducing the hydrogen concentration to acceptable levels at other locations. Such a strategy requires the containment volume to be divided into an upflow path, past the hydrogen source and the recombiner, and a downflow path to complete the circuit. The flow could be generated actively using fans or passively using buoyancy forces arising from the difference in density of gases in the upfiow and downflow paths; the gases in the downflow path being cooled at an elevated heat sink. (author)

  18. Portal pressure correlated to visceral circulation times

    Energy Technology Data Exchange (ETDEWEB)

    Friman, L [Serafimerlasarettet, Stockholm (Sweden)

    1979-01-01

    Visceral angiography was performed in 7 patients with normal portal pressure and in 10 with portal hypertension. Circulation times, size of vessels and portal pressure were determined. At celiac angiography, a direct correlation was found between time for maximum filling of portal vein and portal pressure, provided no vascular abnormalities existed. At superior mesenteric angiography such a correlation was not found; loss of flow by shunts in portal hypertension being one explanation. Portocaval shunts are common in the celiac system, but uncommon in the superior mesenteric system.

  19. Portal pressure correlated to visceral circulation times

    International Nuclear Information System (INIS)

    Friman, L.

    1979-01-01

    Visceral angiography was performed in 7 patients with normal portal pressure and in 10 with portal hypertension. Circulation times, size of vessels and portal pressure were determined. At celiac angiography, a direct correlation was found between time for maximum filling of portal vein and portal pressure, provided no vascular abnormalities existed. At superior mesenteric angiography such a correlation was not found; loss of flow by shunts in portal hypertension being one explanation. Portocaval shunts are common in the celiac system, but uncommon in the superior mesenteric system. (Auth.)

  20. Numerical optimization of circulation control airfoils

    Science.gov (United States)

    Tai, T. C.; Kidwell, G. H., Jr.; Vanderplaats, G. N.

    1981-01-01

    A numerical procedure for optimizing circulation control airfoils, which consists of the coupling of an optimization scheme with a viscous potential flow analysis for blowing jet, is presented. The desired airfoil is defined by a combination of three baseline shapes (cambered ellipse, and cambered ellipse with drooped and spiralled trailing edges). The coefficients of these shapes are used as design variables in the optimization process. Under the constraints of lift augmentation and lift-to-drag ratios, the optimal airfoils are found to lie between those of cambered ellipse and the drooped trailing edge, towards the latter as the angle of attack increases. Results agree qualitatively with available experimental data.

  1. Turnover of circulating hematopoietic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Dorie, M J; Maloney, M A; Patt, H M

    1979-10-01

    Short-term parabiosis of male and female CBA/CaJ mice was used to investigate the turnover of circulating hematopoietic stem cells. The change and subsequent disappearance of donor stem cells were monitored by spleen colony assay and chromosome analysis of individual colonies. The results revealed an exponential disappearance of pluripotent stem cells from blood with a characteristic half time of 1.7 h. Blood-borne stem cells were shown to be equilibrated with a subpopulation of marrow stem cells exhibiting a disappearance half time of 9.5 h. Splenectomy did not change the apparent rate of stem cell removal from the blood.

  2. Steam generator of the forced circulation type

    International Nuclear Information System (INIS)

    Forestier, Jean; Leblanc, Bernard; Monteil, Marcel; Monteil, Pierre

    1977-01-01

    The steam generator described is of the forced circulation single passage type comprising an outer casing including a vertical generally cylindrical side ring, an internal skirt coaxial with the outer casing, the bottom of this skirt having a free edge separated from a bottom end closing the outer casing, a central tube plate extending horizontally near a top end, in opposition to the bottom end, a peripheral tube plate, parallel to the central plate and located in the annular space under this central plate, a bundle of J shaped tubes [fr

  3. [New theory of holistic integrative physiology and medicine. III: New insight of neurohumoral mechanism and pattern of control and regulation for core axe of respiration, circulation and metabolism].

    Science.gov (United States)

    Sun, Xing-guo

    2015-07-01

    Systemic mechanism of neurohumoral control and regulation for human is limited. We used the new theory of holistic integrative physiology and medicine to approach the mechanism and pattern of neurohumoral control and regulation for life. As the core of human life, there are two core axes of functions. The first one is the common goal of respiration and circulation to transport oxygen and carbon dioxide for cells, and the second one is the goal of gastrointestinal tract and circulation to transport energy material and metabolic product for cells. These two core axes maintain the metabolism. The neurohumoral regulation is holistically integrated and unified for all functions in human body. We simplified explain the mechanism of neurohumoral control and regulation life (respiration and circulation) as the example pattern of sound system. Based upon integrated regulation of life, we described the neurohumoral pattern to control respiration and circulation.

  4. Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders

    DEFF Research Database (Denmark)

    Petersen, K A; Birk, S; Kitamura, K

    2009-01-01

    Adrenomedullin (ADM) is closely related to calcitonin gene-related peptide, which has a known causative role in migraine. Animal studies have strongly suggested that ADM has a vasodilatory effect within the cerebral circulation. For these reasons, ADM is also likely to be involved in migraine....... However, the hypothetical migraine-inducing property and effect on human cerebral circulation of ADM have not previously been investigated. Human ADM (0.08 microg kg(-1) min(-1)) or placebo (saline 0.9%) was administered as a 20-min intravenous infusion to 12 patients suffering from migraine without aura...... in a crossover double-blind study. The occurrence of headache and associated symptoms were registered regularly 24 h post infusion. Cerebral blood flow (CBF) was measured by (133)Xenon single-photon emission computed tomography, mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial...

  5. Three-pattern decomposition of global atmospheric circulation: part II—dynamical equations of horizontal, meridional and zonal circulations

    Science.gov (United States)

    Hu, Shujuan; Cheng, Jianbo; Xu, Ming; Chou, Jifan

    2018-04-01

    The three-pattern decomposition of global atmospheric circulation (TPDGAC) partitions three-dimensional (3D) atmospheric circulation into horizontal, meridional and zonal components to study the 3D structures of global atmospheric circulation. This paper incorporates the three-pattern decomposition model (TPDM) into primitive equations of atmospheric dynamics and establishes a new set of dynamical equations of the horizontal, meridional and zonal circulations in which the operator properties are studied and energy conservation laws are preserved, as in the primitive equations. The physical significance of the newly established equations is demonstrated. Our findings reveal that the new equations are essentially the 3D vorticity equations of atmosphere and that the time evolution rules of the horizontal, meridional and zonal circulations can be described from the perspective of 3D vorticity evolution. The new set of dynamical equations includes decomposed expressions that can be used to explore the source terms of large-scale atmospheric circulation variations. A simplified model is presented to demonstrate the potential applications of the new equations for studying the dynamics of the Rossby, Hadley and Walker circulations. The model shows that the horizontal air temperature anomaly gradient (ATAG) induces changes in meridional and zonal circulations and promotes the baroclinic evolution of the horizontal circulation. The simplified model also indicates that the absolute vorticity of the horizontal circulation is not conserved, and its changes can be described by changes in the vertical vorticities of the meridional and zonal circulations. Moreover, the thermodynamic equation shows that the induced meridional and zonal circulations and advection transport by the horizontal circulation in turn cause a redistribution of the air temperature. The simplified model reveals the fundamental rules between the evolution of the air temperature and the horizontal, meridional

  6. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

    Science.gov (United States)

    Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

    2008-01-01

    Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

  7. Impairment of circulating endothelial progenitors in Down syndrome

    Directory of Open Access Journals (Sweden)

    Costa Valerio

    2010-09-01

    Full Text Available Abstract Background Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions Our data provide evidences for a reduced number and altered

  8. Correlates of Circulating 25-Hydroxyvitamin D

    Science.gov (United States)

    McCullough, Marjorie L.; Weinstein, Stephanie J.; Freedman, D. Michal; Helzlsouer, Kathy; Flanders, W. Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J.; Hankinson, Susan E.; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B.; Horst, Ronald L.; Shu, Xiao-Ou

    2010-01-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes. PMID:20562191

  9. Potential vorticity dynamics for global scale circulations

    International Nuclear Information System (INIS)

    Lu, C.; Schubert, W.

    1994-01-01

    One of the most notable advances in extratropical dynamics this decade has been the understanding of large-scale atmospheric and oceanic processes by using potential vorticity dynamics, the so called open-quotes IPV thinking.close quotes This analysis method has also been successfully extended to some tropical atmospheric circulation systems such as hurricanes and the Hadley circulation. The fundamental idea behind such a dynamic system rests with the fact that PV is a tracer-like quantity since it is conserved (in the absence of friction and diabatic heating) following a fluid particle and carries both significant dynamic and thermodynamic information regarding fluid motion. Thus, the prediction and inversion of PV form the most succinct dynamic view of atmospheric and oceanic motions. Furthermore, PV dynamics provides access to many insightful dynamic analyses such as: Propagation of Rossby waves, barotropic and baroclinic instabilities for shear flows, and wave-mean flow interactions. All these features make IPV analysis a very attractive tool for studying geophysical fluid systems

  10. Sustaining observations of the unsteady ocean circulation.

    Science.gov (United States)

    Frajka-Williams, E

    2014-09-28

    Sustained observations of ocean properties reveal a global warming trend and rising sea levels. These changes have been documented by traditional ship-based measurements of ocean properties, whereas more recent Argo profiling floats and satellite records permit estimates of ocean changes on a near real-time basis. Through these and newer methods of observing the oceans, scientists are moving from quantifying the 'state of the ocean' to monitoring its variability, and distinguishing the physical processes bringing signals of change. In this paper, I give a brief overview of the UK contributions to the physical oceanographic observations, and the role they have played in the wider global observing systems. While temperature and salinity are the primary measurements of physical oceanography, new transbasin mooring arrays also resolve changes in ocean circulation on daily timescales. Emerging technologies permit routine observations at higher-than-ever spatial resolutions. Following this, I then give a personal perspective on the future of sustained observations. New measurement techniques promise exciting discoveries concerning the role of smaller scales and boundary processes in setting the large-scale ocean circulation and the ocean's role in climate. The challenges now facing the scientific community include sustaining critical observations in the case of funding system changes or shifts in government priorities. These long records will enable a determination of the role and response of the ocean to climate change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  11. Pipe Decontamination Involving String-Foam Circulation

    International Nuclear Information System (INIS)

    Turchet, J.P.; Estienne, G.; Fournel, B.

    2002-01-01

    Foam applications number for nuclear decontamination purposes has recently increased. The major advantage of foam decontamination is the reduction of secondary liquid wastes volumes. Among foam applications, we focus on foam circulation in contaminated equipment. Dynamic properties of the system ensures an homogeneous and rapid effect of the foam bed-drifted chemical reagents present in the liquid phase. This paper describes a new approach of foam decontamination for pipes. It is based on an alternated air and foam injections. We called it 'string-foam circulation'. A further reduction of liquid wastes is achieved compared to continuous foam. Secondly, total pressure loss along the pipe is controlled by the total foam length in the pipe. It is thus possible to clean longer pipes keeping the pressure under atmospheric pressure value. This ensures the non dispersion of contamination. This study describes experimental results obtained with a neutral foam as well with an acid foam on a 130 m long loop. Finally, the decontamination of a 44 meters pipe is presented. (authors)

  12. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  13. Using information theory to assess the communicative capacity of circulating microRNA.

    Science.gov (United States)

    Finn, Nnenna A; Searles, Charles D

    2013-10-11

    The discovery of extracellular microRNAs (miRNAs) and their transport modalities (i.e., microparticles, exosomes, proteins and lipoproteins) has sparked theories regarding their role in intercellular communication. Here, we assessed the information transfer capacity of different miRNA transport modalities in human serum by utilizing basic principles of information theory. Zipf Statistics were calculated for each of the miRNA transport modalities identified in human serum. Our analyses revealed that miRNA-mediated information transfer is redundant, as evidenced by negative Zipf's Statistics with magnitudes greater than one. In healthy subjects, the potential communicative capacity of miRNA in complex with circulating proteins was significantly lower than that of miRNA encapsulated in circulating microparticles and exosomes. Moreover, the presence of coronary heart disease significantly lowered the communicative capacity of all circulating miRNA transport modalities. To assess the internal organization of circulating miRNA signals, Shannon's zero- and first-order entropies were calculated. Microparticles (MPs) exhibited the lowest Shannon entropic slope, indicating a relatively high capacity for information transfer. Furthermore, compared to the other miRNA transport modalities, MPs appeared to be the most efficient at transferring miRNA to cultured endothelial cells. Taken together, these findings suggest that although all transport modalities have the capacity for miRNA-based information transfer, MPs may be the simplest and most robust way to achieve miRNA-based signal transduction in sera. This study presents a novel method for analyzing the quantitative capacity of miRNA-mediated information transfer while providing insight into the communicative characteristics of distinct circulating miRNA transport modalities. Published by Elsevier Inc.

  14. Development of a radioimmunoassay for circulating levels of gonadotropin releasing hormone

    International Nuclear Information System (INIS)

    Moodbidri, S.B.; Joshi, L.R.; Sheth, A.R.; Rao, S.S.

    1976-01-01

    A specific and sensitive radioimmunoassay system has been developed for measuring gonadotropin releasing hormone (GnRH) in unextracted human serum. Circulating levels of GnRH, LH and FSH were determined in 37 serum samples obtained from twenty normal healthy women on different days of the menstrual cycle. GnRH and LH but not FSH exhibited similar patterns during the menstrual cycle. 125 I-labelled GnRH was used in the RIA system. (author)

  15. Demonstration of circulating 1,24,25-trihydroxyvitamin D3 in man by radioimmunoassay

    International Nuclear Information System (INIS)

    Clemens, T.L.; Fraher, L.J.; Sandler, L.M.; O'Riordan, J.L.H.

    1982-01-01

    1,24,25-trihydroxyvitamin D 3 has been detected in human serum using a sensitive radioimmunoassay. Tritiated 1,24,25-trihydroxyvitamin D 3 was synthesized biologically and used as tracer to monitor the recovery of endogenous metabolite during isolation from serum. Circulating 1,24,25(OH) 3 D 3 in normal subjects ranged from 9.3 to 18.5 pmol/l but was not detectable ( 3 . (author)

  16. Detection of circulating breast cancer cells using photoacoustic flow cytometry

    Science.gov (United States)

    Bhattacharyya, Kiran

    According to the American Cancer Society, more than 200,000 new cases of breast cancer are expected to be diagnosed this year. Moreover, about 40,000 women died from breast cancer last year alone. As breast cancer progresses in an individual, it can transform from a localized state to a metastatic one with multiple tumors distributed through the body, not necessarily contained within the breast. Metastasis is the spread of cancer through the body by circulating tumor cells (CTCs) which can be found in the blood and lymph of the diagnosed patient. Diagnosis of a metastatic state by the discovery of a secondary tumor can often come too late and hence, significantly reduce the patient's chance of survival. There is a current need for a CTC detection method which would diagnose metastasis before the secondary tumor occurs or reaches a size resolvable by current imaging systems. Since earlier detection would improve prognosis, this study proposes a method of labeling of breast cancer cells for detection with a photoacoustic flow cytometry system as a model for CTC detection in human blood. Gold nanoparticles and fluorescent polystyrene nanoparticles are proposed as contrast agents for T47D, the breast cancer cell line of choice. The labeling, photoacoustic detection limit, and sensitivity are first characterized and then applied to a study to show detection from human blood.

  17. Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS.

    Science.gov (United States)

    Nielsen, M J; Lehmann, J; Leeming, D J; Schierwagen, R; Klein, S; Jansen, C; Strassburg, C P; Bendtsen, F; Møller, S; Sauerbruch, T; Karsdal, M A; Krag, A; Trebicka, J

    2015-11-01

    Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.

  18. Analysis and research on natural circulation capacity of HFETR

    International Nuclear Information System (INIS)

    Xu Taozhong; Duan Tianyuan

    2010-01-01

    For the operating characteristics of HFETR, the numerical model of HFETR was established by RELAP5/MOD3 to analysis the maximal natural circulation capacity. Combining with the reactor running condition, the influence of the system pressure was analyzed by ascending power in step method and the pool water temperature on natural circulation characteristics was analyzed by integral power method. The results show that the natural circulation capacity are 0.9 and 2.0 MW separately under low pressure and high pressure, the natural circulation capacity increases as the running pressure increases, however the natural circulation capacity decreases as the coolant temperature increases in the pressure vessel. Based on the computational result and the theoretical deduction, a correlation was proposed to predicate the relationship between the natural circulation mass flow and the core power under different coolant temperatures. (authors)

  19. Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque

    Directory of Open Access Journals (Sweden)

    Krystina eSorwell

    2014-06-01

    Full Text Available The adrenal steroid dehydroepiandrosterone (DHEA and its sulfate (DHEAS are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens (DHEA, testosterone and 5α-dihydrotestosterone [DHT] to aged male rhesus macaques (Macaca mulatta. While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profile resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

  20. Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults.

    Science.gov (United States)

    Wang, Rui; Hong, Jie; Cao, Yanan; Shi, Juan; Gu, Weiqiong; Ning, Guang; Zhang, Yifei; Wang, Weiqing

    2015-03-01

    MicroRNAs (miRNAs) are involved in the regulation of adiposity, but functional studies have yielded inconclusive results. Examining the associations of circulating miRNAs levels with obesity and insulin sensitivity in humans may lead to improved insights. Serum samples collected from 112 obese and control subjects (50.0% men) were randomly divided and combined into four pools (28 samples in each obese or control pool). The genome-wide circulating miRNA profiles were detected via microarray. Elevated miR-122 was selected and validated in individual serum samples from 123 obese (46.7% men) and 107 control (50.0% men) young adults. Associations between circulating miR-122 levels and parameters related to adiposity, insulin resistance, lipid profiles and hepatic enzymes were further assessed. Thirty-four miRNAs were found to be expressed differently in the sera of obese patients compared with control subjects (Pobese patients had 3.07-fold higher circulating miR-122 levels than controls (Pobesity and insulin resistance in young adults. These findings provide a better understanding regarding the role of miRNAs in adiposity and insulin sensitivity. © 2015 European Society of Endocrinology.

  1. Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α

    Directory of Open Access Journals (Sweden)

    Anne H van der Spek

    2017-11-01

    Full Text Available Innate immune cells have recently been identified as novel thyroid hormone (TH target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα, which is the predominant TR in these cells, has not been studied to date. Studies in TRα0/0 mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G. Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T3 found in patients with RTHα.

  2. The circulation of the cerebrospinal fluid (CSF) in the spinal canal

    Science.gov (United States)

    Sanchez, Antonio L.; Martinez-Bazan, Carlos; Lasheras, Juan C.

    2016-11-01

    Cerebrospinal Fluid (CSF) is secreted in the choroid plexus in the lateral sinuses of the brain and fills the subarachnoid space bathing the external surfaces of the brain and the spinal canal. Absence of CSF circulation has been shown to impede its physiological function that includes, among others, supplying nutrients to neuronal and glial cells and removing the waste products of cellular metabolism. Radionuclide scanning images published by Di Chiro in 1964 showed upward migration of particle tracers from the lumbar region of the spinal canal, thereby suggesting the presence of an active bulk circulation responsible for bringing fresh CSF into the spinal canal and returning a portion of it to the cranial vault. However, the existence of this slow moving bulk circulation in the spinal canal has been a subject of dispute for the last 50 years. To date, there has been no physical explanation for the mechanism responsible for the establishment of such a bulk motion. We present a perturbation analysis of the flow in an idealized model of the spinal canal and show how steady streaming could be responsible for the establishment of such a circulation. The results of this analysis are compared to flow measurements conducted on in-vitro models of the spinal canal of adult humans.

  3. Glacial ocean circulation and stratification explained by reduced atmospheric temperature

    OpenAIRE

    Jansen, Malte F.

    2016-01-01

    To understand climatic swings between glacial and interglacial climates we need to explain the observed fluctuations in atmospheric carbon dioxide (CO2), which in turn are most likely driven by changes in the deep ocean circulation. This study presents a model for differences in the deep ocean circulation between glacial and interglacial climates consistent with both our physical understanding and various proxy observations. The results suggest that observed changes in ocean circulation and s...

  4. Circulating Tumor Cells, Enumeration and Beyond

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Jian-Mei [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Krebs, Matthew [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Ward, Tim; Morris, Karen; Sloane, Robert [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Blackhall, Fiona [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Dive, Caroline, E-mail: cdive@picr.man.ac.uk [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom)

    2010-06-09

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  5. Electromagnetic circulation pump for corrosive gases

    International Nuclear Information System (INIS)

    Noe, P.; Delafosse, D.; Deletre, G.

    1965-01-01

    In order to transport very corrosive products (fluorinated compounds) we have been led to develop a totally metallic circulation pump capable of operating at above room temperatures and with a molecular vacuum. We have aimed at maximum simplicity both in its conception and in its operation. The tests showed that the compression ratios produced, although not high are interesting (1.5 at a pressure of 100 torr) (see curve I). The flow-rate range is very wide: about one hundred ccs/atm/min. to 3000 ccs/atm/min. (see curves IV, V, VI). The desorption of this pump presents no difficulty if both the aspiration and the reject sides are pumped together. A hole of 2 mm diameter drilled in the piston makes it possible to desorb the space between the two segments. The price of this pump is not high: 1300 F, with the electrical cabinet. (authors) [fr

  6. Passive decay heat removal by natural circulation

    International Nuclear Information System (INIS)

    Vijayan, P.K.; Venkat Raj, V.; Kakodkar, A.; Mehta, S.K.

    1990-01-01

    The standardised 235 MWe PHWRs being built in India are the pressure tube type, heavy water moderated, heavy water cooled and natural uranium fuelled reactors. Several passive safety features are incorporated in these reactors. These include: (1) Containment pressure reduction and fission product trapping with the help of suppression pool following LOCA. (2) Emergency coolant injection by means of accumulators. (3) Large heat sink provided by the low temperature moderator under accident conditions. (4) Low excess reactivity, through the use of natural uranium fuel and on power fuelling. (5) Residual heat removal by means of natural circulation, etc. of which the last item is the subject matter of this report. (author). 8 refs, 10 figs

  7. Circulating tumor cells in breast cancer.

    Science.gov (United States)

    Bidard, Francois-Clement; Proudhon, Charlotte; Pierga, Jean-Yves

    2016-03-01

    Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Circulating tumor cells: clinical validity and utility.

    Science.gov (United States)

    Cabel, Luc; Proudhon, Charlotte; Gortais, Hugo; Loirat, Delphine; Coussy, Florence; Pierga, Jean-Yves; Bidard, François-Clément

    2017-06-01

    Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

  9. Nanotoxicity in Systemic Circulation and Wound Healing.

    Science.gov (United States)

    Bakshi, Mandeep Singh

    2017-06-19

    Nanotoxicity of nanomaterials is an important issue in view of their potential applications in systemic circulation and wound healing dressing. This account specifically deals with several characteristic features of different nanomaterials which induce hemolysis and how to make them hemocompatible. The shape, size, and surface functionalities of naked metallic as well as nonmetallic nanoparticles surfaces are responsible for the hemolysis. An appropriate coating of biocompatible molecules dramatically reduces hemolysis and promotes their ability as safe drug delivery vehicles. The use of coated nanomaterials in wound healing dressing opens several new strategies for rapid wound healing processes. Properly designed nanomaterials should be selected to minimize the nanotoxicity in the wound healing process. Future directions need new synthetic methods for engineered nanomaterials for their best use in nanomedicine and nanobiotechnology.

  10. Circulating Tumor Cells, Enumeration and Beyond

    International Nuclear Information System (INIS)

    Hou, Jian-Mei; Krebs, Matthew; Ward, Tim; Morris, Karen; Sloane, Robert; Blackhall, Fiona; Dive, Caroline

    2010-01-01

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology

  11. The collateral circulation of the heart

    Science.gov (United States)

    2013-01-01

    The coronary arteries have been regarded as end arteries for decades. However, there are functionally relevant anastomotic vessels, known as collateral arteries, which interconnect epicardial coronary arteries. These vessels provide an alternative source of blood supply to the myocardium in cases of occlusive coronary artery disease. The relevance of these collateral arteries is a matter of ongoing debate, but increasing evidence indicates a relevant protective role in patients with coronary artery disease. The collateral circulation can be assessed by different methods; the gold standard involves intracoronary pressure measurements. While the first clinical trials to therapeutically induce growth of collateral arteries have been unavailing, recent pilot studies using external counterpulsation or growth factors such as granulocyte colony stimulating factor (G-CSF) have shown promising results. PMID:23735225

  12. Circulating tumor cells: utopia or reality?

    Science.gov (United States)

    Conteduca, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Condelli, Valentina; Troiani, Laura; Aieta, Michele

    2013-09-01

    Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia', but its actual utility remains among the fastest growing research fields in oncology.

  13. Particle pollution changes the atmospheric circulation

    International Nuclear Information System (INIS)

    Kristjansson, Jon Egill; Iversen, Trond; Kirkevaag, Alf; Seland, Oeyvind; Debernard, Jens; Roeed, Lars Petter

    2002-01-01

    Industrial emissions and combustion of fossil fuels create large amounts of sulfate- and carbon containing soot particles. These mix with natural particles to change the natural aerosols. Such anthropogenic changes in the aerosols may have a great impact on the climate of the earth. Altered properties of the aerosols may change the atmosphere's absorption and reflection of solar radiation and contribute to heating or cooling. This is the direct effect. Changes in the properties of aerosols may also affect the number and size of recently formed cloud droplets. This may change the ability of the clouds to reflect solar radiation and to produce precipitation. This is the indirect effect. Recent research at the University of Oslo shows that anthropogenic particles significantly change the atmospheric circulation, in particular in the tropics, but also at European latitudes

  14. Nucla circulating atmospheric fluidized bed demonstration project

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Raymond E.

    1991-10-01

    Colorado-Ute Electric Association began a study to evaluate options for upgrading and extending the life of its Nucla power station in 1982. Located in southwestern Colorado near the town of Nucla, this station was commissioned in 1959 with a local bituminous coal as its design fuel for three identical stoker-fired units, each rated at 12.6 MW(e). Poor station efficiency, high fuel costs, and spiraling boiler maintenance costs forced the Nucla Station into low priority in the CUEA dispatch order as early as 1981. Among the options CUEA considered was to serve as a host utility to demonstrate Atmospheric Fluidized Bed Combustion (AFBC) technology. The anticipated environmental benefits and apparent attractive economics of a circulating AFBC led to Colorado-Ute's decision to proceed with the design and construction of a demonstration project in 1984 at the Nucla facility.

  15. Circulating Tumor Cells, Enumeration and Beyond

    Directory of Open Access Journals (Sweden)

    Jian-Mei Hou

    2010-06-01

    Full Text Available The detection and enumeration of circulating tumor cells (CTCs has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  16. Instability of single-phase natural circulation

    International Nuclear Information System (INIS)

    Xie Heng; Zhang Jinling; Jia Dounan

    1997-01-01

    The author has investigated the instability of single-phase flows in natural circulation loops. The momentum equation and energy equation are made dimensionless according to some definitions, and some important dimensionless parameters are gotten. The authors decomposed the mean mass flowrate and temperature into a steady solution and a small disturbance equations. Through solving the disturbance equations, the authors get the neutral stability curves. The authors have studied the effect of the two parameters which represent the ratio of buoyancy force to the friction loss in the loop on the stability of loops. The authors also have studied the effect of the difference of height between the center of heat source and the heat sink on the stability

  17. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    Hu, Brian; Rochefort, Holly; Goldkorn, Amir

    2013-01-01

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management

  18. NUCLA Circulating Atmospheric Fluidized Bed Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Raymond E.; Heller, Thomas J.; Bush, Stuart A.

    1991-01-01

    This Annual Report on Colorado-Ute Electric Association's NUCLA Circulating Fluidized Bed (CFB) Demonstration Program covers the period from February 1987 through December 1988. The outline for presentation in this report includes a summary of unit operations along with individual sections covering progress in study plan areas that commenced during this reporting period. These include cold-mode shakedown and calibration, plant commercial performance statistics, unit start-up (cold), coal and limestone preparation and handling, ash handling system performance and operating experience, tubular air heater, baghouse operation and performance, materials monitoring, and reliability monitoring. During this reporting period, the coal-mode shakedown and calibration plan was completed. (VC)

  19. Ocean circulation code on machine connection

    International Nuclear Information System (INIS)

    Vitart, F.

    1993-01-01

    This work is part of a development of a global climate model based on a coupling between an ocean model and an atmosphere model. The objective was to develop this global model on a massively parallel machine (CM2). The author presents the OPA7 code (equations, boundary conditions, equation system resolution) and parallelization on the CM2 machine. CM2 data structure is briefly evoked, and two tests are reported (on a flat bottom basin, and a topography with eight islands). The author then gives an overview of studies aimed at improving the ocean circulation code: use of a new state equation, use of a formulation of surface pressure, use of a new mesh. He reports the study of the use of multi-block domains on CM2 through advection tests, and two-block tests

  20. Re-circulating linac vacuum system

    International Nuclear Information System (INIS)

    Wells, Russell P.; Corlett, John N.; Zholents, Alexander A.

    2003-01-01

    The vacuum system for a proposed 2.5 GeV, 10ΜA recirculating linac synchrotron light source [1] is readily achievable with conventional vacuum hardware and established fabrication processes. Some of the difficult technical challenges associated with synchrotron light source storage rings are sidestepped by the relatively low beam current and short beam lifetime requirements of a re-circulating linac. This minimal lifetime requirement leads directly to relatively high limits on the background gas pressure through much of the facility. The 10ΜA average beam current produces very little synchrotron radiation induced gas desorption and thus the need for an ante-chamber in the vacuum chamber is eliminated. In the arc bend magnets, and the insertion devices, the vacuum chamber dimensions can be selected to balance the coherent synchrotron radiation and resistive wall wakefield effects, while maintaining the modest limits on the gas pressure and minimal outgassing

  1. Circulating tumor cells in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  2. Circulating prostacyclin metabolites in the dog

    International Nuclear Information System (INIS)

    Taylor, B.M.; Shebuski, R.J.; Sun, F.F.

    1983-01-01

    The present study was designed to determine the concentration of prostacyclin (PGI2) metabolites in the blood of the dog. After a bolus i.v. dose of [11 beta- 3 H]PGI2 (5 micrograms/kg) into each of five dogs, blood samples were withdrawn at 0.33, 0.67, 1, 3, 5, 20, 30, 60 and 120 min postdrug administration. Plasma samples were extracted and the radioactive components were analyzed by two-dimensional thin-layer chromatography with autoradiofluorography and radio-high-performance liquid chromatography. The compounds were identified by comparing their mobility with synthetic standards; only parallel responses observed in both tests constituted positive identification. Seven metabolites were identified by these two techniques: 6-keto-prostaglandin (PG)F1 alpha; 6-keto-PGE1; 2,3-dinor-6-keto-PGF 1 alpha; 2,3-dinor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha; and 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha. Several additional compounds, both polar and nonpolar in nature, which did not co-chromatograph with any of our standards were also detected. Early samples consisted predominantly of 6-keto-PGF 1 alpha and other 20-carbon metabolites. By 30 min, the predominant metabolites were the 16- and 18-carbon dicarboxylic acids. By 60 min, 85% of the radioactivity was associated with two unidentified polar compounds. The evidence suggests that 6-keto-PGF 1 alpha probably reflects only the transient levels of freshly entering PGI2 in the circulation, whereas levels of the most polar metabolites (e.g., dihydro-diketo-carboxyl tetranor-PGF 2 alpha) may be a better measure of the overall PGI2 presence due to its longer half-life in circulation

  3. Genetic Variants Associated with Circulating Parathyroid Hormone.

    Science.gov (United States)

    Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E; Nielson, Carrie M; Mitchell, Braxton D; Bis, Joshua C; Eny, Karen M; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W; Orwoll, Eric; Zmuda, Joseph M; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J; Ryan, Kathleen A; Ohlsson, Claes; Paterson, Andrew D; Psaty, Bruce M; Siscovick, David S; Rotter, Jerome I; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S; de Boer, Ian H; Kestenbaum, Bryan

    2017-05-01

    Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies ( n =22,653 and n =6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 ( P =4.2 × 10 -53 ), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 ( P =6.6 × 10 -17 ), rs219779 adjacent to CLDN14 ( P =3.5 × 10 -16 ), rs4443100 near RTDR1 ( P =8.7 × 10 -9 ), and rs73186030 near CASR ( P =4.8 × 10 -8 ). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued. Copyright © 2017 by the American Society of Nephrology.

  4. Hydrodynamics of circulating and bubbling fluidized beds

    International Nuclear Information System (INIS)

    Gidaspow, D.P.; Tsuo, Y.P.; Ding, J.

    1991-01-01

    This paper reports that a review of modeling of the hydrodynamics of fluidization of bubbling beds showed that inviscid two-fluid models were able to predict a great deal of the behavior of bubbling beds because the dominant mechanism of energy dissipation is the drag between the particles and the fluid. The formation, the growth and the bursting of bubbles were predicted. Predicted wall-to-bed heat transfer coefficients and velocity profiles of jets agreed with measurements. Time average porosity distributions agreed with measurements done using gamma-ray densitometers without the use of any adjustable parameters. However, inviscid models could not correctly predict rates of erosion around tubes immersed into fluidized beds. To correctly model such behavior, granular stresses involving solids viscosity were added into the computer model. This viscosity arises due to random collision of particles. Several models fro this viscosity were investigated and the results compared to measurements of solids distributions in two-dimensional beds and to particle velocities reported in the literature. While in the case of bubbling beds the solids viscosity plays the role of a correction, modeling of a circulating fluidized bed (CFB) without a viscosity is not possible. Recent experimental data obtained at IIT and at IGT show that in CFB the solids viscous dissipation is responsible for as much as half of the pressure drop. From such measurement, solids viscosities were computed. These were used in the two fluid hydrodynamic model, to predict radial solids distributions and solids velocities which matched the experimental distributions. Most important, the model predicted cluster formation and transient internal circulation which is responsible for the favorable characteristics of CFBs, such as good wall-to-bed heat transfer. Video tape movies of computations compared favorably with high speed movies of the experiments

  5. Circulating steroids negatively correlate with tinnitus.

    Science.gov (United States)

    Chrbolka, Pavel; Palúch, Zoltán; Hill, Martin; Alušík, Štefan

    2017-07-01

    While not a disease entity in itself; symptoms of tinnitus (from Latin tinnio - clink) accompany a number of diseases. Tinnitus prevalence increases with age, deteriorates one's quality of life, and may even result in suicidal behavior. Tinnitus develops in response to a variety of risk factors, otoxic substances, noise exposure, hearing disorders, and psychological alterations. Tinnitus is closely related to mood, depression, and psychological state. In the present study, we focused on alterations of the steroid metabolome and particularly neuroactive, neuroprotective, and immunomodulatory steroids in patients with tinnitus. The study group consisted of 28 patients without evidence of an organic cause of tinnitus as well as without associated diseases or the effect of ototoxic medications. All patients underwent a complete audiological assessment and laboratory tests including routine biochemical markers and quantification of circulating steroids using gas chromatography/mass spectrometry and immunoassays. To rule out a pathology in the cerebellopontine angle area, CT scan or MRI were performed. To diagnose stem lesions, evoked potentials were also measured. Pearson's correlations and multivariate regression were used to assess any links between tinnitus intensity and frequency on the one hand, and steroid levels on the other. Results indicated a significant and consistent negative correlation between tinnitus indices and intensity of adrenal steroidogenesis. The circulating steroid metabolome including hormones and neuroactive, neuroprotective, and immunomodulatory steroids negatively correlates with the degree of tinnitus due to hypothalamo-pituitary-adrenal axis malfunction. Our results may help explain the pathophysiology of tinnitus and improve its diagnosis. However, further studies are needed to verify our postulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer

    International Nuclear Information System (INIS)

    Hurwitz, Mark D.; Kaur, Punit; Nagaraja, Ganachari M.; Bausero, Maria A.; Manola, Judith; Asea, Alexzander

    2010-01-01

    Background and purpose: Hsp72 found in the extracellular milieu has been shown to play an important role in immune regulation. The impact of common cancer therapies on extracellular release of Hsp72 however, has been to date undefined. Materials and methods: Serum from 13 patients undergoing radiation therapy (XRT) for prostate cancer with or without hormonal therapy (ADT) was measured for levels of circulating serum Hsp72 and pro-inflammatory cytokines (IL-6 and TNF-α) using the classical sandwich ELISA technique and the relative expression of CD8 + T lymphocytes and natural killer (NK) cells was measured using flow cytometry. Mouse orthotopic xenograft of human prostate cancer tumors (DU-145 and PC-3) were used to validate and further characterize the response noted in the clinical setting. The biological significance of tumor released Hsp72 was studied in human dendritic cells (DC) in vitro. Results: Circulating serum Hsp72 levels increased an average of 3.5-fold (median per patient 4.8-fold) with XRT but not with ADT (p = 0.0002). Increases in IL-6 (3.3-fold), TNF-α (1.8-fold), CD8 + CTL (2.1-fold) and NK cells (3.2-fold) also occurred. Using PC-3 and DU-145 human prostate cancer xenograft models in mice, we confirmed that XRT induces Hsp72 release primarily from implanted tumors. In vitro studies using supernatant recovered from irradiated human prostate cancer cells point to exosomes containing Hsp72 as a possible stimulator of pro-inflammatory cytokine production and costimulatory molecules expression in human DC. Conclusions: The current study confirms for the first time in an actual clinical setting elevation of circulating serum Hsp72 with XRT. The accompanying studies in mice and in vitro identify the released exosomes containing Hsp72 as playing a pivotal role in stimulating pro-inflammatory immune responses. These findings, if validated, may lead to new treatment paradigms for common human malignancies.

  7. Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women.

    Science.gov (United States)

    Park, Heyjun; Wood, Madeleine R; Malysheva, Olga V; Jones, Sara; Mehta, Saurabh; Brannon, Patsy M; Caudill, Marie A

    2017-12-01

    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13 C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. Results: In placental tissue, 25-hydroxyvitamin D 3 [25(OH)D 3 ] was strongly correlated ( r = 0.83, P D 3 Moreover, these placental metabolites were strongly correlated ( r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations ( P ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 ( LRP2 , also known as megalin) with 25(OH)D 3 and the C3 epimer of 25(OH)D 3 [3-epi-25(OH)D 3 ]; cubilin ( CUBN ) with 25(OH)D 3 ; 25-hydroxylase ( CYP2R1 ) with 3-epi-25(OH)D 3 ; 24-hydroxylase ( CYP24A1 ) with 25(OH)D 3 , 3-epi-25(OH)D 3 , and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]; and 1α-hydroxylase [( CYP27B1 ) with 3-epi-25(OH)D 3 and 1,25(OH) 2 D 3 ]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D 3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment. Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with

  8. Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons.

    Science.gov (United States)

    Tan, Carlyn Rose C; Zhou, Lanlan; El-Deiry, Wafik S

    2016-06-01

    Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC-and ctDNA-based liquid biopsies is envisioned.

  9. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer.

    Science.gov (United States)

    Riva, Francesca; Dronov, Oleksii I; Khomenko, Dmytro I; Huguet, Florence; Louvet, Christophe; Mariani, Pascale; Stern, Marc-Henri; Lantz, Olivier; Proudhon, Charlotte; Pierga, Jean-Yves; Bidard, Francois-Clement

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Climatology of the HOPE-G global ocean general circulation model - Sea ice general circulation model

    Energy Technology Data Exchange (ETDEWEB)

    Legutke, S. [Deutsches Klimarechenzentrum (DKRZ), Hamburg (Germany); Maier-Reimer, E. [Max-Planck-Institut fuer Meteorologie, Hamburg (Germany)

    1999-12-01

    The HOPE-G global ocean general circulation model (OGCM) climatology, obtained in a long-term forced integration is described. HOPE-G is a primitive-equation z-level ocean model which contains a dynamic-thermodynamic sea-ice model. It is formulated on a 2.8 grid with increased resolution in low latitudes in order to better resolve equatorial dynamics. The vertical resolution is 20 layers. The purpose of the integration was both to investigate the models ability to reproduce the observed general circulation of the world ocean and to obtain an initial state for coupled atmosphere - ocean - sea-ice climate simulations. The model was driven with daily mean data of a 15-year integration of the atmosphere general circulation model ECHAM4, the atmospheric component in later coupled runs. Thereby, a maximum of the flux variability that is expected to appear in coupled simulations is included already in the ocean spin-up experiment described here. The model was run for more than 2000 years until a quasi-steady state was achieved. It reproduces the major current systems and the main features of the so-called conveyor belt circulation. The observed distribution of water masses is reproduced reasonably well, although with a saline bias in the intermediate water masses and a warm bias in the deep and bottom water of the Atlantic and Indian Oceans. The model underestimates the meridional transport of heat in the Atlantic Ocean. The simulated heat transport in the other basins, though, is in good agreement with observations. (orig.)

  11. Plausible Effect of Weather on Atlantic Meridional Overturning Circulation with a Coupled General Circulation Model

    Science.gov (United States)

    Liu, Zedong; Wan, Xiuquan

    2018-04-01

    The Atlantic meridional overturning circulation (AMOC) is a vital component of the global ocean circulation and the heat engine of the climate system. Through the use of a coupled general circulation model, this study examines the role of synoptic systems on the AMOC and presents evidence that internally generated high-frequency, synoptic-scale weather variability in the atmosphere could play a significant role in maintaining the overall strength and variability of the AMOC, thereby affecting climate variability and change. Results of a novel coupling technique show that the strength and variability of the AMOC are greatly reduced once the synoptic weather variability is suppressed in the coupled model. The strength and variability of the AMOC are closely linked to deep convection events at high latitudes, which could be strongly affected by the weather variability. Our results imply that synoptic weather systems are important in driving the AMOC and its variability. Thus, interactions between atmospheric weather variability and AMOC may be an important feedback mechanism of the global climate system and need to be taken into consideration in future climate change studies.

  12. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    Science.gov (United States)

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  13. Circulating Histones Are Major Mediators of Cardiac Injury in Patients With Sepsis.

    Science.gov (United States)

    Alhamdi, Yasir; Abrams, Simon T; Cheng, Zhenxing; Jing, Shengjie; Su, Dunhao; Liu, Zhiyong; Lane, Steven; Welters, Ingeborg; Wang, Guozheng; Toh, Cheng-Hock

    2015-10-01

    To investigate the impact of circulating histones on cardiac injury and dysfunction in a murine model and patients with sepsis. Prospective, observational clinical study with in vivo and ex vivo translational laboratory investigations. General ICU and university research laboratory. Sixty-five septic patients and 27 healthy volunteers. Twelve-week-old male C57BL/6N mice. Serial blood samples from 65 patients with sepsis were analyzed, and left ventricular function was assessed by echocardiography. Patients' sera were incubated with cultured cardiomyocytes in the presence or absence of antihistone antibody, and cellular viability was assessed. Murine sepsis was initiated by intraperitoneal Escherichia coli injection (10(8) colony-forming unit/mouse) in 12-week-old male C57BL/6N mice, and the effect of antihistone antibody (10 mg/kg) was studied. Murine blood samples were collected serially, and left ventricular function was assessed by intraventricular catheters and electrocardiography. Circulating histones and cardiac troponins in human and murine plasma were quantified. In 65 patients with sepsis, circulating histones were significantly elevated compared with healthy controls (n = 27) and linearly correlated with cardiac troponin T levels (rs = 0.650; p histone levels were significantly associated with new-onset left ventricular dysfunction (p = 0.001) and arrhythmias (p = 0.01). Left ventricular dysfunction only predicted adverse outcomes when combined with elevated histones or cardiac troponin levels. Furthermore, patients' sera directly induced histone-specific cardiomyocyte death ex vivo, which was abrogated by antihistone antibodies. In vivo studies on septic mice confirmed the cause-effect relationship between circulating histones and the development of cardiac injury, arrhythmias, and left ventricular dysfunction. Circulating histones are novel and important mediators of septic cardiomyopathy, which can potentially be utilized for prognostic and therapeutic

  14. Ability of the CCSR-NIES atmospheric general circulation model in the stratosphere. Chapter 3

    International Nuclear Information System (INIS)

    Sugata, S.

    1997-01-01

    A quantitative evaluation of climate change such as global warming is impossible without a high-quality numerical model which describes the dynamics of the climate system and the circulation of energy and materials. The Center for Climate Research - National Institute for Environmental Studies (CCSR-NIES) atmospheric general circulation model (hereafter, GCM for a general circulation model) has been developed to obtain such a high-quality model. The emphasis of the development has been laid on the troposphere and the lower stratosphere below about 30 km altitude. This is natural because human beings live on the Earth's surface and the condition of the lower atmosphere directly affects human life. However, the stratosphere and the upper atmosphere beyond it have recently been the focus even in investigations of climate change, because they are relevant to many issues which relate closely to tropospheric climate change, such as the ozone hole, material exchange between the stratosphere and the troposphere, and physical interaction between the stratosphere and troposphere. This study extended the region of the CCSR-NIES GCM to the lower mesosphere (about 70 km from the surface). This is our first attempt to investigate this GCM's climatology in the upper atmosphere, although some studies for QBO in the middle and lower stratosphere had been done with the GCM

  15. Experimental studies in the bronchial circulation. Which is the ideal animal model?

    Science.gov (United States)

    Panagiotou, Ioannis; Tsipas, Panteleimon; Melachrinou, Maria; Alexopoulos, Dimitrios; Dougenis, Dimitrios

    2014-01-01

    Background The importance of the role of bronchial arteries is notable in modern days thoracic surgery. The significance of their anastomoses with adjusted structures has not yet been sufficiently rated, especially in cases of haemoptysis, heart-lung transplantations and treatment of aneurysms of the thoracic aorta. The need of a thorough study is more relevant than ever and appropriate laboratory animals are required. Methods We review the literature in order to highlight the ideal experimental animal for the implementation of pilot programs relative to the bronchial circulation. A comparative analysis of the anatomy of the bronchial arterial system in humans along with these of pigs, dogs, rats, and birds, as being the most commonly used laboratory animals, is presented in details. Results The pig has the advantage that the broncho-oesophageal artery usually originates from the aorta as a single vessel, which makes the recognition and dissection of the artery easy to perform. In dogs, there is significant anatomical variation of the origin of the bronchial arteries. In rats, bronchial artery coming from the aorta is a rare event while in birds the pattern of the bronchial artery tree is clearly different from the human analog. Conclusions The pig is anatomically and physiologically suited for experimental studies on the bronchial circulation. The suitable bronchial anatomy and physiology along with the undeniable usefulness of the pig in experimental research and the low maintenance cost make the pig the ideal model for experiments in bronchial circulation. PMID:25364530

  16. Distinct proteome pathology of circulating microparticles in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer Tandrup; Tanassi, Julia Tanas

    2017-01-01

    BACKGROUND: The pathogenesis of systemic lupus erythematosus (SLE) is poorly understood but has been linked to defective clearance of subcellular particulate material from the circulation. This study investigates the origin, formation, and specificity of circulating microparticles (MPs) in patien...... generation of MPs may partake in the pathology of SLE and that new diagnostic, monitoring, and treatment strategies targeting these processes may be advantageous....

  17. Forcing mechanisms of the Bay of Bengal circulation

    Digital Repository Service at National Institute of Oceanography (India)

    Vinayachandran, P.N.; Shetye, S.R.; Sengupta, D.; Gadgil, S.

    A state-of-the-art ocean general circulation model, set up for the North Indian Ocean and driven by climatological wind stress simulates most of the observed features of the near-surface circulation of the Bay of Bengal. The prominent features...

  18. Circulation of the surface waters in the north Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Varadachari, V.V.R.; Sharma, G.S.

    The circulation pattern of the surface waters in the North Indian Ocean for different months of the year is discussed. In order to arrive at a reliable and detailed picture of the circulation pattern, streamlines are drawn using the isogon technique...

  19. Lost circulation technology workshop, October 9-10, 1984

    Energy Technology Data Exchange (ETDEWEB)

    Caskey, B.C. (ed.)

    1985-03-01

    This report summarizes the presentations and discussions of a workshop on lost circulation technology. The workshop identified and defined lost circulation problem areas in field operations, materials, mud effects, and standards. Problem solution needs were also categorized as requiring analytical evaluation and procedure, instrument, and material development.

  20. Metabolites associated with circulating interleukin-6 in older adults

    Science.gov (United States)

    Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in ...

  1. Computer Simulation of the Circulation Subsystem of a Library

    Science.gov (United States)

    Shaw, W. M., Jr.

    1975-01-01

    When circulation data are used as input parameters for a computer simulation of a library's circulation subsystem, the results of the simulation provide information on book availability and delays. The model may be used to simulate alternative loan policies. (Author/LS)

  2. Circulation Price Elasticity in the Daily Newspaper Industry.

    Science.gov (United States)

    Grotta, Gerald L.; Taylor, Michael Lee

    Pricing of subscriptions and single copies has historically been arbitrary. Evidence indicates that the newspaper industry has tended to overestimate the elasticity of demand for newspaper circulation. This study analyzed price changes, circulation changes, and population changes for all daily newspapers in the United States between 1970 and 1975.…

  3. Single particle behaviour in circulating fluidized bed combustors

    DEFF Research Database (Denmark)

    Erik Weinell, Claus

    1994-01-01

    An investigation of single particle behaviour in a circulating fluidized bed combustor is described, relating to sulphur capture reactions by limestone under alternate oxidizing and reducing conditions present in a circulating fluidized bed combustor, and to the devolatilization and burn out...

  4. Circulating tumor cell isolation and diagnostics: toward routine clinical use

    NARCIS (Netherlands)

    Stolpe, van de A.; Pantel, K.; Sleijfer, S.; Terstappen, L.W.; Toonder, den J.M.J.

    2011-01-01

    From February 7–11, 2011, the multidisciplinary Lorentz Workshop Circulating Tumor Cell (CTC) Isolation and Diagnostics: Toward Routine Clinical Use was held in Leiden (The Netherlands) to discuss progress and define challenges and potential solutions for development of clinically useful circulating

  5. Natural Circulation Characteristics of a Symmetric Loop under Inclined Conditions

    Directory of Open Access Journals (Sweden)

    Xingtuan Yang

    2014-01-01

    Full Text Available Natural circulation is an important process for primary loops of some marine integrated reactors. The reactor works under inclined conditions when severe accidents happen to the ship. In this paper, to investigate the characteristics of natural circulation, experiments were conducted in a symmetric loop under the inclined angle of 0~45°. A CFD model was also set up to predict the behaviors of the loop beyond the experimental scope. Total circulation flow rate decreases with the increase of inclined angle. Meanwhile one circulation is depressed while the other is enhanced, and accordingly the disparity between the branch circulations arises and increases with the increase of inclined angle. Circulation only takes place in one branch circuit at large inclined angle. Also based on the CFD model, the influences of flow resistance distribution and loop configuration on natural circulation are predicted. The numerical results show that to design the loop with the configuration of big altitude difference and small width, it is favorable to reduce the influence of inclination; however too small loop width will cause severe reduction of circulation ability at large angle inclination.

  6. Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer; Iversen, Line V

    2013-01-01

    To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases.......To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases....

  7. Pirates, stewards, and the securitisation of global circulation

    NARCIS (Netherlands)

    Lobo-Guerrero, Luis

    2008-01-01

    This article is a contribution to the theorization of global maritime circulation as a key category of a global biopolitics of security. It seeks to advance knowledge on the ways in which liberal life is promoted and protected by exacerbating global circulation. It focuses on the security effects of

  8. Tablets: A Survey of Circulation Policies at Academic Libraries

    Science.gov (United States)

    Derr, Janice; Tolppanen, Bradley P.

    2015-01-01

    This article presents the results of a Web-based survey regarding the circulation of tablets in academic libraries. The survey, which was completed by 61 respondents, identifies the most common circulation policies and procedures used. These results will help other academic institutions develop their own policy or update existing ones. Areas of…

  9. Circulating osteogenic cells: implications for injury, repair, and regeneration

    DEFF Research Database (Denmark)

    Pignolo, Robert J; Kassem, Moustapha

    2011-01-01

    The aim of this review is to provide a critical reading of recent literature pertaining to the presence of circulating, fluid-phase osteoblastic cells and their possible contribution to bone formation. We have termed this group of cells collectively as circulating osteogenic precursor (COP) cells...

  10. Atlantic Meridional Overturning Circulation During the Last Glacial Maximum.

    NARCIS (Netherlands)

    Lynch-Stieglitz, J.; Adkins, J.F.; Curry, W.B.; Dokken, T.; Hall, I.R.; Herguera, J.C.; Hirschi, J.J.-M.; Ivanova, E.V.; Kissel, C.; Marchal, O.; Marchitto, T.M.; McCave, I.N.; McManus, J.F.; Mulitza, S.; Ninnemann, U.; Peeters, F.J.C.; Yu, E.-F.; Zahn, R.

    2007-01-01

    The circulation of the deep Atlantic Ocean during the height of the last ice age appears to have been quite different from today. We review observations implying that Atlantic meridional overturning circulation during the Last Glacial Maximum was neither extremely sluggish nor an enhanced version of

  11. Reliability evaluation of a natural circulation system

    International Nuclear Information System (INIS)

    Jafari, Jalil; D'Auria, Francesco; Kazeminejad, Hossein; Davilu, Hadi

    2003-01-01

    This paper discusses a reliability study performed with reference to a passive thermohydraulic natural circulation (NC) system, named TTL-1. A methodology based on probabilistic techniques has been applied with the main purpose to optimize the system design. The obtained results have been adopted to estimate the thermal-hydraulic reliability (TH-R) of the same system. A total of 29 relevant parameters (including nominal values and plausible ranges of variations) affecting the design and the NC performance of the TTL-1 loop are identified and a probability of occurrence is assigned for each value based on expert judgment. Following procedures established for the uncertainty evaluation of thermal-hydraulic system codes results, 137 system configurations have been selected and each configuration has been analyzed via the Relap5 best-estimate code. The reference system configuration and the failure criteria derived from the 'mission' of the passive system are adopted for the evaluation of the system TH-R. Four different definitions of a less-than-unity 'reliability-values' (where unity represents the maximum achievable reliability) are proposed for the performance of the selected passive system. This is normally considered fully reliable, i.e. reliability-value equal one, in typical Probabilistic Safety Assessment (PSA) applications in nuclear reactor safety. The two 'point' TH-R values for the considered NC system were found equal to 0.70 and 0.85, i.e. values comparable with the reliability of a pump installed in an 'equivalent' forced circulation (active) system having the same 'mission'. The design optimization study was completed by a regression analysis addressing the output of the 137 calculations: heat losses, undetected leakage, loop length, riser diameter, and equivalent diameter of the test section have been found as the most important parameters bringing to the optimal system design and affecting the TH-R. As added values for this work, the comparison has

  12. CIRCULATING MOVING BED COMBUSTION PROOF OF CONCEPT

    Energy Technology Data Exchange (ETDEWEB)

    Jukkola, Glen

    2010-06-30

    Circulating Moving Bed (CMB) combustion technology has its roots in traditional circulating fluidized bed technology and involves a novel method of solid fuel combustion and heat transfer. CMB technology represents a step change in improved performance and cost relative to conventional PC and FBC boilers. The CMB heat exchanger preheats the energy cycle working fluid, steam or air, to the high temperature levels required in systems for advanced power generation. Unique features of the CMB are the reduction of the heat transfer surfaces by about 60% as a result of the enhanced heat transfer rates, flexibility of operation, and about 30% lower cost over existing technology. The CMB Phase I project ran from July 2001 through March 2003. Its objective was to continue development of the CMB technology with a series of proof of concept tests. The tests were conducted at a scale that provided design data for scale up to a demonstration plant. These objectives were met by conducting a series of experiments in ALSTOM Power’s Multi-use Test Facility (MTF). The MTF was modified to operate under CMB conditions of commercial interest. The objective of the tests were to evaluate gas-to-solids heat transfer in the upper furnace, assess agglomeration in the high temperature CMB bubbling bed, and evaluate solids-to-tube heat transfer in the moving bed heat exchanger. The Phase I program results showed that there are still some significant technical uncertainties that needed to be resolved before the technology can be confidently scaled up for a successful demonstration plant design. Work remained in three primary areas: • scale up of gas to solid heat transfer • high temperature finned surface design • the overall requirements of mechanical and process design. The CMB Phase II workscope built upon the results of Phase I and specifically addressed the remaining technical uncertainties. It included a scaled MTF heat transfer test to provide the necessary data to scale up gas

  13. Thermohaline circulation in the Gulf of California

    Science.gov (United States)

    Bray, N. A.

    1988-05-01

    The Gulf of California, a narrow, semienclosed sea, is the only evaporative basin of the Pacific Ocean. As a result of evaporative forcing, salinities in the gulf are 1 to 2 ‰ higher than in the adjacent Pacific at the same latitude. This paper examines the thermohaline structure of the gulf and the means by which thermohaline exchange between the Pacific and the gulf occurs, over time scales of months to years. In addition to evaporative forcing, air-sea heat fluxes and momentum fluxes are important to thermohaline circulation in the gulf. From observations presented here, it appears that the gulf gains heat from the atmosphere on an annual average, unlike the Mediterranean and Red seas, which have comparable evaporative forcing. As a result, outflow from the gulf tends to be less dense than inflow from the Pacific. Winds over the gulf change direction with season, blowing northward in summer and southward in winter. This same seasonal pattern appears in near-surface transports averaged across the gulf. The thermohaline circulation, then, consists of outflow mostly between about 50 m and 250 m, inflow mostly between 250 m and 500 m, and a surface layer in which the direction of transport changes with seasonal changes in the large-scale winds. Using hydrographic observations from a section across the central gulf, total transport in or out of the northern gulf is estimated to be 0.9 Sv, heat gain from the atmosphere is estimated to be 20 to 50 W m-2, and evaporation is estimated to be 0.95 m yr-1. These estimates are annual averages, based on cruises from several years. Seasonal variations in thermohaline structure in the gulf are also examined and found to dominate the variance in temperature and density in the top 500 m of the water column. Salinity has little seasonal variability but does exhibit more horizontal variablility than temperature or density. Major year-to-year variations in thermohaline structure may be attributable to El Niño-Southern Oscillation

  14. Circulating Immune Complexes among Diabetic Children

    Directory of Open Access Journals (Sweden)

    George Nicoloff

    2004-01-01

    Full Text Available Insulin dependent diabetes mellitus (IDDM is an autoimmune disease associated with the presence of different types of autoantibodies. The presence of these antibodies and the corresponding antigens in the circulation leads to the formation of circulating immune complexes (CIC. CIC are known to persist in the blood for long periods of time. Such CIC following deposition in the small blood vessels have the potential to lead to microangiopathy with debilitating clinical consequences. The aim of our pilot study was to investigate whether a correlation exists between CIC and the development of microvascular complications in diabetic children. Isolation of a new glycoprotein complement inhibition factor (CIF from the parasitic plant Cuscuta europea seed, which appears to bind specifically to complement component C3 has provided an unique tool for the measurement of immune complexes by means of ELISA-type techniques (CIF-ELISA. We studied the levels of CIC (IgG, IgM and IgA in 58 diabetic children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years, 29 of them had vascular complications (group 1 and the other 29 were without vascular complications (group 2. As controls, we studied sera samples from 21 healthy children (mean age 13.54±4.03 years. Sera from the diabetic patients showed statistically significant higher levels of CIC IgG ( p=0.03 than sera from the control group. In sera from group 1 values of CIC IgG showed statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045; p=0.011 Sera from 59% of the patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from 17/26 (65% were positive for CIC IgG, 8/26 (31% for CIC IgM and 2/26 (8% for CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005 and microalbuminuria (r=0.42, p=0.033. CIC IgA correlated with age (r=0.44, p=0.03. CIC IgM correlated with the duration of diabetes (r=0.63, p=0.02. These

  15. Circulating Fetuin-A and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Kröger, Janine; Meidtner, Karina; Stefan, Norbert

    2018-01-01

    with those from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 cases) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistical evidence for an effect of fetuin-A on insulin sensitivity and secretion......Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian...... score of theAHSGSNPs was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 µg/ml higher fetuin-A concentration with diabetes risk (HR 1.02 [95%-CI 0.97, 1.07]). Combining our results...

  16. Increased Circulating Betatrophin Concentrations in Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Daniel Espes

    2014-01-01

    Full Text Available Betatrophin has recently been described as a key hormone to stimulate beta-cell mass expansion in response to insulin resistance and obesity in mice. The finding has generated an interest in the development of antidiabetic drugs with betatrophin as the active component. However, the circulating levels of betatrophin in patients with type 2 diabetes are not well known. Betatrophin concentrations in plasma of 27 type 2 diabetes patients and 18 gender-, age-, and BMI-matched controls were measured. Study participants were characterized with regard to BMI, waist and hip circumference, blood pressure, and fasting plasma blood lipids, creatinine, glucose, HbA1c, and C-peptide. HOMA2 indices were calculated. Betatrophin was 40% higher in patients with type 2 diabetes (893±80 versus 639±66 pg/mL. Betatrophin positively correlated with age in the controls and with HbA1c in the type 2 diabetes patients. All study participants were insulin resistant with mean HOMA2B IR in both groups exceeding 2 and HOMA2%S<50%. Control individuals had impaired fasting glucose concentrations. In this report on betatrophin concentrations in type 2 diabetes and insulin resistance, elevated betatrophin levels were measured in the patients with type 2 diabetes. Future studies are clearly needed to delineate the exact role, if any, of betatrophin in regulating human beta-cell mass.

  17. Genomic Analysis of Circulating Cells: A Window into Atherosclerosis

    Science.gov (United States)

    Kang, Ju-Gyeong; Patino, Willmar D.; Matoba, Satoaki; Hwang, Paul M.

    2006-01-01

    Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments using diseased tissue or surrogate specimens. This review details the rationale and findings of a study using freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched normal subjects. Using this cardiovascular tissue surrogate, the mRNA levels of the Finkel-Biskis-Jinkins osteosarcoma (FOS) gene in circulating monocytes were found to correlate with atherosclerosis severity in patients, and with HMG CoA reductase inhibitor (statin) therapy in normal subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate their reports. They also provide us with insights into pathogenesis that may impact future translational applications. PMID:16781950

  18. The development and study on passive natural circulation

    International Nuclear Information System (INIS)

    Zhou Tao; Li Jingjing; Ju Zhongyun; Huang Yanping; Xiao Zejun

    2013-01-01

    Passive natural circulation is getting more and more important in the field of nuclear power engineering. This article cited a passive natural circulation in the nuclear power system application, analyzed the potential problems during operation, described current mathematical research methods of the reliability of passive natural cycle analysis, briefly summarized the advantages and disadvantages of these methods, and finally got an outlook of the direction of passive natural circulation. Since the presence of passive natural circulation may get failure, sufficient attention and active research should be paid in response to the physical process failure of the running passive natural circulation system and its reliability. To ensure system security during the operation, the operation process should combine active with non-dynamic; while selecting an accurate model, perfect passive reliability analysis methods to achieve accurate theoretical calculations and experimental verification. (authors)

  19. SCDAP/RELAP5 applications to RCS natural circulation

    International Nuclear Information System (INIS)

    Bayless, P.D.

    1988-01-01

    The effects of natural circulation flows in the reactor coolant system during a TMLB' sequence were investigated. Both in-vessel circulation and hot leg countercurrent flow were modeled in the Surry nuclear power plant using the SCDAP/RELAP5 computer code. The transient was analyzed until after fuel rod relocation had begun. The delays in the onset of relocation resulting from the natural circulation flows were not significant compared to SCDAP/RELAP5 calculations without natural circulation modeled, but were large compared to the analyses presented in NUREG-1150. The most significant aspect of the natural circulations flows was the heating of ex-vessel structures. Surge line failure is likely to occur before the vessel is breached by the molten core, while steam generator tube failure is not expected

  20. Natural Circulation Characteristics of an Integral Pressurized Water Reactor

    International Nuclear Information System (INIS)

    Junli Gou; Suizheng Qiu; Guanghui Su; Dounan Jia

    2006-01-01

    Natural circulation potential is of great importance to the inherent safety of a nuclear reactor. This paper presents a theoretical investigation on the natural circulation characteristics of an integrated pressurized water reactor. Through numerically solved the one-dimensional model, the steady-state single phase conservative equations for the primary circuit and the steady-state two-phase drift-flux conservative equations for the secondary side of the once-through steam generator, the natural circulation characteristics are studied. Based on the preliminary calculation analysis, it is found that natural circulation mass flow rate is proportional to the exponential function of the power, and the value of the exponent is related to working conditions of the steam generator secondary side. The higher height difference between the core center and the steam generator center is favorable to the heat removal capacity of the natural circulation. (authors)

  1. A Thermodynamically General Theory for Convective Circulations and Vortices

    Science.gov (United States)

    Renno, N. O.

    2007-12-01

    Convective circulations and vortices are common features of atmospheres that absorb low-entropy-energy at higher temperatures than they reject high-entropy-energy to space. These circulations range from small to planetary-scale and play an important role in the vertical transport of heat, momentum, and tracer species. Thus, the development of theoretical models for convective phenomena is important to our understanding of many basic features of planetary atmospheres. A thermodynamically general theory for convective circulations and vortices is proposed. The theory includes irreversible processes and quantifies the pressure drop between the environment and any point in a convective updraft. The article's main result is that the proposed theory provides an expression for the pressure drop along streamlines or streamtubes that is a generalization of Bernoulli's equation to convective circulations. We speculate that the proposed theory not only explains the intensity, but also shed light on other basic features of convective circulations and vortices.

  2. Inflammaging and Frailty Status Do Not Result in an Increased Extracellular Vesicle Concentration in Circulation

    Directory of Open Access Journals (Sweden)

    Ainhoa Alberro

    2016-07-01

    Full Text Available In the last decades extracellular vesicles (EVs have emerged as key players for intercellular communication. In the case of inflammation, several studies have reported that EV levels are increased in circulation during inflammatory episodes. Based on this, we investigated whether aging results in elevated EV number, as a basal proinflammatory status termed “inflammaging” has been described in aged individuals. Moreover, we also hypothesized that frailty and dependence conditions of the elderly could affect EV concentration in plasma. Results showed that inflammaging, frailty or dependence status do not result in EV increase, at least in the total number of EVs in circulation. These results open a new perspective for investigating the role of EVs in human aging and in the inflammaging process.

  3. Inflammaging and Frailty Status Do Not Result in an Increased Extracellular Vesicle Concentration in Circulation.

    Science.gov (United States)

    Alberro, Ainhoa; Sáenz-Cuesta, Matías; Muñoz-Culla, Maider; Mateo-Abad, Maider; Gonzalez, Esperanza; Carrasco-Garcia, Estefania; Araúzo-Bravo, Marcos J; Matheu, Ander; Vergara, Itziar; Otaegui, David

    2016-07-20

    In the last decades extracellular vesicles (EVs) have emerged as key players for intercellular communication. In the case of inflammation, several studies have reported that EV levels are increased in circulation during inflammatory episodes. Based on this, we investigated whether aging results in elevated EV number, as a basal proinflammatory status termed "inflammaging" has been described in aged individuals. Moreover, we also hypothesized that frailty and dependence conditions of the elderly could affect EV concentration in plasma. Results showed that inflammaging, frailty or dependence status do not result in EV increase, at least in the total number of EVs in circulation. These results open a new perspective for investigating the role of EVs in human aging and in the inflammaging process.

  4. Simultaneous circulation of genotypes I and III of dengue virus 3 in Colombia

    Directory of Open Access Journals (Sweden)

    Domingo Cristina

    2008-09-01

    Full Text Available Abstract Background Dengue is a major health problem in tropical and subtropical regions. In Colombia, dengue viruses (DENV cause about 50,000 cases annually, 10% of which involve Dengue Haemorrhagic Fever/Dengue Shock Syndrome. The picture is similar in other surrounding countries in the Americas, with recent outbreaks of severe disease, mostly associated with DENV serotype 3, strains of the Indian genotype, introduced into the Americas in 1994. Results The analysis of the 3'end (224 bp of the envelope gene from 32 DENV-3 strains recently recovered in Colombia confirms the circulation of the Indian genotype, and surprisingly the co-circulation of an Asian-Pacific genotype only recently described in the Americas. Conclusion These results have important implications for epidemiology and surveillance of DENV infection in Central and South America. Molecular surveillance of the DENV genotypes infecting humans could be a very valuable tool for controlling/mitigating the impact of the DENV infection.

  5. Applications of environmental radon-222 to some cases of water circulation

    International Nuclear Information System (INIS)

    Kimura, S.; Komae, T.

    1980-01-01

    We have proposed three methods to analyze water circulation and the changes caused by human activities by studying the changing distribution patterns of 222 Rn concentrations in water. We investigated the results by applying the methods to some water circulation problems of Japan. The first method was a detailed analysis of the hydrogeological structure of an area, using the fact that the 222 Rn concentration of water takes a value characteristic of the aquifer. In the second method we analyzed the state of mixing of surface water and groundwater by taking advantage of the fact that the 222 Rn concentrations of the two are quite different. In the third method, we used the differing 222 Rn concentrations in vadose water and in retention water to analyze the pressure acting on the aquifer or the groundwater

  6. Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

    DEFF Research Database (Denmark)

    Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens

    2005-01-01

    Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...... has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range...... of asymptomatic MR (median serum IGF-1: 76.7 µg/L; 25-75 percentile, 59.8-104.9 µg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated...

  7. Natural Circulation Phenomena and Modelling for Advanced Water Cooled Reactors

    International Nuclear Information System (INIS)

    2012-03-01

    The role of natural circulation in advanced water cooled reactor design has been extended with the adoption of passive safety systems. Some designs utilize natural circulation to remove core heat during normal operation. Most passive safety systems used in evolutionary and innovative water cooled reactor designs are driven by natural circulation. The use of passive systems based on natural circulation can eliminate the costs associated with the installation, maintenance and operation of active systems that require multiple pumps with independent and redundant electric power supplies. However, considering the weak driving forces of passive systems based on natural circulation, careful design and analysis methods must be employed to ensure that the systems perform their intended functions. Several IAEA Member States with advanced reactor development programmes are actively conducting investigations of natural circulation to support the development of advanced water cooled reactor designs with passive safety systems. To foster international collaboration on the enabling technology of passive systems that utilize natural circulation, in 2004 the IAEA initiated a coordinated research project (CRP) on Natural Circulation Phenomena, Modelling and Reliability of Passive Systems that Utilize Natural Circulation. Three reports were published within the framework of this CRP. The first report (IAEA-TECDOC-1474) contains the material developed for the first IAEA training course on natural circulation in water cooled nuclear power plants. The second report (IAEA-TECDOC-1624) describes passive safety systems in a wide range of advanced water cooled nuclear power plant designs, with the goal of gaining insights into system design, operation and reliability. This third, and last, report summarizes the research studies completed by participating institutes during the CRP period.

  8. Regulation of leucocyte homeostasis in the circulation.

    Science.gov (United States)

    Scheiermann, Christoph; Frenette, Paul S; Hidalgo, Andrés

    2015-08-01

    The functions of blood cells extend well beyond the immune functions of leucocytes or the respiratory and hemostatic functions of erythrocytes and platelets. Seen as a whole, the bloodstream is in charge of nurturing and protecting all organs by carrying a mixture of cell populations in transit from one organ to another. To optimize these functions, evolution has provided blood and the vascular system that carries it with various mechanisms that ensure the appropriate influx and egress of cells into and from the circulation where and when needed. How this homeostatic control of blood is achieved has been the object of study for over a century, and although the major mechanisms that govern it are now fairly well understood, several new concepts and mediators have recently emerged that emphasize the dynamism of this liquid tissue. Here we review old and new concepts that relate to the maintenance and regulation of leucocyte homeostasis in blood and briefly discuss the mechanisms for platelets and red blood cells. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  9. Modeling the Middle Jurassic ocean circulation

    Directory of Open Access Journals (Sweden)

    Maura Brunetti

    2015-10-01

    Full Text Available We present coupled ocean–sea-ice simulations of the Middle Jurassic (∼165 Ma when Laurasia and Gondwana began drifting apart and gave rise to the formation of the Atlantic Ocean. Since the opening of the Proto-Caribbean is not well constrained by geological records, configurations with and without an open connection between the Proto-Caribbean and Panthalassa are examined. We use a sea-floor bathymetry obtained by a recently developed three-dimensional (3D elevation model which compiles geological, palaeogeographical and geophysical data. Our original approach consists in coupling this elevation model, which is based on detailed reconstructions of oceanic realms, with a dynamical ocean circulation model. We find that the Middle Jurassic bathymetry of the Central Atlantic and Proto-Caribbean seaway only allows for a weak current of the order of 2 Sv in the upper 1000 m even if the system is open to the west. The effect of closing the western boundary of the Proto-Caribbean is to increase the transport related to barotropic gyres in the southern hemisphere and to change water properties, such as salinity, in the Neo-Tethys. Weak upwelling rates are found in the nascent Atlantic Ocean in the presence of this superficial current and we discuss their compatibility with deep-sea sedimentological records in this region.

  10. The epistemological status of general circulation models

    Science.gov (United States)

    Loehle, Craig

    2018-03-01

    Forecasts of both likely anthropogenic effects on climate and consequent effects on nature and society are based on large, complex software tools called general circulation models (GCMs). Forecasts generated by GCMs have been used extensively in policy decisions related to climate change. However, the relation between underlying physical theories and results produced by GCMs is unclear. In the case of GCMs, many discretizations and approximations are made, and simulating Earth system processes is far from simple and currently leads to some results with unknown energy balance implications. Statistical testing of GCM forecasts for degree of agreement with data would facilitate assessment of fitness for use. If model results need to be put on an anomaly basis due to model bias, then both visual and quantitative measures of model fit depend strongly on the reference period used for normalization, making testing problematic. Epistemology is here applied to problems of statistical inference during testing, the relationship between the underlying physics and the models, the epistemic meaning of ensemble statistics, problems of spatial and temporal scale, the existence or not of an unforced null for climate fluctuations, the meaning of existing uncertainty estimates, and other issues. Rigorous reasoning entails carefully quantifying levels of uncertainty.

  11. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Directory of Open Access Journals (Sweden)

    Peter R. C. Gascoyne

    2014-03-01

    Full Text Available Dielectrophoresis (DEP is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a the principles of DEP; (b the biological basis for the dielectric differences between CTCs and blood cells; (c why such differences are expected to be present for all types of tumors; and (d instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  12. Circulating tumor cells in lung cancer.

    Science.gov (United States)

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. Copyright © 2012 S. Karger AG, Basel.

  13. Microfluidic Platform for Circulating Tumor Cells Isolation

    Energy Technology Data Exchange (ETDEWEB)

    Figueras-Mari, I.; Rodriguez-Trujillo, L.; Samitier-Marti, J.

    2016-07-01

    Circulating tumor cells (CTCs) are released from primary tumors into the bloodstream and transported to distant organs, promoting metastasis, which is known to be responsible for most cancer‐related deaths. Currently tumors are not found until symptoms appear or by chance when the patient undergoes a medical test, which in both situations can be too late. Once a tumor is found it is studied from tissue samples obtained directly from the patient in an invasive way. This invasive procedure is known as biopsy and apart from being invasive, it is costly, time consuming and can sometimes be painful and even risky for the patients’ health condition. Therefore, CTCs detection in blood also addressed as “liquid biopsy” would be very useful because by running routine blood analysis CTCs could be detected and collected suggesting tumor presence. However, due to the scarce presence in blood of these cells and to the huge amount of contamination from other cellular components a perfect method providing good capture and purity of CTCs has not been developed yet. In this project, a spiral size sorter microfluidic device has been manufactured and tested in order to determine its performance and limitations. Device performance was tested with different dilutions of healthy donor blood samples mixed with 30 micron particles simulating CTCs. The results obtained from these experiments show very good CTC recovery of up to 100% and the depletion of blood cellular components is around 99.9%. (Author)

  14. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Gascoyne, Peter R. C., E-mail: pgascoyn@mdanderson.org [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Shim, Sangjo [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, C0800, Austin, TX 78712 (United States); Present address: Micro & Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, 208 North Wright Street, Urbana, IL 61801 (United States)

    2014-03-12

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  15. Circulating CXCL16 in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Usama Elewa

    2016-09-01

    Full Text Available Background/Aims: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. Methods: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. Results: Plasma CXCL16 levels were 4.0±0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33±1.03 vs 3.88±0.86 ng/ml; p=0.013. In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. Conclusion: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels.

  16. Isolation of Circulating Tumor Cells by Dielectrophoresis

    International Nuclear Information System (INIS)

    Gascoyne, Peter R. C.; Shim, Sangjo

    2014-01-01

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies

  17. Methods of quantifying circulating IgE

    International Nuclear Information System (INIS)

    Merrett, T.G.; Merrett, J.

    1978-01-01

    Four radioimmunoassay techniques, two conventional and two sandwich, have been used to measure circulating IgE levels in 100 sera. The test sera had IgE levels ranging from 1.0 to 20,000 u/ml, and each was measured at five dilutions, ranging from three-fold to 400-fold. The same IgE standards were used throughout, and the optimal range for each assay was determined by assessing data for quality control sera and the WHO standard 69/204. To be of general use in the United Kingdom an IgE test must measure accurately levels as low as 20-30 u IgE/ml. The Phadebas RIST method failed to meet this criterion, and of the remaining tests the double antibody method had the most useful operating range and produced the most reliable results. However, the double antibody method is not available commercially and so, for the majority of laboratories, the Phadebas PRIST technique should be the method chosen. (author)

  18. Isotopes as tracers of the oceanic circulation: Results from the World Ocean Circulation Experiment

    International Nuclear Information System (INIS)

    Schlosser, P.; Jenkins, W.J.; Key, R.; Lupton, J.

    2002-01-01

    During the past decades, natural and anthropogenic isotopes such as tritium ( 3 H), radiocarbon ( 14 C), 3 He, or the stable isotopes of water have been used in studies of the dynamics of natural systems. Early applications of tracers to studies of the ocean were directed at determination of circulation patterns and mean residence times of specific water masses, as well as estimates of mixing coefficients. These exploratory studies suggested that tracers can add significantly to our understanding of the oceanic circulation. In order to fully exploit this potential, the first global tracer study, the GEochemical Ocean SECtions Study (GEOSECS), was launched. From the GEOSECS results it was immediately apparent that very close coordination of tracer programs with physical oceanography studies is required for full utilization of tracer data. During the 1980s plans for the World OCean Experiment (WOCE) were developed. As part of its Hydrographic Program (WHP), especially during the one-time survey, a set of tracers were measured on a global scale with unprecedented spatial resolution (both lateral and vertical). The original plan included a larger number of tracers (CFCs, 3 H/ 3 He, 14 C, 39 Ar, stable isotopes of water, helium isotopes, 228 Ra, 90 Sr, 137 Cs, 85 Kr) than could actually be measured systematically (CFCs, 3 H/ 3 He, 14 C, H 2 18 O/H 2 16 O, helium isotopes). Nevertheless, the resulting data set, which presently is under evaluation, exceeds those obtained from pre-WOCE tracer studies by a wide margin. In this contribution, we describe the existing WOCE data set and demonstrate the type of results that can be expected from its interpretation on the basis of a few selected examples. These examples include: (1) the application of tritium and 3 He to studies of the ventilation of the upper waters in the Pacific Ocean, (2) the spreading of intermediate water in the Pacific and Indian oceans as derived from the distribution of 3 He, and (3) the evaluation of

  19. Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

    Science.gov (United States)

    Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

    2015-07-01

    Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc

  20. Circulation in the Mediterranean Sea: evidences, debates and unanswered questions

    Directory of Open Access Journals (Sweden)

    Claude Millot

    2005-06-01

    Full Text Available The overall counterclockwise alongslope circulation of Atlantic Water (AW in the western basin of the Mediterranean Sea is now generally accepted. As the eastern basin displays similar general features, why is it generally assumed to function in a different way, and why is AW now said to circulate across the interior of the eastern basin? Relatively huge mesoscale anticyclonic eddies induced by the instability of the AW circulation in the south of the western basin have lifetimes up to several years. It is possible that they extend down to the sea bottom and play a major role in the distribution of all water masses. Why have apparently similar eddies generated in the eastern basin never received specific attention? Once formed, Mediterranean Waters (MWs must spread and circulate before outflowing. Why have simple dynamical arguments for understanding the circulation of AW, such as the Coriolis effect, rarely been considered for the circulation of MWs? In this paper we address these major aspects of water circulation in the Mediterranean Sea. In order to be as objective and convincing as possible, and to write a paper that can be understood by as broad a readership as possible, we have chosen to present only raw data sets that can be easily interpreted by the reader without any help from the author. Based on the evidence provided by these data sets, we specify the current debates and list what we think are the main unanswered questions.

  1. Characteristic of onset of nucleate boiling in natural circulation

    International Nuclear Information System (INIS)

    Zhou Tao; Yang Ruichang; Liu Ruolei

    2006-01-01

    Two kinds of thermodynamics quality at onset of nucleate boiling with sub-cooled boiling were calculated for force circulation by using Bergles and Rohesenow method or Davis and Anderson method, and natural circulation by using Tsinghua University project group's empirical equations suggested in our natural circulation experiment at same condition. The characteristic of onset of nucleate boiling with subcooled boiling in natural circulation were pointed out. The research result indicates that the thermodynamics quality at onset of nucleate boiling with subcooled boiling in natural circulation is more sensitive for heat and inlet temperature and system pressure. Producing of onset of nucleate boiling with subcooled boiling is early at same condition. The research result also indicates more from microcosmic angle of statistical physics that the phenomena are caused by the effects of characteristic of dissipative structure of natural circulation in self organization, fluctuation force and momentum force of dynamics on thermodynamics equilibrium. these can lay good basis for study and application on sub-cooled boiling in natural circulation in future. (authors)

  2. West Nile Virus Surveillance in 2013 via Mosquito Screening in Northern Italy and the Influence of Weather on Virus Circulation

    Science.gov (United States)

    Calzolari, Mattia; Pautasso, Alessandra; Montarsi, Fabrizio; Albieri, Alessandro; Bellini, Romeo; Bonilauri, Paolo; Defilippo, Francesco; Lelli, Davide; Moreno, Ana; Chiari, Mario; Tamba, Marco; Zanoni, Mariagrazia; Varisco, Giorgio; Bertolini, Silvia; Modesto, Paola; Radaelli, Maria Cristina; Iulini, Barbara; Prearo, Marino; Ravagnan, Silvia; Cazzin, Stefania; Mulatti, Paolo; Monne, Isabella; Bonfanti, Lebana; Marangon, Stefano; Goffredo, Maria; Savini, Giovanni; Martini, Simone; Mosca, Andrea; Farioli, Marco; Gemma Brenzoni, Laura; Palei, Manlio; Russo, Francesca; Natalini, Silvano; Angelini, Paola; Casalone, Cristina; Dottori, Michele; Capelli, Gioia

    2015-01-01

    West Nile virus (WNV) is a recently re-emerged health problem in Europe. In Italy, an increasing number of outbreaks of West Nile disease, with occurrences of human cases, have been reported since 2008. This is particularly true in northern Italy, where entomological surveillance systems have been implemented at a regional level. The aim of this study was to use, for the first time, all the entomological data collected in the five regions undergoing surveillance for WNV in northern Italy to characterize the viral circulation (at a spatial and temporal scale), identify potential mosquito vectors, and specify relationships between virus circulation and meteorological conditions. In 2013, 286 sites covering the entire Pianura Padana area were monitored. A total of 757,461 mosquitoes were sampled. Of these, 562,079 were tested by real-time PCR in 9,268 pools, of which 180 (1.9%) were positive for WNV. The largest part of the detected WNV sequences belonged to lineage II, demonstrating that, unlike those in the past, the 2013 outbreak was mainly sustained by this WNV lineage. This surveillance also detected the Usutu virus, a WNV-related flavivirus, in 241 (2.6%) pools. The WNV surveillance systems precisely identified the area affected by the virus and detected the viral circulation approximately two weeks before the occurrence of onset of human cases. Ninety percent of the sampled mosquitoes were Culex pipiens, and 178/180 WNV-positive pools were composed of only this species, suggesting this mosquito is the main WNV vector in northern Italy. A significantly higher abundance of the vector was recorded in the WNV circulation area, which was characterized by warmer and less rainy conditions and greater evapotranspiration compared to the rest of the Pianura Padana, suggesting that areas exposed to these conditions are more suitable for WNV circulation. This observation highlights warmer and less rainy conditions as factors able to enhance WNV circulation and cause virus

  3. Evidence of the Lower Thermospheric Winter-to-Summer Circulation

    Science.gov (United States)

    Qian, L.; Burns, A. G.; Yue, J.

    2017-12-01

    Numerical studies showed that the lower thermospheric winter-to-summer circulation is driven by wave dissipation, and it plays a significant role in trace gas distributions in the mesosphere and lower thermosphere (MLT), and in the composition of the thermosphere. Direct observations of this circulation are difficult. However, it leaves clear signatures in tracer distributions. Recent analysis of CO2 observed by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) onboard the Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite showed dynamically driven dense isolines of CO2 at summer high latitudes. We conduct modeling and observational studies to understand the CO2 distribution and circulation patterns in the MLT. We found that there exists maximum vertical gradient of CO2 at summer high latitudes, driven by the convergence of the upwelling of the mesospheric circulation and the downwelling of the lower thermospheric circulation; this maximum vertical gradient of CO2 is located at a higher altitude in the winter hemisphere, driven by the convergence of the upwelling of the lower thermospheric circulation and the downwelling of the solar-driven thermospheric circulation. Based on SABER CO2 distribution, the bottom of the lower thermospheric circulation is located between 95 km and 100 km, and it has a vertical extent of 10 km. Analysis of the SABER CO2 and temperature at summer high latitudes showed that the bottom of this circulation is consistently higher than the mesopause height by 10 km; and its location does not change much between solar maximum and solar minimum.

  4. Gas-cooled reactor coolant circulator and blower technology

    International Nuclear Information System (INIS)

    1988-08-01

    In the previous 17 meetings held within the framework of the International Working Group on Gas-Cooled Reactors, a wide variety of topics and components have been addressed, but the San Diego meeting represented the first time that a group of specialists had been convened to discuss circulator and blower related technology. A total of 20 specialists from 6 countries attended the meeting in which 15 technical papers were presented in 5 sessions: circulator operating experience I and II (6 papers); circulator design considerations I and II (6 papers); bearing technology (3 papers). A separate abstract was prepared for each of these papers. Refs, figs and tabs

  5. Natural circulation in an integral CANDU test facility

    International Nuclear Information System (INIS)

    Ingham, P.J.; Sanderson, T.V.; Luxat, J.C.; Melnyk, A.J.

    2000-01-01

    Over 70 single- and two-phase natural circulation experiments have been completed in the RD-14M facility, an integral CANDU thermalhydraulic test loop. This paper describes the RD-14M facility and provides an overview of the impact of key parameters on the results of natural circulation experiments. Particular emphasis will be on phenomena which led to heat up at high system inventories in a small subset of experiments. Clarification of misunderstandings in a recently published comparison of the effectiveness of natural circulation flows in RD-14M to integral facilities simulating other reactor geometries will also be provided. (author)

  6. Nongeostrophic theory of zonally averaged circulation. I - Formulation

    Science.gov (United States)

    Tung, Ka Kit

    1986-01-01

    A nongeostrophic theory of zonally averaged circulation is formulated using the nonlinear primitive equations (mass conservation, thermodynamics, and zonal momentum) on a sphere. The relationship between the mean meridional circulation and diabatic heating rate is studied. Differences between results of nongeostropic theory and the geostrophic formulation concerning the role of eddy forcing of the diabatic circulation and the nonlinear nearly inviscid limit versus the geostrophic limit are discussed. Consideration is given to the Eliassen-Palm flux divergence, the Eliassen-Palm pseudodivergence, the nonacceleration theorem, and the nonlinear nongeostrophic Taylor relationship.

  7. The circulation of Amway's discourse: from control to social practice

    OpenAIRE

    Brunelli, Anna Flora

    2013-01-01

    In this paper, we intend to contribute to the debate about the circulation of the discourses. To do that, we analyze aspects regarding the circulation of Amway's discourse, a North-American network sales company that has been working in Brazil for a while. Precisely, we analyze the conditions of this circulation at the time it was more intensively, ie, in the 90s, when there were thousands of people in several parts of the country selling the company's products or consuming them. This study h...

  8. Natural-circulation-cooling characteristics during PWR accident simulations

    International Nuclear Information System (INIS)

    Adams, J.P.; McCreery, G.E.; Berta, V.T.

    1983-01-01

    A description of natural circulation cooling characteristics is presented. Data were obtained from several pressurized water reactor accident simulations in the Loss-of-Fluid Test (LOFT) pressurized water reactor (PWR). The reliability of natural circulation cooling, its cooling effectiveness, and the effect of changing system conditions are described. Quantitative comparison of flow rates and time constants with theory for both single- and two-phase fluid conditions were made. It is concluded that natural circulation cooling can be relied on in plant recovery procedures in the absence of forced convection whenever the steam generator heat sink is available

  9. Study of the effects of D2O circulation

    International Nuclear Information System (INIS)

    Oblath, N.S.; Poon, A.W.P.

    2000-01-01

    The Sudbury Neutrino Observatory (SNO) has been collecting data since November 1999. The study of whether or not the D 2 O circulation affects the data is an important part of understanding how the SNO detector behaves. This report looks at several characteristics of the data to determine to what extent the D 2 O circulation affects the data. We found that there is no evidence for any dependence of event rates in the cleaned data sets on the state of D 2 O circulation

  10. Filthy lucre: A metagenomic pilot study of microbes found on circulating currency in New York City.

    Directory of Open Access Journals (Sweden)

    Julia M Maritz

    Full Text Available Paper currency by its very nature is frequently transferred from one person to another and represents an important medium for human contact with-and potential exchange of-microbes. In this pilot study, we swabbed circulating $1 bills obtained from a New York City bank in February (Winter and June (Summer 2013 and used shotgun metagenomic sequencing to profile the communities found on their surface. Using basic culture conditions, we also tested whether viable microbes could be recovered from bills.Shotgun metagenomics identified eukaryotes as the most abundant sequences on money, followed by bacteria, viruses and archaea. Eukaryotic assemblages were dominated by human, other metazoan and fungal taxa. The currency investigated harbored a diverse microbial population that was dominated by human skin and oral commensals, including Propionibacterium acnes, Staphylococcus epidermidis and Micrococcus luteus. Other taxa detected not associated with humans included Lactococcus lactis and Streptococcus thermophilus, microbes typically associated with dairy production and fermentation. Culturing results indicated that viable microbes can be isolated from paper currency.We conducted the first metagenomic characterization of the surface of paper money in the United States, establishing a baseline for microbes found on $1 bills circulating in New York City. Our results suggest that money amalgamates DNA from sources inhabiting the human microbiome, food, and other environmental inputs, some of which can be recovered as viable organisms. These monetary communities may be maintained through contact with human skin, and DNA obtained from money may provide a record of human behavior and health. Understanding these microbial profiles is especially relevant to public health as money could potentially mediate interpersonal transfer of microbes.

  11. Circulating tumor cells and circulating tumor DNA: What surgical oncologists need to know?

    Science.gov (United States)

    Cabel, L; Proudhon, C; Mariani, P; Tzanis, D; Beinse, G; Bieche, I; Pierga, J-Y; Bidard, F-C

    2017-05-01

    As a result of recent progress in detection techniques, circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) can now be accurately detected in the blood of most cancer patients. While these new biomarkers can provide a better understanding of key biological mechanisms underlying cancer growth and dissemination, they also open up a wide range of possible clinical applications in medical oncology, radiation oncology and surgical oncology. In this review, we summarize the results obtained with ctDNA and CTC together with their potential future clinical applications in the field of surgical oncology, with particular focus on the perioperative setting of various types of cancer. These applications include, but are not limited to, cancer screening, early diagnosis, prognostic assessment, evaluation and management of preoperative systemic or local therapies, post-surgical detection of minimal residual disease and early detection of cancer relapse. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  12. Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation

    International Nuclear Information System (INIS)

    Molloy, Janelle A.

    2010-01-01

    Purpose: Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these ''sequential'' techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Methods: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than ±10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times

  13. Statistical analysis of dose heterogeneity in circulating blood: implications for sequential methods of total body irradiation.

    Science.gov (United States)

    Molloy, Janelle A

    2010-11-01

    Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these "sequential" techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than +/- 10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times. However, the EUD was

  14. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

    Directory of Open Access Journals (Sweden)

    Peter Arner

    Full Text Available Cancer cachexia (CC is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32 or without (n = 27 cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1 was confirmed by sandwich immunoassay to be lower in CC (p = 0.008. In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  15. Ticagrelor Improves Endothelial Function by Decreasing Circulating Epidermal Growth Factor (EGF

    Directory of Open Access Journals (Sweden)

    Francesco Vieceli Dalla Sega

    2018-04-01

    Full Text Available Ticagrelor is one of the most powerful P2Y12 inhibitor. We have recently reported that, in patients with concomitant Stable Coronary Artery Disease (SCAD and Chronic Obstructive Pulmonary Disease (COPD undergoing percutaneous coronary intervention (PCI, treatment with ticagrelor, as compared to clopidogrel, is associated with an improvement of the endothelial function (Clinical Trial NCT02519608. In the present study, we showed that, in the same population, after 1 month treatment with ticagrelor, but not with clopidogrel, there is a decrease of the circulating levels of epidermal growth factor (EGF and that these changes in circulating levels of EGF correlate with on-treatment platelet reactivity. Furthermore, in human umbilical vein endothelial cells (HUVEC incubated with sera of the patients treated with ticagrelor, but not with clopidogrel there is an increase of p-eNOS levels. Finally, analyzing the changes in EGF and p-eNOS levels after treatment, we observed an inverse correlation between p-eNOS and EGF changes only in the ticagrelor group. Causality between EGF and eNOS activation was assessed in vitro in HUVEC where we showed that EGF decreases eNOS activity in a dose dependent manner. Taken together our data indicate that ticagrelor improves endothelial function by lowering circulating EGF that results in the activation of eNOS in the vascular endothelium.

  16. Observing a fictitious stressful event: haematological changes, including circulating leukocyte activation.

    Science.gov (United States)

    Mian, Rubina; Shelton-Rayner, Graham; Harkin, Brendan; Williams, Paul

    2003-03-01

    The aim of this study was to assess the effect of watching a psychological stressful event on the activation of leukocytes in healthy human volunteers. Blood samples were obtained from 32 healthy male and female subjects aged between 20 and 26 years before, during and after either watching an 83-minute horror film that none of the subjects had previously seen (The Texas Chainsaw Massacre, 1974) or by sitting quietly in a room (control group). Total differential cell counts, leukocyte activation as measured by the nitroblue tetrazolium (NBT) test, heart rate and blood pressure (BP) measurements were taken at defined time points. There were significant increases in peripheral circulating leukocytes, the number of activated circulating leukocytes, haemoglobin (Hb) concentration and haematocrit (Hct) in response to the stressor. These were accompanied by significant increases in heart rate, systolic and diastolic BP (P<0.05 from baseline). This is the first reported study on the effects of observing a psychologically stressful, albeit fictitious event on circulating leukocyte numbers and the state of leukocyte activation as determined by the nitrotetrazolium test.

  17. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

    Science.gov (United States)

    Lacroix, Romaric; Plawinski, Laurent; Robert, Stéphane; Doeuvre, Loïc; Sabatier, Florence; Martinez de Lizarrondo, Sara; Mezzapesa, Anna; Anfosso, Francine; Leroyer, Aurelie S.; Poullin, Pascale; Jourde, Noémie; Njock, Makon-Sébastien; Boulanger, Chantal M.; Anglés-Cano, Eduardo; Dignat-George, Françoise

    2012-01-01

    Background We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and Methods Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography. Results Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes. Conclusions Endothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium. PMID:22733025

  18. Weakened tropical circulation and reduced precipitation in response to geoengineering

    International Nuclear Information System (INIS)

    Ferraro, Angus J; Highwood, Eleanor J; Charlton-Perez, Andrew J

    2014-01-01

    Geoengineering by injection of reflective aerosols into the stratosphere has been proposed as a way to counteract the warming effect of greenhouse gases by reducing the intensity of solar radiation reaching the surface. Here, climate model simulations are used to examine the effect of geoengineering on the tropical overturning circulation. The strength of the circulation is related to the atmospheric static stability and has implications for tropical rainfall. The tropical circulation is projected to weaken under anthropogenic global warming. Geoengineering with stratospheric sulfate aerosol does not mitigate this weakening of the circulation. This response is due to a fast adjustment of the troposphere to radiative heating from the aerosol layer. This effect is not captured when geoengineering is modelled as a reduction in total solar irradiance, suggesting caution is required when interpreting model results from solar dimming experiments as analogues for stratospheric aerosol geoengineering. (letter)

  19. The South China Sea Thermohaline Structure and Circulation

    National Research Council Canada - National Science Library

    Chu, Peter C; Ma, Binbing; Chen, Yuchun

    2002-01-01

    ...), consisting of 116,019 temperature and 9,617 salinity profiles, during 1968-1984 to investigate the temporal and spatial variabilities of South China Sea thermohaline structures and circulation...

  20. Evaluation of Circulating Current Suppression Methods for Parallel Interleaved Inverters

    DEFF Research Database (Denmark)

    Gohil, Ghanshyamsinh Vijaysinh; Bede, Lorand; Teodorescu, Remus

    2016-01-01

    Two-level Voltage Source Converters (VSCs) are often connected in parallel to achieve desired current rating in multi-megawatt Wind Energy Conversion System (WECS). A multi-level converter can be realized by interleaving the carrier signals of the parallel VSCs. As a result, the harmonic perfor......-mance of the WECS can be significantly improved. However, the interleaving of the carrier signals may lead to the flow of circulating current between parallel VSCs and it is highly desirable to avoid/suppress this unwanted circulating current. A comparative evaluation of the different methods to avoid....../suppress the circulating current between the parallel interleaved VSCs is presented in this paper. The losses and the volume of the inductive components and the semiconductor losses are evaluated for the WECS with different circulating current suppression methods. Multi-objective optimizations of the inductive components...

  1. Circulation and geostrophic transport in the Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, D.P.; Murty, V.S.N.

    Utilising the hydrographic data collected during the early northeast monsoon of 1983 and southwest monsoon of 1984, the circulation of waters of the Bay of Bengal and the associated volume transport have been studied in the upper 1000 m...

  2. Analysis of the hydrodynamic stability of natural circulation

    International Nuclear Information System (INIS)

    Olive, J.; Baby, J.P.

    1980-01-01

    A mathematical model (EOLE) for the analysis of the stability of boilers with natural circulation is discussed. The method employed consists in linearizing one-dimensional flow equations and in integrating them while employing the Laplace transformation. The properties of a two-phase fluid are schematized by a homogeneous model with slip. The computation results in the circulation loop transfer functions and its natural modes of oscillation (frequency and damping). A discussion follows which compares results obtained with this method to those of other existing models in the case of a straight pipe with forced circulation. Agreement proved to be satisfactory. The results are then given of a parametric study involving the stability of a PWR natural circulation steam generator. These results show that the model can satisfy, at least qualitatively, trends observed empirically or obtained with other more complex theoretical models. (author)

  3. LEUKOCYTE AND PLATELET ACTIVATION DURING EXTRACORPOREAL-CIRCULATION

    NARCIS (Netherlands)

    VANOEVEREN, W

    1994-01-01

    Extracorporeal circulation of blood has become a routine procedure in plasmapheresis, hemodialysis and cardiopulmonary bypass. Specifically in cardiopulmonary bypass, blood is exposed to a large material surface area, which induces an inflammatory reaction and bleeding disorders. It has been

  4. Circulating mesenchymal stem cells and their clinical implications

    Directory of Open Access Journals (Sweden)

    Liangliang Xu

    2014-01-01

    Full Text Available Circulating mesenchymal stem cells (MSCs is a new cell source for tissue regeneration and tissue engineering. The characteristics of circulating MSCs are similar to those of bone marrow-derived MSCs (BM-MSCs, but they exist at a very low level in healthy individuals. It has been demonstrated that MSCs are able to migrate to the sites of injury and that they have some distinct genetic profiles compared to BM-MSCs. The current review summaries the basic knowledge of circulating MSCs and their potential clinical applications, such as mobilizing the BM-MSCs into circulation for therapy. The application of MSCs to cure a broad spectrum of diseases is promising, such as spinal cord injury, cardiovascular repair, bone and cartilage repair. The current review also discusses the issues of using of allogeneic MSCs for clinical therapy.

  5. Natural circulation cooling in US pressurized water reactors

    International Nuclear Information System (INIS)

    Berta, V.T.; Wilson, G.E.; Boyack, B.E.

    1989-01-01

    The research into the modes of, and heat removed by, natural circulation in PWR systems is reviewed for the purpose of determining the status of this method for off-nominal recovery procedures. The referenced information comes from all facets of the nuclear industry, both domestic and international. The information focuses on recent research (1986--1988); however, pre-1986 research is summarized and referenced. Particular attention is paid to the role of scaling in the experimental facilities and analytical tools. Three modes of natural-circulation cooling are covered: condensation. The conclusion of the review is that the new research reconfirms the pre-1986 conclusion that natural circulation is a viable means of decay heat removal. In addition, the new research sufficiently completes the acquisition of an appropriate experimental data base and the development of system codes to permit the design of valid plant recovery procedures incorporating all three modes of natural circulation. 48 refs., 1 fig., 3 tabs

  6. performance simulation of a natural circulation solar air

    African Journals Online (AJOL)

    User

    in a single glazed flat plate natural circulation solar a prepared in modules .... Nigerian Journal of Technology, used instead of ... boundary associated with the melting the phase ...... Mathematical Modeling of the Thin Layer Drying of Sweet ...

  7. Main gas circulator for VG-400 reactor plant

    International Nuclear Information System (INIS)

    Mitenkov, F.M.; Kostin, V.I.; Novinskij, E.G.; Kuropatov, A.I.; Protsenko, A.N.; Smirnov, V.P.; Stolyarevskij, A.Ya.

    1988-01-01

    Principle parameters and operating conditions of the main gas circulator (MGC) in VG-400 reactor plant are presented. Brief MGC design description and experimental work scope are given. (author). 4 refs, 4 figs, 1 tab

  8. Ocean Circulation and Mixing Relevant to the Global System

    National Research Council Canada - National Science Library

    Gordon, Arnold

    1999-01-01

    .... Arlindo's goal is to resolve the circulation and water mass stratification within the Indonesian Seas in order to formulate a thorough description of the source, spreading patterns, inter-ocean...

  9. 40 CFR 230.23 - Current patterns and water circulation.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Current patterns and water circulation. 230.23 Section 230.23 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN... the water body; and water stratification. ...

  10. An Oceanic General Circulation Model (OGCM) investigation of the Red Sea circulation: 2. Three-dimensional circulation in the Red Sea

    Science.gov (United States)

    Sofianos, Sarantis S.; Johns, William E.

    2003-03-01

    The three-dimensional circulation of the Red Sea is studied using a set of Miami Isopycnic Coordinate Ocean Model (MICOM) simulations. The model performance is tested against the few available observations in the basin and shows generally good agreement with the main observed features of the circulation. The main findings of this analysis include an intensification of the along-axis flow toward the coasts, with a transition from western intensified boundary flow in the south to eastern intensified flow in the north, and a series of strong seasonal or permanent eddy-like features. Model experiments conducted with different forcing fields (wind-stress forcing only, surface buoyancy forcing only, or both forcings combined) showed that the circulation produced by the buoyancy forcing is stronger overall and dominates the wind-driven part of the circulation. The main circulation pattern is related to the seasonal buoyancy flux (mostly due to the evaporation), which causes the density to increase northward in the basin and produces a northward surface pressure gradient associated with the downward sloping of the sea surface. The response of the eastern boundary to the associated mean cross-basin geostrophic current depends on the stratification and β-effect. In the northern part of the basin this results in an eastward intensification of the northward surface flow associated with the presence of Kelvin waves while in the south the traditional westward intensification due to Rossby waves takes place. The most prominent gyre circulation pattern occurs in the north where a permanent cyclonic gyre is present that is involved in the formation of Red Sea Outflow Water (RSOW). Beneath the surface boundary currents are similarly intensified southward undercurrents that carry the RSOW to the sill to flow out of the basin into the Indian Ocean.

  11. Flow and separation in gas centrifuge with Beams type circulation

    International Nuclear Information System (INIS)

    Ajsen, Eh.M.; Borisevich, V.D.; Levin, E.V.

    1992-01-01

    Structure of the secondary circulation flows in the working chamber of gas centrifuge for uranium isotope separation is studied using the numerical methods. Influence of the circulation thermal component on the centrifuge efficiency is analyzed. The contribution of useful component concentration difference of binary isotope mixture in feeding flows to the centrifuge efficiency is determined. Dependence of concentration optimal difference, whereby the maximum efficiency is achieved, on temperature distribution on the rotor side wall is found

  12. Dampening Enthusiasm for Circulating MicroRNA in Breast Cancer

    OpenAIRE

    Leidner, Rom S.; Li, Li; Thompson, Cheryl L.

    2013-01-01

    Genome-wide platforms for high-throughput profiling of circulating miRNA (oligoarray or miR-Seq) offer enormous promise for agnostic discovery of circulating miRNA biomarkers as a pathway for development in breast cancer detection. By harmonizing data from 15 previous reports, we found widespread inconsistencies across prior studies. Whether this arises from differences in study design, such as sample source or profiling platform, is unclear. As a reproducibility experiment, we generated a ge...

  13. Calculation analysis on steady state natural circulation characteristics

    International Nuclear Information System (INIS)

    Wang Fei; Nie Changhua; Huang Yanping

    2005-01-01

    The calculation results of single-phase steady state natural circulation characteristics by using Retran02 code have been presented, good agreement is achieved between the verified calculation result and the experimental data which were conducted at a test facility. Based on the calculation model, some sensibility analyses were made and much deeper understanding for single-phase steady state natural circulation characteristics was obtained. (author)

  14. BIM-enabled Conceptual Modelling and Representation of Building Circulation

    OpenAIRE

    Lee, Jin Kook; Kim, Mi Jeong

    2014-01-01

    This paper describes how a building information modelling (BIM)-based approach for building circulation enables us to change the process of building design in terms of its computational representation and processes, focusing on the conceptual modelling and representation of circulation within buildings. BIM has been designed for use by several BIM authoring tools, in particular with the widely known interoperable industry foundation classes (IFCs), which follow an object-oriented data modelli...

  15. Asian genotype of Chikungunya virus circulating in Venezuela during 2014.

    Science.gov (United States)

    Camacho, Daría; Reyes, Jesús; Negredo, Ana; Hernández, Lourdes; Sánchez-Seco, María; Comach, Guillermo

    2017-10-01

    Chikungunya virus emerged on Saint-Martin Island in the Caribbean in late 2013. Since then in July of 2104 Venezuela reported autochthonous cases. This study reports the first phylogenetic characterization of CHIKV autochthonous cases in Venezuela, 2014. The phylogenetic analysis showed that the CHIKV circulating in Venezuela (Aragua state) belong to the Asian genotype (Caribbean clade) and it is related to viruses that circulated in the same year in the Caribbean. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Melanocortin signaling in the CNS directly regulates circulating cholesterol

    OpenAIRE

    Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

    2010-01-01

    Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

  17. Twentieth century Walker Circulation change: data analysis and model experiments

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Qingjia [Leibniz-Institut fuer Meereswissenschaften, Kiel (Germany); Chinese Research Academy of Environmental Sciences, River and Coastal Environment Research Center, Beijing (China); Chinese Academy of Sciences, Key Laboratory of Ocean Circulation and Waves, Institute of Oceanology, Qingdao (China); Latif, Mojib; Park, Wonsun; Keenlyside, Noel S.; Martin, Thomas [Leibniz-Institut fuer Meereswissenschaften, Kiel (Germany); Semenov, Vladimir A. [Leibniz-Institut fuer Meereswissenschaften, Kiel (Germany); A.M. Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences, Moscow (Russian Federation)

    2012-05-15

    Recent studies indicate a weakening of the Walker Circulation during the twentieth century. Here, we present evidence from an atmospheric general circulation model (AGCM) forced by the history of observed sea surface temperature (SST) that the Walker Circulation may have intensified rather than weakened. Observed Equatorial Indo-Pacific Sector SST since 1870 exhibited a zonally asymmetric evolution: While the eastern part of the Equatorial Pacific showed only a weak warming, or even cooling in one SST dataset, the western part and the Equatorial Indian Ocean exhibited a rather strong warming. This has resulted in an increase of the SST gradient between the Maritime Continent and the eastern part of the Equatorial Pacific, one driving force of the Walker Circulation. The ensemble experiments with the AGCM, with and without time-varying external forcing, suggest that the enhancement of the SST gradient drove an anomalous atmospheric circulation, with an enhancement of both Walker and Hadley Circulation. Anomalously strong precipitation is simulated over the Indian Ocean and anomalously weak precipitation over the western Pacific, with corresponding changes in the surface wind pattern. Some sensitivity to the forcing SST, however, is noticed. The analysis of twentieth century integrations with global climate models driven with observed radiative forcing obtained from the Coupled Model Intercomparison Project (CMIP) database support the link between the SST gradient and Walker Circulation strength. Furthermore, control integrations with the CMIP models indicate the existence of strong internal variability on centennial timescales. The results suggest that a radiatively forced signal in the Walker Circulation during the twentieth century may have been too weak to be detectable. (orig.)

  18. Dynamical characteristics of the seasonal circulations over the Korea peninsula

    International Nuclear Information System (INIS)

    1989-10-01

    This paper reports dynamical characteristics of the seasonal circulations over the Korean peninsula. It consists of summary, research method, result, consideration and conclusion. It introduces the method of research ; characteristics of circulation over seasonal wind in Asia, characteristic of upper jet stream related cold wave and monsoon in East Asia and dynamics of pulsation and maintain of high atmospheric pressure in siberia in winter. It was reported by Korea science foundation in 1989.

  19. Computation of the q -th roots of circulant matrices

    Directory of Open Access Journals (Sweden)

    Pakizeh Mohammadi Khanghah

    2014-05-01

    Full Text Available In this paper‎, ‎we investigate the reduced form of circulant matrices‎ ‎and we show that the problem of computing the $q$-th roots of a‎ ‎nonsingular circulant matrix $A$ can be reduced to that of computing‎ ‎the $q$-th roots of two half size matrices $B-C$ and $B+C$. 

  20. Targeting tumor cell invasion and dissemination in vivo by an aptamer that inhibits urokinase-type plasminogen activator through a novel multifunctional mechanism

    DEFF Research Database (Denmark)

    Botkjaer, Kenneth A; Deryugina, Elena I; Dupont, Daniel Miotto

    2012-01-01

    , because the topology of the proteases' active sites are highly similar. In an effort to generate highly specific uPA inhibitors with new inhibitory modalities, we isolated uPA-binding RNA aptamers by screening a library of 35 nucleotides long 2'-fluoro-pyrimidine RNA molecules using a version of human pro......-uPA lacking the epidermal growth factor-like and kringle domains as bait. One pro-uPA-binding aptamer sequence, referred to as upanap-126, proved to be highly specific for human uPA. Upanap-126 delayed the proteolytic conversion of human pro-uPA to active uPA, but did not inhibit plasminogen activation...... catalyzed by two-chain uPA. The aptamer also inhibited the binding of pro-uPA to uPAR and the binding of vitronectin to the preformed pro-uPA/uPAR complex, both in cell-free systems and on cell surfaces. Furthermore, upanap-126 inhibited human tumor cell invasion in vitro in the Matrigel assay and in vivo...